Why Cannabis Is Medicine A Book by Leafwell PDF

Why
Cannabis
is Medicine
A guide
to understanding
medical marijuana
A book by With contributions by
LeafWell
Prof. Roger Pertwee
Prof Lumir Hanus
Prof. Jeff Raber
Dr. Michael Masterman-Smith
Mara Gordon
Dipak Hemraj
2
Acknowledgements
Dipak Hemraj, Emily Fisher, Rebecca Tanner-Rolf, Emily Ludolf, Mark Summers,
Prof. Roger Pertwee, Prof. Lumir Hanus, Mara Gordon, Dr. Michael Masterman-
Smith, Prof. Jeff Raber, Dr. Frank D’Ambrosio, Dr. Cristina Sanchez, Prof. William
DeVane, Prof. Raphael Mechoulam, Dr. Dedi Meiri, Dr. Ethan Russo, Digamma
Labs (Marco Troiani & Savino Sguera), Prof. David Nutt, and all the patients, carers,
doctors, scientists and cannabis enthusiasts who are helping us discover the
medical potential of this amazing plant.
LeafWell
3
Preface
Cannabis is a hugely misunderstood plant, and its legal status makes studying it
scientifically and getting to understand the plant even more difficult. Yet, even
if cannabis stopped being the maligned plant it is today, we would still have
great difficulty understanding it. Why? The pharmacology of cannabis and its
constituents - cannabinoids, terpenes/terpenoids, flavonoids and other parts, as
well as the interplay between them - is hugely complex. The legal issues and the
complex pharmacology are two main factors that prevent patients from truly
understanding why cannabis is medicine, and how to use it.
The purpose of this book and the Leafwell organization in general is to tackle
this complexity and make an otherwise very intricate, knotted and very young
area of science more easily understood, for patients, healthcare practitioners and
everyone else who wants to look beyond the hype and understand the potential
of cannabis as medicine.
LeafWell
Table of Contents
6 Introduction
10 The ECS: an Overview
12 Conversation with Dr. Lumir Hanus
17 History of Medical Cannabis
28 Chapter 1: The Endocannabinoid System

30 How Does the ECS Work?
34 The ECS and Its Parts
36 What Other Receptors Do Cannabinoids Affect?
40 Conversation with Prof. Roger Pertwee
49 Overall
52 Chapter 2: Cannabis and Conditions

54 Cannabis and Acne
56 Cannabis and Addiction Treatment
60 Cannabis and Alzheimer’s Disease
63 Cannabis and Amyotrophic Lateral Sclerosis (ALS) / Lou Gehrig’s Disease
65 Cannabis and Anterior Cruciate Ligament (ACL) Reconstruction
67 Cannabis and Anxiety
69 Cannabis and Arthritis
71 Cannabis and Attention Deficit Hyperactivity Disorder/Attention Deficit Disorder (ADHD/ADD)
73 Cannabis and Asthma
76 Cannabis and Autism/Asperger Syndrome
78 Cannabis and Autoimmune Disorders
80 Cannabis and Bipolar Disorder
83 Cannabis and Cardiovascular Diseases (CVDs)
88 Cannabis and Cancer
95 Conversation with Dr. Michael Masterman-Smith
101 Cannabis and Chronic Pain/Muscle Pain
104 Cannabis and Cystic Fibrosis (CF)
106 Cannabis and Diabetes
109 Cannabis and Depression
112 Cannabis and Eating Disorders
114 Cannabis and Eczema and Psoriasis
116 Cannabis and Ehlers-Danlos Syndrome (EDS)
119 Cannabis and Endometriosis
121 Cannabis and Epilepsy
125 Cannabis and Fibromyalgia
127 Cannabis and Glaucoma
130 Cannabis and HIV/AIDS
132 Cannabis and Huntington’s Disease (HD) aka Huntington’s Chorea
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134 Cannabis and Inflammatory Bowel Diseases (IBDs)
138 Cannabis and Insomnia
141 Cannabis and Kidney Disease/Kidney Failure
143 Cannabis and Migraine/Headache
145 Cannabis and Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS)
147 Cannabis and Multiple Sclerosis (MS)
149 Cannabis and Liver Diseases
151 Cannabis and Nausea Mitigation
154 Cannabis and Peripheral Neuropathy (PN)
156 Cannabis and Parkinson’s Disease (PD)
158 Cannabis and Premenstrual Syndrome (PMS)
160 Cannabis and Post-Traumatic Stress Disorder (PTSD) and Complex-PTSD (c-PTSD)
162 Cannabis and Spinal Cord Injuries (SCIs)
164 Cannabis and Sickle Cell Diseases (SCDs)
166 Cannabis and Stroke/Traumatic Brain Injury (TBI)
168 Cannabis and Tourette Syndrome (TS, Tourette’s)
171 Cannabis and Trigeminal Neuralgia (TN)
174 Chapter 3: Dosage and Usage

176 A Guide to Dosing/Titration
185 Conversation with Mara Gordon
194 On Hemp-Based Products
195 Synthetic Cannabinoids (SCBs)
200 Chapter 4: Medication and Side-Effects

202 Cannabis vs. Other Medications
205 Effects on the Brain and Cardiac Problems
206 Cancer
208 Chapter 5: The Biology of the Cannabis Plant

210 The Basics
214 The Growth Cycle
217 Conversation with Jeff Raber
220 A Brief Guide to Some of the Most Popular Strains
228 Chapter 6: Conclusion
234 Bibliography
246 Appendix
274 Contributors
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INTRODUCTION
8 INTRODUCTION
Introduction
Cannabis sativa, aka marijuana, pot, weed, tea or any other number of slang terms,
is a plant containing hundreds of compounds, including cannabinoids, terpenes/
terpenoids and flavonoids. Many of these compounds may have a huge number
of medical applications, whether on their own or together as a whole, in what
is known as the entourage effect. Due to the parts of the nervous system these
compounds affect - the endocannabinoid system (ECS) - these compounds are
quite well-tolerated and much safer than many drugs and medications currently
used.
The discovery of the ECS and learning how to modulate it using phytocannabinoids
derived from the cannabis plant could well help us treat a huge number of
conditions, from the everyday (e.g. headaches/migraines, pain) to the life-
threatening (e.g. cancer). Sadly, due to overbroad and short-sighted drug
legislation, the cannabis plant has been unfairly maligned and criminally under-
researched. This is despite the fact that cannabis has been used for hundreds, and
in some instances, thousands of years as a medicine by cultures all over the world.
This book aims to help readers understand the concept of cannabis as medicine,
which conditions it may be helpful for and what the current state of research says
about cannabis. We also speak to some of the world’s leading experts and patients
about cannabis, its medical potential and why they use the plant or are intrigued so
much by its pharmacology.
We understand that this is a complex area of research that can be difficult to

understand, even for those who are familiar with medical, biological and scientific
terminology. This is made even more difficult due to the ECS only having recently
been discovered and the legal hurdles in place researching the plant. We have
therefore tried to make the science as simple and straightforward as possible.
However, we hope that readers will come away with a deeper understanding of
cannabis as medicine, as well as understanding the impact the discovery of the
ECS has had on pharmacology, neuroscience and even our understanding of the
evolution of life.
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INTRODUCTION 9
This is by no means a be-all-and-end-all look at the cannabis plant as medicine.

Rather, it can be used as a sort of “guide” for navigating something that exists in
either a black market or legal grey area in so many countries around the world.
There are thousands of patients worldwide who are desperate for information on
how to use cannabis as medicine and what for. We hope that this book comes
in useful for them especially, and that it spurs further research so more definite
answers can be given.
@erik.nugshots
LeafWell
10 INTRODUCTION
The ECS: an Overview
Our body’s ability to shut off certain cells once they have completed their job is
run through a negative feedback system. The mechanism is like turning off the
faucet once the water glass is filled. Many negative feedback systems like this
exist in the body. Essentially, the body controls the levels of circulation of different
chemicals and proteins, by inhibiting further secretion of a particular hormone
that has effects on them. In some disorders, there can be a malfunction in this
negative feedback loop, and when the system breaks down, it can result in either
too high or too low a concentration of these chemicals and proteins. For years we
have speculated why we even have an endocannabinoid system (ECS). The real
function of the endocannabinoid system may actually be involved in correcting
these negative feedback loops should they malfunction, and to help reestablish the
body’s ability to regulate itself.
The term “cannabinoids” refers to all cannabinoids, endo- or phyto-, that trigger
the body’s response to abnormal functioning, through the ECS. Cannabinoids are
ligands, which means they are molecules that bind to others, to form complex
structures that produce specific chemical signals or neurotransmissions. As an
analogy, a ligand acts like a key and the receptors are the lock. Engaging the lock
with the correct key turns the ECS on, and starts a biochemical reaction. THC and
CBD are often called “phytocannabinoids”, because they are produced by a plant,
rather than inside the body, hence the term ‘phyto-’. Meanwhile, cannabinoids
such as anandamide and 2-AG are often called “endocannabinoids”, and they are
produced naturally by the body.
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INTRODUCTION 11
That is the crux of how the endocannabinoid system works, but for those looking
for some extra-curricular details, we have broken down the more complex science
behind the processes in Chapter 1 of this book. This is heavy information, but
fascinating from a scientific perspective. That said, if you are reading this book
with the objective of finding advice about conditions and dosage - please feel free
to skip ahead. However, for physicians, researchers, and the curious, it is hugely
important to understand the underlying principles behind the ECS if you want to
truly comprehend how cannabinoid-terpenoid based medications are able to help
such a wide range of conditions.
We must also stress that our advice on dosage and ingestion methods is based
on patient reports and anecdotal data, not clinical trials. Due to the nature of the
endocannabinoid system, what may work for one person may not necessarily work
for another. Yes, patterns may emerge regarding specific cannabinoid-terpenoid
ratios for specific physiologies and conditions, but this pattern does not necessarily
match everyone.
The ECS is involved in the regulation of a variety of physiological and cognitive

processes, including appetite, pain, mood, memory, fertility, pre- and postnatal
development, immune system function, motivation, and body temperature, as well
as mediating the pharmacological effects of cannabis. They can even influence
our taste, and activate CB1 receptors that may actually make sweet things taste
sweeter.1
One remarkable fact about this intrinsic system of ‘checks and balances’ is that its
existence was not even discovered until 1992. We have had a little more than 25
years to disentangle and delineate how the endocannabinoid system functions at
the cellular level. Unfortunately, progress has been slowed down, because of the
fact that cannabis is a highly regulated Schedule I drug. Despite the difficulties,
diligent scientists continue to progress our understanding of the endocannabinoid
system forward every year. As legalization efforts continue to succeed nationwide,
we should expect quicker advances in this field, as it becomes easier to overcome
the bureaucratic difficulties of researching a controlled substance.
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12 INTRODUCTION
Dr. Lumír Ondřej Hanuš, PhD, DSc, Dr.h.c.mult.

_ School of Pharmacy, Ein Kerem Campus, Hebrew University of Jerusalem · Institute of
Drug Research. Dr. Lumír Ondřej Hanuš is one of the scientists to have first described
the structure of anandamide.
Hello, Dr. Hanuš. How are you?
Very good, thank you. I hear you’re calling from the UK. How is the situation in the UK
concerning medical cannabis?
Well, Sativex is available on prescription …
… Yes, but it’s very expensive. The problem is, I tell you …
I’m from Czechoslovakia originally … I taught for 20 years at the Department of Hygiene
and Epidemiology in the medical faculty of the University of Olomouc. At the same time,
I was researching cannabis. This had several parts. This was a study of cannabis from a
medical point of view and from a criminalistic point of view - fighting against drug abuse.
When Professor Zdeněk Krejčí, my boss at the university, he discovered cannabis’s antibiotic
properties. Then, in 1955, he identified, alongside professors Jan Kabelík and František
Šantavý, cannabidiol (CBD).
So, they started using it in hospitals from about 1955, and I was working in the medical
faculty between 1970 and 1990. During this time, I created extracts for the hospital drug
store. They used these extracts up until 1990 for treatments in hospital. I then went to Israel
to try an isolate endogenous compounds, and thought I’d be researching cannabis. What
I didn’t know until Professor Mechoulam told me, “No. I have here a specialist in molecular
pharmacology, William Devane, who has found endocannabinoid receptors. I want you to
try and find what binds to these receptors.”
So I thought, “No chance”. But I would manage to isolate and identify the chemical
compound, anandamide. Later, they checked what amounts there are in the body, and
found that it’s found in large concentrations throughout the body. I cannot explain to you
how I managed to successfully isolate anandamide, because when I isolated it and had it
pure in the cube and I evaporated it, the cube was clean. I checked it and isolated more, and
found that the anandamide was active.
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INTRODUCTION 13
Up until 1990, cannabis was legal in Czechoslovakia, and after I left, nobody made cannabis-
based medications anymore and it became illegal. About 12 years ago, I started to work
intensively to legalize medical cannabis in the Czech Republic. 5 years ago, medical
cannabis was legalized in the Czech Republic, but it is not available. They had 4 patients out
of a population of around 20 million, who had maximum of 5 kg in five years. Here in Israel,
there’s around 7 million people, and we produce several thousand pounds for patients. So
there’s a big difference.
Then they sent over Sativex, but just one package was 14,000 Czech crowns. For your
imagination, the pension in the Czech Republic was between 9 and 11,000. So, unaffordable
and not accessible to the ordinary person. In Israel, it’s different. Medical cannabis has been
legal for about 10 years over here, and we have around 32,000 patients. They pay 370 shekels
per month (about 10% of the pension), which goes to the grower. Grower supplies the
patient and gives them the instructions on how to use it. So it’s a good situation in Israel,
and patients needn’t pay anything beyond 370 shekels - the cannabis is free of charge. The
patient can get between 20 and 200 grams per month, and they pay a fixed rate.
Now, there’s been a big change for new patients, and cannabis has now entered drug
stores in Israel. 1 gram is 140 shekels. For older patients, they get the fixed rate, but newer
patients must pay 140 shekels per gram, again making it inaccessible. In about half-a-year,
these new prices may be extended to all patients. The biggest problem isn’t just the price.
Patients had growers, and if one particular strain didn’t work, they’d try another one. For
instance, there’s one company that had 10 strains with consistent THC and CBD ratios,
and all the other cannabinoids and terpenoids were measured as well. Now that it’s in
drug stores, they only give the THC and CBD ratio, and no strain name. This is a big step
backwards.
Now, all eyes are on the money. The patient comes last. This is a serious problem. Chronic
patients, who have been using various drugs all their lives, and with cannabis these
can be replaced, and potentially even treating some conditions in a week. This means
drug companies can’t make money from these patients. It is not in the interests of
pharmaceutical companies for patients to use cannabis, because they cannot patent it.
So, up till now, everything the drug companies have tried to develop in terms of synthetic
cannabinoids has failed. Only natural cannabinoids and compounds, such as the ones
used in Sativex, have been successful. They develop names such as Sativex (THC and CBD),
Epidiolex (CBD), marinol (THC), dronabinol (THC), as the name makes money. But really, I
want to do something for patients, not pharmaceutical companies. And you can be sure,
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14 INTRODUCTION
pharmaceutical companies can still make money from cannabinoid-based medications and
still be cheap or free of charge for patients. But they don’t want to, and this is a problem.
Yes, agreed. We’re very supportive of people growing their own cannabis, as
this way they can learn about the plant and see what helps them. They can self-
medicate with something that they can grow themselves …
Yes. Sadly, the situation for patients is still a little bit black. It’s also important to mention
that cannabis is not medicine for everybody, and it’s not for every patient. There are small
numbers of patients whom it can harm. Fortunately, mostly it’s OK. Palliatively, it may
work for around 80-90% of patients. Curatively, we only have anecdotal cases, because
there’s a lack of clinical trials. However, we found medical properties in cannabis as far
back as 1921, and was used as medicine into the 30s. We found anandamide 25 years ago,
but they complicate the process. They want stage 1, stage 2, stage 3 trials, and this is a
problem, and only pharmaceutical companies can afford to do this. Of course, working on
cannabinoid-based medicines is not in their interests, so it falls behind. Universities cannot
do such research, due to cannabis being illegal and not having the same resources. Going
through all the stages is expensive, and at the end only a small percentage of drugs will be
developed into actual medications.
Another problem, and this is the case in Israel as well, is that patients must try all possible
drugs before they can try cannabis. Patients must be crippled by these drugs’ side-effects,
and they only qualify for cannabis if these medications do not work. They can also give it
in cases of terminal cancer, but by that point it’s usually too late. Not every patient can be
treated with cannabis. There are several conditions.
First, you must have the right genes to be treated. There are families where everybody
died by the age of fifty. If you are from such a family even if you live an otherwise healthy
life, you may extend your life to some extent, but not to the age of 90. There are families
where people live to their 100s, and even if you live a less healthy lifestyle, you may still
have a longer life. We can only give cannabis to families with a long life expectancy. There
is a second condition. Much of a disease is suffered in the head (i.e. mentally). You must be
optimistic, because optimism can help defeat a disease, and so mental health is a factor.
But this can be difficult for a patient with heart disease or terminal cancer!
Then it becomes a matter of finding your strain and dose. Patients usually start with very
small amounts and then go up until they feel better and start to tolerate cannabis better.
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INTRODUCTION 15
Some patients can take up to 1,000 mg of THC a day, with no psychoactive effect. This can
be helpful, as the patient doesn’t want to be “high” or “stoned” - just treated. Moreover, you
cannot overdose on cannabis, and people cannot die from an overdose of cannabis.
I tell you, in Czechoslovakia, they cultivated cannabis at the Agricultural Institute. There
was no fence! Anybody could come and take a few plants, but never did I see this happen! I
never lost one leaf. Nobody was interested. If I tried to cultivate it today in the same spot, it
would not survive the night, even if I fenced it!
Addiction to cannabis is almost zero. The only reason why a cannabis user may become
“addicted” to cannabis is if they mix it with tobacco - it is the tobacco that is addictive. But
because they smell the cannabis in the smoke, they think it’s the cannabis they’re addicted
to. We tell patients not to mix cannabis with tobacco.
Have you noticed any particular patterns? Do patients in Israel use cannabis for any
specific conditions?
Mainly it’s pain. Before it was cancer, but today it’s pain. Also, it’s important how a patient
uses it. I don’t think it should be smoked in most instances. Smoking can be useful for
patients that need immediate relief, such as multiple sclerosis patients. I have a friend who
suffers from MS. He was sitting in a wheelchair for several years and blind in one eye. He
tried cannabis. One puff, miracle! After one puff, he walked one mile. Without it, he is sitting
in his wheelchair. He was able to walk again.
For other conditions, this might not be the case, and you might not need immediate effects.
In cancer, for example, you can use other forms such as suppositories and so on. I’ve seen
patients use cannabis for cancer, and it didn’t do anything, even palliatively; but I’ve also
seen patients where their cancer was treated fully thanks to cannabis.
Do you see particular cannabinoid-terpenoid profiles being used for specific

conditions?
There is no specific strain or dose. You can have two patients with the same condition need
an entirely different strain or profile. For one, a 4:1 THC:CBD ratio could be too much, for
another it may not be enough. One of my friends, he used different cancer cells in vivo and
treated them with extracts from three different strains. He found that 2 strains treated the
cancer and the other one didn’t. This means that there are active compounds in cannabis
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16 INTRODUCTION
that provide a synergistic effect - the entourage effect. The strain that didn’t treat the
cancer was missing several key compounds. I want to find which compounds are active,
and which ones work synergistically. It’s been 120 years now since we’ve found cannabis to
have medical benefits, and we have only just truly begun to understand it. This is because
it’s illegal.
I saw interest in strains in many countries, but I couldn’t bring sample because of cannabis
being illegal. From a scientific point of view, this is a problem. So, I asked a friend who grew
in the US to send me samples. Instead, he told me to come down and stay, but I won’t send
you anything. This is why a lot of scientists couldn’t study cannabis properly. This is also why
when you tell physicians about cannabis, they say “No, no, no, no …”. This is the problem of
making cannabis illegal.
I did a seminar with some physicians in Poland on using cannabis as medicine. Before this
seminar, I used to think that cannabis needed to be controlled in some way. Afterwards,
I came away thinking differently. That, if it’s 100% legal, then patient can get what they
need. Otherwise, the patient has no chance to access cannabis safely. Most people who use
cannabis for non-medical reasons do so for curiosity, and they usually stop by the end of
university or by the time they’re married. There are no so many chronic cannabis users.
@erik.nugshots
LeafWell
INTRODUCTION 17
History of Medical Cannabis
12000 China, Siberia and Mongolia. Cannabis is one of the world’s oldest culti-
BC vated crops, and both Cannabis sativa and Cannabis sativa L. (aka hemp,
the non-psychoactive plant used for oil, cloth and fuel) have been har-
vested for around 12,000 years. The plant likely flourished in nutrient-rich
dump sites of hunters and gatherers, found mostly in Mongolia, China and
SIberia, and it could be argued that the diverse uses and vigor of this plant
meant that people had likely started to farm it for multitudinal uses.
2000 Japan, India, Middle East and East Europe. By this point, many cultures
BC had written about the medical applications of cannabis. The first two
recorded applications of cannabis as medicine was in 2,900 BC by Chinese
Emperor Fu Hsi and in 2,737 BC by Emperor Shen Neng of China. Bhang
is mentioned in the ancient Hindu text Atharvaveda (Science of Charms,
written between 2000 and 800 BCE) and is described as the “Sacred
Grass”. Egyptians use cannabis for inflammation. Korea and Thailand use
hemp to make fabrics, with evidence of usage dating back to 3,000 BC.
1400_ Western to Southern Africa. The concept of cannabis as medicine is also

1100 AD written about by Roman nobleman and scientist, Pliny the Elder.
1200 Central and Eastern Europe, and the UK. Cannabis plants would have likely
been used to make paper. Vikings and medieval Germans used cannabis
for relieving toothaches and pain during childbirth.
1000 The word “Hempe” is listed in the English dictionary, and hemp pa-
per-making starts in England in 1494.
1000_ Northern Africa. Cannabis is written about as medicine in the Middle
700 Eastern world. Making hemp for paper becomes an industry in the Islamic
world, and is distributed through to Europe.
South and Central America. Hemp is grown in Europe by this point, and
1600_
botanist William Turner mentions hemp in New Herball (1538).
1800
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18 INTRODUCTION
1600 North America. Mostly hemp was grown – however, there was major pro-
liferation of psychoactive cannabis between 1890 and 1930, which may be
partially due to alcohol prohibition, as well as it being used in various med-
ical tinctures). Hemp becomes a widespread plant, and herbalists such as
Nicholas Culpeper write about medical uses of hemp.
1700 Hemp and cannabis become more widespread, as it is taken from North
Africa, and other equatorial regions, and brought to Northern America
and Europe. George Washington and Thomas Jefferson are also well-
known for growing hemp. Carl Linnaeus classifies Cannabis sativa in 1753.
Late Australia, being geographically isolated from many other continents, dis-
1800 covers cannabis relatively late in the 1800’s. Meanwhile Cannabis becomes
mainstream medicine throughout Europe and North America.
1900 Canada, (extremely cold climates have prevented extensive cannabis

growth in the far North– the same as in the northern regions of Russia).
However, cannabis is still used in many medications, particularly for asth-
ma, bronchitis and loss of appetite.
1906 Pure Food and Drugs Act, signed by President Roosevelt, requires label-
ling of medicine, meaning ingredients must be listed. Cannabis is includ-
ed.
1911 Massachusetts outlaws cannabis.
1915 President Wilson signs the Harrison Act, which served as a template for
future drug regulations. The US was a major producer of cannabis in 1918,
during the First World War. Before the US started growing its own canna-
bis, most of it came from India. Mississippi was the US’s main producer of
cannabis at this time.
1925 The League of Nations - the precursor to today’s United Nations (UN) -
signs a multilateral treaty restricting cannabis use to scientific and medi-
cal use only.
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INTRODUCTION 19
1928 The United Kingdom (UK) adds cannabis to its “Dangerous Drugs Act”.
1915_ Wyoming, Texas, Iowa, Nevada, Oregon, Washington, Arkansas, Nebraska
1927 and New York all join Massachusetts in outlawing cannabis.
1920s_ Increase in the usage of the term “marijuana”, which coincides with the
1930s release of the film Reefer Madness. The Federal Bureau of Narcotics is
set up, and Harry J. Anslinger and newspaper tycoon William Randolph
Hearst play a key role in controlling the proliferation of cannabis. At this
time, pharmaceutical companies were still using cannabis extracts in their
medications.
1937 Marihuana Tax Act is introduced. Samuel R. Caldwell becomes the first
convicted cannabis seller under US federal law.
1938 Canada prohibits cannabis cultivation.
1938 At the request of New York City Mayor, Fiorello LaGuardia, the New York
Academy of Medicine conduct an investigation of cannabis. The report
is known as the “LaGuardia Report”, it concludes that many of the claims
of the dangers of cannabis (or “marihuana”) are exaggerated, or untrue.
Despite this, cannabis is removed from the US Pharmacopeia in 1942,
meaning that its therapeutic properties were stricken off the record.
1951 Boggs Act establishes minimum prison sentences for cannabis posses-
sion. In 1956, penalties become stricter as cannabis is included in the Nar-
cotics Control Act. By this point, cannabinoids have also been discovered.
Cannabidiol (CBD) and cannabinol (CBN) were identified. Due to their
similar structure, CBD was thought to be a precursor to THC.
1961 The UN Single Convention on Narcotic Drugs provides the basis for the
future prohibition of cannabis, both in the US and all over the world.
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20 INTRODUCTION
1964 Dr. Raphael Mechoulam, Professor of Chemistry at the Hebrew University

of Jerusalem, identifies and synthesizes delta-9-tetrahydrocannabinol
(THC). Dr. Raphael Mechoulam also identifies THC as the main psychoac-
tive component of cannabis.2
1968 In what feels like history repeating itself, The University of Mississippi be-
comes the first official cannabis grower for the federal government. Pres-
ident Johnson also creates the Bureau of Narcotics and Dangerous Drugs
(BNDD), to replace the Federal Bureau of Narcotics (of Treasury) and the
Bureau of Drug Abuse Control (of FDA). At the same time, the Wootton
Report in the UK finds cannabis to be less dangerous than alcohol and
other drugs, such as opiates, amphetamines and barbiturates.
1970 Despite centuries of medical use, and various scientific reports at the time
suggesting that the hysteria surrounding cannabis was misguided, the
Controlled Substances Act (CSA) classifies cannabis/marijuana as a drug
“with no accepted medical use”. The National Organization for the Reform
of Marijuana Laws (NORML) is established.
1971 The UK introduces the drug classification system, which informs sen-
tencing guidelines. The UK splits drugs into three classes - A, B or C, with
Class A being the most severe. Cannabis is put under Class B, alongside
amphetamines and barbiturates. This classification system forms the
template for other classification systems the world over. The US classifies
cannabis as a Schedule I drug, alongside heroin and LSD. President Nixon
declares “War on Drugs”, and says he will not legalize cannabis despite
Shafer Commission recommendations to decriminalize it. Lester Grin-
spoon, professor of psychiatry at Harvard, releases his book, Marihuana
Reconsidered.
1972 NORML petitions the BNND and the Office of Drug Abuse Law Enforce-
ment (ODALE) - both of which would be merged and form the Drug
Enforcement Agency (DEA) in 1973 - to reschedule cannabis.
1974 The National Institute on Drug Abuse (NIDA) is established and is given a
contract to grow cannabis for research purposes.
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INTRODUCTION 21
1976 The Netherlands decriminalizes cannabis. By 1980, a network of “coffee

shops” are set up, whereby the purchasing of small quantities of cannabis
by adults was tolerated by law enforcement. Robert Randall becomes the
first official “medical marijuana patient”, as the federal court rules his use
of cannabis a “medical necessity”. Robert Randall claims that cannabis
helped prevent him from going blind.
NIDA sets up the compassionate use Investigational New Drug (IND)

1978
Applications program, where NIDA began supplying cannabis to patients
whose physicians apply for and receive USID from the FDA.
1978 - New Mexico becomes the first state to recognize the medical value
of cannabis. By this point, there are several studies that have come out on
the medical applications of cannabis for cancer, multiple sclerosis (MS),
epilepsy and glaucoma.
1980 Marinol (aka Dronabinol), a synthetic version of THC, is developed. Both

Marinol and smoked cannabis are tested on cancer patients.
1981 - Bob Randall (the first medical marijuana patient under the IND pro-
gram) and Alice O’Leary establish Alliance for Cannabis Therapeutics Act
(ACT), helping patients and doctors file Compassionate Care Protocols.3
1981_ Marinol is approved by the FDA, and the US government sells the Marinol
1985 patent.
1986 Despite increasing scientific evidence, the Anti-Drug Abuse Act increases
the penalties for the possession and sale of cannabis.
1988 DEA Judge Francis Young recommends placing cannabis under Schedule
II of the CSA. This recommendation is overruled in 1989.
1990 Miles Herkenham and his research team at the National Institute of
Mental Health (NIMH) discover the cannabinoid receptor system, helping
scientists understand the pharmacological effects of cannabinoids.
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22 INTRODUCTION
1991 In response to criminal prosecutions, a court ruling highlights application

of “Medical Necessity” defense by patients, stating they need cannabis for
their health condition. The federal government suspends the IND’s Com-
passionate Use program.
An anonymous survey using a random sample of members of the Amer-
ican Society of Clinical Oncology (ASCO) is carried out. 53% of oncolo-
gists say cannabis should be available by prescription. The first medical
marijuana initiative is passed in San Francisco, known as “Proposition P”.
Dennis Peron is the co-author of Prop. P, and he would later play a hand in
drafting Proposition 215 in 1996, the Medical Marijuana Initiative.
1992 Dr. Raphael Mechoulam, Dr. William Devane and Dr. Lumir Hanus identify
the presence of the endogenous cannabinoid, anandamide (derived from
ananda, meaning “eternal bliss” or “supreme joy” in Sanskrit). Anandamide
is the brain’s own natural THC, and is said to be responsible for what has
been called the “runner’s high”. Coupled with the discovery of the can-
nabinoid receptors, the existence of the “endocannabinoid system” (ECS)
had been established.4 The IND Compassionate Use program is officially
disbanded, although 13 patients continued to get medical cannabis from
the government.
1993 The American Medical Student Association (AMSA) endorses the resched-
uling of marijuana, and for the reestablishment of the IND Compassionate
Use program.
1994 Cannabis is kept at Schedule I, and the Assistant Secretary of Health an-
nounces the decision not to reopen the IND Compassionate Use program.
In 1995, a second petition to reschedule cannabis is filed.
1996 California becomes the first state to legalize medical marijuana.
1997 New England Journal of Medicine (NEJM) publishes an editorial5 calling

for the rescheduling of cannabis. Institute of Medicine (IOM) begins com-
prehensive survey on the medical effects of cannabis.
National Institute of Health (NIH) says that more research is needed into
the medical potential of cannabis.
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INTRODUCTION 23
1998 Congress prevents the implementation of a medical marijuana law in Wash-

ington, D.C. Presidents Ford, Carter and Bush urge voters to reject medical
marijuana. Alaska, Oregon and Washington legalize medical marijuana. In
1999, Alaska makes enrolment onto the State Patient Registry mandatory.
Dr. Raphael Mechoulam and S. Ben-Shabat introduce the phrase “The En-
tourage Effect”, referring to the way in which all the different compounds in
cannabis interact, in order to work in concert with one another. This theory
postulates that the medical power of cannabis comes from the interplay be-
tween cannabinoids, terpenoids and flavonoids, and that taking any of these
away may diminish the therapeutic effects of cannabis.
GW Pharmaceuticals is founded in Cambridge, England. Doctors Geoffrey
Guy and Brian Whittle obtain a license from the United Kingdom Home Of-
fice and the Medicines and Healthcare products Regulatory Agency (MHRA)
to cultivate cannabis and conduct scientific research.
1999 Marinol - the synthetic THC - is reduced to Schedule III to increase availability
to patients. Maine legalizes medical marijuana. Health Canada announces
funding for medical research on cannabis.
2000 Hawaii becomes the sixth state to legalize medical marijuana. Colorado and
Nevada soon follow.
Court rules that “medical necessity” is not a valid exception to enforcement

2001
of penalties under the CSA.
IND study on medical marijuana patients finds that cannabis improves their
2002
lives. Court in Washington, D.C. blocks medical marijuana initiative. In Conant
v. Walters, the court rules that the government cannot revoke a physician’s
license for recommending medical marijuana.
US House of Representatives rejects amendment to stop federal raids on

2003
establishments and companies providing services for medical marijuana
patients. At the same time, the US government receives a patent for cannab-
inoids,6 specifically CBD. In Canada, Javi Dvorak becomes the first patient
to receive government-grown cannabis. In Holland, pharmacies are legally
obliged to stock medical cannabis and to dispense advice on the plant’s
usage.
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24 INTRODUCTION
2004 California’s Prop. 215 is amended by Senate Bill 420 (SB 420), which creates
patient limits on possession (8 ounces of dried cannabis per qualified
patient, and no more than 6 mature or 12 immature plants). SB 420 also
requires the State Department of Health Services to establish and main-
tain a voluntary program for the issuance of medical marijuana identity
cards. SB 420 also protects patients and caregivers from state criminal
sanctions, at least to some extent.
Montana and Vermont legalize medical marijuana. The DEA instructs the
US Department of Health and Human Services (HHS) to conduct a sci-
entific and medical evaluation of cannabis, to determine whether or not
cannabis should be rescheduled. The UK reclassifies cannabis as a Class C
drug.
2005 US Supreme Court rules that Congress may ban medical marijuana use in
the case of Gonzalez v. Raich. California suspends, then resumes, the state
Medical Marijuana ID Card Program (MMICP). DEA conducts widespread
raids on medical marijuana dispensaries in California.
2006 Oregon’s medical marijuana law is amended to exclude affirmative

defense in cases where patients exceed possession limits. Rhode Island
legalizes medical marijuana. DEA targets those making cannabinoid-con-
taining edibles. FDA confirms opposition to smoking marijuana for medic-
inal purposes. The Presbyterian Church approves resolution to support
medical marijuana.
2007 New Mexico legalizes medical marijuana. Administrative Law Judge Mary
Ellen Bittner rules that Lyle E. Cracker, PhD should be allowed to grow
cannabis for research purposes due to the lack of cannabis available, and
an the inadequate quality of the supply.
Michigan legalizes medical marijuana. The American College of Physicians

2008
(ACP) states its support for the use of non-smoked cannabinoids and re-
search on the benefits of cannabis. California Court rules that the posses-
sion limits on medical marijuana patients are unconstitutional. California
Attorney General Jerry Brown issues guidelines for law enforcement and
medical marijuana patients to clarify the state’s laws. Cannabis is returned
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INTRODUCTION 25
to Class B in the UK, counter to the advice of the Advisory Council on the
Misuse of Drugs (ACMD).
Dr. Ethan Russo comes up with the idea of a “Clinical Endocannabinoid
Deficiency”7 (CECD), which may be the cause of hard-to-treat conditions
such as migraine, fibromyalgia, irritable bowel syndrome (IBS) and other
treatment-resistant conditions.
2009 Maine’s medical marijuana laws are amended so dispensaries can oper-
ate. The American Medical Association (AMA) recommends rescheduling
cannabis and softens its position on the concept of medical marijuana. US
Attorney General says that raids on medical marijuana patients and dis-
pensaries will not continue. Judge Mary Ellen Bittner’s 2007 recommen-
dation is overruled. In the UK, Professor David Nutt releases a pamphlet
criticizing the mismatch between lawmakers’ classification of recreational
drugs and their psychological, physical and social effects. Under Professor
David Nutt’s reclassification, alcohol and tobacco become Class B drugs.8
This study is published in the Lancet on November, 2010.
2010 New Jersey, Washington, D.C. and Arizona legalize medical marijuana. The
Iowa Board of Pharmacy recommends rescheduling cannabis. Washing-
ton expands its list of medical professionals authorized to recommend
medical marijuana. Colorado introduces House Bill 1284 and Senate Bill
109 to increase the regulation of physician recommendations, and medi-
cal marijuana dispensaries. The US Department of Veterans Affairs relaxes
medical marijuana rules for veterans, many of whom may use cannabis
for post-traumatic stress disorder (PTSD) and other injuries. South Dakota
voters reject medical marijuana measure.
GW Pharmaceuticals develops Nabiximols - trade name Sativex - for the
treatment of multiple sclerosis (MS) and to alleviate muscle spasticity,
neuropathic pain, overactive bladder and other symptoms associated with
MS. The treatment is approved.
2011 DEA places five synthetic cannabinoids into Schedule I of the CSA. Del-
aware legalizes medical marijuana. Several US Attorneys send letters to
states with legal medical marijuana laws, threatening federal prosecution.
Montana Senate Bill 423 amends the state’s medical marijuana laws, so
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26 INTRODUCTION
that medical marijuana patients must prove state residency. DEA denies
the 2002 request to reclassify cannabis and take it out of the Schedule
I category. Lyle E. Craker’s application to grow cannabis is rejected. The
Governors of Rhode Island and Washington petition the DEA to reclas-
sify cannabis as a Schedule II drug. Israel’s government arranges for the
supply of cannabis for medical and research purposes. As a result, Israel
becomes a major leader in medical marijuana research.
2012 Connecticut and Massachusetts legalize medical marijuana. LA City

Council bans medical marijuana in unanimous vote. Lawsuits against
government are brought to the government for their raids on medical
marijuana dispensaries, but the Federal Judge dismisses the case. Federal
Court hears case to change the Schedule I classification of cannabis, but it
is rejected in 2013. Colorado legalizes recreational marijuana.
2013 New Hampshire and Illinois legalize medical marijuana. The Justice De-
partment states that it will not challenge state marijuana laws. Dr. Sanjay
Gupta comes out in favor of medical marijuana, helping cause a shift in
the public’s stance on medical marijuana.
Maryland, Minnesota and New York legalize medical marijuana. Federal

2014
guidelines are released to allow banks to provide financial services to legal
marijuana sellers. US Department of Justice decides it will not enforce federal
marijuana laws on Native American reservations. Justice Department is also
banned from using funds to prosecute against medical marijuana in states
where it is legal. Alaska legalizes recreational marijuana.
2015 Puerto Rico and Georgia vote to legalize medical marijuana. The Federal
Government removes obstacle to cannabis research by removing it from The
Public Health Service review process - a measure that wasn’t even required
for research into cocaine and heroin. The DEA also considers moving canna-
bis to a less restrictive scheduling.
GW Pharmaceuticals initiate Phase 3 clinical trials for the use of CBD/CBDa
for epilepsy. The name of this medication is Epidiolex.9
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INTRODUCTION 27
2016 Pennsylvania, Ohio, Arkansas, Florida and North Dakota vote to legalize
medical marijuana. DEA declines to lower cannabis classification, but opens
the door to cannabis research by expanding the number of DEA-registered
cannabis manufacturers. DEA places CBD on list of controlled substances,
making it also a Schedule I drug when it is harvested from psychoactive can-
nabis, despite its lack of psychotropic effects. California votes to pass Proposi-
tion 64, legalizing recreational marijuana. Nevada, Maine and Massachusetts
also legalize recreational marijuana.
2017 West Virginia legalizes medical marijuana. Mexico also legalizes medical
marijuana. Brazil and Germany also begin to establish medical marijuana
programs and/or legalize CBD. As of 2017, Alabama and Indiana allow for the
medical use of non-psychoactive CBD oil only.
GW Pharmaceuticals conducts a Phase 2 clinical trial in the use of THC and
CBD for glioblastoma multiforme (GBM). The clinical trial achieves positive re-
sults.10 National Cancer Institute (NCI) researches cannabis and cannabinoids
for the treatment of cancer.11
2018 Attorney General Jeff Sessions announces end to Obama-era cannabis guide-
lines, and that the US government may try to prosecute those who break federal
laws on cannabis, even in states where it’s legal. FDA authorizes clinical trials for
GW Pharmaceutical’s Epidiolex for rare, hard-to-treat forms of epilepsy. 12
It is estimated that between 128 million and 232 million people worldwide
who are aged between 15 and 65 (2.7% to 4.9% of the global population)
use cannabis (2013). It is also estimated that, in the United States, 43% of
Americans had used cannabis at some point in their lives, as of 2015. In
2016, this increased to 51% of Americans.13 Cannabis is the most common-
ly-used illegal drug in the US, and all over the world. However, it must be
stated that cannabis is not necessarily illegal in all parts of the world, and
physician-recommended cannabis has been implemented in the US, the
Netherlands, Canada, Israel, Belgium, Australia, Germany and Spain. There
is also a cannabinoid-based product named Sativex available on prescrip-
tion in the United Kingdom.
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1
CHAPTER
THE
ENDOCANNABINOID
SYSTEM
30 THE ENDOCANNABINOID SYSTEM
How Does the ECS Work?
To explain how the ECS works, we need to learn about how neurons interact. When
two neurons communicate, they are known as presynaptic and postsynaptic, which
is a fancy way of saying one sends the signal, and the other one receives it. Each
neuron in the brain consists of a cell body with string like axon that reaches out to
other neurons. When two neurons communicate, it is via impulses sent along the
tip of the axon. The axon is triggered by the neuron body to send out the signal
that is to be received by another neuron. Surrounded by small branches called
dendrites, the receiving neuron does not actually touch the axon of the other cell,
and the small gap between the axon and dendrites is known as the synapse. When
a neuron fires, it sends electrochemical signals down the axon. Chemicals known as
neurotransmitters are released from the end of the axon, and then travel across the
synapse, to be received by the dendrites of the other cell. This signalling process
across the synaptic gap, and the complex processes that govern the release,
absorption, inhibition, excitation, and modulation of neurotransmitters across the
synapse underpin all the functions of every neuron in the body.
@curt_ice and John Bayes
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THE ENDOCANNABINOID SYSTEM 31
Endocannabinoids are one of these neurotransmitters, perhaps one of the most

important, and the properties of cannabis come from how it changes the behavior
of the neurotransmitters in the body. “The endocannabinoid system shows
functional activity from early stages of brain development: it plays an important
role in fundamental developmental processes such as cell proliferation, migration,
and differentiation, thus shaping brain organization during pre- and postnatal
life.” 14
To put it simply, for those who have not completed medical school or a course
in electrical engineering, the presynaptic neuron is where the message is
being sent from, and the postsynaptic neuron is where the message is being
sent to. The presynaptic neuron releases different neurotransmitters, such as
endocannabinoids, into the synaptic cleft, which is the space in between two
neurons. The presynaptic-postsynaptic interface is analogous to a baseball
pitcher and catcher. The pitcher (presynaptic neuron) throws a pitch (chemical
neurotransmitter) sixty feet (synaptic cleft) to the waiting catcher (postsynaptic
neuron) where the catcher receives it in his or her glove (receptor). These
neurotransmitters may trigger effects on the postsynaptic neuron, specifically
excitation, inhibition or the initiation of second messenger cascades.
Phytocannabinoids act as “mimics” of endocannabinoids and can have similar

effects to them. By affecting the cannabinoid receptors, Phytocannabinoids make
endogenous cannabinoids more or less available in the bloodstream. Glutamate
- a neurotransmitter that plays a role in long-term memory, learning and brain
development - drives endocannabinoid production. That means that the cannabis
plant contains chemicals that act on the ECS in the same way as the chemicals
made naturally in the body; it is like a duplicate set of keys.
Different cannabinoids act on different parts of the ECS in different ways. 2-AG,
for example, works on presynaptic CB1 receptors and can induce depression.15
Anandamide, meanwhile, triggers autocrine signalling (when a cell secretes a
hormone or chemical agent - called the autocrine agent - binding autocrine
receptors to the cell and changing its structure) in TRPV1 receptors. A fault in this
process can induce long-term depression. Autocrine signalling is also a huge factor
in the development of cancerous cells and tumors, and cannabinoids may affect
this signalling, to help prevent them from developing. For those people who use
memory clues … Depression and cancer, bottom line, autocrine.
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To break down the production of endogenous cannabinoids as simply as possible:
1 On our presynaptic and postsynaptic neurons, there are cannabinoid

receptors - known as cannabinoid receptor 1 (CB1) and cannabinoid receptor
2 (CB2). CB1 and CB2 are G-protein coupled receptors (GPCRs), meaning they
can influence the way the nervous system and cells behave.
2 Both receptors are found throughout the body, meaning that they can
influence a wide range of physiological functions. CB1 receptors are thought
to be responsible for neuromodulation in the nervous system. CB2 receptors
are thought to be responsible for modulating the immune system.
3 Glutamate is the main neurotransmitter involved in endocannabinoid

production.
4 We know most about 2-AG and anandamide - both activate CB1 receptors.
5 2-AG production: The enzyme, diacylglycerol lipase (DAGL), converts

diacylglycerol (DAG) into 2-arachidonoylglycerol (2-AG).
6 2-AG production: We have a gene that encodes DAGL, diacylglycerol lipase

alpha (DAGLA).16 These genes are expressed on postsynaptic neurons, near to
presynaptic terminals with CB1 receptors.
7 2-AG production: The enzyme phospholipase-C (PLC) helps DAGL synthesize

2-AG. 2-AG regulates synaptic activity in the brain, and is produced
throughout the body.
8 Anandamide production: on our membranes is a phospholipid called N-acyl-

phosphatidylethanolamine (NAPE). The enzyme, NAPE phospholipase D
(NAPE PLD), catalyses NAPE.
9 Should the N-acyl group in NAPE be arachidonic acid (not all N-acyl groups
are), NAPE PLD will break down NAPE into anandamide. Anandamide may
have longer-lasting effects than 2-AG.
10 2-AG and anandamide activate CB1 receptors. This blocks the flow of calcium
into the presynaptic terminal.
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11 In turn, this also reduces the release of glutamate, and its activity on the
postsynaptic neuron.
12 Enter the enzyme, monoacylglycerol lipase (MAGL). MAGL’s function is to

break 2-AG down into arachidonic acid and glycerol through hydrolysis (the
addition of water). Inhibiting MAGL elevates 2-AG levels, meaning that it
is necessary for the downregulation of 2-AG. MAGL stops 2-AG’s ability to
activate the CB1 receptor.
13 This is where another enzyme comes into play, the fatty acid amide
hydrolase (FAAH). FAAH breaks down anandamide into arachidonic acid and
ethanolamine, also through hydrolysis. FAAH stops anandamide’s ability to
activate the CB1 receptor.
14 THC is thought to mimic anandamide and 2-AG. As the ECS metabolizes

anandamide and 2-AG so rapidly, dangerous levels are never built up when
using natural phytocannabinoids (synthetic ones are another matter). This is
one reason why cannabis does not lead to overdoses.
15 CBD is thought to “dampen” THC’s effects to some extent. However, as CBD

seems to boost 2-AG production, it may both take the “edge” off THC, as well
as elongate its effects, depending upon ratio and dosage.
16 THCV, meanwhile, may act as a CB1 antagonist and block THC’s effects, or
perhaps even increase the psychoactive effects of THC in the short term,
leading to a rapid decrease in psychoactive effects in the long-term. This
could be one reason why strains high in THCV (usually sativas) have strong
immediate effects, but are short-lasting (THCV seems to act as an agonist to
both CB1 and CB2 receptors, so is not at all similar to CBD in this manner).
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The ECS and Its Parts
The ultimate goal of the ECS is homeostasis - the maintenance of a constant

internal environment. Endocannabinoids, so called because the body produces
its own cannabinoids, are neurotransmitters - chemical messengers that send
instructions to cells.
The ECS is made up of three main parts:
CB1
RECEPTOR
In the neurons in our nervous system there are
cannabinoid receptors, CB1 and CB2, impacting
our health and wellbeing.
Cannabinoids fit into these receptors like a lock
CB2
RECEPTOR
in a key, influencing how they work, leading to
wide-ranging effects across the body.
Once the keys (cannabinoids) open these locks

(CB1 & CB2 receptors), the body experiences various RECEPTOR
responses, such changes in pain perception,
memory and appetite, as well as anti-inflammatory
effects and altering immune responses.
CB1 and CB2 receptors are found throughout the body.

CB1 receptors are mainly in the nervous system.
CB2 receptors exist in the cells and tissues of the immune system.
Although phytocannabinoids don’t perfectly fit into these locks
(receptors), they can still have an effect, and open the door to
physiological changes.
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5 cannabinoids your
body naturally produces
Arac
A
hido
E
no
yl gly
A
ce
2
ro
a l
e ka
id
m
a a
ak
d
an
-A
An
Anandamide plays a role in our 2-AG is involved in appetite,
G
memory, reward systems, and sleep, and pain perception. It
feeding behavior. Anandamide also plays an important part
may also inhibit the growth of in our immune systems. 2-AG
breast cancer cells, and help is one of two endocannabi-
treat depression and anxiety. noids that are crucial for
2-Ar
suppressing seizures.
achid
NADA
onoyl Glyceryl Eth

NADA displays both antioxidant
and neuroprotective properties, 2-AGE regulates calcium uptake
and appears to also be an in the body, and is neuroprotec-
aka
anti-inflammatory. tive. It also appears to reduce
blood pressure and have a
sedating effect.
er
2-
ine
aka
am
So far we only know A

that O-AEA lowers body
op
temperature, but some

l-D
speculate that it could also

G
oy
possibly help with pain.

E
on
id
ch
O-
ra
-A
AEA
N
ine
ine aka olam
Virodham an
eth
noyl
O-arachido
The takeaway from this section: we have identified the compounds that we know
have something to do with the ECS, but we really do not know exactly what that
is. Check our appendix if your head is not spinning, and you need a even more
detailed list of endocannabinoids.
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What Other Receptors

Do Cannabinoids Affect?
The ECS seems to be an important part of homeostasis as a whole, perhaps
the most important part, and we are just beginning to discover how it works.
Modulating the ECS tends to have knock on effects on other receptors in the body,
such as the TRPV1 receptor (aka the vanilloid receptor), which we have already
mentioned above. CBD’s influence on sodium and calcium channels also seems to
have potential therapeutic effects, which include: the detection of pain, reducing
inflammation, preventing seizures in epilepsy sufferers, and potentially providing
relief for those who suffer from disorders that affect the gastrointestinal tract25
(such as irritable bowel syndrome (IBS) and Crohn’s disease). It seems that the key
that opens the vanilloid lock potentially does a lot of really good things.
Additionally, the ECS seems to have an effect, whether directly or indirectly, on

the adrenergic receptors. Adrenergic receptors interact with norepinephrine, a
neurotransmitter produced by the body. Norepinephrine is released when you
encounter a stressor, it mobilizes the brain and body for what is called the ‘flight
or fight’ response. If you are afraid, your body wants to get as much blood to your
muscles as possible, in order to allow you to run away as fast as possible. When
Norepinephrine is released, alpha-adrenergic receptors aid the vasoconstriction
of veins and decrease the motility of smooth muscle in the gastrointestinal tract.
This is because, if you need to escape from a frightening situation, you do not want
to have blood in your small intestines, when it is more useful in your leg muscles.
Sufferers of PTSD often have problems with regulating this ‘flight or fight’ response,
which may be why cannabis seems to be proving to be an effective treatment for
this condition. The alpha-2 adrenergic receptor can also inhibit insulin production
when it is activated by Norepinephrine. Learning how to modulate this receptor, via
the ECS, may help us also treat diabetes and obesity.
The ECS also seems to affect the serotonergic receptors. These receptors play a role
in serotonin regulation. Serotonin is considered a natural mood stabilizer, it helps
with sleeping, eating and digestion, as well as combating anxiety and depression.
Based upon the number of patients, from a significant amount of studies, who
have reported significant therapeutic benefits from cannabis for mood elevation,
we are quite comfortable saying that a mimicry and excitation of the serotonin
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pathways by the phytocannabinoids in the cannabis plant has brought many

people significant relief of their symptoms.
As cannabinoids and terpenoids affect serotonin levels, they could be used to treat
depression and anxiety, as well as pain. It seems that cannabinoids can increase
serotonin production, but this very much depends on the cannabinoid-terpenoid
profile used, and what type of depression is being treated. Again, as we have noted
above, anandamide might induce depression in some, because it causes drastic
changes at the cellular level, which potentially reduces the amount of serotonin
found in the brain and the body. This appears to suggest that cannabinoids and
serotonin levels are connected, but precisely how they relate to one another, is still
up in the air.
You can see tables of which phytocannabinoids affect which receptors in

our appendix, where we give a list of phytocannabinoids, endocannabinoids,
terpenoids, and details on how they interact with the body’s cannabinoid receptors.
We do not yet know the ins and outs of the ECS completely, and our understanding
may change in the future, but this is what we have to go on so far. A lot of research
still needs to be done.
So far, scientists have found 144 unique cannabinoids in the cannabis plant. The
fullest table of cannabinoids we have seen so far is Rudolf Brenneisen’s ‘Chemistry
and Analysis of Phytocannabinoids and Other Cannabis Constituents’26, although
we may be presented with a fuller and more detailed list in the future. Cannabis
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plants can contain up to 1200 compounds, but due to the restrictions imposed by
the DEA, research is still limited on naturally occurring cannabinoids.
Instead, billions of dollars are spent creating synthetic analogues of cannabinoids.

In the current legal framework, rather than discover the efficacy of natural, organic
compounds that grow easily on planet earth, we go to the laboratories and spend
billions on recreating these same cannabinoids, just so we can research them
further. Whilst these cannabinoids can be tested quite safely in labs, when they
get into the public and sold by less-than-scrupulous actors in the market, they are
quite dangerous.
Rather than experiment on the cannabis plant as a whole, pharmaceutical

companies are instead being forced to isolate individual cannabinoids for
experimentation. The cannabinoids in the cannabis plant generally work best
when they work together, not individually, although we will cede that there may
be conditions or particular physiologies where only one or a few cannabinoids
and terpenoids are needed. It is truly a case where the whole is greater than
the sum of its parts. The interplay between cannabinoids, terpenoids and other
phytochemicals found within the natural milieu of a cannabis strain is known as
the “Entourage Effect”. 27
Terpenes and terpenoids were often thought of as only affecting the smell and
taste of cannabis. Anthony Bourdain famously said that he knew a particular strain
was a sativa by its faint aroma of cat urine; that smell was created by the terpene
profile. However, we have now come to realize that terpenes impart physiological
effects of their own.
@erik.nugshots
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Terpenoids can even affect the way cannabinoids behave, and the therapeutic
effects they have.28 For years, terpenoids were not considered very useful, but
that is no longer the case. Terpenoids are as important as cannabinoids, and it
is imperative that research properly determines their medical properties. Even
strains with the exact same cannabinoid profile will have distinctly different effects
if they have different terpenoid profiles. This is what makes the ‘entourage effect’
so important. Please see the Appendix for a list of the most common terpenoids
found in cannabis. To note, a terpenoid is a terpene (which contains a hydrocarbon
group) that has been denatured by oxygen, this is usually achieved by the drying
and curing of the cannabis’ “buds” or flowers.
However, as an academic exercise, there is some value in seeing how individual

cannabinoids and terpenoids work on their own, without interaction with other
chemicals. Arguably, the isolation of individual cannabinoids can help us to determine
their specific physiological effect. This would allow us to compare the difference
between isolated cannabinoids, and those in their natural combined states
However, some research has shown that synthetic or isolated cannabinoids may be
far more harmful or less well-tolerated than naturally occurring ones that, to put it
simply, come as a package. To give an example, THC’s effect on memory may be
negated by pinene to some extent, whilst CBD and low doses of THCV may temper
THC’s psychoactivity to a degree. Cannabis plants, just like humans, have a series
of checks and balances, where overabundance of one compound is “checked” by
another compound, which potentially negates some of the more extreme negative
effects. The ECS is a very powerful system, and synthetic cannabinoids may have far
more harmful effects than their natural counterparts if not used properly.
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Prof. Roger Pertwee

_ Emeritus Professor, University of Aberdeen, School of Medical Sciences
Why is cannabis medicine, and why does it seem to work for so many conditions?
The starting point, I suppose, is that cannabis has been used as a medicine for thousands
of years. In fact, Queen Victoria I think was given it as medicine. This was at a time when
there were relatively few other medicines about, and for some reason or another, it was
discovered that cannabis could help with problems such as pain. So cannabis has been
around a long time as a medicine.
Cannabis again became medicine in the UK in the form of tincture of cannabis. That was
actually very useful for our research, because we used to extract cannabinoids from this
tincture, which was still available in the late 1960s and early 1970s. But this tincture was
banned in the 1970s, and then a cannabis-based medicine didn’t come back into the clinic
until Sativex.
So, the reason why cannabis works for so many conditions … Well, I suppose mainly it’s
because cannabis is like a treasure chest, really. It’s full of a large number of compounds,
some of which have very interesting pharmacological properties which could be exploited,
and some of which are already exploited therapeutically. The thing is that it’s complicated
because of the mixture of all these chemicals, and it’s not necessarily the best way forward
to take cannabis as a whole. It might be better to take individual compounds or just two or
three of the compounds.
But of course, people who have illnesses which aren’t being treated properly by licensed
medicines, are finding cannabis works for them. And so they go for cannabis. So it’s used
today as a form of self-medication. Way back in the early 1990s, we devised a questionnaire
for multiple sclerosis (MS). There was a journalist who used to write about cannabis in a
newspaper who had MS. She was self-medicating and wrote under a false name to avoid
getting arrested. Clare Hodges was her pseudonym. We were eventually able to contact a
lot of patients who were self-medicating, sending out a questionnaire to each of them with
her help.
We published the results of that study in a paper called ‘The perceived effects of cannabis
smoking in patients with multiple sclerosis’. That was input from patients. And there were
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a lot of other disorders for which patients self-medicated as well. I don’t think myself
that cannabis is a final solution, but more of a starting point. Patients are telling us that
cannabis is working for them. The ideal now would be to maximize the benefit:risk ratios
by doing various things.
You mentioned separating out the compounds. There are a lot of people who feel
that a full spectrum of cannabinoids and terpenoids are needed, or a mixture of
specific cannabinoids and full-spectrum oils. What would you say about this?
Well, it could well be that you need more than one. You could need several of them,
or even all of them. But that’s to be demonstrated really. The trouble is that it’s such a
challenge, but at the end of the day, we need to do clinical studies. For the sake of the
patients, really - to optimize the best benefits and minimize the side-effects. But it could
well be that we need a large number of the constituents of cannabis for that. Then the
question is, “What dose of each beneficial constituent do we need”?
Which leads nicely onto my next question, and one that many patients ask: how
much should I take, and what strain or profile is best for me?
Well, I think patients probably have to try and discover which strain is best for their
condition by trying out lots of different strains, and they’d be a very useful source of
information about that. The problem is, I don’t know how easy it is for patients to get a
consistent strain, or whether they go to the same place and get a different type of strain
each time. The trouble is, when you grow cannabis and you go from generation-to-
generation, the plant can change and doesn’t necessarily stay the same.
GW Pharmaceuticals have a very good system, because their plants do stay the same
from generation-to-generation, because they use genetic techniques. So they don’t
have plants breeding together - they have them genetically controlled. So GW always
have one plant that’s very high in THC and low in CBD and other phytocannabinoids,
and another that’s very high in CBD and low in THC and other phytocannabinoids. That’s
consistent from generation-to-generation, which makes it easier to come up with their
medicines. Sativex is one example of such a medicine. It contains both THC and CBD,
each extracted from different cannabis plants, and so is a cannabis-based medicine.
LeafWell
That’s a 1:1 THC:CBD ratio?
Yes an approximately 1:1 ratio.
So, did your studies find that the 1:1 ratio was most therapeutic for MS?
We didn’t study that at all. This was before Sativex, and really we were more interested in the
benefits that were claimed. But we never asked anyone what constituents of cannabis they
were taking or what kind of cannabis they were taking. Remember, this was way back at a
time when that was of less interest. What was of particular interest was whether cannabis
could be a source of modern medicines or not.
Have people become more interested in these differing ratios and components of
cannabis?
I imagine so! There’s a lot going on at the moment and a lot we don’t know, really. Many
different companies are being set up in the USA and elsewhere to develop cannabis-based
medicines for the shops. It’s in an early stage at the moment, and it would be interesting to
see how good their products are. I’m not sure how well-controlled they will be.
What would you say is the best method of ingestion?
I think we still have to decide on that. Sativex, for example, is absorbed from the mouth.
The advantage of that is that it goes from the mouth straight to the heart. In contrast, if
you absorb plant cannabinoids from the gut, their rate of absorption is very variable - but
eventually they do get to the liver, and from there to other parts of the body. If they go
through the liver first, there’s a lot of metabolism that can take place before they go on. And
some of the plant cannabinoids, for example CBD, are not a problem as far as the brain is
concerned. But CBD does target certain enzymes in the liver, both as an inhibitor and as
an inducer of some of those enzymes. Particularly cytochrome P450 enzymes, and so CBD
can have complicated effects. CBD will, for example, modulate the metabolism of other
cannabinoids, including THC.
So the best way of taking cannabis remains to be seen. Some people talk about vaping, but
I don’t know if that’s been studied enough. It’s probably better than smoking it, where you
burn the cannabis; and if you burn the cannabis, you form new products, some of which
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may be toxic. Some claim that these could be carcinogenic, but there’s a debate about
that. The good thing is that it goes straight from the lungs to the heart, and then from
the heart to the brain. Also, the absorption is very quick, so it’s almost instant, whereas
if you take cannabis by eating it, it can be very slow to take effect - half an hour or more.
So I think there’s a lot to be looked at before we can say anything for sure. Transdermal
patches are other possibilities, as are topicals and salves. Another way could be synthetic
compounds, but I will come back to synthetics later.
Is there much difference between these synthetics and the ones that are
naturally derived?
Well, you can get some which are identical. THC, for example, can be made. CBD can be
made. But you can also get ones where they’re structurally similar but not the same, so
they’re analogues. You can do that for various reasons. One thing we did recently, was to
publish a paper earlier this year on a compound called “HU-580”’. HU-580 is an analogue
of cannabidiolic acid (CBDA), and CBDA is a precursor of CBD in cannabis. CBDA is very
unstable, so it’s not a very good potential medicine; but that said, if you study it in the
lab, it has interesting properties. CBDA is even better than CBD for reducing nausea
and vomiting induced by chemotherapy, for example. It has a bell-shaped response
curve, so at low does it doesn’t do anything and at high doses it doesn’t do anything - it
only works at intermediate doses. Same with CBD. But the HU compound has a much
broader bell-shape, which is good, and is more stable, meaning it can be stored for a very
long time. Structurally, HU-580 is very similar to CBDA, just with a methyl group added
to this chemical, making it more stable.
Another reason why you might want a synthetic compound is that, if you’re interested
in using THC to treat disorders of the eye, like glaucoma for example, the problem of
getting the THC into the eye is that THC is lipid soluble and water insoluble. One way
around that would be to give a water soluble prodrug. So that would be THC modified
so that it is made water soluble - which we did about 25 years ago - but since then more
recently someone’s come up with another such compound. They’ve shown that, if they
put it into the eyes of animals, it gets straight to the retina as it is water soluble, and
the compound then breaks down very quickly to form THC. This has an anti-glaucoma
effect by reducing pressure in the eye. That prodrug strategy might have other potential
clinical applications.
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From what we’ve gathered, CBD could affect the uptake of many drugs, in
particular benzodiazepines. Are there any other drugs CBD could interact negatively
with, in your experience?
Gosh, I’ll think about that! But there could well be interactions with CBD and other drugs
due to its ability to affect the metabolism of certain compounds for good or ill, that’s for
sure. CBD can also affect the blood-brain barrier (BBB) for good or bad.
There’s so much complexity, and it seems like we’ve just scratched the surface …
… Yes, well of course, many drugs are like that. They very rarely have just one action - they
usually have a whole range. THC itself has many different actions. It targets CB1 receptors,
but has lots of other targets as well. THC has quite a complicated pharmacology. It’s not
straightforward.
Is this an advantage or disadvantage, in your view?
Well, it’s both, really. If the targets are good targets, then it’s good; if it targets bad targets,
then it’s bad! This certainly makes it more complicated. At the end of the day, what you
need, which are missing a lot of the time, are the clinical data, which is why it’s great
we have input from patients, really. We don’t have much of this information from drug
companies, because there’s only so much they can do. So we very often have preclinical
data, and we also have in vivo animal data, but very rarely do we have clinical data except for
the drugs that have been approved as medicines, like Sativex and like THC. Of course, THC
was a medication before Sativex, in the form of Marinol (dronabinol), as was its synthetic
analogue, Cesamet (nabilone). They were approved to boost appetite in AIDS patients and
as antiemetics. So, most drugs in the clinic have various modes of action. What’s important
is the benefit-to-risk ratio.
Does cannabis have any long-lasting effects, positive or negative?
Yes, it can do. And again, to some extent it’s age-dependent. Young people should avoid
taking THC-rich cannabis while their brain is still developing. The endocannabinoid system
(ECS) plays an important role in the developing brain, so if you target that, you should do
so with care. There’s a certain amount of evidence that suggests that adolescents are more
susceptible to schizophrenia and psychosis as a result of taking cannabis. Older people
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are usually less affected by that. This is probably to a large extent due to the THC in
cannabis. CBD is actually an anti-schizophrenic, and will likely be developed as an
antipsychotic drug.
Would you say the plant itself has checks and balances, like people do?
Indeed it does. Of course, its constituents sometimes have opposite effects. We call
them “phytocannabinoids”, but we should perhaps call them “fightocannabinoids”,
as they often fight each other by having opposite effects. Tetrahydrocannabivarin
(THCV) is one example. That was a phytocannabinoid we discovered in Oxford in the
late 60s/early 70s in the tincture of cannabis I mentioned. We have since discovered
that THCV activates CB2 receptors (which, if you activate with cannabinoids, has an
anti-inflammatory effect). But it also targets the CB1 receptor. But, unlike THC, THCV
acts as a CB1 receptor antagonist. So it has an opposite CB1 effect to THC. And the
combined CB1 and CB2 effects of THCV could be good for disorders such as stroke.
THCV acts as an antagonist of THC …
Yes, that’s right. THCV antagonizes THC at CB1 receptors. In our initial paper,
published in 1970 I think, we obtained in vivo evidence - long before the discovery of
cannabinoid receptors - that it actually had similar behavioral effects as THC, and we
thought it might be acting like THC. Subsequently, we thought that THCV acts as a
CB1 receptor agonist when the receptors were discovered. And certainly, THCV does
act as an agonist of the CB1 receptors at high doses, but it acts as a CB1 antagonist
at lower doses. We’ve seen this in vivo in animals, but have not investigated it in
humans.
What is the endocannabinoid system (ECS)?
Eventually, in the late 1980s and early 1990s, cannabinoid receptors were discovered
and named CB1 and CB2. Once these receptors were discovered - and CB1 receptors
for example were found in high amounts throughout the brain and body - the
question became “Why do we have those receptors?” Probably not so we can get
high on cannabis! So that prompted a search for endogenous compounds that could
target those receptors. That led to the discovery of endocannabinoids, which are
released onto cannabinoid receptors centrally and peripherally. I co-authored the
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paper on anandamide, which was the first endocannabinoid to be discovered. We

first published that in 1992.
That research was headed by Professor Raphael Mechoulam, and he extracted

anandamide from pig brain and then sent it to us so we could study it
pharmacologically and we were able to show that it behaved like THC. This was
before the time there were any antagonists around, so it wasn’t possible to block
the CB1 receptors, but subsequently this became possible once the CB1 antagonist
rimonabant came along.
So the ECS is a system of cannabinoid receptors and chemicals that are produced
in our bodies that act on those receptors. They’re not stored but are synthesized as
needed, then released, for example from neurons, to act on these receptors. Very
often they’re released in an auto-protective way. They’re released in a way which
seems to be good for our health. Sometimes they may be released in a harmful way.
For example, they can possibly contribute to obesity, but usually they’re released in
a very beneficial way. That’s raised the idea of new medicines that can modulate the
levels of endocannabinoids - usually by increasing their levels, but sometimes by
decreasing their actions.
Do you see a lot of the medications of the future being cannabinoid-based?
Oh yes, I’m sure. It’ll take a while, because it’s quite expensive to bring a drug into
the clinic. I think there’s a lot of interest in drugs that can inhibit the metabolism
of endocannabinoids. There was a bit of a setback last year during a clinical trial in
France, with a drug developed by a Portuguese company. It was developing a fatty
acid amide hydrolase (FAAH) inhibitor as a potential medicine. It was a phase 1 study,
and unfortunately one of the participants was killed by the drug. But the chances
are that that was an off-target effect and not due to it blocking the metabolism of
anandamide, but maybe some other action, probably. That’s the general opinion at
the moment. But it’s a setback nonetheless.
There was another setback with rimonabant (SR 141716A), which is a CB1 antagonist
and was approved as an anti-obesity medicine but was withdrawn after people had
become suicidal after they took it. Presumably because it was blocking some of the
beneficial effects of endocannabinoids, as well as the harmful effects of obesity. But
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it’s complicated, because rimonabant is what is called an “inverse agonist”, so what

it does is “switch off” spontaneous signalling of cannabinoid CB1 receptors as well as
blocking activation of these receptors.
Another potential kind of medicine that I think may emerge in the future would
come from a group of drugs that I work on in collaboration with medicinal chemists,
which are allosteric modulators. So we discovered an allosteric site on the CB1
receptor around 2005, whilst working, for example, with a compound called Org
27569. The way it was behaving suggested that it is a CB1 allosteric modulator, and
indeed it is. Now I’m working with, for example, a medicinal chemist from Boston,
and we’re looking at this as it could be a medical way forward. What these allosteric
modulators do is to strengthen or weaken the activation of cannabinoid receptors by
endocannabinoids like anandamide and 2-arachidonoylglycerol, and so alter the CB1
efficacy, potency or both of an endocannabinoid that’s being released. We’ve already
published a paper showing that one allosteric modulator that strengthens CB1
activation works well as an analgesic in an animal model of pain. It doesn’t produce
some of the side-effects that can result from directly activating the CB1 receptor - it
doesn’t produce signs of dependence, for example.
You’re speaking about many compounds being withdrawn during phase 1

of their trials. Does that not suggest to you that the ECS is a very powerful
system?
Oh, it is a very powerful system, and you have to modulate it very carefully. Another
example of a synthetic compound is called a “peripherally restricted” compound -
one which doesn’t go into the brain, but will target peripheral cannabinoid receptors.
One reason for wanting to do that would be to treat things like renal nephropathy,
or kidney damage, usually associated with diabetes. For that, what might be
good would be to use a drug that blocks the CB1 receptor, to block effects of
endocannabinoids in the kidney, which might be good for ameliorating nephropathy
- but to give this together with a drug that activates the CB2 receptor. One possibility
might be to develop a synthetic analogue of THCV that does not get into the brain.
As THCV has both of these CB1 and CB2 pharmacological properties, it could perhaps
be done with just the one compound rather than two, but two may be required.
LeafWell
Could you tell us a little bit about cannabigerol (CBG)?
CBG has an interesting pharmacology. CBG activates alpha-2 adrenergic receptors, and
it seems to be good for relieving pain because of that.
Do cannabinoids need to be decarboxylated in order to have therapeutic effects?
No, but the trouble is that they’re not very stable when they’re un-decarboxylated.
But CBDA seems to be particularly good for reducing nausea and vomiting in
chemotherapy. Like CBD, CBDA seems to have this effect by targeting serotonin 5HT1A
receptors. That’s also something to bear in mind: cannabinoids have targets other than
cannabinoid receptors, some of which could mediate beneficial effects. THCV, CBD and
CBDA can strengthen the activation of 5HT1A receptors, an action which can produce
plenty of potential beneficial effects, including an anti-schizophrenic effect. We’ve
obtained strong evidence for that from in vivo experiments performed in the laboratory
of an Italian collaborator, Professor Daniela Parolaro.
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Overall
The exact purpose of the ECS and the way in which endocannabinoids and
phytocannabinoids function is not yet fully known. The ECS was discovered
only relatively recently (with the first cannabinoid receptor CB1 being found in
1990). Fast forward to today, and most of the mechanisms are nowhere near fully
understood. Part of the reason for this is because of the federal government’s
stance on cannabis research, researchers are still playing catch up to effectively
make sense of it all.
However, many doctors and scientists are very excited about the discovery of the
ECS, and how it may help us manage serious medical conditions in the future.For
many people, the discovery of the ECS gave scientific grounding for the popular
view that “marijuana is medicine”. In the past, we never had the research, language,
and scientific explanations to truly back up this idea. Now we do, and the idea
of “medical marijuana” no longer exists just for fantasists. Even moral naysayers,
chairmen and women of the DEA, or attorney generals, need to wake up to the
power of this healing plant.
LeafWell
Note on “Potential Value of Cannabis Based on Current Evidence”: this rating is

based upon the quality of evidence we have so far, and is by no means a “hard-and-
fast” rating. We have simply broken it down into three categories: little evidence so
far, average and significant. A meta-analysis of peer-reviewed studies can be found
here, but some of the more recent studies on cannabinoids may make older data
redundant or not as reliable:
Peer-reviewed studies on medical marijuana, # of studies

listed by condition treated Not Clearly
PRO CON Pro or Con
ALS 1 0 0
Bipolar Disorder 2 0 0
Cancer 5 1 1
General Use 2 0 0
Glaucoma 0 0 1
HIV/AIDS 5 1 2
Huntington's Disease 0 0 1
IBD/Crohn's 1 0 1
Multiple Sclerosis 11 3 5
Nausea 1 0 0
Pain 6 0 1
Parkinson's Disease 2 0 1
PTSD 1 0 0
Psychosis / Schizophrenia 1 0 1
Rheumatoid Arthritis 1 0 0
Tourette's Syndrome 2 0 0
TOTALS 41 (68.3%) 5 (8.3%) 14 (23.3%)
You may notice that we have a list of over 40 conditions, so there’s a lot of research
that needs to be done. We hope that there’s people paying attention and thinking to
themselves, “let’s do some clinical trials, preferably looking at all the compounds and
not just THC and CBD, or cannabis generically!” Please also note that many of the
studies we reference are often on mice and various rodents, and these early studies
do not necessarily always translate to humans.
LeafWell
There has also been a wave of new research over the 3-5 years where specific
cannabinoid and terpenoid ratios are being tested for different conditions to see
which formulations match which conditions. This means that some of the older
studies may be useful, but not necessarily completely accurate as they may have
been treating cannabinoids generically. Unfortunately, this method of approach
is relatively recent, so there is little research in this area regarding specific
cannabinoid-terpenoid ratios for particular conditions - for now, anyway. Another
issue is that cannabis may be useful for some people with a certain physiology,
but not others, even if both people suffer from the same condition. Of course, this
is the case with any medication or treatment, so we should not necessarily single
cannabis out in this regard.
LeafWell
2
CHAPTER
CANNABIS
AND
CONDITIONS
54 CANNABIS AND CONDITIONS
Cannabis and Acne
General
Acne, also known as acne vulgaris, is a long-term skin disease where hair follicles
become clogged with oil and dead skin cells on the skin. This usually occurs in
areas of the skin that have a high number of oil glands, such as the face, neck,
upper chest and back. Blackheads, whiteheads, pimples, oily skin and scarring
are common characteristics of acne. Acne usually forms during puberty, but can
also occur due to using medications such as steroids, which increase testosterone
production. Approximately 80%-90% of teenagers in the western world develop
acne, and for half of those affected, acne can persist into their 20s and 30s. Around
60 million people in the US have acne, and it is bad enough to leave scarring for
20% of them.29 On rare occasions, acne may continue past one’s 40s. Acne affects
9.4% of the global population, making it the 8th most common disease in the
world.30
Another factor contributing to acne is the growth of Propionibacterium acnes

bacterium on the skin. Although, it seems that the chances of developing it have
little to do with cleanliness and exposure to sunlight. The link between acne and
diet, and how smoking affects it, are not fully understood. However, treatment
methods include avoiding refined sugars and following a healthy diet, azelaic
acid, benzoyl peroxide, salicylic acid, antibiotics and retinoids. In moderate-to-
severe cases of acne, where acne may cause a significant change in appearance
and hence affect a person’s self-esteem, antidepressants and anxiolytics may be
prescribed. Exercise can help with stress and therefore prevent anxiety-triggered
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CANNABIS AND CONDITIONS 55
acne outbreaks, but sweat can aggravate the condition, so good personal hygiene is
paramount.
Due to acne being a bacterial infection, antibiotics may be used to beat acne.
Unfortunately, this also leads to antibiotic resistance, meaning that this method of
treatment should ideally be avoided, except in the most severe cases. Unfortunately,
other than using chemicals that could also cause the skin to peel and itch, there are
relatively few ways of treating acne effectively.
The evidence of the efficacy of cannabis for treating acne is mixed. Some state that
THC causes a spike in testosterone, which may cause outbreaks of acne. Others point
out that, after this spike, we see a drop in testosterone, so THC may diminish acne in
the long-term. Although THC may increase sebum production and the chances of
an acne outbreak, CBD, on the other hand, seems to stop sebum production and dry
out the skin. Both cannabinoids have anti-inflammatory properties, which may aid in
the prevention of acne, as do terpenoids such as pinene and linalool.
POSITIVES NEGATIVES
• CBD and THC are anti-inflammatories, which • Getting the right skin care product may be
may help prevent acne. difficult to find - THC may increase sebum
production, whereas CBD based products may
• Could replace antibiotics. decrease sebum production, thereby drying out
the skin.32 33
• Contains other terpenoids that may help with
inflammation, such as pinene and linalool.31 • No definite evidence that cannabinoids will
work for acne, although it does seem that the
• Topicals and salves made with cannabis are
ECS plays some sort of role in the production
unlikely to have any psychoactive effect, as they
of skin oils.
are unlikely penetrate the first few layers of skin.
TREATMENT
VALUE OF MMJ
For dry skin, a THC-infused topical cream or skin
First of all, cannabinoid-based treatments may care product may help, whereas for oily skin, a
help reduce the need for antibiotics for acne, CBD topical cream or skin care product may be a
which means less chance of antibiotic resistance better treatment. Terpenes and terpenoids such
occurring. The proliferation of incredibly virulent as pinene may also help.
bacteria such as MRSA (Methicillin Resistant
Staph. Aureus) should warn every physician that
overprescribing antibiotics is not innocuous. Cystic
acne, which can be quite painful, may be soothed POTENTIAL VALUE OF CANNABIS
by THC and/or CBD due to their anti-inflammatory BASED ON CURRENT EVIDENCE
Average
effects.
LeafWell
Cannabis and Addiction Treatment
General
Treating addiction is an expensive process. According to the National Institute of
Drug Abuse, if one includes actual treatment costs, crime and loss of productivity,
the annual expenditures in the U.S. for tobacco is $300 billion (2010), $249 billion
alcohol (2010), illicit drugs, and between $193 billion (2007) and $78.5 billion (2013)
for prescription opioids.34
For many, it may seem counterintuitive to treat addiction with cannabis, as they
see cannabis as another “drug” and think we are merely replacing one intoxicating
substance with another.
Yet, we can legitimately ask, “So what?” After all, studies have shown35 that
cannabis is far safer than painkillers, alcohol, amphetamines and many other drugs,
prescription or not. In fact, it is not at all unusual to wean people off heroin and
alcohol by using other opioids, such as methadone, and benzodiazepines, in order
to prevent potentially fatal withdrawal symptoms.
LeafWell
Of course, this form of treatment often means that alcohol and opioid addicts
end up being addicted to other, sometimes similar drugs - this time ones that
have been prescribed to them by doctors. With this method of treatment, the
risk of relapse is quite high, especially as dosages taper off. Cannabis treatment
seems, so far, to be a much safer alternative36 to many current treatments involving
substitutes, such as methadone. To date, there are no documented reports of fatal
cannabis overdose, and the safety margins are significantly higher with cannabis
than with other traditional substitutes. Every medication has a ‘lethal dose 50’
(LD50), which denotes the amount of medication that must be consumed for a
50% fatality rate inpatients. The theoretical LD50 for cannabis is the consumption
of 1,500 pounds in 15 minutes - and remember, that is theoretical, as well as being
nigh on impossible. It is possible that the LD50 for cannabis could never actually be
reached.37
LeafWell
Collin Wells, California
“ I joined the army at 26 and lived a full life before it. I served in the military 4 years, and
did one 12 month tour in Afghanistan, from July 2009-August 2010. When I got back
from Afghanistan, I had lost everything. I got married 10 days later, but everything
went downhill quickly after. I was still in the army during this period and they were
treating me with opiates. They gave me any uppers and downers they could to keep
me training. I had 2 knee surgeries, so I was trying to push through a lot of pain.
When I was discharged, I was a raging opiate addict who didn’t care. I used every
dollar I had to get drugs to maintain the numb feeling I wanted. My wife couldn’t do
anything else for me, so she took me to the Veteran’s Hospital when we moved to
California.
I was in therapy and things were going great until I got in a fight with my roommate
there, was kicked out, and quickly went to even harder drugs than before.
A friend of mine was supposed to come over with pills but instead brought cannabis.
I was pissed. When I smoked it though, it was the first time I was content in as long
as I could remember. And I spent the next few weeks getting cannabis, withdrawing
from drugs, and watching Game of Thrones. Now I microdose with CBD and THCA
everyday, and medicate throughout the day as needed. I’m finally in my son’s life,
I’m the leader of a hiking program, and I have a great job I’m excelling at. Basically,
”
everything prescription drugs promised to give me but couldn’t, cannabis has
LeafWell
POSITIVES NEGATIVES
• Cannabis has the potential to stave off any pain • Will not help on its own with other contributing
that is usually treated with opioids. factors that can lead to addiction - e.g. a bad
environment at home or negative peer groups.
• Increased appetite.
• Patient needs extensive follow-ups, in order to
• Better sleep. prevent the chances of relapse.
• Relaxes “restless legs”. • May not be effective for extreme long-term

users, or, alternatively, long-term users may
• Euphoric effects that boost mood.
need to use powerful cannabis concentrates -
• Can help stave off boredom, anxiety, depression which may prove uncomfortable for some.
and cravings.
• Some opioids and cannabis may produce
• Helps relax the muscles. harmful effects when mixed.
• The serotonin receptor system 5-HT plays a • Many addiction treatment programs find this
huge role in the development of addiction.38 form of treatment “problematic”, which could
Could modulation of serotonin receptors using force patients out of otherwise supportive
cannabinoids be helpful in battling addiction?39 programs.
If so, cannabinoids can potentially play a huge
part in breaking the addictive cycle, or the
“loser script”. TREATMENT
For those struggling with opioid addiction,

VALUE OF MMJ some may suggest using a high-THC strain
or form of cannabis product in order to create
Cannabis could effectively act as a “crutch” for euphoric effects, and prevent “cravings”. Using
those who are addicted to other drugs. One cannabis strains products that are high in beta-
major factor is which drug the patient is abusing. caryophyllene, myrcene and humulene may
Cannabis may be effective for treatment of potentially also help.
addiction to some drugs, and not others. One
theory as to why cannabis might help with opioid
addiction, for example, is that THC activates opioid
receptors, specifically mu- and delta- opioid
receptors (they “talk” with one another). This gives
cannabis the potential to be used as a potential
treatment method for both opioids and alcohol.40
Moreover, it is a replacement “drug” that is far POTENTIAL VALUE OF CANNABIS
safer than either opioids or benzodiazepines, BASED ON CURRENT EVIDENCE
Significant
which are both often used in the treatment of
opioid and/or alcohol addiction. Terpenes such as
beta-caryophyllene,41 myrcene and humulene may
also provide therapeutic value for those suffering
from addiction.
LeafWell
Cannabis and Alzheimer’s Disease
General
Alzheimer’s disease is a chronic neurodegenerative disease that, over time, can
cause dementia. Alzheimer’s disease is genetic in around 70% of cases, but head
injuries, hypertension and depression are also risk factors. Alzheimer’s disease is
characterized by amyloid plaque building up in the brain, caused by the “clumping
together” of Beta amyloid. Symptoms include loss of memory, mood swings,
difficulty processing language, loss of motivation, and an inability to care for
oneself. Alzheimer’s disease tends to lead to dementia, and it is believe that, as of
2017, approximately 50 million people worldwide are afflicted with dementia.42 As
we have an aging population, this number is likely to increase, and more effective
treatments are desperately needed.
Using cannabis for Alzheimer’s Disease is proving a somewhat controversial.

One reason for this is because Alzheimer’s Disease is a neurological condition,
and as tetrahydrocannabinol (THC) can cause sensorial changes, many would
warn Alzheimer’s sufferers to be sceptical of cannabis. Yet, there are more and
more studies suggesting that cannabis can actually be beneficial for those with
Alzheimer’s Disease.
LeafWell
At present, there is no cure for Alzheimer’s disease, and most medications

currently available only treat the symptoms, or deal with slowing the progression
of Alzheimer’s. Whether cannabinoids are any different in this regard, we do not
yet know. Current Alzheimer’s medications include acetylcholinesterase inhibitors
(AChE inhibitors) such as donepezil, rivastigmine and galantamine.43 These work
by inhibiting the enzyme acetylcholinesterase, which leads to an accumulation
of the neurotransmitter acetylcholine and causes hyperstimulation of nicotinic
and muscarinic receptors - both hugely important receptors in the formation of
memory, motor coordination and muscle contraction. AChE inhibitors are usually
used for early- to mid- stage Alzheimer’s. For late-stage Alzheimer’s and for those
who cannot tolerate AChE inhibitors, the NMDA receptor- blocking, glutamatergic
system- targeting memantine is used. Side-effects of such medications include:
• Nausea • Dizziness
• Vomiting • Slowing down of heartbeat (AChE inhibitors)
• Headache • Seizures (memantine)
• Agitation • Shortness of breath (memantine)
• Muscle cramps • Increased confusion (memantine)
• Diarrhoea (AChE inhibitors) • Depression
• Constipation (memantine)
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As can be seen, many of these side-effects can be similar to Alzheimer’s itself. In

the case of memantine, there is no definitive evidence that it works for humans,
although animal results have proved promising. Other treatments include
occupational therapy, cognitive behavioral therapy (CBT), and music and art
therapy. For late-stage Alzheimer’s and the onset of dementia, advanced care is
often required.
POSITIVES NEGATIVES
• THC may help remove Beta-Amyloid - the • Cannabis can have negative effects on short-
plaque-causing protein - from brain cells.44 term memory - not ideal for those suffering
from Alzheimer’s!
• Cannabidiol (CBD) appears to be a
neuroprotective, and could well help prevent • Altered senses can increase confusion.
Beta-Amyloid-induced toxicity in PC12 cells.45
• Difficulty in quick-thinking and problem-
• Cannabinoids may help promote neurogenesis solving.
- the growth of new neural pathways.46 47
• Cannabis may only be effective for the long-
term prevention of Alzheimer’s.
VALUE OF MMJ TREATMENT
CBD can act as a neuroprotectant and anti- Although THC can help with the pain and mood
inflammatory, and help prevent the buildup of swings that are associated with Alzheimer’s,
amyloid plaque. It could potentially even promote it may also exacerbate other issues, such as
neurogenesis, the re-growth of neurons and brain memory loss. A CBD-rich product or strain may
tissue, and thereby stave off the development of possibly be ideal to help reduce inflammation,
dementia. but this is not to say that THC has no value in
treating Alzheimer’s, especially when it comes
to controlling any anxiety or rage that sufferers
may go through. In some instances, a synthetic
form of THC, named “Marinol”, may be prescribed
POTENTIAL VALUE OF CANNABIS for patients, though how effective this is in
comparison to non-synthetic versions, where all
BASED ON CURRENT EVIDENCE
the other cannabinoids are present, remains to be
Average seen. A CBD:THC ratio of 20:1 and/or 1:1 may both

be equally useful.
LeafWell
Cannabis and Amyotrophic Lateral Sclerosis

(ALS) / Lou Gehrig’s Disease
General
Amyotropic Lateral Sclerosis (ALS) is a devastating and debilitating degenerative
neurological disorder that affects the spinal cord. Muscle weakness and the wasting
of muscle tissue lead to paralysis of the limbs and the deterioration of speech. It
also affects the patient’s ability to swallow and breathe, which ultimately leads to an
early demise. Approximately 222,801 cases of ALS presented themselves across the
globe in 2015, and this number is likely to increase as the population ages.48
The condition is named after the baseball legend, Lou Gehrig, and it is also the
condition to which Stephen Hawking succumbed. Most of those who suffer from
ALS only survive 2 - 5 years after diagnosis, and 5% survive longer than 20 years.
LeafWell
There is not enough evidence to say whether or not cannabis helps with ALS.
However, some preliminary studies in mice have shown that cannabis may help
slow the onset49 of ALS and increase life expectancy.50 There are also two very
interesting case studies - those of Cathy Jordan51 and Bob Strider52 - both of whom
used cannabis to help control ALS.
POSITIVES NEGATIVES
• Will help battle chronic pain and inflammation. • Lack of any major studies on humans - the
evidence is mostly anecdotal, or based on
• Acts as a muscle relaxant. research conducted with mice.
• Stimulates appetite. • As with other neurological problems, THC may

be a “double-edged sword” - although it helps
• It’s aids bronchodilation, which can make
prevent cell degeneration, it may also cause
breathing easier by decreasing airway
sensory distortion.
resistance and letting more airflow enter the
lungs.
• Saliva reduction & dry mouth (thought to be TREATMENT

caused by the terpenoid Delta-3-Carene) is
usually seen as a negative side-effect, but can This is difficult to assess, especially when there is
help prevent drooling in ALS. so much conflicting information about cannabis’s
efficacy for ALS. Relatively high amounts of both
• Causes vasodilation, the dilation of blood
THC and CBD in equal concentrations may help,
vessels, and decreases blood pressure
but there is just not enough data from which to
• THC may slow the disease process,53 help draw accurate conclusions.
increase life expectancy, and improve quality
of life.
• Strong antioxidative and neuroprotective

effects, which help ALS patients keep healthy
physically and mentally.
POTENTIAL VALUE OF CANNABIS
VALUE OF MMJ
Little
evidence
There are very few drugs and treatments available
for ALS sufferers. One is riluzole, which purports
so far
to block harmful levels of the neurotransmitter,
glutamate, from being released into the brain.
However, at close to $10 per pill, riluzole is
prohibitively expensive, and its efficacy is not
entirely proven as of yet. Cannabinoids may
very well prove to be a much-needed, hopefully
affordable treatment for ALS.
LeafWell
Cannabis and Anterior Cruciate Ligament

(ACL) Reconstruction
General
The anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL)
are two of the major stabilizing ligaments in the knee. The ACL and PCL “criss-
cross” one another, and because of this, they are sometimes known as cruciform
ligaments. The ACL is important for movement, and provides most of the
restraining force (85%) to prevent anterior tibial displacement. The ACL is crucial for
stabilizing the knee for pivoting, or turning quickly. ACL tears are a very common
sports injury, with around 150,000 cases occurring annually in the U.S., costing
approximately $500 million per year to treat.54
The ACL endures significant strain in its lifetime. For many highly active people,
especially athletes, the ACL can tear from an acute strain, following repetitive
trauma. To return to competitive athletics, and prevent early onset osteoarthritis,
a torn ACL requires surgical intervention. ACL reconstruction, is the procedure of
choice for restoration of knee joint function. It can take the form of a tissue graft,
or a replacement ligament can be harvested from the patient. Post surgery, many
athletes are given a powerful cocktails of opioids and NSAIDs for pain relief.
Cannabinoid receptors can be found throughout the body, including in the bones
and joints. This means we can target the ECS for bone and joint injuries as well. To
quote from “Endocannabinoids and the regulation of bone metabolism:
“Recently, the main components of the endocannabinoid system have been

reported in the skeleton. Osteoblasts, the bone forming cells, and other cells
of the osteoblastic lineage, as well as osteoclasts, the bone resorbing cells,
and their precursors, synthesise the endocannabinoids anandamide and
2-arachidonoylglycerol (2-AG). CB(1) cannabinoid receptors are present in
sympathetic nerve terminals in close proximity to osteoblasts. Activation of these
CB(1) receptors by elevated bone 2-AG levels communicates brain-to-bone signals
as exemplified by traumatic brain injury-induced stimulation of bone formation.
In this process, the retrograde CB(1) signalling inhibits noradrenaline release
and alleviates the tonic sympathetic restrain of bone formation. CB(2) receptors
are expressed by osteoblasts and osteoclasts. Their activation stimulates bone
LeafWell
formation and suppresses bone resorption. CB(2)-deficient mice display a markedly

accelerated age-related bone loss. Ovariectomy-induced bone loss can be both
prevented and rescued by a CB(2) specific agonist.” 55
Using cannabis to help with the healing of the ACL could stimulate the proliferation
of osteoblasts, which restore bones, by altering the action of the regulatory function
of CB(2), and potentially lead to shorter recovery times, and a reduced risk of long-
term issues, like osteoarthritis.
POSITIVES NEGATIVES
• THC and CBD, along with the terpenoids; • No definite proof that cannabinoids work,
linalool, pinene and limonene have powerful although the signs are promising, and many
anti-inflammatory effects, and could prove to seem to prefer using cannabis-based products
be an excellent substitute for opioids when it for relief from chronic pain.
comes to managing long-term, chronic pain
from sports injuries. • Cannabis is on the list of banned substances for
many sports.
• CBD may help repair bones as well,56 which can
also be damaged in an ACL injury.
TREATMENT
Anecdotally, there does seem to be a preference

towards 1:1 CBD:THC ratios for the management
VALUE OF MMJ of many conditions, including chronic pain, and
many athletes use CBD to help with injuries, or
Much of the value of medical marijuana comes even potentially prevent them by strengthening
from its potential as an anti-inflammatory, and the bones.58 59
an alternative to opioid-based medications. Both
THC and CBD are powerful anti-inflammatories,
as are terpenoids such as pinene, linalool and
limonene.57

Average
LeafWell
Cannabis and Anxiety
General
Anxiety is an umbrella term for a broad range of anxiety-related conditions,
including generalized anxiety disorder (GAD), social anxiety disorder , obsessive-
compulsive disorder (OCD) and, until recently, post-traumatic stress disorder
(PTSD). Anxiety disorders are one of the most common forms of mental illness in
the United States, affecting 40 million adults in the US aged 18 and over, or around
18.1% of the population, every year. 60
Anxiety is often comorbid with conditions such as depression and bipolar

disorder, and may have a part to play in irritable bowel syndrome (IBS) and other
inflammatory bowel diseases (IBD). Chronic pain may also cause anxiety which,
in turn, may exacerbate pain. Due to the effect of anxiety on serotonin receptors,
selective serotonin reuptake inhibitors (SSRIs) are the most common first line of
medicinal therapy. Treatments also include benzodiazepines, such as lorazepam
(Ativan), alprazolam (Xanax) and diazepam (Valium), but these medications can
lead to addiction, and they can also be ineffective for certain types of anxiety (e.g.
PTSD).
Cannabis can make some patients feel more anxious, while in others, we see a
reduction in anxiety. This could be attributed to the patient’s choice of strain.
For novice patients, a good rule of thumb when seeking cannabis strains for the
treatment of anxiety is to stick to those with high CBD ratios, because CBD has
been shown to reduce anxiety, and to avoid strains with high levels of THC, which
can increase anxiety.
As with most research on cannabis and different medical problems, evidence is

limited due to legal restrictions. However, cannabis seems to be a very powerful
anxiolytic, which means it modulates anxiety-related51 behaviour, and the release of
the neurotransmitter norepinephrine, which evokes the ‘flight or fight’ response, in
otherwise stressful situations.
LeafWell
Also, it is worth mentioning that a major component of our perception of physical

pain is actually anxiety. Due to this, pain can cause anxiety and, conversely, an
increase in anxiety can make pain worse. Panic attacks can also make a person
“hypersensitive” to pain.
POSITIVES NEGATIVES
• Cannabis contains several stress-reducing • Some strains may increase anxiety, especially
terpenes like linalool, caryophyllene and those with high THC concentrations.
borneol.
• Where low-to-medium dosages may help
• CBD may improve regional cerebral blood flow62 anxiety, higher dosages may make anxiety
(rCBF) in the brain, helping reduce anxiety. worse.
• Terpenes like pinene can help prevent • Can cause an initial increase in heart rate, which
hyperventilation, which can cause chest pains may exacerbate the effects of anxiety.
and further anxiety.
• Can cause trouble with breathing.
• CBD and caryophyllene work on CB2 receptors,
helping reduce anxiety.63 • In high doses, can cause depersonalization in
some people.
• Anxiety and depression are often comorbid,

and THC can be very useful for the treatment
of depression. However, because high doses
VALUE OF MMJ
of THC can make anxiety worse, care must be
taken with depression-anxiety comorbidity.
Anxiety sufferers respond reasonably well to
Microdosing THC may be useful in such
antidepressants such as SSRIs. However, if
instances.
benzodiazepines are recommended, cannabis
may prove to be a less addictive alternative.
Cannabinoids take effect immediately, and TREATMENT
therefore may be a potential solution for anxiety
attacks, as most antidepressant medications take Linalool and limonene heavy strains/products
several weeks to become effective, if they are may be of particular interest for those with
effective at all. anxiety. Limonene is a selective activator of the
adenosine A(2A) receptor. When this receptor is
inactive, it can cause anxiety, as well as insomnia
and impaired dopamine transmission (dopamine
is often associated with feelings of happiness).
This means that high amounts of limonene may
work in a similar manner to diazepam. Linalool
ingestion, meanwhile, may decrease serotonin,
dopamine, and norepinephrine production, which
POTENTIAL VALUE OF CANNABIS can also have anti-anxiety effects. The regulatory
effects of these terpenes in concert may prove
effective for the treatment of anxiety. Some
Significant
suggest that high amounts of CBD and some
CBDA & THCA can be effective for anxiety, even as
high as CBD:THC ratios of 20:1. 1:1 ratios may also
prove effective. Care must be taken with regard
to THC - too much THC may trigger an anxiety
attack, so low doses may be best.
LeafWell
Cannabis and Arthritis
General
Arthritis is an umbrella term describing any degenerative disorder that affects the
joints and bone interfaces. Symptoms include joint pain, stiffness, swelling, warmth
and redness, as well as a decreased range of motion. Between 2013 - 2015, around
22.7% (54.4 million) of Americans were diagnosed some form of arthritis, which
tends to worsen with age. Chronic pain from arthritis is a common cause of lost
work hours, and can lead to reduced quality of life.64
Osteoarthritis (degenerative joint disease) is the most common form of arthritis,

and usually occurs with age, trauma, or as a side-effect of certain medications
(e.g. steroid-based ones). However, arthritic symptoms can also be the result of
autoimmune disorders, such as rheumatoid arthritis, psoriasis and systemic lupus
erythematosus (SLE). Arthritis can also result from the degenerative effects of
other diseases, and is often associated with celiac disease, Ehler-Danlos syndrome,
hepatitis, gout and many other conditions.
LeafWell
A study by Dr. Sheng-Ming Dai of China’s Second Military Medical University65 found
that there are unusually high concentrations of CB2 receptors in the joint tissues
of arthritic patients. CBD could help activate the pathway of these CB2 receptors
and decrease inflammation. Other studies, like those undertaken by Dr. Jason
McDougall,66 show that cannabinoids may help repair the joint tissue itself. There
are lots of anecdotal experiences showing that this may indeed be the case.67
POSITIVES NEGATIVES
• May help treat arthritic pain.68
• No proven efficacy, as of yet.
• Could be an effective anti-arthritic.

69
• More research is needed in order to look at
what types of arthritis can be treated with
• CBD oil may be both an anti-inflammatory and cannabis.
“lubricant”70 for joints affected by arthritis.
Medical marijuana potentially acts as a painkiller, Arthritis sufferers are usually given a trial of
lubricant, anti-inflammatory for arthritis, and nonsteroidal antiinflammatory drugs (NSAIDs)
could even help actively repair bones and such as ibuprofen, steroids like prednisone,
joints. CB2 receptors seem to be found in high and disease-modifying antirheumatic drugs
concentrations around the join tissue of arthritic (DMARDs) including azathioprine (purine
patients, suggesting that CBD may be used synthesis inhibitor) and chloroquine (an IL-1
to activate these pathways, in order to fight receptor suppressor and anti-malarial).
inflammation. CBD may also provide “protection”
around nerves that have been stripped of their If a combination of two or more of the above does
natural coating. not work, cannabinoid treatment may certainly be
an option. CBD-rich strains and products may be
of particular use, but some amount of THC may
help sufferers deal with the associated pain of
POTENTIAL VALUE OF CANNABIS arthritis. More severe types of arthritis may require
BASED ON CURRENT EVIDENCE more THC, whilst lower doses of THC may be
Average
suitable for those with milder forms of arthritis.
LeafWell
Cannabis and Attention Deficit

Hyperactivity Disorder/Attention Deficit
Disorder (ADHD/ADD)
General
ADHD, which was formerly known as ADD, is a neurodevelopmental mental
disorder, characterized by problems paying attention, excessive fidgeting and
difficulty controlling behavior. Symptoms usually appear before the age of 12 years
old and last for at least 6 months, leading to significant problems at home, school
and during recreational activities.
LeafWell
ADHD is estimated to affect 51.1 million people globally. It is estimated that ADHD
affects about 5% - 7% of children, and 2% - 5% of adults, depending what criteria
are used. According to the CDC, around 11% of children (6.4 million) suffered from
ADHD in 2011-12 in the US.71 Treatments for ADHD include counselling, planned
routines, lifestyle changes and stimulant medications, such as methylphenidate
(Ritalin) and dextroamphetamine (Adderall). It is thought that ADHD is linked to
the sub-performance of dopamine and norepinephrine receptors.
POSITIVES NEGATIVES
• As most medications for ADHD are essentially • Cannabis might not be effective for everyone
amphetamines, patients must be aware of side- with ADHD.
effects, such as insomnia, nausea, vomiting,
headaches, numbness, tingling, and heart • For some people, it may increase the difficulty
palpitations. In contrast, cannabis does not of being able to focus.
have the range of negative side-effects that
• Caution needs to be taken with children and
Ritalin, Adderall and similar medications have.
adolescents, because cannabis may have
• CBD and THC act on dopamine and negative effects on the developing brain.
norepinephrine receptors in a non-direct way,
as well as enhancing serotonin receptor activity.
TREATMENT
Limonene, pinene and beta-caryophyllene are
terpenoids that could have some therapeutic
A sativa high in limonene and THC could possibly
effects on ADHD
approximate the effects of medications such as
• Cannabis also enhances appetite. Adderall and Ritalin. CBD may also help for anxiety
issues associated with ADHD, and high doses of
CBD combined with terpenes such as limonene
may be similarly effective at times when high
VALUE OF MMJ amounts of THC may not be ideal. CBDA, THCA
and THC may all be helpful to some degree, as
Cannabinoid-based medications present an could CBD:THC ratios of 20:1, 3:1 and 1:1.
alternative to amphetamine-based medications,
which are often prescribed for ADHD. There
are fewer negative side-effects, and medical
marijuana is far less addictive.
Average
LeafWell
Cannabis and Asthma
General
In the US every year, over 3,000 people die from asthma attacks, or asthma-related
causes.72 Asthma is a long-term inflammatory disease, and the symptoms include
shortness of breath, wheezing, coughing, chest tightness, bronchospasm and air
flow restriction. Attacks are more likely to happen at night, and may become worse
after exercise. Some people may get several attacks a day or weekly. Allergies,
environmental factors (e.g. living in an area with high amounts of dust and
pollutants), and genetic factors are thought to cause asthma.
As you would assume, smoking cannabis would be contraindicated for asthma.

However, with the availability of edibles, smoking cannabis is no longer the only
option.
Asthma attacks can be caused by several things, such as allergic reactions, stress
and anxiety, exercise, and inflammation. THC, in addition to its anti-anxiety and
anti-inflammatory properties, may well be a bronchodilator, which helps open up
the airways. It is not inconceivable that a cannabinoid-based inhaler may one day
work in tandem, or as a replacement for corticosteroid-based inhalers.
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Jen Michelle, Age 46, North Carolina
“ I have been diagnosed with Asthma since childhood, and since my early 20’s, I have
suffered with Psoriatic Arthritis and Rheumatoid Arthritis. It sent me on a roller
coaster ride with harsh pharmaceuticals, such as Methotrexate, Indomethacin,
Enbrel, Humira, and Remicade. I was also smoking about two packs of cigarettes a
day. All of this led me on more of a downward spiral. I ate horribly, tons of processed
meat, dairy and sweets. In 2011, I was permanently disabled with Chronic Obstructive
Pulmonary Disease (COPD) and Rheumatoid Arthritis. My rock bottom came
on October 30, 2015 when A COPD flare sent me into respiratory distress. I was
transported by ambulance to the hospital. I died in the back of that ambulance, and
it changed me forever.
I had already started smoking cannabis after my mother passed away from COPD in
September 2013, due to stress. So, when I started looking for alternative medicines
and discovered cannabis oil, I jumped on it.
That was in 2016. I was Stage 3 COPD. I was bedridden and on oxygen 24/7. I was
at 300 pounds and diabetic with high cholesterol, and was taking psychiatric
medications for depression and PTSD.
Within days of starting cannabis oil, I was off the oxygen and out of the bed. In just
a few months my diabetes and high cholesterol were gone. Everything was under
control, and the weight started coming off slowly and naturally.
I am two years in and, at 46 (I will be 47 on June 1st), I am the healthiest I have ever
been. I am at 132 pounds and exercising every day, working on building muscle.
Cannabis is my fountain of youth!
I use a Sativa dominant full extract cannabis oil. One rice grain sized drop
sublingually twice a day for six months, and then once a day for maintenance. I also
”
smoke and enjoy edibles. I try to saturate my system.
LeafWell
POSITIVES NEGATIVES
• Cannabis is full of anti-inflammatory terpenoids • Smoking cannabis may not be ideal for many
like myrcene, linalool, Delta-3-Carene, and asthmatics, because the smoke may make
alpha- and beta- pinene. things worse.
• Cannabis also has anti-bacterial, anti-fungal • Some strains of high THC cannabis can induce
and anti-microbial terpenoids like camphene anxiety, increasing the possibility of an asthma
and alpha-bisabolol. attack.
• Some cannabis terpenes are bronchodilators,

helping to open up the airway and/or aid TREATMENT
breathing, such as limonene, borneol and
eucalyptol. Though some people with asthma smoke
cannabis, this method of ingestion is not
• THC may also be a bronchodilator. 73 74
recommend. Vaporizing and even cannabinoid-
based inhalers (which may be available soon)
• Targeting CB1 and CB2 receptors may present
are likely to be better methods of ingestion for
a “novel preventative therapeutic strategy
immediate effect. Alternatively, edibles and
in asthmatic patients” 75 - both CB1 and CB2
tinctures may also provide longer-lasting relief for
receptors help protect the lungs.76
asthma and prevent inflammatory responses. A
CBD:THC ratio of 1:1 may be helpful. THCA may also
be useful
VALUE OF MMJ
THC appears to be a bronchodilator, expanding POTENTIAL VALUE OF CANNABIS

the bronchial tree and facilitating inhalation, BASED ON CURRENT EVIDENCE
Average
while CBD also decreases inflammation. Pinene,
which is also found in many cannabis strains and
products, also acts as a bronchodilator and aids
breathing.
LeafWell
Cannabis and Autism/Asperger Syndrome
General
Autism is generally described as a “neurodevelopmental spectrum disorder”
characterized by impaired social interaction, verbal and nonverbal communication,
and restricted and repetitive behavior. Autism affects the way that sensory
information is processed in the brain by altering how nerve cells and synapses
connect and organize themselves.
Self-harm, ritualistic or compulsive behaviors, delayed speech, an inability to

understand or connect to others’ emotions, and extreme anxiety are some of the
symptoms of autism, though this may differ somewhat between high functioning
and low functioning individuals. However, one of the commonalities between
patients suffering from autism of all “types” seems to be extreme sensitivity to
external stimuli. Additionally, autistics are more likely to be synaesthetic.77
Autism has long been thought to have a genetic basis, although there are a
number of cases where one person has autism, and other members of the family
do not. This may be a result of spontaneous structural variation. Autism has high
heritability rates, but it is not necessarily inherited. Exposure to high amounts of
air pollution and heavy metals during development may increase the chances of a
child developing autism.
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To date, most research, suggests that CB2 receptors should be targeted for the
management of autism,78 because autistic children display immune system
dysregulation. Cannabis may help regulate both CB2 receptors, which are found
peripherally, and CB1 Receptors, which are found in the brain. Other research
suggests that “mutations found in individuals with autism block the action of
molecules made by the brain, upon which marijuana active chemical acts.”79
POSITIVES NEGATIVES
• Cannabis has anti-anxiety effects, easing the • There is no proper evidence of cannabis’
stress of overstimulation and social interactions. efficacy for autism, as of yet.
Decreasing anxiety may help prevent self-
injurious behavior. • May induce anxiety in some, and potentially be
a cause of social withdrawal, panic attacks and
• Cannabis may also help make synaesthesia repetitive behavior.
more “pleasurable”, rather than overwhelming.
• May also induce “over-stimulation”.
• Cannabis could help regulate synapse
signalling problems in people suffering from • Many find they need to medicate when
autism, e.g. anandamide signalling.80 surrounded by trustworthy people in a familiar
environment.
• It appears that only some specific strains could

be effective for autism.
VALUE OF MMJ
At the moment, more than half of those

TREATMENT
with autism are prescribed drugs such as
Could cannabinoid-based medications be a way of
antidepressants, antipsychotics (e.g. risperidone,
managing autism? Possibly, although there is little
aripiprazole) and stimulants, in order to
evidence other than anecdotal reports. Cannabis
treat irritability, the propensity to self-harm,
may potentially help children with Fragile X
sleeplessness and repetitive behavior. However,
syndrome, and having an effect on the CB2
there is little evidence that proves the efficacy
receptors may help manage autism. One theory,
of these drugs, and many of them (in particular
postulated by Dr. Daniele Piomelli et al81 is that
antipsychotics) have debilitating side-effects such
anandamide may help treat autism by regulating
as increased risk of suicide, increased likelihood
social reward. However, the theory for using
of developing diabetes and movement disorders
medical marijuana for autism is in its infancy,
such as tardive dyskinesia.
although it could very well be a new method of
treatment for the negative aspects of autism.
Dosage is another concern. CBD and CBDA seem
to be potentially most useful for autism, but THC
POTENTIAL VALUE OF CANNABIS and THCA also may have their benefits.
Average
LeafWell
Cannabis and Autoimmune Disorders
General
Autoimmune diseases happen when the immune system attacks the body.
Usually, the immune system recognizes the difference between foreign invaders
(i.e pathogens, such as bacteria and viruses), when a person has an autoimmune
condition, however, their body’s antibodies sees parts of their own body as
foreign and starts attacking them. Approximately 50 million Americans have an
autoimmune disorder of some form.82 Examples include:
• Type 1 Diabetes, which damages the pancreas and its ability to produce insulin.
• Systemic Lupus Erythematosus (SLE), which affects multiple organ systems.
• Multiple Sclerosis (MS), which damages the myelin sheath surrounding nerve cells.
• Hashimotos thyroiditis.
• Psoriasis, a genetic disease where antibodies target the skin and joints.
• Rheumatoid Arthritis, where antibodies attack the joints.
Genetics, environmental factors (i.e exposure to radiation or chemicals) and diet are
thought to be the main causes of various autoimmune disorders. Some, like MS, are
congenital, whereas others may have other environmental triggers, which has been
suggested by the fact that there are rising incidences of autoimmune disorders in
the western world.
LeafWell
POSITIVES NEGATIVES
• Theoretically, targeting the endocannabinoid • The effects could be dependant on which
system may help prevent the immune system autoimmune disorder you have. Using cannabis
attacking itself or at least minimize the for different autoimmune diseases may have
damage.83 84 different positives and negatives.
• Many autoimmune conditions involve

inflammation and the body attacking itself.
Cannabinoids could help modulate the
immune system and help prevent the body
from attacking itself to some extent, as well as
prevent inflammation. TREATMENT
• Autoimmune conditions are often related to Indicas may be preferred for their tendency to
one another. For example, Crohn’s disease produce more CBD, which may help due to its
and Type 1 diabetes share the same genetic anti-inflammatory purposes. The “best” set of
identifiers, whereas those with vitiligo are cannabinoids could very much depend on the
more likely to suffer from other autoimmune autoimmune disorder being treated, but it does
conditions. Could autoimmune conditions seem that CBD is particularly useful in helping
develop due to a lack of the gene/s that code treat the inflammation and neuropathic pain
for a specific endocannabinoid or cannabinoid associated with such conditions.
receptor?
VALUE OF MMJ POTENTIAL VALUE OF CANNABIS

Average
Medical cannabis could be useful for a number
of conditions that fall under the umbrella of
“autoimmune diseases”. Both THC and CBD
have anti-inflammatory effects, and many
with more evidence for some disorders than
of the terpenoids do as well (on top of their
others. As autoimmune disorder include
stress-busting and pain killing properties).
conditions such as Crohn’s disease and type
Neuropathy is also a common problem for those
1 diabetes, as well as many other conditions
with autoimmune conditions, and there are
causing significant amounts of inflammation, in
few effective pharmaceutical medications that
some instances the evidence is significant.
are truly effective for autoimmune disorder.
Cannabinoids present a possible method of
treatment.
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Cannabis and Bipolar Disorder
General
Bipolar disorder is often lumped together with “classic” depression .
Understandably so, because a persistent low mood is often a major part of bipolar
disorder, and it is not uncommon for bipolar disorder to be misdiagnosed as
unipolar depression. However, bipolar disorder is characterized by “mania” or
“hypomania” (a milder form of mania) at the other extreme, which are periods
of extremely elevated mood. Hence the previous name of “manic depression”
was used for bipolar disorder. A less severe form of bipolar disorder is called
“cyclothymic disorder”.
Classic hallmarks of bipolar disorder are delusional thinking, sleep disturbances

before the onset of a manic or depressive episode, impulsive decision-making,
and periods of extreme excitement and energy, followed by extremely low moods..
Hallucinations and even psychosis are also possible with bipolar disorder. Bipolar
disorder is often divided into three types:
• Bipolar I disorder - at least one manic episode, with or without depressive episodes.
• Bipolar II disorder - at least one hypomanic episode and one major depressive episode,
but not any manic episode.
• Cyclothymic disorder - less severe symptoms of bipolar disorder, presenting over short
periods of time.
The precise cause of manic depression is not known, but it is thought that genetics
play a role, along with a history of abuse, long-term stress and suffering, and
significant hardship are all thought to be contributing factors. Conditions such
as traumatic brain injury (TBI), ADHD, multiple sclerosis (MS) and HIV infection,
personality disorders, substance misuse disorder, and schizophrenia may also
present symptoms similar to bipolar disorder.
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Many people with bipolar disorder tend to have at least one relative with the
same disorder, suggesting a genetic link. Polymorphisms in BDNF, DRD4, DAO
and TPH1 genes have been implicated in the developments of bipolar disorder.
As for signaling pathways implicated in the development of bipolar disorder, they
include: CRH, cardiac β-adrenergic, Phospholipase C, glutamate receptor, cardiac
hypertrophy, Wnt, Notch, and endothelin 1 signaling pathways.
Bipolar disorder affects approximately 1%-3% of the global population, with

approximately 2.6% of US citizens (5.7 million) suffering from bipolar disorder.
Symptoms usually arise from the age of 25 onwards, and seem to affect both males
and females equally. In 1991, it was estimated that bipolar disorder cost the United
States $45 billion. Those with bipolar disorder are more likely to die from heart
disease, and are at higher risk of suicide.
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Due to the difference between depression and bipolar disorder, antidepressants are
contraindicated for people suffering from bipolar disorder during a manic episode,
as using them during a manic/hypomanic episode can worsen the condition.
However, antidepressants may still be used during the depressive periods, but
these must be carefully monitored. Other medications, such as benzodiazepines,
anticonvulsants, mood stabilizers (e.g. lithium) and antipsychotics are often used as
well for those with bipolar disorder. Therapy, regulated sleeping patterns, exercise,
regimented activity and following a healthy diet have also been shown to be helpful.
POSITIVES NEGATIVES
• Cannabinoid-terpenoid-based medications • Bipolar disorder is a complex condition, and
may help replace a cocktail of drugs used to the medications used to control it can either
control bipolar episodes. Moreover, they may be help, or actually trigger episodes. Although,
less harmful than many of the drugs currently cannabis can treat many of the associated
prescribed, and switching between different problems of Bipolar, determining which
cannabinoid-terpenoid profiles could enable cannabinoid-terpenoid profiles are suitable
effective treatment of both depression and and at what doses can be difficult to gauge.
mania. Cannabis also has a very good safety Cannabis may work for the majority of those
profile, with little risk of overdosing. with bipolar, but it may not work at all for
others, and could actually make bipolar worse
• CBD could well work as an antipsychotic. 87 for some. Moreover, certain cannabinoid-
terpenoid profiles may be helpful at some
• Cannabis may help stabilize the mood.
times, and harmful at other times, depending
• Could also help those suffering from bipolar on the mood of the patient, just as with other
disorder get to sleep. medications.
TREATMENT
VALUE OF MMJ Sativas, with their tendency to produce terpenes
like limonene, may be used for their mood-
CBD could be a powerful anti-anxiety medication,
boosting properties, and may help patients keep
along with terpenes like linalool. Additionally,
focused during the more disorganized periods of
CBD appears to be a powerful antipsychotic and
a bipolar episode. However, THC, which mimics
anticonvulsant, while THC could help lift mood.
anandamide and hence may increase serotonin
production, may not necessarily be ideal during
manic periods. CBD could potentially be better
during these manic periods, but more research
needs to be done before anything can definitively
be stated.
Average
LeafWell
Cannabis and Cardiovascular Diseases
General
Cardiovascular Diseases (CVDs) cover a broad range of health issues. They
include coronary artery diseases (CADs), myocardial infarction (heart attacks),
stroke, hypertensive heart disease, rheumatic heart disease, cardiomyopathy,
heart arrhythmia, congenital heart disease, valvular heart disease, carditis, aortic
aneurysm, peripheral artery disease, thromboembolic disease and venous
thrombosis. Depending upon which CVD a person is suffering from, heart disease
may be caused by genetic factors, high blood pressure, obesity, smoking, air
pollution, exposure to ionizing radiation, excessive alcohol intake, poor diet, high
blood cholesterol or a lack of exercise. The cardiovascular system is complex and
affects the entire body. With so many aspects to it, there are many ways things can
go wrong.
CVDs are the leading causes of death globally, resulting in 17.9 million deaths (32.1%)
in 2015 - up from 12.3 million (25.8%) in 1990. CVD death rates in the developed
world have been dropping since the 1970s, but is still a common cause of death in
both the developed and developing parts of the world.88 Diabetes is also linked to
a greater risk of developing CVDs. Treatment methods include exercise, cutting
alcohol intake, quitting tobacco chewing/smoking, following a healthy diet, taking
aspirin and preventing stress. Statins (3-hydroxy-3-methyl-glutaryl-coenzyme A
reductase, HMGCR) are commonly prescribed cholesterol-reducing drugs.
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Cannabis use has a complex relationship with CVD. It is known that inhaling smoke
can increase your risk for CVD. Despite the associated risk of inhaling smoke,
tobacco and cannabis are not equally carcinogenic89, and we do not yet know if
cannabinoids themselves may induce CVDs. Cannabinoids may actually decrease
the likelihood of developing CVD, because it has been suggested that they lower
blood pressure and cut stress and anxiety.
Cannabis Use and Blood Pressure
The relationship between cannabis and high blood pressure is complex. There are
various studies on cannabis and blood pressure, showing a wide variety of results.
Some studies show that, while there may be a rise in blood pressure immediately
after consumption of cannabis, it is followed by a decrease in blood pressure as
exposure is repeated, and “orthostatic hypotension disappears, blood volume
increases, heart rate slows and circulatory responses to exercise and Valsalva
movement are diminished ...” This explains why some patients have been able to
decrease their intake of blood pressure tablets after using cannabis for a while.
However, it should be noted that there may be an increase in blood pressure if you
abruptly stop using cannabis after daily use.
Another interesting study looks at the effects of THC on the increase in blood
pressure in arteries and eyes, specifically with regards to glaucoma patients.
“The salient observation after THC inhalation was that the changes in
ocular pressure paralleled the changes in blood pressure in each glaucoma
patient. These findings suggest that the positive chronotropic response
to THC tends to maintain cardiac output which limits further decreases
in blood pressure and the capillary filtration of aqueous humor decreases
or the reabsorption of aqueous humor increases because of the systemic
hypotensive effect attending THC inhalation.”90
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Unfortunately, at the moment we cannot answer the question of cannabis’

relationship to blood pressure definitively until more research is completed. It
seems that in some people, possibly many, cannabis initially increases blood
pressure, but could then decrease it over time.
Stroke
A stroke, or cerebrovascular accident (CVA), is the result of decreased blood flow

to the brain, usually as a result of a migrating blood clot, or an intracranial bleed.
Earlier this year, the American College of Cardiology, stated in a press release:
“Comparing cardiovascular disease rates in these patients to disease rates

in patients not reporting marijuana use, researchers found marijuana use
was associated with a significantly increased risk for stroke, heart failure,
coronary artery disease and sudden cardiac death.”
Marijuana use was also linked with a variety of factors that are known to increase
cardiovascular risk, such as obesity, high blood pressure, smoking, and alcohol use.
After researchers adjusted the analysis to account for these factors, marijuana use
was independently associated with a 26% increase in the risk of stroke and a 10%
increase in the risk of developing heart failure.91
Yet, as it has been postulated that cannabidiol (CBD) is a neuroprotectant, it may

also help protect brain cells from glutamate toxicity after ischemic stroke, and
other chronic conditions like Parkinson’s disease, Alzheimer’s disease and chronic
traumatic encephalopathy (CTE).92 To add to this discussion further, there is also
a study based on 45,000 Swedish men, entitled ‘Cannabis, Tobacco, Alcohol Use,
and the Risk of Early Stroke’, which found no evident association between cannabis
use in young adulthood and an increased risk of stroke, including strokes that
happened before 45 years of age. Tobacco smoking, however, showed a clear, dose–
response association with stroke.
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However, some have pointed out that this Swedish study has many flaws.93 A few
important ones to consider include:
• The lack of follow-up data.

• Although confounding factors were taken into account, they were done so
crudely.
• Other medications weren’t listed.
• The study may not have looked at “pure” marijuana users (i.e. the ones who
don’t mix it with tobacco, which is more common in Europe).
• It also did not take into account if the subjects suffered from a lifelong disease
or medical conditions. (Even though these were somewhat controlled for, but
again crudely so.)
Heart Disease
The problem with calling a medical condition “heart disease” or “cardiovascular

disease” (CVD) is that it covers a broad range of conditions, such as hypertensive
heart disease, heart arrhythmia, heart failure, as well as the aforementioned stroke
and blood pressure, or anything involving atherosclerosis (the thickening of artery
walls by white blood cells and proliferation of smooth muscle cells, which form a
plaque.)
There are a number of “triggers” that can cause heart disease or CVD, of which
smoking is one. There is also another study, entitled ‘Comparing cannabis with
tobacco’, which states:
“Myocardial infarction is 4.2 times more likely to occur within an hour

of smoking cannabis.94 However, despite these alarming facts, there is
no evidence at present on whether smoking cannabis contributes to
the progression of coronary artery disease, as smoking cigarettes does.
More studies of the cardiovascular and pulmonary effects of cannabis are
essential.”
The follow-up paper, “Comparing cannabis with tobacco - again” is also worth
reading, because it questions some of the conclusions made by the previous
study.95
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As there are so many different CVDs, all with different causes, it can be very difficult
to state definitively that cannabis is one of those causes. But it is best not to rule
it out as a possibility, and it could be a factor for some people at least ,depending
upon the method of ingestion and family history. It appears advisable that those
with CVD ingest cannabis medicines, instead of smoking them.
POSITIVES NEGATIVES
• Cannabinoids and terpenoids may be used to • Long-term effects of cannabis use and its
reduce stress, and thereby decrease the risk of relationship to the development of CVDs has
CVDs developing. not been fully defined yet.
• Endocannabinoids, such as virodhamine may • Ingestion method is important - there may be

lower blood pressure, so cannabinoids may help safer ways of using cannabis than smoking,
do this too. such as using tinctures or edibles.
• Using THC in the long-term may lower blood • Although THC has been shown to possibly
pressure. lower blood pressure and heart rate in the
long-term, it increases it in the short-term.
• Cannabinoids may help prevent cell death.
• CBD may help prevent inflammation.

TREATMENT
There is no defined treatment for CVDs as of

VALUE OF MMJ yet, although CBD can be used to balance
out high-THC varieties, in order to prevent any
The research suggests that a combination of THC overwhelming anxiety attacks, ensuring the
and CBD may reduce anxiety and lower blood more relaxing aspects of cannabinoids are
pressure. Cannabinoids and terpenoids may help exploited. Cannabis can be used in tandem with
with stress for many people, and can potentially traditional CVDs medications, such as statins
be used as a replacement for alcohol, a leading (HMG-CoA inhibitors), which lower the level
contributor to CVDs. Cannabis could prove to of low-density lipoprotein (“bad cholesterol”)
be very useful for heart health, when used in in the blood, ACE inhibitors, beta-blockers,
combination with the more established ways of anticoagulants and NSAIDs, such as aspirin.
treating CVDs. Cannabinoids may help keep the
heart in a “regular rhythm”96. and could potentially
replace beta blockers. As NSAIDs (i.e aspirin)
can lead to the development of stomach ulcers,
cannabinoid-based medications may provide a
long-term alternative for these as well. THC and BASED ON CURRENT EVIDENCE
Little
THCV have been shown to aid weight loss, so they
may be particularly useful for those who have
evidence
trouble with weight control.
so far
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Cannabis and Cancer
General
Cancer is probably one of the most exciting foci for medical cannabis research.
Cancer, in its many forms, affects millions of people. It is nondiscriminatory
regarding age or sex and can attack every organ system in the body. The history of
medical cannabis ‘re-legalization’, especially in the latter half of the 20th century,
can be traced to the search for treatments for cancer, as well as glaucoma, epilepsy,
asthma and AIDS/HIV. In 2018 alone, an estimated 1,735,350 new cases of cancer will
be diagnosed in the United States and 609,640 people will die from the disease.97
Cancer is a group of diseases that involves abnormal cell growth that can
potentially spread or invade other areas of the body. Signs include abnormal
breathing, prolonged coughing, unexplained weight loss, a change in bowel
movements and unexplained bleeding. Tobacco use causes approximately 22%
of all cancers, another 10% are due to obesity, lack of exercise and poor nutrition,
and around 5% - 10% develop due to inheritance. In the developing world 20%
of all cancers are due to infections such as hepatitis B, hepatitis C and human
papillomavirus infection (HPV). Exposure to high amounts of ionizing radiation or
heavy industrial pollutants are other risk factors.98
Worldwide, approximately 8.8 million deaths per year are due to cancer. The
most common types of cancer amongst males are lung, prostate, colorectal and
stomach. For females the most common are are breast, colorectal, lung and
cervical cancer.
Lots of people ask me, “How does cannabis help with cancer?” We can’t explain it
better than Dr. Michael Masterman-Smith:
LeafWell
“In order to answer this we have to look at some basic tenets of cancer
biology and how cancer cells mutate to stay alive and proliferate as
cancer cells. If we look at the classic biological definition of cancer,
it is “unregulated cellular proliferation”. The mechanisms that allow
unregulated proliferation is a realigning of cellular circuitry to for growth
cues.
The genetic machinery is essentially altered to overproduce cell surface

receptors, called growth factor receptors. These are antennas which
amplify and activate chemical signals that run along complex molecular
pathways in the cancer cell to drive cancer cell growth and proliferation.
Many cancer cancer drugs we use today target these signalling pathways.
There is some evidence to show that cannabinoid receptors are expressed

on cancer cells. This supports the pharmacological basis for why
cannabinoid receptor agonists (i.e. cannabinoids) could be effective for
cancer. A cancer cell is trying to figure out ways to grow so it puts its
receptors on the cell, one of which happens to be cannabinoid receptors.
The pharmacological action of a cannabinoid receptor agonist depends on
the cell type. In cancer cells it may be like a trojan horse.
Current understanding appears that cannabinoids goes through these

receptor and activates the production of a compound called ceramide,
which regulates the differentiation, proliferation and death of cells. In
cancer cells, and perhaps cancer stem cells, this effect is widestream
system outage, shutting down cancerous signalling pathways, several of
which are major targets in cancer drug development and, often difficult to
target pathways, I might add.
This is the emerging understanding of the relationship between cancer

cells, cannabinoids and cannabinoid receptor agonists that can advance
new ways to understand and treat cancer.”99
One of the main theories behind using cannabis for cancer is using specific
cannabinoid-terpenoid profiles for specific cancers and specific endocannabinoid
systems (ECSs) as a form of “phytochemical therapy”, as a supplement to
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chemotherapy and radiotherapy. Another theory, the “Rick Simpson” method,

involves essentially “flooding” the body with high doses of cannabinoids and
terpenoids, in order to prevent the metastasizing of cancer cells in the body,
regardless of where they are. However, there is anecdotal evidence that certain
cancers respond better to certain cannabinoid profiles than others, and according
to some, “Treatment Must Match Classification” 100, as certain profiles may actually
increase cancer cell proliferation.
Cannabis seems to work for so many cancer patients because it not only helps
manage the side-effects of chemotherapy,101 but may also help battle cancer of
many types,102 including: bladder,103 brain,104 breast,105 colon,106 endocrine,107 kaposi
sarcoma,108 leukemia,109 lung,110 prostate111 and skin112. For research into the use of
cannabis for cancer in general ,and specific types of cancer as well, the following
studies show some promise:
1
Cannabidiol as potential anticancer drug113
“Over the past years, several lines of evidence support an antitumourigenic
effect of cannabinoids including Δ(9)-tetrahydrocannabinol (Δ(9)-THC),
synthetic agonists, endocannabinoids and endocannabinoid transport
or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative
and pro-apoptotic effects and they are known to interfere with tumour
neovascularization, cancer cell migration, adhesion, invasion and
metastasization. However, the clinical use of Δ(9)-THC and additional
cannabinoid agonists is often limited by their unwanted psychoactive
side effects, and for this reason interest in non-psychoactive cannabinoid
compounds with structural affinity for Δ(9)-THC, such as cannabidiol (CBD),
has substantially increased in recent years. The present review will focus on
the efficacy of CBD in the modulation of different steps of tumourigenesis
in several types of cancer and highlights the importance of exploring CBD/
CBD analogues as alternative therapeutic agents.”
2 The influence of biomechanical properties and cannabinoids on tumor

invasion.114
“BACKGROUND:
Cannabinoids are known to have an anti-tumorous effect, but the
underlying mechanisms are only sparsely understood. Mechanical
characteristics of tumor cells represent a promising marker to distinguish
between tumor cells and the healthy tissue. We tested the hypothesis
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whether cannabinoids influence the tumor cell specific mechanical and

migratory properties and if these factors are a prognostic marker for the
invasiveness of tumor cells.
METHODS:
3 different glioblastoma cell lines were treated with cannabinoids and
changes of mechanical and migratory properties of single cells were
measured using atomic force microscopy and time lapse imaging. The
invasiveness of cell lines was determined using a co-culture model with
organotypic hippocampal slice cultures.
RESULTS:
We found that cannabinoids are capable of influencing migratory
and mechanical properties in a cell line specific manner. A network
analysis revealed a correlation between a “generalized stiffness” and the
invasiveness for all tumor cell lines after 3 and 4 d of invasion time: r3d =
-0.88 [-0.52;-0.97]; r4d = -0.90 [-0.59;-0.98].
CONCLUSIONS:
Here we could show that a “generalized stiffness” is a profound marker for
the invasiveness of a tumor cell population in our model and thus might be
of high clinical relevance for drug testing. Additionally cannabinoids were
shown to be of potential use for therapeutic approaches of glioblastoma.”
3 Cannabinoids - a new weapon against cancer?115

““Many scientific studies indicate the potential use of cannabinoids in
the fight against cancer. Experiments carried out on cell lines in vitro
and on animal models in vivo have shown that phytocannabinoids,
endocannabinoids, synthetic cannabinoids and their analogues can lead
to inhibition of the growth of many tumor types, exerting cytostatic and
cytotoxic neoplastic effect on cells thereby negatively influencing neo-
angiogenesis and the ability of cells to metastasize. The main molecular
mechanism leading to inhibition of proliferation of cancer cells by
cannabinoids is apoptosis. Studies have shown, however, that the process of
apoptosis in cells, treated with cannabinoids, is a consequence of induction
of endoplasmic reticulum stress and autophagy. On the other hand, in
the cellular context and dosage dependence, cannabinoids may enhance
the proliferation of tumor cells by suppressing the immune system or by
activating mitogenic factors. Leading from this there is a an obvious need
to further explore cannabinoid associated molecular pathways making it
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possible to develop safe therapeutic drug agents for patients in the future.”
4 GW Pharmaceuticals Achieves Positive Results in Phase 2 Proof of

Concept Study in Glioma116
“London, UK, 7 Feb 2017: GW Pharmaceuticals plc (Nasdaq: GWPH, “GW,”
“the Company” or “the Group”), a biopharmaceutical company focused on
discovering, developing and commercializing novel therapeutics from its
proprietary cannabinoid product platform, today announced positive top-
line results from an exploratory Phase 2 placebo-controlled clinical study of
a proprietary combination of tetrahydrocannabinol (THC) and cannabidiol
(CBD) in 21 patients with recurrent glioblastoma multiforme, or GBM. GBM is
a particularly aggressive brain tumor, with a poor prognosis. GW has received
Orphan Drug Designation from the U.S. Food and Drug Administration (FDA)
and the European Medicines Agency (EMA) for THC:CBD in the treatment of
glioma.
The study showed that patients with documented recurrent GBM treated
with THC:CBD had an 83 percent one year survival rate compared with 53
percent for patients in the placebo cohort (p=0.042). Median survival for
the THC:CBD group was greater than 550 days compared with 369 days in
the placebo group. THC:CBD was generally well tolerated with treatment
emergent adverse events leading to discontinuation in two patients in
each group. The most common adverse events (three patients or more and
greater than placebo) were vomiting (75%), dizziness (67%) nausea (58%),
headache (33%), and constipation (33%). The results of some biomarker
analyses are still awaited.
“The findings from this well-designed controlled study suggest that the
addition of a combination of THC and CBD to patients on dose-intensive
temozolomide produced relevant improvements in survival compared with
placebo and this is a good signal of potential efficacy,” said Professor Susan
Short, PhD, Professor of Clinical Oncology and Neuro-Oncology at Leeds
Institute of Cancer and Pathology at St James’s University Hospital and
principal investigator of the study. “Moreover, the cannabinoid medicine
was generally well tolerated. These promising results are of particular
interest as the pharmacology of the THC:CBD product appears to be distinct
from existing oncology medications and may offer a unique and possibly
synergistic option for future glioma treatment.””
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5 Cannabinoids as therapeutic agents in cancer: current status and future

implications117
“Cannabinoids comprise of (a) the active compounds of the Cannabis
sativa plant, (b) endogenous as well as (c) synthetic cannabinoids. Though
cannabinoids are clinically used for anti-palliative effects, recent studies
open a promising possibility as anti-cancer agents. They have been shown
to possess anti-proliferative and anti-angiogenic effects in vitro as well as
in vivo in different cancer models. Cannabinoids regulate key cell signaling
pathways that are involved in cell survival, invasion, angiogenesis, metastasis,
etc. There is more focus on CB1 and CB2, the two cannabinoid receptors
which are activated by most of the cannabinoids.”
Gabriela Olmeda
“ I was diagnosed with several tumors and cysts in my brain, thyroid and lower abdomen.
I’ve had 10 surgeries since Dec. 2014.
5 months after brain surgery, I started having seizures. I’ve been rushed to the hospital 4
times in a year. The first time, I flatlined, and I had an out of body experience. The second
time, which was 2 days before my 37 birthday, I was placed in a coma that lasted for 10
days. This year, just 3 weeks ago, I was rushed to the hospital for the 4th time. My brain is
weak, but after 5 years of dealing with so much pain, humiliation and hurt, I feel like my
body is finally getting strong and healthy. I had an MRI and ultrasounds to follow up on
the remaining cysts and tumors that cannot be operated on.
In July of 2016, a few months before my brain surgery, my surgeon allowed me to use
cannabis and CBD oil. Since then, I’ve been using cannabis and CBD oil as my #1 pain
medication, and as medicine for my body. I was placed on several medications to shrink
the tumors and cysts in my body. However, nothing reduced the size of my masses.
Once I stopped taking medications, and started using cannabis, after 18 months, my
cysts and tumors have shrunk significantly. I’ve shared this with several of my doctor’s,
and they were in an awe when I assured them that it’s the use of cannabis and a healthy,
vegan diet.
I’m blessed to have a twin brother, and we’ll be having a birthday get-together to
celebrate our 38th birthday, and my 37th as well. I wanted to share this with you, because
I know that my journey will touch a life or two. I don’t have any complaining to do. I’m
blessed, grateful and thankful for my journey as it’s molding me into the strong, happy,
”
positive woman I’ve always wanted to become.
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POSITIVES NEGATIVES
• Helps battle both the chemotherapy side- • Though there is no proven link between
effects and the cancer. smoking cannabis alone and lung cancer,124
intuitively it makes sense to perhaps avoid
• Cannabinoids may help make chemotherapy combusting any plant material and breathing
more effective.118 119 the resulting smoke into your lungs. This is
especially the case if you suffer from lung
• Helps cancer patients treat pain, inflammation,
cancer and/or breathing problems.
nausea, improper sleep and cachexia (wasting
syndrome). • One of the side-effects of chemotherapy is
a suppressed immune system. Therefore, it
• Cannabis may actually kill cancer cells in a
is of utmost importance that your cannabis-
highly specific manner. Where chemotherapy
based medication is as pathogen-free and
kills all the cells in the body, cannabinoids seem
clear of nasty pesticides as possible. Also, as
to target cancer cells only.
cannabinoids affect the immune system and
• Other than cannabinoids, there are a number inflammation response, it is wise to avoid
of terpenes like pinene and humulene, that cannabinoid treatment if you are undergoing
have significant antibacterial and antitumoral immunotherapy.
properties.120
• For some cancer types, the wrong
• There is some suggestion that THCA and CBDA cannabinoid-terpenoid profile may cause the
work in conjunction with other cannabinoids cancer to grow.
to beat cancer.121 122 CBDA may be particularly
• Some evidence suggesting that low doses of
useful for some types of breast cancer.123
CBD and CBDV may cause cell damage and
be a factor in the development of cancer.
VALUE OF MMJ
TREATMENT
Needless to say, cancer (or cancers) is a
complicated condition with many different factors .Theoretically, one can use as many cannabinoids
involved when it comes to treating it successfully. and terpenes as possible in very high
Some cancers respond better to certain types of concentrations to utilize the entourage effect to
treatment than others, including cannabinoids. beat cancer but, ultimately, directed profiles for
specific cancers is preferable, but we realize that
However, targeting specific types of cancer cells in this is not always possible. It is also important
a directed manner is where cannabis potentially to note, at this time, we do not know to what
comes into play. This means that even hard- extent cannabinoids cross react with other cancer
to-treat cancers that don’t respond too well to medications. Ethanol-derived cannabinoids and
chemotherapy and other treatment methods terpenoids seem to work best for treating cancers
may potentially be treated using highly specific of various types.
cannabinoid-terpenoid-based medications.

Significant
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Dr. Michael Masterman-Smith

Chief scientific officer, CA Labs, Inc., cancer biologist and pharmacologist
Why is cannabis medicine, and why does it seem to work for so many conditions?
Cannabis has many what we call a “broad spectrum” compounds, and it works in ways that
… Let’s put it this way. Because of its effects on the nervous system, immune system and
metabolic functions, which are key things related to disease, and the endocannabinoid
system is a highly complex network of receptors that help mediate these three functions.
This is why they believe it to be medicine. Cannabis is a broad-spectrum compound that
impacts health function in the body.
How much should I take, and what strain or cannabinoid profile is ideal for me?
Well, that’s all patient-defined circumstance. It depends upon what the condition is and
the makeup of the individual’s endocannabinoid system. It is the extent to which the
endocannabinoid system is expressed throughout the person’s body that will dictate
the function of cannabinoids. It’s a very individual thing. It depends upon the individual’s
composition in terms of their endocannabinoid system, and it depends upon the condition
they’re afflicted with, as well as the severity of their condition.
With respect to what strain, the strain concept gives way to the question, “What is the
chemovariance?” This is whether it’s in a particular medication or a whole plant. Folks are
moving away from specific strains and looking at the chemovariance. In some formulations,
you’re only dealing with one or two cannabinoids, and you’re not necessarily getting the
rarer and sub-classes of cannabinoids. And that’s really where the field of cannabis as
medicine hails from - what is the chemovariance of what I’m taking? This is not necessarily
a particular “strain”. There is a general perception that sativas have a certain composition
and indicas with another, but this is not always the case. But we have strains that produce
high levels of CBD, but your condition may require THC, so people shouldn’t necessarily
look at certain compounds as medical and others not. There’s been some interest in some
landrace strains that may contain rare chemovariance of compounds such as CBDV and
THCV. The science still needs to be done as to why that’s important.
One thing that happens in this field is that something becomes popular and is treated as
a “cure-all”. They watch a news program or an episode of something, and everybody goes
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looking for these things and believing things that may or may not be true. It’s an elusive
thing to say, “This strain can be used for such-and-such”. The only thing that we know is that
indicas are subtly different to sativas in terms of the cannabinoids they contain.
Have you noticed any particular cannabinoid profiles to be useful for specific
cancers?
We know from published data that cannabinoid receptors 1 and 2, with CB1 being
responsive to THC and CBD having indirect effects on both receptors, that cannabinoids
are helpful in killing off cancer stem cells. The literature suggests that THC might be a
more powerful anti-cancer compound than CBD, although both have powerful anti-
cancer effects. That being said, there is a growing consensus that ratios are important in
a therapeutic regime. A 1:1 CBD:THC ratio might be more useful in some cases, but we’ve
been increasingly working with things like 1:3 and 3:1 CBD:THC ratios out of convenience
to the patient, so that they can utilize it their own way. For example, they may not want
psychoactive effects during the daytime, so choose a CBD:THC ratio of 3:1, but may want a
ratio of 1:3 at night in order to get them to sleep. The goal is to use both THC and CBD and
let the patient control their intake.
Patients have different responses to THC. In some cases, when you’re dealing with cancer,
the requirement may be higher. Those doses can be very, very psychoactive, so care must
be taken to get a therapeutic dose, but to get around the psychoactivity. So, in the work
we’re doing, the high THC usually comes at night and the high CBD during the day. So, they
are essentially getting a 1:1 ratio in their blood over the course of the day. You have to take
into account the practicality of the medication.
When it comes down to pain, some patients do very well and have good response to CBD.
Other patients need THC as well. On a day-to-day basis, not everyone wants psychoactivity.
But, if the condition is severe enough, they might need the distraction that THC provides.
The key thing here, though, is that it depends on the person, the condition, and the severity
of the condition.
I think what’s interesting about cancer is that it appears that we have these intractable
proteins, and the proteins that are activated by cancer and cancer stem cells are very
difficult to develop drugs for. What we’re learning is that cannabinoids, once they get into
these cells, they “shut down” some of these proteins. So that’s the definition of a “targeted
chemotherapy” in the future. Conventional drug development is falling short in trying to
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deactivate these proteins. Cannabinoids seem to do a very good job of shutting them down
and prevent the cancer cell from growing. These proteins keep cancerous cells alive, and
cannabinoids help kill these proteins and thus kill off the cancerous cells.
We’re actually learning a tremendous amount about cancer and how cannabinoids operate.
The theory is that, in order for cancer cells to grow, they express a cannabinoid receptor as
an “antenna”. In normal cells, that would be a cue for self-survival, but in cancer cells these
cannabinoids act as like a “trojan horse”, where instead of being a cue for growth they cause
the cancerous cells to die. That’s the theory at the moment. The relationship between the
cannabinoid receptors and those intractable proteins is still being worked out.
We do know that there’s a bunch of receptors expressed on a cancer cell, like epidermal
growth factor receptor (EGFR), and there’s a whole class of drugs just to shut down that
receptor. So with cannabinoid receptors, there’s this same kind of mutation that goes on.
The cell is rearranging its contents and entire structure and function, to grow that antennas
that signal to drive cancerous growth. But, most of cancer biology and cancer treatment is
developed with blocking those receptors in mind. Whereas, with cancer, the cannabinoid
receptors agonists act as a “trojan horse” and tells the cancer to effectively kill itself.
With respect to why it might work for autoimmune diseases is the fact that CBD calm the
immune system and act like an immunosuppressant. They also calm the brain down. So
if you look at neurological disorders, where you’ve got circuitry in the brain that’s going
haywire, and CBD is very effective at calming that.
Would a person need to carry on taking cannabinoid medications in order to

prevent the cancer from regrowing again?
Yes, I mean, prevention in cancer is a thing … But, not to scare people, we get cancer all the
time. Our bodies are generating and regenerating cells all the time. In most people, our
immune system recognizes these cancer cells and kills them off. We have an active immune
“surveillance” system which checks through our bodies and looking for things that aren’t
supposed to be there. When cancer cells start to “win”, they overtake the immune system’s
ability to kill those cells, and they start to grow. We also understand that cancer stem cells
have a way of avoid detection from this immune surveillance and carry on growing. So they
can shield themselves from the immune system’s ability to attack or even recognize the cell.
That’s the classical understanding of what cancer is now.
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Cancer stem cells are essentially cells that have gone “bad”. They become malignant
as opposed to cells that have important functions for our body. They harbor all the
characteristics of stem cells that helps keep them alive. Stem cells will take a drug and then
spit them out, in what’s called a “drug reflux”. If you put a toxin in a stem cell, the stem cells
has a unique way of spitting those drugs out. Cancer cells behave in the same way, where
they have these drug reflux transporters. So the drugs come in and they spit them out. They
also don’t divide as rapidly, so when we get a conventional chemotherapy course, a lot of
what happens with drug development and cancer, where the conventional understanding
of cancer is “unregulated cell growth” … Well, this doesn’t happen with the cancer stem cell
population.
The cancer stem cell population is what we call a “quiescent cell”, so doesn’t divide as much.
The theory was that we should develop drugs to go after these constantly dividing cells,
but this way of treatment doesn’t really apply to cancer stem cells. So cancer stem cells
may create these cells that are highly dividing, but we can instead go for cells that aren’t so
highly dividing. So when you’re talking about trying to prevent cancer, there is this theory
that, if you were to take cannabinoids before and after your treatment and as a part of your
diet, then that might have some effect on killing cancerous cells before they start to take
hold. Cannabinoids could potentially act as a preventative, and stop cancerous cells from
becoming cancerous in the first instance.
An example of this could apply to brain trauma or brain injury, where cannabinoids can
protect the brain from injury and physiological stress, where it does this thing that protects
the neurons in the brain from being killed off by signals that cause brain injury. So if we’re
looking at treating or preventing brain injury, using cannabinoids may help. The only drug
we have for the prevention of cancer out on the market today is tamoxifen, which is for
hormone receptive cancers. Tamoxifen is not necessarily a cure-all, and is only used for
breast cancer that is oestrogen responsive.
But once we know more about the preventative mechanisms of cannabinoids when it
comes to cancer, there is the potential there. But you always have to be very careful about
saying things like “prevent”. The concept of prevention is a very, very difficult thing to prove,
and is commonly used in the air of epidemiology versus the medical and treatment side,
so the research is a little more challenging. If you want to look at how we reign into the
circumstance of the United States, we have all of these medical cannabis programs and less
prescription drug use. Whether that applies to a lot of different drugs, or whether it’s just
pain, I have to look at the data a little more.
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But we do know that medical cannabis programs are definitely leading to a reduction in
deaths from opioids. There’s another thing that came out in 2016, with a father-daughter
team looking at Medicare Part D (the prescription drug part), and they showed that each
state that had medical cannabis saw less prescription drug abuse in general. And we do
see that in patients, where they’ll be on a number of drugs, and they need other drugs less.
That may be to do with the fact we’re taking these drugs to treat these conditions and, by
the time cannabinoids come in, they start to shape up the body and those conditions aren’t
as bad anymore, so fewer drugs are needed. That’s a surprising thing that we see, because
in some cases, we’re seeing a reduction in drugs that we wouldn’t ordinarily think that
cannabinoids will have an effect on.
For example, a pre-diabetic condition. Some people might be in a pre-diabetic condition,

undergo cannabinoid therapy, and then not need a prescription drug anymore as the
condition is reversed. This is anecdotal and there’s a lot of things we need to learn, but it’s
an aspect I’m intrigued by. Because if cannabis is reducing drug use, then is it a treatment
or prevention? And I think this is a good question for health systems. Productive health
systems have good prevention in place, as well as good treatment. A dysfunctional
health system will only focus on treatment, and that’s not healthy. We ought to embrace
prevention a bit more. We see this with the opioid crisis in the US, which will impact our life
expectancy.
We also have data from the RAND Corporation and several other publications showing that
medical cannabis reduces deaths from the opioid crisis. So that’s a prevention. Cannabis
is a pain treatment, as well as preventing opioid use and abuse. We also use drugs to
compensate for the side-effects of other drugs, which becomes a cycle. Cannabis could
help with ending that cycle. It’s a phenomenon that we should try and embrace and try to
understand. Another thing to remember is that, when our brains are calm, our body is able
to fight disease better. You might also need to consider the method of intake. For instance,
if you’re smoking cannabis, it might not be giving you the cannabinoids you need for a truly
therapeutic effect. Smoking doesn’t give you a defined dose, and typically with medicines
you need a defined dose in the bloodstream for long enough for it to take effect.
So, you might not be able to kill cancer by smoking a joint everyday; but you might be
able to kill it by using a defined dose, over a period of months or even years. Another thing
with cannabinoids is that they work synergistically with chemotherapy and radiation
therapy. Now, there’s no agreement on how to do this properly, but hopefully we’ll get more
scientific data on this in the future.
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So, is there an ideal way of using cannabis? Is there a “best” method of ingestion?
Well, people are self-medicating. I was teaching people last week, and i said, “If your
medicine has a lot of sugar in it, that’s not medicine.” This is because refined sugar is
harmful to the body. But we have a lot of people who love their edibles, so we have to go in
the direction of, if we’re to treat cannabis as medicine, it really shouldn’t have a lot of sugar
in it.
I believe that, when it comes to treating a serious condition, you need defined doses. This
will most likely come from a tincture, a capsule, a spray or a transdermal. With tinctures
and sprays, you’re going to have a lot of the cannabinoids going into the bloodstream from
the mouth, and the rest of it systemically. But because you’re taking it orally and the mouth
has a lot of blood vessels in it, it will “suck up” an intense amount of cannabinoids, but it
might not be consistent. Whereas, with a capsule, the body will take it in and give a defined
dose, but may take longer to take effect. We find that patients will use capsules for their
long-term use and then a spray for immediate relief or as a backup. So it’s a matter of a high
concentration in a short period of time combined with a defined concentration spread over
a long period of time.
Some conditions, like MS or epilepsy, might require an effect that takes hold immediately to
prevent spasms and seizures. On the flipside, there are a lot of conditions where we might
not need to have specific dosages and so on. This can complicate the situation. So there
are a lot of things to consider, and we’re not going to be able to get to the answers until
healthcare professionals actually step up, learn what they need to know and are trained
well enough. So, they have an understanding of all of these conditions, how cannabis is
medicine and why it may help these conditions, and how to integrate and apply medical
training, understanding of patients, and how to utilize this new medication into the medical
toolkit. I think we’ll be much better for it, and our medical bills will go down. We need to
learn how to insure it properly, too, as well as bring in reimbursement strategies to get
people thinking about cannabis as medicine.
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Cannabis and Chronic Pain/Muscle Pain
General
Chronic pain is persistent pain that lasts more than 12 weeks, often for months or
even years. Chronic pain can arise as a side-effect from all sorts of conditions, as well
as being a side-effect of treating those conditions (e.g. chemotherapy). Chronic pain
is thought to afflict around 100 million American adults, and costs the U.S. around
$635 billion every year.125
Frankie Ray, 23, California
“ After competing in track and field in college, I was a familiar face in the trainer’s
office. Most of the time, it was nothing some ice and an Advil couldn’t fix, but that
soon changed after I went from being high jumper to a decathlete. I had competed
in most of the events involved in a decathlete throughout my amateur career, so
it was easy to pick up, but I had to learn some events from scratch, like shot put,
javelin, pole vault, and hurdles. After a year of practicing twice as long as the rest of
the team, lifting and training twice as hard, as well as learning and then competing
in all 10 events, my body was at a breaking point.
As my junior year came to a close, I had just turned 21 and was already seeing
trainers and doctors for chronic back pain, a dislocated shoulder, meniscus pain,
constant shin splints, sprained ankles, sheer bunion pain and a fractured talus
bone in my left foot, as well as all around muscle soreness. The end result was that
my times tanked, my jumps weren’t as high and long, and my competition days
ended with me being carried off the track. I decided not to compete anymore, but
the pain stayed with me. I couldn’t sit in a car for more than 45 minutes without my
back hurting, I couldn’t run more than a mile without back pain, I couldn’t wear my
favorite types of shoes because of bunion pain, and I was constantly losing sleep over
all of this.
I did not even consider medical marijuana as it got such a hard rap in college.
Getting caught using it meant getting kicked off the team, with your scholarship
ripped away. The first time I tried an edible for pain it was almost like someone took
the painful part of my back out of my body. I remember it perfectly, and exactly
where I was, because it was such a life-changing moment. It was a great feeling to
be able to sit on a plane, or in a car for a few hours without being restless.
As I started experimenting with THC, CBD, edibles, and vapes, I found the best
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consumption strategy for all my conditions. Rather than taking meds like Tylenol and
pain killers, I am able to take something that is all-natural and doesn’t affect my liver.
I am able to dose myself correctly, so that even though I am consuming marijuana,
it does not affect my daily energy, work ethic, and even workouts. It’s ironic that a
substance that could have taken away my dreams as an athlete is now helping me in
”
ways I would have never thought could have been possible.
Muscle aches and pains are sometimes called “myalgia”, and are often caused by
overexertion, injury or high amounts of tension in one particular muscle of the
body. However, conditions like fibromyalgia, thyroid problems (hypothyroidism or
hyperthyroidism), low levels of potassium (hypokalemia, which is also common
in athletes who don’t replenish their minerals), flu or bacterial infections, use of
drugs such as statins or angiotensin-converting-enzyme (ACE) inhibitors, and
autoimmune conditions such as lupus may cause muscle pain.
SSRIs have in recent times proven themselves to be effective painkillers, due to
alterations in the 5-hydroxytryptophan (5-HT) found in chronic pain sufferers. Sadly,
benzodiazepines and highly addictive opioids have often also been prescribed,
leading to what many call the “opioid epidemic”, with opioid overdose quadrupling
between 1999 and 2015. Costs of up to $78.5 billion are estimated when accounting
for health care, lost productivity, criminal justice and substance abuse costs arising
from the over-prescription of opioid painkillers.
Karen Kinne, California, Chronic Pain
“ “As I aged, I started having aches and pains that didn’t go away. Soon, pain controlled
what activities I could do for the whole day. I was an avid rollerblader. I would
rollerblade 40-50 miles a week in Michigan, where there are tons of flat areas.
I’m a lightweight when it comes to opiates, but I used the magical Ibuprofen. I
thought, “eh, 400mg...I could pop some more...and a couple more”. My pain would
go away, but my stomach would become unbearable. I wasn’t eating, and I was still
having such bad pain that I wasn’t able to hike or rollerblade. One of my sons, who is
an athlete, also suffers from chronic pain and he was using cannabis to treat it.
So I went over to his place and use some of his medicine. Within 15 minutes, I had no
more pain in my lower back. You try it once and think, “Eh, maybe that was lucky,”
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but the next day, I used 3 spritz of a medicated spray under my tongue and took
my dog out for a walk. And we walked and we walked, and we walked...and then
we walked some more. Not only was there no pain during the walk, there was no
recovery period afterwards. Afterwards when I went home, I didn’t sit down and
then couldn’t move for the rest of day, which is what would happen when I was on
”
Ibuprofen. I was so amazed.
POSITIVES NEGATIVES
• A replacement for opioids, benzodiazepines and • May not be useful for extreme pain, although
powerful NSAIDs for the treatment of chronic cannabinoids may still function as a “pain
pain - far less addictive, with fewer negative distractor” 133 and still lessen pain to some
side-effects.126 extent.
• Can be used for various kinds of pain, including • Much of the evidence for cannabis’ efficacy of
neuropathic pain, for which opioids may be being a pain killer or distractor is anecdotal.
ineffective.127 128 129
• CBDa inhibits the enzyme cyclooxygenase-2 TREATMENT

(COX-2), which helps control inflammation.130
Many NSAIDs also target COX-2 enzymes.131 Indica strains can potentially be used to replace
painkillers, benzodiazepines, antidepressants,
• CBG also acts as an anti-inflammatory.132 anxiolytics and anticonvulsants (all of which are
medications that may control pain) more than
any other type of cannabis - 37.88% of those
VALUE OF MMJ surveyed used indica strains to replace these
Cannabis has been touted as a potential alternative to types of medications. Using cannabis in place
prescription opioids. Several surveys and studies have of painkillers seems to be one of the most if not
reported that cannabis may decrease pain of various the most common use of medical marijuana.
types. Many patients have also stated a preference for This is perhaps unsurprising, as opioids are often
cannabis over opioids. States with legalized cannabis prescribed for physical pain of all types. Pain, like
show a decrease in opioid analgesic overdose depression, anxiety, insomnia, and headaches, are
mortality. The evidence suggesting that cannabis also all common side-effects of other illnesses and
could be an effective painkiller and work as an adjunct medications, so it is not surprising that these turn
to SSRIs is intriguing, to say the least, and a robust, out to be the sorts of health problems for which
country-wide medical marijuana program could well most people use medical marijuana. Different
help reduce the personal, social and economic costs cannabinoid profiles may work for different types
that addiction to prescription opioid-, barbiturate- and of pain. Anecdotally, THCA may work better for
benzodiazepine- based painkillers bring with them. nerve pain, whilst CBDA may work better for dull,
Determining types of cannabis, cannabinoid and achy pain. CBDA is also a COX-2 inhibitor. The
terpenoid profiles for specific individuals and disease terpene linalool is not only anti-inflammatory,
states could well prove to be a breakthrough in pain but has analgesic properties as well. Evidence
management medications and significantly reduce suggests an affinity for opioid receptors. Both
the risk of death for thousands of patients every year. THC and CBD are allosteric modulators at mu-
and delta- opioid receptors. More research must
be done to explore cannabis as an alternative to
POTENTIAL VALUE OF CANNABIS opioids for pain relief so that we can minimize the
scourge of the opioid and pain-pill epidemic that
Significant
is causing so many unnecessary fatalities each
year.
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Cannabis and Cystic Fibrosis (CF)
General
Cystic Fibrosis (CF) is a genetic disorder that mostly affects the lungs and causes
abnormal amounts of viscous mucus production. Other symptoms include frequent
chest infections, poor growth & weight gain, clubbed fingers and toes, shortness
of breath and salty-tasting skin. CF also affects the pancreas, liver, kidneys and
intestines. CF is most common amongst people of Northern European ancestry, and
affects around 1 in every 3,000 newborns. There are approximately 30,000 people in
the U.S. who suffer from CF.134 The average life expectancy for those with CF is 42 - 50
years old, and there is no known cure for CF.
CF is caused by mutations in the gene for the cystic fibrosis transmembrane

conductance regulator (CFTR) protein.135 People can be carriers if they have a single
working copy of the gene. People with CF are often on one or more antibiotics at
all times in order to prevent infection. There are also relationships between CF and
diabetes, as both conditions affect the islets of Langerhans in the pancreas, which
is an endocrine cell responsible for the production of insulin. Poor vitamin D uptake
also leads to osteoporosis.
Though many antibiotics are generally safe, antibiotics in the aminoglycoside

class 136 can cause hearing loss, loss of balance and renal failure with long-term
use. Antibiotics may also become ineffective over time due to resistance. Other
treatments for CF include vitamin supplements, pancreatic enzyme replacement,
lung transplantation if lung function continues to worsen, high protein diets, chest
percussion and postural drainage to help keep the airways clear for more short-term
relief.
Suffering from CF means an increased likelihood of developing bowel problems,

diabetes, infertility, respiratory problems, pneumonia, arthritis, sinusitis and lots
more. Though a relatively rare disease, CF is one of the most common life-shortening
inherited diseases.
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POSITIVES NEGATIVES
• Many strains of cannabis have high amounts • Smoking cannabis may make things worse for
of limonene, borneol and eucalyptol - all those with CF.
bronchodilators that can help ease breathing.137
• Important that the cannabis is free of
• THC is also a potential bronchodilator - see the pathogens (e.g. moulds, bacteria etc.) that
Asthma section. may harm those with a suppressed immune
system.
• Cannabis can help manage the aches and pains
associated with CF and the effects of regular • CBD may interact with the immune system,
chest percussion. so care must be taken if a CF patient has
had a transplant and is on anti-rejection
• Medicine that targets the endocannabinoid medication.
receptors may help prevent coughing.138
• Help increase appetite and decrease nausea.

TREATMENT
• Help reduce inflammation.139
Smoking cannabis flower should be
• May help defeat superbugs that have contraindicated for those with CF and evidence
developed due to antibiotic resistance.140 of pulmonary involvement. Vaporizing, edibles
and tinctures are likely to be a somewhat better
method of ingestion for CF patients. As with all
cannabinoid medications regardless of one’s
VALUE OF MMJ health state and conditions, care must be taken
to ensure it is clean and free of pathogens. Strains
Cannabis is not necessarily a “cure” for CF and products high in THCV, CBD and pinene may
per sé, but could well be a form of palliative potentially help those with CF, but again, until we
care. However, there are several areas where have the definitive research stating so, we can
cannabinoid treatment may be very useful for only theorize.
those with CF. One is the cirrhosis of the liver
that often occurs with CF - CBD could well help
prevent inflammation of the liver. Another is
insulin regulation - again, CBD can potentially
help against neuropathic pain associated with
diabetes, and THCV may well help regulate insulin.
Pinene, limonene and THC may help clear the
Average
airways and help with breathing. The antiemetic
effects of THC and CBD could also prove to be
beneficial for those with CF.
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Cannabis and Diabetes
General
Diabetes mellitus (DM), often shortened to diabetes, is a group of metabolic
disorders in which there are high blood-sugar levels over prolonged periods due
to the pancreas either not producing enough insulin, or the body not responding
properly to the insulin produced.
Symptoms of high blood sugar include frequent urination, sugar found in the
urine due to malabsorption of glucose, skin rashes called “diabetic dermadromes”,
increased thirst and hunger, and may include many complications if left untreated.
Those with diabetes have an increased chance of stroke, cardiovascular disease,
kidney disease, foot ulcers and damage to the eyes.
There are three main types of diabetes:
1 Type 1 Diabetes or Type 1 DM - Results from the pancreas’ inability to

produce enough insulin. Those with type 1 DM may also experience diabetic
ketoacidosis, which causes nausea, vomiting and abdominal pain. There is no
known cause of type 1 DM, but there does seem to be a genetic basis for it.
Interestingly, type 1 DM shares the same genetic link as crohn’s disease.
2 Type 2 Diabetes or Type 2 DM - Insulin resistance. This is when cells fail

to respond to insulin properly. A lack of insulin may also develop as the
condition progresses. Insufficient exercise and excessive body weight are the
most common causes of type 2 DM.
3 Gestational Diabetes - a type of diabetes that develops in pregnant women

with no history of diabetes.
In practical terms, diabetics can have persistently low blood-sugar (hypoglycemia),

high blood-sugar (hyperglycemia) and/or rapidly cycle between the two,
although hyperglycemia is more common in type 2 DM. Effects of can include
sweating, feelings of unease, trembling and increased appetite. In more severe
cases, confusion, seizures, unconsciousness and behavioral changes such as
aggressiveness are experienced. Mild-to-moderate cases of hypoglycemia can be
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abated by eating or drinking something sugary. Unconsciousness must be treated

by glucagon injections.
As of 2015, an estimated 415 million people worldwide have diabetes, or some form
of diabetes, with 90% of cases being Type 2. In 2012, diabetes cost the US $245
billion. Diabetes doubles the risk of an early death, and can either be the cause or
result of another potentially life-threatening condition.141
Simply put, some researchers believe that CBD’s anti-inflammatory properties could
benefit sugar metabolism, the immune system, cell growth, heart function. Studies
taken place at the Hebrew University of Jerusalem142 suggest that, as chronic
inflammation plays a key role in the development of insulin resistance and type-2
diabetes,143 CBD could help treat this inflammation and suppress diabetes. CBD
could possibly even reverse and cure diabetes, though more research is needed.
Another issue that often arises from diabetes, especially those who have been
suffering from diabetes for a long time, is neuropathic pain. Neuropathic pain is a
complex and chronic form of pain, often caused by tissue injuries. Diabetes often
causes damage to the nerve fibers, which sends incorrect signals to other pain
centers.
Cannabis may therefore be potentially useful for a range of issues associated with
diabetes. Not only is CBD neuroprotective,144 but it could also lower the incidence of
diabetes and prevent insulin resistance,145 146 as well as help treat the pain of diabetic
neuropathy.
LeafWell
POSITIVES NEGATIVES
• Cannabis - in particular CBD and THCV - could • The “munchies” could be either a positive or
help regulate glucose levels and prevent insulin negative for diabetics - the wrong foods must
resistance. be avoided.
• Cannabis more effectively and safely manages • THC may have a negative effect on memory,
the pain associated with diabetic neuropathy in concentration, perception and coordinated
comparison to opioids. movement - all negatives for a person with
nerve problems. Pinene and CBD may help
• Rapidly fluctuating blood-sugar levels can mitigate this to a certain extent.
cause mood swings and depression, which
cannabis can help manage. • Dry mouth and eyes may be particularly
unpleasant for diabetics.
• May improve carbohydrate metabolism,
helping control weight.147 148
• Keep blood vessels open and improve

TREATMENT
circulation.
• Topicals can be applied to the skin to prevent Equatorial sativas tend to produce more THCV, so
the “tingles”. it would not be surprising if those with diabetes
tended towards those. However, many of those
• Cannabinoid receptors may well help sweet with diabetes seem to enjoy indicas as well,
things taste more sweet,149 which could be of suggesting that CBD could well be sought just
great help for those are hypoglycemic. as frequently, likely for nerve pain. Some of the
preference might be based upon the type of
diabetes, but, unfortunately, there is no way to
VALUE OF MMJ
draw significant conclusions when we have no
definite proof of preference for one of the other.
Cannabis is known for giving people “the
munchies”. This could help offset weight loss for
those with diabetes. Interestingly, despite the
common depiction of cannabis giving people
hunger pangs, THCV may actually reduce hunger
pangs. This means that, for those with type 2 DM,
cannabis may actually reduce hunger over a long
period. The idea behind this is related to the idea
that cannabinoids affect our taste for sweet things
- by making sweet things taste sweeter, people
may be satisfied by eating less sugar, and cravings POTENTIAL VALUE OF CANNABIS
for high sugar are kept at bay. This can help BASED ON CURRENT EVIDENCE
maintain weight for those with type 2 DM.
CBD may also be a neuroprotectant, and

additionally an aid in preventing insulin resistance.
Significant
Both CBD and THC have anti-inflammatory and
antiemetic properties. They are also possibly far
more effective for neuropathic pain than opioids,
which are not really effective for nerve pain, or the
evidence for their efficacy is mixed at best.
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Cannabis and Depression
General
Depression affects almost everyone at some point in their lives. However, for
some people it becomes persistent and all consuming. Depression of more than
several months duration can be classed as clinical depression. It is also often
called unipolar depression, as it stands in contrast to bipolar depression/disorder,
which includes erratic shifts in mood from extreme euphoria to extreme sadness.
Although the two conditions can be mistaken for one another on occasion, there
are some significant differences between the two.
Depression, statistically, is the most common type of mental health condition

in the U.S., affecting just over 26% of the population, although major depression
affects around 16.1 million Americans, which is 6.7% of the population.150 Due to the
persistence of a condition like depression, as well as the time it can take to treat it
properly, the social impacts cannot be overestimated or necessarily even measured
properly. Those with recurrent depression can expect their life expectancy to be
shortened by 7 - 11 years.151 Depression can also dampen the immune system and
make one more prone to illness. Depression may be comorbid with many other
conditions, and can both be a factor in causing another mental or physical health
problem, as well as a symptom of another, deeper underlying problem.
Despite its prevalence in the mental health universe, it is often overlooked that
depression has a reinforcing relationship to stress associated with pain. One of
the most common causes and sequelae of recurring physical pain is stress and
depression.152 This is perhaps not surprising as both chronic and acute pain is a well
recognized stressor.
Antidepressants as they currently stand have a very high therapeutic index, and
are not highly addictive. They work by increasing the levels of neurotransmitters
like serotonin (selective serotonin reuptake inhibitors - SSRIs) and noradrenaline
(noradrenaline and specific serotonergic antidepressants - NASSAs). The increasing
levels of neurotransmitters may also disrupt pain signals,153 making them a
mainstay in treating chronic pain conditions.
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Cannabis can have many antidepressant-like effects, in particular the cannabinoids

THC, CBC and CBD.154 This means cannabis can be an immensely useful adjunct to
current antidepressants, or be of potential use for anyone who does not handle SSRIs
or other antidepressants.
Celia Behar
“ I was diagnosed with postpartum depression after my first daughter was born. At
that point, they put me on Prozac, which was really bad for me. To start, I couldn’t
even get out of bed and I was always sobbing. It took me a little while to realize that
it was because of PPD. Which is kind of crazy, because I’m a therapist!
I probably should have known, but I think I was in denial. Honestly, when you’re in
the middle of PPD, you just don’t realize it a lot of the time. Then, I went on Prozac
and stayed on it for a couple of months. Once I was up and functioning, I stopped
using it. I wasn’t depressed or crying anymore and I could definitely function, but my
anxiety – and I always had a general anxiety disorder – went through the roof.
I mentioned this to my doctors, and they would prescribe me valium and stuff like
that. But I didn’t like it, and it didn’t really help. I just sort of decided, “this is what
being a mom is supposed to be like” and “this is being a parent.” I ended up being
able to have a second daughter after two years of struggling with infertility, and I had
her and didn’t have the same kind of PPD, so I thought I was in the clear.
After I stopped nursing her, my hormone levels just changed drastically. The anxiety
became overwhelming. I could barely sit down, I had cycling thoughts, I cried all
the time, I was enraged, and I had insomnia. It was awful. I ended up taking a trip
to Connecticut, where I grew up and hung out with a bunch of my old friends. One
of them, a guy by the name of Tom Grubbs, ended up confronting me and asking
what was wrong. He could tell I wasn’t myself. I told him what was going on with me
since I had my kids. He suggested that I use cannabis because he had several friends
who used it for anxiety, with really great success. I really balked at the idea. I used to
smoke pot when I was in my teens and twenties, and I stopped before becoming
a mom because I thought “Moms don’t do that”. That’s what I said to Tom: “Moms
don’t do that!” Tom said, “Well, I think you should try it.”
I went back to New York – where I lived at the time – and I really thought about it.
Then I mentioned it to a friend of mine from California, who grew his own. He ended
up sending me some, but it took a couple of weeks to convince myself that I should
try it. I did one night and I slept 8 hours for the first time in probably 6 years, by then.
I woke up feeling like a different person.
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I secretly started using cannabis at night once my kids would go to bed. And
it made all the difference! Something really changed in me when I had kids,
chemically, and I think that happens to a lot of moms, and they don’t talk about
it. Cannabis just has a way of really levelling me out. It helps me relax and feel
connected. I don’t feel “stoned”, I’m not trying to get high when I’m around my kids.
”
That’s not the point.
POSITIVES NEGATIVES
• Can help provide relief from depression arising • Though sativas can be great for those with
from physical pain. depression, anyone prone to anxiety as well
may want to avoid certain sativas.
• Can potentially help control the side-effects of
antidepressants, such as nausea, insomnia and • Getting the dosage right is important - too
even loss of sexual desire. high a dose could make things worse
• Not all antidepressants work for everyone, • Though most antidepressants are not
meaning that cannabis could prove to be a contraindicated by cannabis, some
valuable alternative. are, especially older ones like tricyclic
antidepressants (TCAs).
• Cannabis has various cannabinoids and
terpenes that can help fight depression, e.g. • Like other antidepressants, will not sort
limonene, CBC, CBD and THC. other sources of depression, e.g. a bad home
environment, grief, pain.

There are a number of cannabinoids and terpenoids
Although antidepressants have proven that can potentially treat depression, including
themselves very useful for depression and a whole limonene, cannabichromene (CBC), CBD and THC.
host of other conditions, they can also take several As with most things in life, a careful balance of
weeks to start taking effect. Moreover, after several these phytocannabinoids is preferable, to combat
weeks of trying, the antidepressant might not depression or lift a low mood. Care must also be
even work, and the patient has to try another taken if a patient is suffering from anxiety, which
antidepressant. Cannabis, on the other hand, has is often comorbid with depression. Most sensible
more immediate effects. advice would be to microdose THC, as too large
an amount may cause a depressive episode and/
or anxiety attack. Some suffering from depression
may be highly sensitive to THC, so care must be
taken. Anecdotally speaking, many with depression
seem to prefer sativa-leaning strains, but as with
many people, preferences may be dependent
upon time of day or even just simply personal
Average
preferences. Caryophyllene seem to be particularly
useful terpenes for those with depression, as well as
limonene and pinene. Nerolidol may be beneficial,
too. Beta-caryophyllene, which is a CB2 receptor
agonist, may have antidepressant effects.155 Linalool
and pinene may produce an antidepressive effect
through interaction with the monoaminergic
system.
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Cannabis and Eating Disorders (e.g.

Anorexia, Bulimia, Obesity)
General
While there are some physical conditions (e.g. cancer, AIDS/HIV, diabetes) that can
cause anorexia- (cachexia156) or obesity- like symptoms, there exist eating disorders
which are independent from other disease processes. The use of cannabis in
the treatment of eating disorders is not a novel idea when it comes to anorexia
nervosa and bulimia nervosa; cannabis for the treatment of obesity is a less intuitive
connection. It is recommended that you read our section on diabetes, as the theory
behind using cannabinoid-based medications for obesity is similar.
There is increasing evidence delineating the relationship between

endocannabinoids and eating disorders. Some speculate that all eating disorders
like obesity and anorexia are caused at least in part by a defective endocannabinoid
system (ECS)157. Anorexia has a high mortality rate, and managing it is very difficult,
with little evidence of effective treatments; leptin, ghrelin and cannabinoids158
are exciting avenues of exploration in dealing with the tragic consequences of
malnutrition.
There are various ways in which eating disorders can be defined, but the
overarching theme is the relationship between patient and food. Those with
anorexia nervosa tend to avoid or fear food, imagining themselves to be
overweight. Those with bulimia nervosa tend to binge-and-purge on food.
Those with obesity are not necessarily suffering from an eating disorder in the
strictest sense (it is a result of endocrine, genetic disorders, other conditions or
medications in some instances, rather than just a case of over-eating and lack of
exercise, although this is still the main cause of obesity). However, for most cases of
obesity, it could be argued that obesity is a “food addiction” of sorts - in particular,
foods with high amounts of refined sugar.
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Obesity affects an estimated 600 million adults and 100 million children worldwide.
The 2015-16 figures from the National Center for Health Statistics at the CDC
showed that 39.6% of U.S. adults aged 20 or over are obese. Obesity is cited as a
major cause or contributing factor for deaths in the United States, with between
100,000 and 400,000 deaths per year. Obesity costs the U.S. approximately $117
billion in direct health costs, making up between 6% to 12% of national healthcare
expenditure in the U.S., rendering obesity as one of the most expensive health care
problems in in the world.159
POSITIVES NEGATIVES
• Improve and stimulate appetite; using • May increase paranoia, anxiety and depressive
tetrahydrocannabivarin (THCV) may help episodes in some.
decrease hunger.
• Can help control hunger for those prone to

overeating, due to controlling blood-sugar
levels (similar to diabetes).
• Euphoria can help overcome anxiety and

TREATMENT
depression.
Treatment may well depend on the eating disorder

in question. For obesity, a strain or product high in
VALUE OF MMJ THCV may be best, whereas for anorexia or bulimia
it’s the THC that may help convince our brains that
Medical marijuana may essentially help people we are starving.160 CBD, meanwhile, may not work
eat properly and maintain body weight. The ECS for the ‘munchies’ so well, but may help ease anxiety.
seems to play a part in all areas of homeostasis,
including appetite.

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LeafWell
Cannabis and Eczema and Psoriasis
General
There are key differences between eczema and psoriasis. First of all, eczema
describes a group of diseases that lead to inflammation of the skin. Eczema is
also known as “dermatitis”, and is usually triggered by allergies, irritation and poor
venous return (slow blood flow to the veins). Psoriasis, on the other hand, is an
autoimmune condition that results in patches of red, itchy, scaly skin. Psoriasis is
thought to be a genetic condition, with environmental triggers. Psoriasis is also
associated with conditions such as Crohn’s disease, arthritis, cardiovascular disease
and depression.
There are five types of psoriasis: plaque; guttate (small lesions appearing around
the arms, hands and feet); inverse (affecting the ears, naval, lips, web spaces
in between the fingers and toes, and other folds in the skin around the body);
pustular; and erythrodermic (all over the body). 90% of cases of psoriasis are plaque
psoriasis.
Eczema is usually treated with paraffin-based moisturizers and topical

creams. Steroid-based creams (corticosteroids) and antibiotics may need to
be used. Capsaicin cream may also be used to treat allergy-triggered eczema.
Antihistamines, oatmeal baths, coconut oil and olive oil may also be effective
treatments for eczema. Psoriasis sufferers may also use corticosteroids, as well as
vitamin D3 topical creams, ultraviolet light treatment and immunosuppressants
such as methotrexate. Beta blockers and NSAIDs can potentially make psoriasis
worse. HIV/AIDS sufferers may also get a more severe case of psoriasis.
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245 million people worldwide suffer from dermatitis, as of 2015. In the US, it
affects between 10% and 30% of people, and most commonly starts in early
childhood. Females are more commonly affected, and dermatitis may continue
into adulthood, as hypersensitive skin doesn’t necessarily stop becoming highly
sensitive after a certain age. Around 40 million people in the United States have
psoriasis. Total direct cost of psoriasis is estimated to be between $51.7 billion and
$63.2 billion per year.161
POSITIVES NEGATIVES
• Cannabinoid-based medications - in
162
• Some people may be allergic to cannabis.166
particular topical creams - could be an adjunct
or alternative to steroid-based creams and • No proven efficacy as of yet.
moisturizers.
• Pinene has significant antibacterial and anti- VALUE OF MMJ

inflammatory properties,163 as does CBD, which
may be useful for psoriasis and dermatitis. Medical marijuana may be useful for a whole host
of skin conditions, and its application as a topical
• Both THC and CBD may be used as an
cream is unique and, to some, unusual. Cannabis
alternative to NSAIDs, which are not ideal for
also represents a potential palliative treatment
those with psoriasis.
for eczema and psoriasis where other treatments
• CBD may help joint pain and inflammation, may have failed. For psoriasis in particular,
which is common in psoriasis which has no known cure, cannabinoid-based
medications may prove to be a useful painkiller,
• Applied as a topical cream, so no psychoactive especially when NSAIDs are not ideal for use by
effects are necessarily felt. However, this does those with psoriasis.
not mean ingesting some decarboxylated
cannabinoids aren’t an effective treatment for One way in which cannabinoids may help
psoriasis as well. psoriasis is by inhibiting keratinocyte production.166
A keratinocyte is an epidermal cell that produces
• Cannabis contains CBG and various keratin, a protein that produces hair and skin,
cannabinoid acids such as CBGV, which as well forming a barrier against environmental
may prove useful for psoriasis and eczema damage and pathogens. In psoriasis, keratin
patients.164 is often overproduced as the immune system
attacks harmless cells within the body, and the
body produces more skin cells in response. CBG
may attenuate the immune system in some way
TREATMENT to prevent overproduction of keratin.
CBD-, CBGV-, CBG- and pinene- based topical

creams, tinctures and salves could potentially be
very useful for both eczema and psoriasis. Although POTENTIAL VALUE OF CANNABIS
it may not seem so, ingesting cannabinoids in BASED ON CURRENT EVIDENCE
Significant
combination with topicals may provide relief for any
pain associated with psoriasis as well.
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Cannabis and Ehlers-Danlos Syndrome (EDS)
General
Ehlers-Danlos syndrome (EDS) is a group of genetic disorders where the connective
tissue that supports the skin, bones, blood vessels and other organs and tissues
fails to form properly due to mutations in genes that produce the fibrous proteins
and enzymes that make collagen. This can result in: chronic pain; difficulty in
recovering from other injuries; soft, velvety, fragile skin; organ rupture; early onset
of osteoporosis; a greater chance of joint dislocations due to hyperflexibility of
joints; scoliosis, where the spine has a sideways curve; and aortic dissection, where
injury to the innermost layer of the aorta allows blood to flow between the layers of
the aortic wall, forcing the layers apart.
EDS affects approximately 1 in every 5,000 people globally. It is thought that

around 10,000,000 Americans are affected. Though many EDS sufferers can expect
a normal life expectancy, those suffering from th types of EDS that affect blood
vessels can expect a significantly shorter lifespan. There is no known cure for
EDS, and current treatments are palliative, including physiotherapy, occupational
therapy, close monitoring of the cardiovascular system and orthopedic instruments
such as wheelchairs, bracing, and casting. There are 13 types of EDS, some of which
are more common than others:
• Hypermobile EDS (hEDS) - characterized primarily by joint hypermobility

affecting both large and small joints. Frequent joint dislocations and
subluxations (partial dislocations). A common form of EDS.
• Classical EDS - associated with extremely elastic, stretchy, smooth skin that
is fragile and bruises easily; wide, atrophic scars (flat or depressed scars);
and joint hypermobility. A common form of EDS
• Vascular EDS - characterized by thin, translucent, extremely fragile skin
that bruises easily. The intestines, arteries and uterus are also fragile and
prone to rupture.
• Kyphoscoliosis EDS - associated with severe hypotonia (a state of low tonal
muscle, commonly known as “floppy baby syndrome”) at birth, delayed
motor development, progressive scoliosis (present from birth), and scleral
fragility.
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• Arthrochalasia EDS - severe joint hypermobility and congenital hip

dislocation
• Dermatosparaxis EDS - associated with extremely fragile skin
leading to severe bruising and scarring; saggy, redundant skin,
especially on the face; and hernias.
• Classical-like EDS (clEDS) - skin hyperextensibility with velvety
skin texture and absence of atrophic scarring, generalized joint
hypermobility (GJH) and easily bruised skin or spontaneous
ecchymoses (discolorations of the skin resulting from bleeding
underneath).
• Spondylodysplastic EDS (spEDS) - short stature (progressive in
childhood), muscle hypotonia (ranging from severe congenital, to
mild later-onset), and bowing of limbs.
• Musculocontractural EDS (mcEDS) - characterized by
congenital multiple contractures, characteristically adduction-
flexion contractures and/or talipes equinovarus (clubfoot),
characteristic craniofacial features, and skin features such as skin
hyperextensibility, easy bruisability, fragility with atrophic scars,
increased wrinkling on the palms.
• Myopathic EDS (mEDS) - characterized by congenital muscle
hypotonia and/or muscle atrophy, that improves with age.
Proximal joint contractures (joints of the knee, hip and elbow) and
hypermobility of distal joints (joints of the ankles, wrists, feet and
hands) are also common.
• Periodontal EDS (pEDS) - severe, early onset (childhood or
adolescence) and intractable periodontitis, lack of attached gingiva,
pretibial plaques. Has a family history of a first-degree relative who
meets clinical criteria.
• Cardiac-valvular EDS (cvEDS) - severe progressive cardiac-
valvular problems (aortic valve, mitral valve), skin problems
(hyperextensibility, atrophic scars, thin skin, easy bruising), and joint
hypermobility (generalized or restricted to small joints).
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Medications prescribed include beta blockers (e.g. celiprolol), angiotensin-

converting-enzyme (ACE) inhibitors (e.g. benazepril/Lotensin, zofenopril),
acetaminophen (Tylenol/paracetamol), NSAIDs such as ibuprofen and possibly
desmopressin (DDAVP, Minrin). Minrin is an analogue of vasopressin and is an
antidiuretic that limits the amount of water lost in the urine. Regular surgery may
also be needed for EDS, for which opioids may be prescribed.
POSITIVES NEGATIVES
• For those coming out of surgery and/or chronic • Cannabinoids’ effects on blood pressure are
pain due to EDS, cannabis represents a possible not fully understood as of yet
alternative to opioids and powerful NSAIDs,
which may cause kidney problems. • How cannabinoids affect connective tissue is
not properly understood as of yet
• Although THC can raise blood pressure in the
short-term, it lowers blood pressure in the long-
term. CBD may also reduce blood pressure.167
TREATMENT
Cannabinoids may help with chronic pain

VALUE OF MMJ
associated with EDS, but whether or not it helps
with other symptoms associated with EDS
The treatments available for EDS at the moment are
remains to be seen. There are some anecdotal
palliative, and in some instances may require a host
reports of CBD and herbal cannabis being
of pills, some of which may interact negatively with
effective for the pain associated with EDS. 168 169
each other (e.g. ACE inhibitors and NSAIDs may have
moderate levels of negative interaction). Medical
marijuana could help replace at least some of these
pills and lower the chances of negative interactions.

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LeafWell
Cannabis and Endometriosis
General
Endometriosis is an often painful condition where tissue that lines the uterus
(endometrium) grows on other organs in the pelvis, most commonly the fallopian tubes
and ovaries (although other parts of the body may be affected). Endometrial tissue can
thicken and bleed outside of the uterus, similar to how the endometrium bleeds during
the normal menstrual cycle. 50% of those with endometriosis suffer from chronic pain,
and 70% of those with endometriosis suffer from pain during menstruation, called
dysmenorrhea. The pain associated with endometriosis can be excruciating, and is said
to be akin to having hundreds or thousands of blisters inside you.
Around 25% of women with endometriosis have no symptoms at all. Endometriosis

affects an estimated 176 million women (that’s 1 in 10) worldwide.170 There are few deaths
associated with endometriosis, but it does happen in extremely rare circumstances.
The cause is not known, although those with a family history of endometriosis are more
likely to develop the condition.
Due to the timing of the pain, some cases of endometriosis may be confused with
premenstrual syndrome (PMS). Other symptoms of endometriosis include infertility,
bowel and urinary problems and pain during sexual intercourse. Pelvic inflammatory
disease, irritable bowel syndrome (IBS), fibromyalgia and interstitial cystitis can cause
similar symptoms to endometriosis. Symptomatology, medical imaging and biopsy are
required to rule out other causes and confirm the diagnosis of endometriosis.
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Current treatments include non-steroidal anti-inflammatory drugs (NSAIDs) such as

naproxen and ibuprofen, oral contraceptives (continuous use of birth control pills),
intrauterine devices with progesterone, gonadotropin-releasing hormone agonists
for those who are infertile and in some severe cases, surgery. Exercise and avoiding
excessive alcohol intake may also be a preventative.
POSITIVES NEGATIVES
• Cannabinoids such as tetrahydrocannabinol (THC) • May increase sensitivity to pain in some.
and cannabidiol (CBD) may reduce inflammation
by suppressing T-cell function.171 • Women could be more prone to the negative
effects of THC.
• The uterus contains the reproductive system’s
highest concentration of the endocannabinoid
anandamide (AEA). Anandamide is analogous
to THC, and taking THC may increase estrogen VALUE OF MMJ
production, and cannabidiol may bind to estrogen
receptors. 172 While many of the aforementioned treatments
are relatively effective for endometriosis, the
• Anandamide “regulates function and implantation recommended NSAID - naproxen - may cause
of the developing embryo”. 173 Cannabinoids stomach ulcers. Proton-pump inhibitors are
therefore may function as an aid to fertility. often prescribed alongside naproxen in order to
reduce the chances of stomach ulceration. As
• Women with endometriosis have lower levels of
endometriosis cannot be cured, surgery is perhaps
CB1 receptors in their endometrial tissue. Reduced
best avoided except in the most necessary of
endocannabinoid system (ECS) function may lead
circumstances, as complications may arise.
to growth of endometriosis and increase pain.
Cannabinoids may promote embryonic and adult Of course, taking a cornucopia of pills that
hippocampus neurogenesis, and may induce includes NSAIDs, antidepressants, birth control,
growth of CB1 receptors in endometrial tissue as hormone agonists and proton pump inhibitors
well as the brain. 174 can affect a person’s mood and mental health -
taking tens of pills a day and possibly hundreds
• Cannabinoids may be useful in reducing muscle
in a week can be very tiring, psychologically-
cramps and spasticity, 175 usually associated with
speaking. Cannabinoid-based medications may
conditions like multiple sclerosis. Cannabinoids
help reduce inflammation and improve one’s
may also be useful for treating cramps associated
mood, thereby potentially decreasing the number
with endometriosis.
of pills needed to treat endometriosis.
• TRPV1 receptors and calcium ion channels are said
to be associated with menstrual bleeding, and
desensitizing this receptor may help beat pain TREATMENT
associated with PMS.
CBD could reduce inflammation and help improve
one’s mood. THC may also help reduce inflammation,
POTENTIAL VALUE OF CANNABIS pain and nausea. Although there’s no definite proof
BASED ON CURRENT EVIDENCE that cannabis works for endometriosis, some may
Average
find it helpful. A 1:1 THC:CBD ratio could be useful
without necessarily being overwhelming. A mixture
of ingesting cannabis and suppositories/cannabinoid-
but could potentially be significant. laced tampons may be useful.
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Cannabis and Epilepsy
General
Much of the move towards legalization in the US today may be because of its potential
to help prevent epileptic seizures. Probably one of the most popular stories today is
that of Charlotte Figi, who saw a drastic reduction of her epileptic seizures brought
on by Dravet Syndrome after being administered a CBD oil derived from “Charlotte’s
Web” - a strain developed by the Stanley Brothers.176 We have interviewed Alexis Bortell,
a teenage epileptic intent on suing the federal government for denying her and others
like her a medication that could save and improve the quality of many lives.177 Many
theories have been postulated regarding the physiologic effect of cannabis in the
epileptic patient.
Tom Jesse, 72
“ It was back in ‘98, that I was diagnosed with epilepsy at the Mayo Clinic. I was 52 at
the time, which is an odd age to develop it. I was having what they called “complex
partial seizures”. I honestly didn’t even know I was having them. I had a terrier named
Rip. He was a rat terrier on the farm I had at the time. I noticed that every once in
awhile, he would jump up on me, to try to get me to sit down. Then I noticed that
every time I sat down, there would seem to be like a blank space, and then I would
wake up. I couldn’t figure out what was going on, so I just ignored it for awhile.
One day I could feel myself losing control of my body and called the ambulance. The
doctor said that it was probably a one time occurrence. It wasn’t until I sold the farm,
and moved in with my mother and sister that I was certain something was wrong.
They said I would just be sitting and all of a sudden stop answering their questions. I
never blinked, my hands would get real cold, and I’d be blank for 5-7 minutes, which
is incredibly long for seizures. I never knew if I was going to have one, so I started
listening to Rip. The I noticed that when he would start jumping on me, I would start
seeing little halos and light, and that’s when I knew one was coming on. To me the
time would pass in a blink of an eye, but in reality, 10 minutes could have passed. So I
got Rip certified as my service dog, and his daughter, Pixie, could detect seizures too.
I learned that my triggers were objects changing position, things moving fast, like in
a car ride, and magazine pictures/drawings because everything nowadays is made of
“pixels” and my brain has a problem putting them together, so everything falls apart.
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They prescribed me all these pills, but after two years of taking them, the side effects
were just awful. I tried Valerian, which helped a little, but I was still having seizures.
A friend of mine from Europe suggested cannabis. I smoked when I was in the
Navy, in 1971, during my second enlistment, but rarely after that. Seven years ago, I
started using a tincture that was basically hemp leaves, Valerian, motherwort and
everclear. Three drops a day in warm water was all I needed. I became seizure-free
as of January 2013. Then my dog, Homer, started having grand mal seizures, where
he would convulse and foam at the mouth. After a month of using the tincture, his
seizures were almost completely gone. Recently, he did have one seizure, but that
was his first one in 2 years.
”
1 CBD blocks sodium channels when in high concentrations, and can antagonize
both CB1 and CB2 receptors, suggesting it has anticonvulsant properties.178
2 Whilst CBD seems to have a weak affinity to CB1 and CB2 receptors, it
acts on them indirectly and exerts influence on serotonergic, vanilloid and
norepinephrine receptors.
3 CBD also exerts an influence on calcium channels.179 CBD also acts as an

anti-inflammatory as “cannabinoids downregulate cytokine and chemokine
production and, in some models, upregulate T-regulatory cells (Tregs) as a
mechanism to suppress inflammatory responses.”180
4 We noted above that CBD affects the vanilloid receptors. The vanilloid receptor
is also sometimes called the TRPV1 receptor, and is responsible for the detection
of pain and heat, and regulates body temperature. CBD may desensitize the
TRPV1 receptor, and thereby reduce neuronal excitability.181
5 Many people who suffer from epilepsy may have mutations in the liver enzyme
cytochrome P450 (CYP450), CYP2C9, CYP3A, CYP2C19, and CYP2D6, which are
all enzymes that are responsible for the metabolism of many anti-epileptic
drugs (AEDs) like Clobazam. This means that, due to these malformations, many
children with certain types of epilepsy may be being given benzodiazepine- and
barbiturate- based AEDs that might not even work for them. Many AEDs are
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also inhibitors of these kinds of enzymes. CBD also inhibits these enzymes,182
meaning that epilepsy sufferers can get a cannabinoid that’s much safer and
more well-tolerated than many AEDs.
6 Taking people off AEDs can be a huge benefit for the epilepsy sufferer - many
AEDs have nasty side-effects such as addiction, constant drowziness, nausea,
headache, vomiting, fatigue, blurred vision, tremors and death-via-overdose.
Also, as CBD is such a powerful inhibitor of CYP450 and other such enzymes, it
may have negative interactions with certain AEDs.183
The evidence for CBD being helpful for epilepsy is strong. The medical use of cannabis
for the treatment of epilepsy began in the 70s, making it one of the first conditions
studied despite the restrictions imposed upon medical cannabis research inherent in
prohibition. Since Charlotte’s story was aired on national television in the U.S.,research in
this area has accelerated, with GW Pharmaceuticals creating Epidiolex for rare forms of
epilepsy.184 Several volunteers have reported positive experiences with CBD.185
At the moment, there is significant anecdotal and empirical evidence suggesting
that cannabis could be immensely useful for epilepsy treatment, with several parents
reporting a drop in seizures after cannabidiol-enriched cannabis.186 Questions still
exist regarding how the endocannabinoid signalling affects epilepsy, but signs so far
are showing that cannabis may be extremely useful for some types of rare epilepsy.187
Occasional seizures may still be a concern, but overuse of the medications usually used
for epilepsy are also of serious concern.
Shelby and Kristen, Kentucky
“ No child should have to suffer the way that Shelby does. She was born completely
healthy on Christmas Eve, but was soon diagnosed with Dravet Syndrome and I was
told that there was no cure. She was having hundreds of seizures a day.
Everytime she had a seizure, I had to shoot her up with 20-50mg of rectal Valium,
which leaves her asleep, sometimes for days. She’s 12-years-old and she has the liver
of an 80-year-old alcoholic. Her seizures have lasted up to 16 hours and she’s had to
be airlifted to the hospital 26 times.
After 2 years of trying, we were approved for a clinical trial of the cannabis infused
drug, Epidiolex. I saw a change almost immediately. I can’t even explain it… I can’t
even describe it, but It was like a light started coming back into her eyes. Overnight,
LeafWell
her seizures became almost nonexistent. Her teachers even surprised me with a
video of her feeding herself for the first time.
However, cannabis is illegal in Kentucky. She is only safe for as long as this clinical
trial is going on. It can end at literally any moment. Everytime she has a seizure, I
record it and send it to everyone in political office who can make a change. I refuse
to move to some place where it is legal. I’m a single mother and I can’t afford it. The
lawmakers are the ones with health and wealth, so if they don’t like it, then they
should move.
”
POSITIVES NEGATIVES
• CBD may have anticonvulsant effects. 188
• May not work for every form of epilepsy, and
some reports have suggested that CBD may
• CBD may have antiepileptic effects. 189 190
not be suitable for all epileptics, and may
in some cases may make seizures worse.
• Cannabinoids may help treat neuronal
Using too much CBD may also be a concern
hyperexcitability. 191
- remember cannabinoids are biphasic, and
• Other cannabinoids such as THCA, CBDA, THCV extremely high doses may have no effect or
and CBDV may also help.192 193 However, their opposite of the desired effect.
pharmacology is less well understood.194
• Concerns surrounding side-effects such as
sedation, interactions with other drugs and
TREATMENT how cannabinoids affect brain development.
Little is known on whether or not CBD will
Usually, tinctures high in CBD and/or CBDV work for epilepsy in adults.195
(mostly CBD as it’s more abundant in the cannabis
• Care must be taken when using CBD derived
plant) are the main types of cannabis strains or
from badly-grown hemp, as the pollutants
products used. This means CBD:THC ratios of 20:1
found in such products may make problems
or higher. However, having small concentrations
worse.
of THC helps the CBD synergistically. High-quality,
non-hemp-based cannabinoid-based tinctures
are likely to be best. Under proper supervision,
VALUE OF MMJ
other cannabinoids may also help an epilepsy
CBD and CBDV are the main two cannabinoids of
patient overcome withdrawal from AEDs. THCA
interest when it comes to medical marijuana for
may also be of use. CBDA could be useful as well,
epilepsy. THCA also has some antiseizure properties.
although, as Prof. Roger Pertwee states, it seems
to be most effective in moderate amounts.

Significant
although it does depend on the type of epilepsy.
LeafWell
Cannabis and Fibromyalgia
General
Fibromyalgia is a condition where pain signals are abnormally processed by the central
nervous system (CNS). Characteristics of fibromyalgia include but are not limited
to chronic pain, restless leg syndrome, migraine, depression, anxiety, irritable bowel
syndrome (IBS), bladder problems, heightened pain response to pressure, numbness
& tingling, and sensitivity to lights, sounds and temperatures. Post-traumatic stress
disorder (PTSD) is also frequently associated with fibromyalgia, as is sensitivity to
gluten.
Fibromyalgia is estimated to affect between 2% and 8% of the population, with females

tending to be more affected than males. Both environmental and genetic factors
are thought to cause fibromyalgia. Around 10 million people in the US are affected
by fibromyalgia.196 Conditions that present themselves similarly to fibromyalgia are
polymyalgia rheumatica, rheumatoid arthritis, osteoarthritis and thyroid disease.
People with fibromyalgia do not necessarily have a shortened life expectancy,
although other conditions connected to it may be implicated.
LeafWell
Treating fibromyalgia can be very difficult. Sufficient sleep, healthy diet and
exercise are the most common courses of treatment. As for medications, serotonin-
norepinephrine reuptake inhibitors (SNRIs) such as duloxetine and milnacipran,
and the CNS depressant pregabalin (Lyrica). Opioids are not recommended for
fibromyalgia, and many claim that they do not necessarily work very well for the
condition.
POSITIVES NEGATIVES
• If fibromyalgia caused by a clinical • Very few studies have been done, and some
endocannabinoid deficiency (CECD),197 then show that Nabilone is not necessarily any
cannabinoids may treat the condition. Please better than placebo. Be aware though, that
remember that to date, all reports of cannabis these studies are only testing for the efficacy
treatment for fibromyalgia are anecdotal. of a synthetic form of THC. 199
• While SNRIs are well-tolerated by most people, • May potentially cause undesirable side-effects
pregabalin may have negative side-effects, such for some.
as confusion, sleepiness, troubles with memory
and vision, dry mouth, weight gain, poor motor
coordination, potential addiction, and an
increased risk of suicide. Cannabinoid-based
medications could prove to be an alternative.
TREATMENT
Anecdotally speaking, many people with
• Opioids are not well-tolerated by those with
fibromyalgia seem to prefer indica-leaning
fibromyalgia - cannabinoids may be an
varieties of cannabis. This suggests that the focus
alternative.
on THC or THC synthetics for the treatment of
• Nabilone - a synthetic form of THC - has been fibromyalgia might not be ideal, and that the
shown to be well-tolerated by those with combination of THC with other cannabinoids
fibromyalgia.198 like CBD and CBG “help” the THC do a better job,
whilst also ensuring the side-effects of THC are
not overwhelming.
VALUE OF MMJ
Cannabis may potentially be a form of pain
relief for those with fibromyalgia and could act
Average
as a replacement for pregabalin and opioids.
Cannabinoid-based medications could also help
with other conditions associated with fibromyalgia,
such as IBS and depression. but could be significant.
LeafWell
Cannabis and Glaucoma
General
Glaucoma is a group of eye diseases which result in damage to the optic nerve
and vision. Glaucoma leads to increased pressure in the eye (intraocular pressure).
Migraines, high blood pressure, prolonged steroid use, diabetes and obesity are all risk
factors for glaucoma. Though optic damage through elevated intraocular pressure is
most common form of glaucoma, another condition, normal-tension glaucoma, leads
to optic nerve damage despite a normal range of eye pressure. Gradual loss of vision,
“halos” surrounding light, headaches and optic nerve changes, as well as dilation of
pupils and hazy corneas, are the main signs of glaucoma.
Glaucoma is the second most common reason for sight loss worldwide after cataracts,
and it mainly affects older people. Approximately 67 million people worldwide suffer
the sequelae of glaucoma with 2 million people in the U.S. alone.
LeafWell
Glaucoma was one of the first conditions for which cannabis was deemed therapeutic,
based upon its ability to decrease intraocular eye pressure200 but the effect only lasts
while the active cannabinoids are circulating in the bloodstream. Currently, there
appear to be more effective and longer-lasting medications for glaucoma treatment
such as Latanoprost/Xalatan, Timolol/Timoptic. These medications, though longer
lasting have poor compliance rates and side-effects such as joint/muscle pain, flu-like
symptoms, blurred vision, depression and impotence.
Jon Hamm (aka Ganja Jon), California, 32
“ I was born blind in my left eye. It felt like I was being drilled on the side of the skull
constantly. I went to three E.R.s. The first two told me to just take an Advil. The third
finally tested the pressure in my eye. They brought out three machines because they
thought the results weren’t possible. My pressure was at 95. During all of this, I was
also on dialysis for kidney failure. I have a very rare condition called Renal Coloboma.
When I was born, there were 8 cases in the U.S, 6 of which were related to each
other. Now, it’s about 140 cases. Mine is a spontaneous genetic mutation and very
severe. So out of the 140 cases, only a third experience kidney failure like me. I started
dialysis at 16, got a transplant at 17, which lasted me 5 years. I couldn’t use marijuana
during this time because if I was caught, I’d be taken off the transplant list.
I lost my eye on my 25th birthday. I don’t remember what happened, but apparently
I tried to take it out with my thumb and then a spoon, because of all the pain from
my glaucoma. I looked in the mirror one day and said, “I will no longer be made to
feel bad for feeling good”. It was the only thing that made me feel happy. I was at the
point of having suicidal thoughts.
Eventually, me and my brother learned to make cannabis concentrates together. We

began to compete. We’ve won the Cannabis Cup through High Times, and L.A. Kush
Con. In fact, we won every contest that we entered, to the point where it wasn’t fun
anymore. I now focus on making the purest products
”
LeafWell
Cannabis may also be a neuroprotectant, meaning that it could help protect against
retinal neurotoxicity as well.201
POSITIVES NEGATIVES
• Helps lower eye pressure • Cannabis may not prove effective for all
glaucoma sufferers
• Fewer side-effects than other medications
• Smoke can cause irritation to the eye
• Can help treat the side-effects of other
medications, as well as the pain of both the • Not as long-lasting as other medications -
medications and glaucoma usually around 2 - 4 hours
• May lower retinal neurotoxicity • As cannabis may lower blood pressure overall,
blood flow to the retinas can also be reduced,
• Only small amounts of THC may be necessary - which may also damage the retinas in the
5 mg of THC temporarily reduced IOP and was long-term. Cannabinoid treatments are
well-tolerated by most patients.202 Higher doses perhaps best used as an adjunct with other
of CBD produced a transient increase of IOP. treatments when it comes to glaucoma.
• High doses of CBD may increase intraocular

VALUE OF MMJ pressure.
THC may help lower eye pressure as well as distract

from pain. CBD may help lower retinal toxicity. The TREATMENT
effect of CBD and THC on the serotonin receptors in
the body may help reduce headaches. THC may well be the ideal cannabinoid for
glaucoma, coupled with some amount of CBD in
order to temper any anxiety high amounts of THC
may cause in some. There is some suggestion
POTENTIAL VALUE OF CANNABIS that too much CBD may increase intraocular eye
BASED ON CURRENT EVIDENCE pressure, so care must be taken if using doses of
Significant
CBD greater than 20 mg.203
LeafWell
Cannabis and HIV/AIDS
General
Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome
(AIDS) wreak havoc on the body’s immune system. This means the sufferer is
more likely to develop illnesses and have difficulty fighting off infections. Effects
include cachexia (wasting syndrome, or sudden weight loss), nausea, peripheral
neuropathy and joint and muscle pain. In 2016, 36.7 million people worldwide were
living with HIV. Approximately 1.2 million people were living with HIV in the US in
2013.204
HIV is most commonly spread via unprotected sex, contaminated blood

transfusions, needle sharing, and from mother to child during pregnancy, delivery
or breastfeeding. “AIDS” is a term usually applied to late-stage HIV infection
symptoms. Initially, only flu-like symptoms display themselves for a brief period.
This is followed by a period with no symptoms, during which the virus spreads and
wreaks havoc on the immune system.
There is no known cure for HIV/AIDS, but highly active antiretroviral therapy
(HAART) slows the progression of the disease. Current medications include non-
nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside analog reverse
transcriptase inhibitors (NRTIs) such as zidovudine, tenofovir, lamivudine and
emtricitabine. Protease inhibitors (PIs), integrase inhibitors (IAs) and entry inhibitors
are used if other treatments aren’t effective.
Antiretroviral treatment is recommended for anyone who contracts HIV/AIDS,

including pregnant women. Avoiding overly high intakes of zinc, iron vitamin A is
also recommended for those with HIV/AIDS. For pregnant women diagnosed with
HIV/AIDS, multivitamin supplements improve outcomes.
Thanks to the development of antiretroviral drugs, many people with HIV/AIDS may
now live long, fruitful, normal lives. However, the medications may have significant
side-effects, some of which aren’t so different from the effects of HIV/AIDS itself,
including nausea, cachexia, muscle aches, insomnia and fatigue.
LeafWell
POSITIVES NEGATIVES
• CBD may inhibit growth of certain types of • Badly-grown cannabis may contain
herpes virus.205 pathogens that cause harm, especially to an
immunocompromised system.
• Cannabis can help stimulate the appetite
- “cachexia” and “wasting syndrome” is a • Can cause dry mouth and exacerbate this
common side-effect of both HIV/AIDS and the effect from other medications.
medications used to treat it.
• Smoking cannabis may irritate the throat and
• Battle nausea. lungs, which takes longer to recover from for
AIDS/HIV patients and increases the chance
• Improve the mood. of infection.
• Cannabis can be used as an analgesic. • How the cannabinoid receptors react to

endocannabinoids and phytocannabinoids,
• HIV/AIDS sufferers may suffer neuropathic pain,
and how they interact with the immune
for which both THC and CBD may help.
system, is not fully understood yet - there
could be positives and negatives.
VALUE OF MMJ
Cannabinoids like THC and CBD may help stimulate

TREATMENT
appetite, prevent nausea, and lessen migraines and
neuropathic pain often associated with HIV/AIDS.
High THC concentrations might help stimulate
Cannabinoids and terpenoids may be an effective
appetite, which is so often lost due to the side-
form of palliative care for those with HIV/AIDS, as the
effects of antiretroviral treatment. The high
side-effects from the other medications are often
THC and terpenoids often found in higher
overwhelming for many.
concentrations in sativas (limonene, beta-
caryophyllene, pinene) may help against fatigue
associated with HIV/AIDS and the medications
used to treat it.

Average
LeafWell
Cannabis and Huntington’s Disease (HD),

aka Huntington’s Chorea
General
Huntington’s disease (HD) is mostly an inherited neurodegenerative disorder that
results in the death of brain cells. HD is caused by an autosomal mutation of either
one or both copies of an individual’s Huntingtin gene, causing abnormalities in the
Huntingtin protein via expansion of CAG (cytosine-adenine-guanine triplets). Although
HD is usually inherited, approximately 10% of cases arise from a new mutation. HD
effects between 4 and 15 people of European descent, and its prevalence amongst
other populations seems to be rare or unknown. HD affects males and females in
roughly equal numbers. HD affects approximately 1 in every 10,000 people in the US
(approximately 30,000 people), with another 150,000 people being at risk of developing
the condition. 206
Signs of HD include a change in mood and mental abilities, fatigue, hyperexcitability,

depression and anxiety, eventually leading to involuntary, uncoordinated and “jerky”
body movements (myoclonus), hallucinations, violent outbursts and dementia as
the disease advances.207 Symptoms of HD usually arise between the ages of 30
and 50, with symptoms displayed before the age of 20 in around 8% of cases. The
initial stages of HD can present themselves very similarly to Parkinson’s disease
(PD). Life expectancy from initial diagnosis is around 15 - 20 years. HD is associated
with additional complications, such as pneumonia and heart disease, as well as an
increased rate of injury from falls. Suicide is the cause of death in around 9% of cases.
There is no proven treatment at the moment that can stop or reverse the cause of
HD. At the moment deutetrabenazine and tetrabenazine (monoamine depletors,
decreasing the amount of dopamine, serotonin and norepinephrine produced by
the brain) are used to control hyperkinetic movement, and antipsychotics are used
to control mood and hallucinations. However, long-term use of antipsychotics can
actually cause tardive dyskinesia, whilst monoamine depletors can increase the
likelihood of suicide and depression. This means that treatment for HD is very much a
“double-edged sword” at the moment.
LeafWell
POSITIVES NEGATIVES
• Sativex-like phytocannabinoid-based medicines • THC may negatively affect memory and
may act “as a neuroprotective agent capable of can increase the likelihood of developing
delaying disease progression in HD, a disorder psychotic symptoms. 213
that is currently poorly managed in the clinic,
prompting an urgent need for clinical trials with • Some clinical data on CBD use for HD shows
agents showing positive results in preclinical that it is not necessarily any more effective
studies”208. This study was done on rats. than placebo.214 [NB: this is a study from 1991,
and therapeutic doses of CBD may not have
• CBD may act as a neuroprotectant 209 and been used 700 mg may not be effective for
antipsychotic 210. Cannabigerol (CBG) may also HD), and other cannabinoids may be needed
act as a neuroprotectant. 211 in order for the CBD to be effective for HD.]
• Both PD and HD affect the basal ganglia, and • The evidence for cannabinoids’ efficacy for HD
“cannabinoids like Δ(9) -tetrahydrocannabinol is mixed at best.215
or cannabidiol protect nigral or striatal neurons
in experimental models of both disorders, in
which oxidative injury is a prominent cytotoxic VALUE OF MMJ
mechanism. This effect could be exerted, at
least in part, through mechanisms independent There may be some value in using cannabinoid-
of CB(1) and CB(2) receptors and involving the based medications for HD. To what extent, however,
control of endogenous antioxidant defences. is not known, and what evidence there is shows
On the other hand, the activation of CB(2) mixed results. There does seem to be some evidence
receptors leads to a slower progression of that Sativex/Sativex-like medications (a 1:1 CBD:THC
neurodegeneration in both disorders. This ratio) and nabilone are well-tolerated by some.
effect would be exerted by limiting the toxicity
of microglial cells for neurons and, in particular,
by reducing the generation of proinflammatory
factors … [T]he evidence reported so far
supports that those cannabinoids having
TREATMENT
antioxidant properties and/or capability
Unknown, although there may potentially be
to activate CB(2) receptors may represent
some value in a 1:1 CBD:THC ratio.
promising therapeutic agents in HD and PD,
thus deserving a prompt clinical evaluation.” 212

Little evidence
so far
LeafWell
Cannabis and Inflammatory Bowel Diseases

(IBDs) - Irritable Bowel Syndrome (IBS),
Crohn’s, Ulcerative Colitis etc.
General
Though there are key differences between different IBDs, there is one constant across
them all: inflammation. Although IBS isn’t always associated with inflammation and
its symptoms don’t necessarily have an identifiable cause, inflammation is often either
the main cause or side-effect. Other symptoms include abdominal pain, fatigue, an
unwillingness to eat, vitamin D and vitamin B12 deficiency, constipation and/or urgent
and more-than-normal bowel movements (diarrhea).
Crohn’s and colitis also tend to include rectal bleeding, which in turn increases fatigue.
There is no known cure or treatment for IBDs, and in the worst cases of Crohn’s,
surgery may be needed to remove the most severely inflamed parts. Sadly, surgery
is not always effective, and can lead to further complications later on. It is estimated
that approximately 14.1% of people in the US suffer from IBS, and many more are
undiagnosed.216
There are different several medications used to treat IBDs. The type of medication
depends very much on the type of IBD the patient suffers from. Loperamide, an
opioid-receptor agonist (though not a hugely addictive one), is commonly used
and prescribed for IBS, gastroenteritis and short bowel syndrome. However, it is not
recommended for cases where there’s blood in the stool/bloody diarrhea, ulcerative
colitis or bacterial enterocolitis. Loperamide may also cause abdominal cramps,
vomiting, sleepiness and dry mouth, as well as increase the risk of toxic megacolon.
Other medications and treatments include anticholinergics and antispasmodics

that are used for smooth muscle contraction (e.g. dicyclomine/Bentyl, hyoscyamine/
Levsin), antibiotics (e.g. rifaximin/Xifaxan), exercise, changes in diet, avoiding excessive
alcohol intake and even stool transplant (fecal microbiota transplant - transplanting
fecal bacteria from a healthy individual to someone suffering from an IBD)! Some of
these medications have side-effects such as dizziness, sleepiness, triggering glaucoma,
abdominal cramps, vision changes and the possibility of a severe allergic reaction.
LeafWell
IBDs are often classed under autoimmune diseases, as it involves the body’s immune
system attacking elements of its own digestive system (although IBS is a functional
bowel disorder, not an autoimmune disorder). There are thought to be several main
causes of IBDs, including reduced biodiversity of intestinal gut microbiota, intestinal
permeability, which is further exacerbated by the fact that there are fewer intestinal
microbiota, inducing an uncontrolled immune responses and potentially some
genetic causes, which are not properly understood. Due to the broad range of IBDs
out there, there are some types of IBD that have more treatment methods available to
them, and there are other types that are very difficult to treat.
Endocannabinoids play an important role in the functioning of the gut,217 including the
control of intestinal inflammation. Stress and anxiety also may trigger IBS attacks in
some instances, and it is not surprising that a “flare-up” of an irritable bowel condition
is going to cause anxiety in many. Some even suggesting that phytocannabinoids can
help overcome a “cannabinoid deficiency” - a condition that could help explain why
cannabis can help overcome IBS, fibromyalgia, migraine and other treatment-resistant
conditions. One of the advantages of utilizing cannabinoids for IBDs is that, unlike
many other medications, they may be tolerated by many regardless of which IBD they
suffer from.
There are a huge number of cannabinoid receptors in the gut and, though the
evidence is anecdotal at the moment,218 it does not seem surprising that cannabis
could be particularly helpful in managing IBDs.219 THC and CBD also seem to be
metabolized by liver enzymes and throughout the digestive system, and cannabinoids
represent an excellent prospect for treatment of IBDs.
LeafWell
Coltyn Turner
“ I was diagnosed with Crohn’s Disease when I was 11-years-old. Crohn’s is more than
just a bathroom disease, and it wasn’t easy. There were times I had to be home-
schooled, sitting on the toilet. When I went to the doctors for surgery to take out a
swollen lymphnode, they accidently took out one of my salivary glands. So now I can
only produce saliva in half of my mouth, which is not good for someone who already
has digestive issues.

After numerous medications, doctor prescribed me Remicade. It caused me to
develop Rheumatoid Arthritis, Drug-induced Lupus, and serum sickness. My
doctors wanted to continue giving me drugs, but I knew they were killing me. After
researching alternative methods, my family and I came across cannabis. We were
willing to get it at any cost. So me and my dad packed up and left our family, in order
to go to Colorado and illegally acquire cannabis. That was the day I decided that I
would rather be illegally alive than legally dead.

We learned how to make edibles quickly and with very little cannabis. In the hotel
room, my dad would take the little crock pot that we have, set it on the roof of
the pool, and lean outside the room to make the brownies. I would stay inside the
hotel room, and pack towels along the door hinges, as well as spraying Febreze
everywhere.
I recently passed my 1000th day in remission from Crohn’s. I was able to get out of
my wheelchair and hike 5 miles up a mountain. I now speak all over the nation to
educate people about treating Crohn’s with cannabis.
”
LeafWell
POSITIVES NEGATIVES
• May prevent colitis. 220
• Smoking cannabis may increase the need to
use the bathroom in some.
• Helps control inflammation.
• May increase nausea and decrease appetite
• Stimulates appetite. in some people after long-term use
(cannabinoid hyperemesis syndrome).
• Could “reduce the increase of intestinal motility
induced by inflammatory stimuli”.221 • No proper evidence of this as of yet, but
cannabinoids may inflame the pancreas
(pancreatitis).
VALUE OF MMJ
There are few treatment options available for IBDs

TREATMENT
(especially Crohn’s), and most are not guaranteed
to be completely effective, although they do
Both THC and CBD have significant anti-
help. A high protein diet, avoiding caffeinated
inflammatory purposes. Pinene and humulene
beverages and eating nuts, beans seeds and kernels,
are also powerful anti-inflammatories. Sativas,
exercise, loperamide hydrochloride, steroids and,
indicas and hybrids of many types could be of
in some instances, immunosuppressants such as
use for those with IBDs when immediate relief is
azathioprine are most often recommended. There is
needed, whilst tinctures could be useful for longer
mixed evidence of the efficacy of probiotic yogurts.
term relief. Suppositories may also be useful for
In some cases, surgery may be required, and sadly a
inflammation associated with IBDs as well.
temporary or permanent colostomy bag may need
to be used.
As cannabinoids have anti-inflammatory properties,

and there are a significant amount of cannabinoid
receptors in the gastrointestinal system, medical
marijuana may well be a highly effective treatment
method for all kinds of IBDs. The invasive treatment BASED ON CURRENT EVIDENCE
Significant
of removing extremely inflamed parts of the
bowel for Crohn’s is arguably self-defeating, as an
endocannabinoid deficiency does not necessarily go
away by cutting away the bowels!
LeafWell
Cannabis and Insomnia
General
Insomnia is a persistent inability or difficulty in getting to sleep. Insomnia can occur as
a condition on its own, but is often associated with other conditions such as chronic
pain, depression and anxiety. Approximately 30% of the population of the US suffers
from some form of sleep disturbance, with 10% having symptoms associated with
insomnia, namely that of an impairment of daytime function. Insomnia may also lead
to a weakened immune system, which increases the likelihood of contracting other
illnesses.
There are three main types of insomnia: transient insomnia, which is insomnia that
lasts less than a week; acute insomnia, aka short-term insomnia, which lasts less than a
month; and chronic insomnia, which is insomnia that lasts longer than a month. Those
with high levels of stress hormones and drastic shifts in the body’s level of cytokines
(small proteins important for cell signalling) are more likely to suffer from insomnia.
LeafWell
Amanda Mendes
“ My cannabis use started with trying to treat my awful insomnia. It was unreal how
bad it was. Over the past 10 years, I was double and even triple dosing over-the-
counter medication, like Diphenhydramine. It called for 25mg, but I had to use
100mg just to feel anything - and that would put most people down for a week. I just
naturally have a high tolerance to medication, such as anesthesia. When I was 7, I
woke up during a tonsil surgery for that very reason.
I had no energy to workout, so I started gaining weight. You need energy when
you’re the mother of two kids under the age of 3. I couldn’t continue taking
prescription drugs and then going into a coma when my husband works nights,
because who would take care of my kids? I decided after I was done breastfeeding, I
would try cannabis and live a healthier lifestyle. My brother is an advocate, and uses
it for his anxiety. I also have a friend who started using it after breaking her back. So,
despite the negative stigma that made me feel nervous trying it for the first time, I
knew it was safe.
I started with vaping and I mean… it worked right away. The very first night, I slept
amazingly. It was the most I had slept in a VERY long time. I also began to get
more energy from the sleep! I joined a powerlifting gym, and now I am a female
powerlifter! I’ve lost a total of 30 lbs over the past 6 months. The cannabis even
helps me work out, by getting rid of soreness and pain. I don’t have to take any
supplements to help me recover. I just keep my vape pen on my nightstand. At
night, when I’m watching TV, I smoke my vape and drift off into lala land. I eat 20mg
chocolates, and smoke a Bumblebee vape. The whole thing is disposable. I’m using
the Cherry Cola strain, which is a pretty hard-hitting indica. So between the vape and
the edible, it’s a perfect combination for me at night.
Thanks to cannabis, I’m not only able to sleep, but I’m also able to wake up and be a
mom.
”
LeafWell
Alcohol/opioid/sedative withdrawal, amphetamine use, use of high amounts of

caffeine, irregular heart rhythms, the after-effects of surgery, hyperthyroidism and
many other conditions may cause insomnia. Exercise-induced insomnia is also
common in many athletes. Those who have disturbed sleep have elevated nighttime
levels of cortisol and adrenocorticotropic hormone, as well as elevated metabolic rate.
Erratic sleeping patterns may also cause insomnia.
POSITIVES NEGATIVES
• Safer and less addictive than benzodiazepine- • Certain cannabinoid and terpenoid profiles
and barbiturate- based medications. may promote wakefulness rather than
sleepiness.
• Can potentially help treat any other health
problems associated with insomnia. • Care must be taken not to use the wrong
cannabinoid-terpenoid profile which may
• A variety of terpenoid and cannabinoid profiles cause anxiety in some people.
may be trialled to see how effective they are.222
• Results are mixed.223
VALUE OF MMJ
TREATMENT
Ideal treatment methods for insomnia include
physical exercise, healthy eating, herbal medications Indicas are often the go-to cannabis variety of choice
such as chamomile and lemon balm, and for insomniacs. Terpenes like myrcene, the myrcene-
establishing a regular sleeping pattern. For older related ocimene, linalool and pinene seem to be
people or those with specific medical conditions most effective for insomnia, as can small amounts
such as circadian rhythm disorder, melatonin may of limonene. Myrcene, ocimene, and pinene are
be prescribed. For those with more extreme and found in many herbal sleep medications, and can
chronic forms of insomnia, benzodiazepines and help regulate circadian rhythms that are controlled
barbiturates may be prescribed. Cannabis could well by the central nervous system (CNS) and gamma-
prove to be a less lethal alternative. aminobutyric acid (GABA) receptors. Limonene may
also regulate 5-HT neuronal function and dopamine
release. CBD may modulate GABA levels. In small
POTENTIAL VALUE OF CANNABIS amounts, CBD seems to promote wakefulness,
BASED ON CURRENT EVIDENCE whilst larger amounts may prove relaxing, but not
necessarily “sleepy”. THC can have excitatory effects
Significant
initially, followed by “sleepy” effects as the effects
go on. Terpenes like myrcene and linalool may also
affect the way THC and CBD behave, influencing
them to have “relaxing” rather than “energetic”
effects.
LeafWell
Cannabis and Kidney Disease

/Kidney Failure
General
There are various diseases and conditions that can cause kidney disease/failure,
including diabetes, high blood pressure, interstitial nephritis (inflammation of the
kidney’s tubules and surrounding structures), glomerulonephritis (inflammation of the
glomeruli - the kidney’s filtering units), polycystic kidney disease, an infection of the
kidneys or repeated infection of the kidneys (pyelonephritis), obstruction of the urinary
tract (such as that caused by kidney stones) and vesicoureteral (a condition that causes
urine to back up into the kidneys). Kidney failure can also be potentially caused by
other treatment methods, such as chemotherapy.224 There are often few or no warning
signs of kidney failure in its early stages. In the more advanced stages, signs include
tiredness, swollen ankles, feet and/or hands, shortness of breath and blood in the urine. 225
The overall prevalence of chronic kidney disease (CKD) in the population of the US is
14%. More than 661,000 Americans have kidney failure, with 468,000 receiving dialysis
and 193,000 people living with a functioning kidney transplant.226 Those of Native
American, Asian-American or African-American descent are at greater risk of CKD.
There are many complications associated with kidney disease, including an increased
risk of diabetes, heart disease, fluid retention (leading to high blood pressure, swelling
of the arms and legs and fluid in the lungs aka pulmonary edema), damages to the
central nervous system (CNS), decreased bone strength, immune response and sex
drive, and potentially sudden rises in potassium levels in the blood (hyperkalemia).
The most common medications for kidney disease include water tablets (diuretics),
antihypertensives (blood pressure tablets), statins (blood cholesterol tablets), sodium
bicarbonate (salt tablets), vitamin D supplements, steroids, iron supplements and
phosphate binders. In cases of kidney transplants, anti-rejection tablets must also
be taken, and those in need of dialysis are advised to have a hepatitis B vaccination.
Whether cannabinoid-based medications can act as a replacement or adjunct for one
or more of these medications is not known, but there could be some potential uses.
LeafWell
POSITIVES NEGATIVES
• Cisplatin - a compound used in chemotherapy • If renal transplant has taken place and
- is nephrotoxic. CBD may attenuate cisplatin- the patient is taking anti-rejection tablets,
induced toxicity and decrease oxidative stress, cannabinoids may interfere with their
inflammation and cell death.227 mechanism. This is the same with statins,
antiretrovirals and many other medications
• Cannabinoids may be used to control blood that are absorbed via the cytochrome P450
pressure.228 and cytochrome P3A pathways.231 However,
cannabinoids may also potentially be used to
• CBD may be used to reduce blood pressure.229
reduce the need for immunosuppressants.
• Cannabinoid receptors may be a promising
• Very few studies on the efficacy of
target in the the treatment of renal diseases,
cannabinoids for kidney diseases.
particularly diabetes.230
• NSAIDs like ibuprofen can damage the kidneys,

and those with kidney damage cannot take
them for pain. Cannabinoids may potentially be TREATMENT
an alternative for chronic pain associated with
kidney damage. Unknown at this time, although there may be some
value in CBD for some types of kidney damage or
disease due to its anti-inflammatory purposes.
VALUE OF MMJ
There may be some use in CBD. This also depends POTENTIAL VALUE OF CANNABIS
very much on the kidney disease being suffered
from. Where CBD and cannabis may potentially
Little
help beat the pain of kidney stones232 and diabetes,
it may not be so great for those with other types of
evidence
kidney disease.
so far
LeafWell
Cannabis and Migraine/Headache
General
Headaches and migraines cost the United States approximately $13 to $17 billion per
year, with more than 37 million people (13%) of the US suffering from migraines at any
one time. Around 2 - 3 million migraine sufferers are chronic.233 There is no known cause
of headache and migraine, although it is a common feature of many other ailments.
Pain, depression, diet, other medications, hormonal changes, stress, illnesses such
as cold and flu, and environmental factors (e.g. a lack of oxygen in the air) may cause
headaches and migraines. Headaches and migraines may be the result of abnormal
brain activity resulting in the nerves, blood vessels and chemicals in the brain being
affected.
As the causes of headaches/migraines are unknown, treatment for migraines, especially

long-lasting, persistent ones, is unsatisfactory because they do not consistently respond
to standard pain relievers. Migraines in particular are difficult to treat, and the usual
course of ibuprofen or paracetamol (acetaminophen) may not work. Cannabis may
prove to be an effective migraine-killer without the need to use opioids and other
potentially addictive and/or dangerous non-steroidal anti-inflammatory drugs (NSAIDs).
The mechanism behind the relief from migraines cannabis provides is unknown, but
it could be because of an endocannabinoid deficiency and an abnormal inflammatory
response.234 Cannabis may also dilate blood vessels, allowing more oxygen to circulate
around the brain. Currently, a class of drugs known as “triptans” are used as they work
by blocking proinflammatory compounds in the brain. However, triptans are expensive,
have lots of side-effects such as nausea and vomiting, and insurance companies often
limit the amount of triptans that can be dispensed to patients.
LeafWell
POSITIVES NEGATIVES
• Safer and cheaper than many drugs used to • “Rebound headaches” may occur after
treat migraines. cessation of cannabis use.
• Cannabinoids may bind to areas of the brain • Some report an initial increase in the migraine
that modulates pain transmission, which can pain, followed by a decrease.
cause migraines.
• Smoking may induce headaches in some.
• THC may reduce serotonin release, which blocks
vomiting and pain in migraine sufferers.235 • Cannabis may not be useful for cluster
headaches (or it might be effective for some
people and not for others)236 - there may
be more effective things to use for cluster
VALUE OF MMJ headaches due to their ability to “unlock”
serotonin, but please do not take this as
Anecdotally, indicas are the go-to choice for advice! 237
migraine & headache sufferers. However, as there
are many conditions that can cause headaches,
from stress to chemotherapy side-effects, the TREATMENT
choice of strain could just be a matter of personal
preference. Many people are likely to think Though many NSAIDs are generally safe, taking too
“headaches = pain = indica is best”, but this could many can cause liver and kidney failure. Some, like
well be a case of confirmation bias as opposed to naproxen, carry with them a high risk of stomach
fact. ulceration. In extreme cases, opioids may be used,
but their use is not recommended in the treatment
of headaches and migraines in anything but the
most extreme cases. Triptans (serotonin receptor
agonists) such as sumatriptan (Imitrex), zolmitriptan
(Zomig) and eletriptan (Relpax) are another class of
drug that may be used in migraine and headache
BASED ON CURRENT EVIDENCE treatment. The precise way in which triptans’
Average antimigraine abilities work is not precisely known,

but it is suspected that it is to do with serotonin
uptake. This is one of the main reasons why
although could be significant depending cannabinoids may be of particular use for insomnia.
upon the source of the headache.
LeafWell
Cannabis and Myalgic Encephalomyelitis

(ME) / Chronic Fatigue Syndrome (CFS)
General
Much like how cannabis functions as a medicine is a mystery, so too are the causes
of ME/CFS. Medical experts have proposed biological, genetic, infectious and
psychological causes, but no definite mechanism has been implicated as of yet.
There is an estimated rate of between 7 and 3,000 ME/CFS sufferers in a population of
100,000. Between 836,000 and 2.5 million people in the US suffer from ME/CFS.238
ME/CFS Symptoms include chronic fatigue, impaired memory and concentration,

muscle pain (myalgia), headaches, sore throat, sensitivity to food & light, extreme
malaise, IBS-like symptoms, night chills and sweats and tender lymph nodes. These
symptoms usually last over an elongated period of time - 6 months or more. Onset
is usually gradual, although critical life events and consistent physical stressors may
exacerbate the likelihood of ME/CFS developing. Rest alone does not solve ME/CFS,
although regular sleep patterns may help prevent irritability, depression and the
development of other illnesses.
Treatment for ME/CFS include activity management, exercise, a managed, healthy

diet, antibiotics, analgesics, antiviral drugs, anxiolytics, antidepressants, analgesics,
hormones such as hydrocortisone, and cognitive behavioral therapy (CBT).
Although there is not a known cause of ME/CFS, sufferers seem to have an

inflammation of the dura and meninges that surround the spinal cord and brain.239
There are no major empirical studies or clinical trials looking at the ability of cannabis
to ameliorate ME/CFS symptoms, but subjective reports from patients so far report
positive experiences.240
There is some tentative evidence that ME/CFS is related to other conditions such as
IBS, fibromyalgia and interstitial cystitis due to potential autonomic nervous system
(ANS) dysfunction. Immunological and endocrine abnormalities have been observed
in some people with ME/CFS.
LeafWell
POSITIVES NEGATIVES
• Patients can enjoy a refreshing sleep, • The mechanism of how ME/CFS is developed
sometimes without night sweats and chills. isn’t known as of yet, and neither is cannabis’s
efficacy for the condition, making it difficult to
• Relief from joint and muscle pain. say for sure that cannabis will help.
• Improved emotional state. • Picking the right strain is important - sativas

are said to be better than indicas for ME/CFS,
• Stress and depression relief.
but it is important to pick a strain that won’t
• CBD may be neuroprotective, lessening brain & leave you more fatigued or feeling “brain fog”.
spinal cord inflammation
• Cannabinoids could be used for recalcitrant TREATMENT

conditions such as fibromyalgia, IBS, ME/CFS
and interstitial cystitis, all of which may be due Some patient reports suggest that sativas are the
at least in part to autonomic nervous system cannabis variety of choice for those with CFS. This
(ANS) dysfunction?241 is not surprising - those who are fatigued are more
likely to go for strains high in THC, THCV, limonene,
pinene and beta-caryophyllene for their more initial
VALUE OF MMJ “energizing” effects, although CBD mixed with
limonene and beta-caryophyllene may be better
As ME/CFS could well be related to other for daytime use due to the more sleepy effects
treatment-resistant conditions such as irritable induced by THC over time. Of course, how these
bowel syndrome (IBS), migraine, fibromyalgia and cannabinoids and terpenoids interact with each
interstitial cystitis, it may well be a condition that other and how they act in the body (and at what
arises from a clinical endocannabinoid deficiency doses) is not know yet, so take this as more theory
(CECD) and/or autonomic nervous system (ANS) than advice.
dysfunction. This means that there may be some
link between the gastrointestinal system, the ANS,
the immune system and the endocannabinoid
system. Anxiety also seems to have an effect on POTENTIAL VALUE OF CANNABIS
these conditions. Cannabis may also be preferable BASED ON CURRENT EVIDENCE
Average
to certain analgesics, and may well help mitigate the
side-effects of powerful antibiotics.
LeafWell
Cannabis and Multiple Sclerosis (MS)
General
MS is a demyelinating disease. The myelin sheath protects and nerve cells are
damaged, impairing the conduction of signals across nerve cells similar to way you
would see rubber coating around a copper wire. The cause of MS is not fully known,
but it could have something to do with the destruction of the immune system, the
body failing to produce myelin cells, genetics, viruses and environmental factors.
Symptoms of MS includes vision problems (occasionally even blindness), fatigue,

numbness, tingling, muscle spasms, mobility problems, confusion and problems with
thinking & planning, depression, anxiety and pain. Symptoms can build over time in
a progressive manner as well as take the form of recurring, isolated attacks. MS is the
most common autoimmune disorder affecting the central nervous system (CNS).
Approximately 2.5 million people worldwide suffer from MS, and of those diagnosed
with MS, the US makes up around 400,000 of them. Rates of MS are higher farther
from the equator. According to Healthline, 200 new cases of MS arise in the US each
week. Onset is usually between 20 and 40 years of age, but can arise at any age from
10 years old to 80 years old, with a mean of 32 years old.
Though there is quite a bit of empirical and anecdotal research showing that CBD
can prove to be helpful for MS 243, it is THC that has proven usefulness in battling MS,
as it helps manage spasticity.244 There is already a medication in the UK developed
for MS using THC, named Sativex. Sativex may also be of use for the neuropathic pain
associated with MS. Sativex is produced by GW Pharmaceuticals. 245 246 247
LeafWell
POSITIVES NEGATIVES
• TTHC helps manage muscle spasms and • Though THC may help control muscle
stiffness. spasms, it may also cause confusion and other
deleterious effects. This is why 1:1 THC:CBD
• Prevents swelling of the brain and optic nerve. ratios are considered most therapeutic for MS
• CBD may be neuroprotective, and may even • Side-effects may be overwhelming for some
counteract MS’s development thanks to the fact
that it may prevent brain inflammation.248
• Help manage the pain of MS, as well as the TREATMENT

side-effects of other medications, often causing
nausea, fatigue and weight problems. GW Pharma’s Sativex is based on a 1:1 THC:CBD ratio.
Overall, it seems most people with MS go CBD-
• Cannabis may promote neurogenesis - the
hunting to an extent, although THC definitely has its
growth of new brain cells.
place. From anecdotal reports, indicas seem to be
the main type of cannabis chosen by MS sufferers.
VALUE OF MMJ
THC may help manage muscle spasms and

stiffness, and CBD may be neuroprotective and
counteract the development of MS in the first
instance. Cannabis can also potentially be used to POTENTIAL VALUE OF CANNABIS
manage neuropathic pain. BASED ON CURRENT EVIDENCE
Significant
LeafWell
Cannabis and Liver Diseases
General
There are more than 100 types of liver disease, and they can be caused by any number
of conditions and problems. Some liver diseases include cirrhosis, autoimmune
hepatitis, hepatitis B and C, hepatotoxicity, Wilson’s disease and fatty liver. The liver
is an immensely important organ, helping fight infections and illnesses, removing
toxins and poisons (e.g. alcohol) from the body, controlling cholesterol levels, clotting
(thicken) blood and breaking down fats and aiding digestion by releasing bile.
Liver disease is a “silent killer”; signs are not obvious until the disease is fairly advanced
and the liver is damaged. Symptoms include a lack of appetite, weight loss and
jaundice. According to the Center for Disease Control and Prevention (CDC), there are
3.9 million adults in the US with diagnosed chronic liver disease and cirrhosis (2015)
which led to 38,170 deaths (2014).249
During chronic liver diseases, the endocannabinoid system (ECS) is highly up-
regulated.250 The ECS also “influences the mechanisms responsible for cell damage
and inflammatory response during acute liver injury”. Targeting CB1 and CB2 receptors
may prevent fat accumulation, slow the progress of fibrosis and help attenuate any
major cardiovascular alterations associated with late-stage liver disease. 251 252
LeafWell
POSITIVES NEGATIVES
• CBD may help improve brain and liver • Ideal not to mix cannabis with alcohol, for
function.253 those with alcoholism (though cannabis may
help treat alcohol addiction)
• May help ameliorate cognitive and motor
impairments in those with bile duct ligation. 254 • Mixing cannabis with tobacco - the tobacco
may cause some liver damage
• CBD may help protect against hepatic
ischemia/reperfusion injury. 255 • Liver transplants may be necessary, and it
is not known precisely how cannabinoids
• Several terpenes in cannabis act as antioxidants interact with immunosuppressants
(e.g. caryophyllene, terpineol)
• May help in the treatment of viral hepatitis,

which can cause liver damage (mechanic
TREATMENT
icter).256
CBD and limonene may well help those with liver
• Can prevent nausea and vomiting. disease, and THC could possibly be a replacement
for alcohol. Beta-caryophyllene may also have
addiction-beating properties.
VALUE OF MMJ
Medical marijuana could potentially be used to

substitute alcohol for those who have liver disease
due to alcoholism. This could be seen as a form
of harm reduction. As for the benefits of using
cannabis for liver disease, CBD may help protect POTENTIAL VALUE OF CANNABIS
against liver damage, such as hepatic ischemia/ BASED ON CURRENT EVIDENCE
Average
reperfusion injury. CBD may also help inhibit
replication of the hepatitis C virus (HCV). There are
also terpenoids such as limonene that may help
fight liver cancer.257
LeafWell
Cannabis and Nausea Mitigation
General
Nausea is a sensation of unease in the stomach, with an involuntary urge to vomit.
In some, it may precede vomiting, but many may feel nauseous without vomiting.
Nausea is a common aspect of many conditions and illnesses, as well as medications
and treatments, e.g. chemotherapy, antibiotics, colds and flus, narcotic pain
medications. Common causes of nausea include low blood sugar, gastroenteritis
(stomach infection), food poisoning, morning sickness in the first trimester of
pregnancy, migraine, motion sickness, dizziness and fainting.
Anxiety, depression and disgust (e.g. seeing or smelling something particularly nasty)
may also cause nausea. There is also a rare condition known as “cyclic vomiting
syndrome” (CVS), which may cause sudden, repeated attacks of nausea and vomiting.
There are a huge number of conditions, both on and off this list, that cause nausea.
Persistent nausea and vomiting can lead to a dramatically reduced quality of life,
cause dehydration, a loss of appetite, weight loss and fatigue. Medications used to
prevent and treat nausea are called antiemetics. The most commonly prescribed
antiemetics include promethazine (a strong sedative with weak psychoactive effects),
metoclopramide (Primperan, Reglan) and ondansetron (Zofran).
LeafWell
There are four pathways that trigger nausea. Antiemetics tend to work by affecting the
receptors and transmitters that trigger or stimulate these pathways.258
1 Central nervous system (CNS): Stimuli can affect areas of the CNS including the
cerebral cortex and the limbic system. These areas are activated by elevated
intracranial pressure, irritation of the meninges (i.e. blood or infection), and
extreme emotional triggers such as anxiety.
2 Chemoreceptor trigger zone (CTZ): Located in the area postrema in the floor of
the fourth ventricle within the brain. This area is outside the blood brain barrier,
and so it is readily exposed to substances circulating through the blood and
cerebrospinal fluid. Common triggers include metabolic abnormalities, toxins,
and medications. Activation is mediated by dopamine (D2) receptors, serotonin
(5HT3) receptors, and neurokinin receptors (NK1). TRPV1 (vanilloid) receptors may
also play a role in nausea.
3 Vestibular system: Activated by disturbances to the vestibular apparatus in the

inner ear. These include movements that cause motion sickness and dizziness.
Histamine (H1) receptors and acetylcholine (ACh) receptors trigger this pathway.
4 Peripheral Pathways: These pathways are triggered via chemoreceptors and

mechanoreceptors in the gastrointestinal tract, as well as other organs such
as the heart and kidneys. Common activators of these pathways include toxins
present in the gastrointestinal lumen, and distension of the gastrointestinal
lumen from blockage or dysmotility of the bowels. Signals from these pathways
travel via multiple neural tracts including the vagus, glossopharyngeal,
splanchnic, and sympathetic nerves.
Signals from any of these pathways travel up through to the brainstem, activate several
structures within the brain, including the nucleus of the solitary tract, the dorsal motor
nucleus of the vagus, and central pattern generator.
LeafWell
POSITIVES NEGATIVES
• Many commonly prescribed antiemetics have • Cannabinoids work on receptors in very
quite a few side-effects, some of which can feel unusual ways that aren’t properly understood
as bad as the nausea itself. Side effects from yet. This means they can be receptor agonists,
such medications can include fatigue, diarrhea, antagonists, partial agonist and inverse
depression, tardive dyskinesia, headache, agonists, and this can change depending
itchiness, irritability and, in rare cases, seizures upon interaction with other cannabinoids and
and neuroleptic malignant syndrome. terpenoids, as well as dosage. This means that
Cannabinoids such as THC and CBD, which cannabinoids may induce nausea as well as
also work on the dopamine, serotonin and combat it. High doses of CBG, for example,
vanilloid receptors, may prove to be powerful may induce vomiting as it is an inverse
antiemetics. agonist of the CB1 receptor.
• Cannabinoids may well work for rare conditions • In some people, persistent, regular, long-term
such as CVS. use of cannabinoids may cause cannabinoid
hyperemesis syndrome (CHS), and ultimately
• Cannabinoids may also work for depression cause nausea and vomiting.
and anxiety, which can make nausea worse,
or contribute to its development in the first
instance.
TREATMENT
• High, psychoactive doses of THC are not CBD may help to an extent, but it seems that THC
necessarily needed for nausea mitigation, and is the main antiemetic, and other terpenes more
the less psychoactive delta-8 THC may be useful commonly found in indicas such as linalool and
as well. 259 myrcene could be more sought-after for their
sedative and analgesic effects. However, acidic
• A moderate dose of CBDA has significant cannabinoids such as CBDA may have more
antiemetic properties - perhaps significantly powerful antiemetic effects than THC, and will
more than CBD or THC, and will work likely work synergistically with THC and/or CBD to
synergistically with these cannabinoids. 260 261 produce a greater antiemetic effect. Delta-8 THC,
which is less psychoactive than delta-9 THC, may
also be a potential antiemetic.
VALUE OF MMJ
Cannabinoids such as THC, CBN, CBDV, CBDA and

CBD represent a novel therapeutic medication for
mitigating nausea. Furthermore, they may do so
with fewer side-effects than other medications. A
combination of these cannabinoids may well help POTENTIAL VALUE OF CANNABIS
prevent nausea, and only low doses of THC may BASED ON CURRENT EVIDENCE
Significant
be needed to prevent nausea. This means that
psychoactive thresholds need not be reached for
mitigating nausea.
LeafWell
Cannabis and Peripheral Neuropathy (PN)
General
Peripheral neuropathy (PN) is a result of damaged peripheral nerves that do not
transmit information from the brain and spinal cord (central nervous system, CNS)
properly. Peripheral neuropathy often causes pain, weakness cramps, twitches, muscle
loss, bone degeneration, dizziness, tingling, pins-and-needles, and numbness, usually
in the hands and feet, but other parts of the body can be affected too. Traumatic
injuries, vitamin deficiencies, infections, genetics/inherited causes, metabolic problems
and exposure to toxins can cause peripheral neuropathy. One of the most common
causes of peripheral neuropathy is diabetes.
Sometimes, antibiotics such as metronidazole and those belonging to the

fluoroquinolone class (e.g. ciprofloxacin, levaquin, avelox) may also cause PN.
Sometimes, there is no known cause of PN (“idiopathic”). Occasionally, neuropathy
can affect just one nerve, where it is called “mononeuropathy”. Neuropathy
that affects the same areas on both sides of the body is known as “symmetrical
polyneuropathy” or “polyneuropathy”, whilst neuropathy affecting two or more
disparate nerves on different parts of the body is called “mononeuritis multiplex”,
“multifocal mononeuropathy” or “multifocal neuropathy”. “Neuritis” is the term
for the inflammation of a nerve or the peripheral nervous system (PNS) in general.
Neuropathy is often chronic, and can affect the motor nerves that control muscles,
sensory nerves or autonomic nerves which control heart rate, body temperature and
breathing.
Approximately 20 million people in the United States suffer from some sort of
neuropathic pain, and approximately 3-4.5% of the global population suffer from
neuropathic pain.262 The causes of this neuropathic pain are diverse, and so they must
be treated differently. For neuropathic pain associated with diabetes, controlling
one’s blood-sugar levels can alter the course of neuropathy. For those with vitamin
deficiencies, a course of high vitamin supplements is given and a vitamin-rich diet is
recommended. For neuropathy arising from autoimmune disorders, immunoglobulin
therapy (replenishing the body’s antibodies) and steroids.
LeafWell
Common medication used for neuropathic pain include antidepressants, especially

tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors (SNRIs)
such as duloxetine. Antiepileptic medications such as gabapentin, pregabalin and
sodium valproate are used. Capsaicin cream may also be used to beat nerve pain.
Strong and weak opioids are also often used.263 Transcutaneous electrical nerve
stimulation therapy may also be useful for people with diabetic neuropathy.
POSITIVES NEGATIVES
• Neuropathic pain may have something to • Although ‘high-quality evidence’ exists
do with the vanilloid receptor (TRPV1, the touting cannabis’s efficacy for neuropathic
capsaicin receptor) and the ability for the body pain, empirical proof is lacking.265
to keep a consistent internal temperature. CBD
desensitizes this receptor.264 • Many of the pain killing or distracting qualities
may be due to specific cannabinoid-terpenoid
• Many antibiotics and antiepileptic medications profiles - the wrong one may increase the
have negative side-effects, including organ sensation of pain.
damage, constipation/diarrhea, headaches,
dizziness and fatigue. Cannabis could prove to
be an alternative. The evolution of superbugs
may also be caused by overprescription of
antibiotics - another area where cannabis could TREATMENT
be helpful.
CBD seems particularly sought out for those with
• Opioids don’t seem to be effective for neuropathy, so it is no surprise that many look
neuropathic pain, and the jury’s out on the towards indica strains. Again, this is anecdotal, so
efficacy of NSAIDs for neuropathic pain as well. personal preferences may differ significantly. Low
Cannabis may well be an answer. amounts of THC may be sufficient for neuropathic
pain.266
• CBD may help induce bone growth.
• THCA may be particularly useful for nerve pain.

The entourage effect of THC, CBD, CBDV, CBG may
prove useful for neuropathic pain.
Significant
LeafWell
Cannabis and Parkinson’s Disease (PD)
General
Parkinson’s Disease (PD) is a particularly nasty progressive condition - one that damages
the brain over a period of many years. Symptoms include involuntary shaking of body
parts (tremors), slow movement, stiff and inflexible muscles, balance issues, sleeping
problems, memory problems and a loss of smell (anosmia). Parkinson’s disease is the
second most common age-related neurodegenerative disorder, after Alzheimer’s
disease. Men are 1.5 times more likely to suffer from PD.
Parkinson’s Disease is caused by a loss of nerve cells in the part of the brain called
substantia nigra, which leads to a reduction of dopamine production in the brain.
Dopamine plays a vital role in regulating the movement of the body, which is why the
dopamine precursor levodopa (L-DOPA) is used as a treatment for PD. The precise cause
of Parkinson’s Disease is unknown, but it is thought that genetic and environmental
factors are at play. Head trauma through impact sports may also have an effect.
As of 2015, PD affected 6.2 million and resulted in the deaths of 117,400 people globally.
Michael J. Fox and Muhammad Ali are perhaps some of the most well-known
Parkinson’s sufferers. An estimated 7 to 10 million people worldwide are thought to
suffer from Parkinson’s as of 2017/2018. In the US, there are around 1 million sufferers,
and approximately 60,000 new cases of Parkinson’s are diagnosed each year. Onset
of Parkinson’s usually begins at around 60 years old, and men are more likely to be
affected.267
LeafWell
Parkinson’s Disease is managed by medication (levodopa, carbidopa), physiotherapy and

in extreme cases, brain surgery. Parkinson’s Disease rarely causes death alone, but puts
great stress on the body and making it more vulnerable to life-threatening conditions.
POSITIVES NEGATIVES
• Cannabis may slow the progress of bradykinesia • THC may cause confusion and make some of
(slowness due to PD) and dyskinesia (abnormal the symptoms of Parkinson’s Disease worse.
bodily movements), as well as potentially
improve appetite, decrease pain, anxiety, • Evidence for efficacy is anecdotal at the
tremors, stiffness and nausea.268 moment.
• CBD may improve sleep and reduce the

frequency of REM sleep behavior disorder
(RBD).269
• CBD may provide protection against

hydroxydopamine toxicity - it is
TREATMENT
neuroprotective.270
Much of the evidence surrounding cannabis’s
• Can help alleviate tremors and spasticity.271
efficacy for PD is anecdotal at the moment, but
• CBD may be an antipsychotic. there is potential that both THC and CBD could be
helpful for the jerks and tremors often associated
• Cannabis may be of use for when other with the condition.
medications are ineffective or unavailable.272
• Depending upon cannabinoid-terpenoid

profile used, cannabinoids may help increase
dopamine production.

CBD could be a neuroprotectant, and both THC
Average
and CBD may increase the amount of dopamine
in the brain. This means that cannabinoids could
potentially promote neurogenesis. However, the
effects of THC must be balanced against the other
side-effects of PD, as THC may have negative as well
as positive side-effects for those with PD. THC and
CBD may also help prevent or ease myoclonic jerks.
LeafWell
Cannabis and Premenstrual Syndrome (PMS)
General
As the names suggest, premenstrual syndrome begins about 1-2 weeks prior to a
woman’s period. Symptoms are quite similar, and include acne, tenderness, fatigue,
bloating, irritability and mood changes. Cramps, back pain and headaches are also
common symptoms of PMS. Post-menstrual syndrome may also be a condition,
though to what extent the symptoms overlap with premenstrual syndrome is not
known, thereby making any distinction between the two very difficult.
@erik.nugshots
LeafWell
PMS is a rather common condition, affecting around 1 in every 20 women. NSAIDs like
ibuprofen are often prescribed for particularly painful bouts of PMS. Antidepressants
may also be prescribed in certain instances. However, for those with kidney problems,
ibuprofen is not ideal, and a powerful, non-toxic phytochemical like CBD may be
an ideal solution. THC may help beat nausea and cramps as well, making medical
marijuana a potentially very useful medication for those with moderate to severe PMS.
Exercise and a healthy, iron-rich diet may also help.
Cannabis, being the anti-inflammatory that it is, can help with all of these symptoms.
Furthermore, there are fewer side-effects than many other medications usually
prescribed for PMS (e.g. ibuprofen), reducing the possibility of kidney and liver damage
or overdose.
POSITIVES NEGATIVES
• May relieve breast pain and tenderness,273 • May make breast tenderness worse in some,
caused by the increased production of as THC mimics anandamide.
progesterone during the luteal phase of the
menstrual cycle. • May also make migraines worse for some.
• Reports suggest that cannabinoid-laced • May not work as well as a mood stabilizer such
tampons reduce and even help beat cramps as SSRIs.
and lower back pain. 274
• May reduce and get rid of migraines.275 TREATMENT

• Ointments using cannabis may reduce acne. 276
Pinene and limonene may help beat any anxiety,
• Cannabis may help act as a mood stabilizer. whilst linalool can act as an effective stress-
buster. THC may work as an antiemetic and
• Aids sleep. improve appetite, whilst CBD can act as an anti-
inflammatory. As for method of ingestion, edibles,
• TRPV1 and calcium ion channels are said tinctures, vaporizers and even cannabinoid-infused
to be associated with menstrual bleeding, tampons may be effective.
and desensitizing it may help beat any pain
associated with PMS.277
VALUE OF MMJ
Both THC and CBD may be effective in small doses, BASED ON CURRENT EVIDENCE
Significant
especially for pain, cramps and nausea. Terpenes like
linalool may be effective stress-busters as well.
LeafWell
Cannabis and Post-Traumatic Stress

Disorder (PTSD) - PTSD and Complex-PTSD
(C-PTSD)
General
PTSD is related to anxiety as a disorder, and is often developed after exposure to a
traumatic event. Warfare, assault, rape/sexual assault, traffic collisions and threats to
a person’s life are common causes of PTSD, especially when the trauma is particularly
devastating, long-lasting and/or persistent. There is usually an increase in flight-or-
fight responses and/or a “shutting down” of emotions. Mental and/or physical distress
to trauma-related cues, dreams related to the traumatic event, dramatic alterations
in thinking and disturbed thinking are other symptoms. PTSD does seem to have a
genetic component to it, and those with a smaller hippocampus.
Approximately 5% of Americans - around 13 million people - have PTSD at any one

given time. It is estimated that approximately 8% of adults, or 1 in 13 people, in the US
will develop PTSD during their lifetime. PTSD leads to an increased risk of suicide and
substance abuse, and being constantly stressed may well make one more susceptible
to other illnesses.
Antidepressants, particularly of the SSRI subgroup, and counselling are the first line
of treatments for those suffering from PTSD. However, this is not always effective, and
many medications like benzodiazepines may make things much worse. While the
efficacy of cannabis for PTSD has, as of yet, not been proven, many veterans have used
it to alleviate the symptoms of what was formerly known as “shell shock”.278
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POSITIVES NEGATIVES
• Cannabis contains several stress-busting • Some strains may increase anxiety - especially
terpenes like linalool, caryophyllene and those with high THC concentrations and little
borneol. CBD.
• CBD may improve regional cerebral blood flow • Can cause an initial increase in heart rate.
(rCBF) in the brain, helping reduce anxiety. 279
• Trouble with breathing.
• Helps to “destress”.
• Can cause depersonalization.
• May help keep the mind off of reliving
traumatic experiences. • May not be useful if suffering from other
physical & psychiatric conditions, where
• Terpenes like pinene can help prevent medications may be contraindicated by
hyperventilation, which can cause chest pains cannabis.
and further anxiety.
• CBD and caryophyllene work on CB2 receptors, TREATMENT

helping reduce anxiety. 280
Finding the right cannabinoid profile for PTSD
is a case of “fine-tuning”. Limonene, bisabolol,
VALUE OF MMJ myrcene and humulene may well all be excellent
anxiolytics and sleep aids, whilst CBD may also act
Although antidepressants have proven effective in a similar way to antidepressants by acting on
for PTSD, there are few other medications out 5-HT serotonin receptors.
there that can potentially help. Sadly, many with
PTSD are prescribed benzodiazepines, barbiturates
and powerful mood stabilizers as well - drugs
that have no proven efficacy for PTSD, and may
actually worsen the situation. Cannabinoid-based
medication may well prove to be an adjunct to POTENTIAL VALUE OF CANNABIS
antidepressants, and a replacement for harsher
pharmaceuticals.
Significant
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Cannabis and Spinal Cord Injuries (SCIs)
General
A spinal cord injury (SCI) is damage to the spinal cord, whether temporary or
permanent. These changes can lead to loss of muscle function, autonomic function
(a subdivision of the peripheral nervous system that supplies smooth muscles and
glands, as well as heart rate, digestion, respiratory rate, pupillary response, urination,
flight-or-fight response and sexual arousal), and sensation. SCIs can cause pain,
numbness and more severe problems such as incontinence, paralysis, quadriplegia
(loss of use of all four limbs) and paraplegia (loss of motor and/or sensory function in
the lower part of the body). SCIs include problems such as herniated discs.
There are many types of SCI, but they can be divided into three main categories:
mechanical forces, toxic and ischemic (from lack of blood flow). Then there are two
further subcategories: primary injury (cell death following the immediate aftermath
of injury and the biochemical cascades from the original injury that cause further
damage). SCIs are also split into where on the spine the injury occured.
In the following chart, the letter represents the part of the spine affected, and the
number the specific discs and spinal nerves affected. At each level of the spinal
column, spinal nerves branch off from either side of the spinal cord and exit between a
pair of vertebrae, innervating a specific part of the body. The area of skin innervated by
a specific spinal nerve is called a dermatome, and the group of muscles innervated by
a single spinal nerve is called a myotome. These categories include:
1 Cervical 1 - 7 (C 1-8) - SCIs that affect the uppermost part of the spine. Areas of
the body affected include the head, neck, shoulders, forearms and hands.
2 Thoracic 1 - 12 (T1 - T12) - SCIs that affect the middle part of the spine and
therefore the middle of the body. This includes the chest, back, stomach and
underarms.
3 Lumbar 1 - 5 (L1 - L5) - SCIs that affect the lower part of the body, specifically
the right leg, parts of the left leg and pelvis.
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4 Sacral 1 - 5 (S1 - S5) - SCIs that affect the lower part of the body, including the
left leg, parts of the right leg and the groin region.
5 Coccyx - tailbone.
SCIs are usually evaluated using X-rays, CT scans or MRIs. SCIs are thought to affect
between 10.4 and 83 people per million every year. In North America, about 39 in every
million people incur a traumatic SCI each year. In the USA specifically, the rate is 40 in
every million people incurring a traumatic SCI every year. Falls and other high impact
injuries are common causes of SCIs, but people with arthritis or multiple sclerosis (MS)
are also at high risk of SCIs.
Treatment for SCIs includes surgery, physiotherapy and rehabilitation exercises,

antihypotensive agents (vasopressors), such as epinephrine or hydrocortisone, central
venous catheters (a catheter put into the heart in order to control blood pressure),
occupational therapy, recreational therapy and psychotherapy. Medications are usually
prescribed to control pain, activate signalling pathways, and prevent inflammation,
such as atorvastatin, fenretinide, opioids, antidepressants and NSAIDs.
POSITIVES NEGATIVES
• There are a number of endocannabinoid • There is little information and research on the
receptors on the spinal cord. Targeting these effect of cannabinoids on spinal cord injuries,
could help prevent further cell damage. although the information we have on the
skeletal ECS shows that cannabinoids may
• CBD may be a neuroprotective, and possibly well be an ideal treatment for illnesses and
protect the myelin sheath from further damage injuries affecting the bones.
as well.
• CBD may help repair broken, fractured and TREATMENT

porous bones - the ECS has been shown to play
a role in the regulation of bone metabolism and Indicas seem to be popular for those with
the formation of bones.285 SCIs. The high amounts of THC, CBD, myrcene,
humulene and linalool usually found in many
• THC and other cannabinoids may prove types of indica could be a clue as to why they are
to be an excellent alternative to opioids, more popular - they are all anti-inflammatories,
benzodiazepines and strong NSAIDs for pain. anxiolytics, sedatives and painkillers/distractors in
one form or another.
VALUE OF MMJ
Cannabinoids may be used to target the ECS and BASED ON CURRENT EVIDENCE
Average
cannabinoid receptors on the spine and in the brain
in order to prevent further cell damage.
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Cannabis and Sickle Cell Diseases (SCDs)
General
Sickle cell diseases are a group of blood disorders that results in abnormalities in the
blood cells, of which the most common disease is sickle cell anemia. Sickle cell anemia
is a sickle cell disease that results in sickle-shaped, rigid blood cells. This is caused by an
abnormality in the oxygen-carrying protein in the hemoglobin found in red blood cells.
There are various subtypes of sickle cell anemia, and they are usually inherited from
one’s parents.
Sickle cell anemia and other such diseases can cause problems such as pain (“sickle
pain”), anemia, bacterial infections, swelling in the hands and feet, and an increased
chance of stroke. The disease mainly affects people of Sub-Saharan origin, where about
80% of cases of sickle cell anemia are found, although people from the Arabia and
India are also affected, due to the high incidence of malaria in such places.286
As of 2015, 4.4 million people worldwide suffer from sickle cell anemia. An estimated 43
million have a sickle cell trait. Around 100,000 people in the US suffer from a sickle cell
disease of some sort, and black- or African- Americans are more likely to be affected.287
LeafWell
The therapeutic effects of cannabis for sickle cell carriers have only been looked at
more recently. Traditionally, the opioids were used to manage “sickle pain”, but it has
problematic side-effects like extreme sedation, nausea, appetite loss, constipation
respiratory depression and, of course, addiction.
POSITIVES NEGATIVES
• Helps manage pain without the need for • Smoking may heighten breathlessness.
opioids. 288 289
• Cannabis may increase the chances of stroke
• May inhibit the chance of infection from other for some individuals.
sources.290
• May cause uncomfortable side-effects such as
• Induces relaxation and aids sleep. racing heart (tachycardia) and dizziness.
• Relieves anxiety and depression. • Cannabis use by patients with sickle cell
diseases may increase the chances of a vaso-
• Lowers heightened sensitivity to pain occlusive crisis, where sickled red blood cells
(hyperalgesia).291 obstruct the circulation of red blood cells..292
VALUE OF MMJ
TREATMENT
Both THC and CBD may help treat pain and act as
Both THC and CBD may have value as an anti-
an alternative to opioid-based pain medications.
inflammatory, painkiller, appetite stimulant and
CBD may also help lower blood pressure and reduce
hypertension relief medication. Finding a high-
hypertension.
quality hybrid strain may be helpful, but again,
this is from various patient reports rather than any
clinical analysis.

Little evidence
so far
LeafWell
Cannabis and Stroke/Traumatic Brain Injury

(TBI)
General
TBIs can cut off the blood supply to parts of your brain either via cutting off of the
blood supply (ischemic stroke) or by bleeding (hemorrhagic). This causes brain cells
to become damaged and eventually die. Signs and symptoms of stroke include an
inability to feel or move on one side of the body, a loss of vision to one side, problems
understanding or speaking and a “spinning” feeling. Severe headaches are also
common. TBIs and strokes can often cause long-term, long-lasting and life-changing
effects. High blood pressure is the most important risk factor for stroke.
In 2013, there were approximately 2.5 million emergency department visits for some
form of TBI, of which 282,000 resulted in hospitalization. 56,000 deaths in 2013 were
attributed to some form of TBI. Stroke, which is the leading cause of serious, long-term
disability in the US, approximately 795,000 people in the US suffer a stroke. Of these,
600,000 are first attacks, and the rest recurrent attacks. The chances of stroke doubles
each decade after the age of 55, with nearly three-quarters of strokes occurring in
those aged 65 or over. In 2006, stroke accounted for 1 in every 13 deaths in the US.
Cannabinoids may help limit and in some cases even reverse some of the negative
consequences of stroke and other TBIs.
LeafWell
POSITIVES NEGATIVES
• CBD may protect against myocardial ischemic • THC may cause further problems with
reperfusion injury.293 memory, balance etc.
• CBD may prevent infarction and cerebral • Some studies show that using cannabis may
infarction via the non-CB1 cannabinoid receptor increase the chances of developing a stroke.
mechanism. 294 295
• Contains neuroprotective antioxidants. 296

TREATMENT
• May reduce and reverse the effects of long-term
brain injury.297 Undoubtedly, people are looking for CBD for its
neuroprotective and anti-inflammatory effects
• CBD may protect against cell death. 298 when it comes to stroke/TBI, and so unsurprisingly
many may think to pick indicas. It also would not
• May be neuroprotective and help prevent an
be surprising to find many athletes in high impact
overabundance of glutamate from forming.299
sports use CBD to help overcome their injuries
VALUE OF MMJ
Many people are focussed on the value of CBD

as a potential neuroprotectant, as it may not only
possibly prevent further damage during and POTENTIAL VALUE OF CANNABIS
after the stroke, but could potentially prevent the BASED ON CURRENT EVIDENCE
Average
likelihood of a TBI in the first instance.
but could be significant.
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Cannabis and Tourette Syndrome

(TS, Tourette’s)
General
Tourette Syndrome (TS, aka Tourette’s) is a relatively rare neuropsychiatric disorder that
usually onsets in childhood. TS is characterized by at least one vocal (phonic) tic and
multiple motor tics. These tics can come and go over the course of a person’s life, can
be suppressed temporarily, and can be preceded by an unwanted urge or sensation in
the affected muscle. Common tics include blinking, coughing, throat clearing, sniffing
and facial movements.
When many people think of a Tourette’s patient, they think of someone who swears
or uses inappropriate language at inopportune moments (coprolalia), with little-to-no
control over their vocalisms. However, this is rare, and most people with Tourette’s go
undiagnosed throughout their lives due to the fact that their tics aren’t severe.
The exact cause of TS is unknown, but it is thought that there is a combination of

genetic and environmental triggers. The majority of cases of TS are inherited, and
there does seem to be a gene polymorphism that causes TS, but which gene and the
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exact mode of inheritance is not known yet. Refined sugar, caffeine and gluten may
exacerbate tics. Tourette’s syndrome may be related to obsessive-compulsive disorder
(OCD) and attention deficit hyperactivity disorder (ADHD). Autism spectrum disorders,
depression and anxiety are also comorbid with TS.
According to the CDC, 1 out of every 360 children (0.3%) aged 6 - 17 suffer from TS, and
children aged 12 - 17 are twice as likely to suffer from TS than children aged 4 - 11.300 37%
of TS sufferers have moderate to severe Tourette’s. Males are three to five times more
likely than females to have TS, although females may be more likely to display tics. It
is thought that 1 out of 162 (0.6%) children have TS, meaning that up to half of sufferers
are undiagnosed.
Treatment methods for TS include psychotherapy, cognitive behavioral therapy (CBT),

planned activities and neuro-linguistic programming (NLP). Medications are usually
used in more severe cases of TS, and can include adrenergic agonists such as clonidine
(Catapres, Nexiclon, Kapvay), antipsychotic medications that dampen dopamine
production such as fluphenazine, haloperidol (Haldol) and pimozide (Orap), and
tetrabenazine (Xenazine, Nitoman). TS usually improves as the sufferer ages due to
management techniques, but may still remain severe in some.
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Joe Powell, Age 18, Birmingham, UK
“ My name is Joe Powell. I’m 18 years old. I suffer from Tourette’s syndrome, anxiety
and depression.
It began 30th September 2016, I noticed a motor tic in my neck. This quickly went
from 1 tic every 2 minutes to a motor tic and a verbal noise every few seconds. This
leads to chronic pain in the muscles in my neck. The ticing doesn’t stop 24/7. No
medication seemed to help ease my symptoms.
Someone mentioned smoking cannabis. The result was almost instant, every motor
and verbal tic stopped - giving me back control over my whole body. However,
cannabis is still illegal in the UK. It’s time for the government to realize that
conventional medications are no longer working.
I am vaping on a dry herb vaporizer called The Mighty.
”
POSITIVES NEGATIVES
• Many medications that are prescribed for TS • Evidence for cannabis’s efficacy is anecdotal
have side-effects such as dizziness, depression, at the moment, and not a huge number of
diarrhea/constipation, nausea and, for certain studies have taken place.
medications, addiction.
• THC may be beneficial for stopping tics.301

TREATMENT
• TS may be comorbid with conditions like ADHD.
Dextroamphetamine-based ADHD medications The high THC found in many hybrid strain may
can increase the occurrence of tics, and well be beneficial in preventing tics, in a similar
cannabinoids may prove to be an alternative. way that it may help prevent spasms.

For those with severe forms of Tourette’s
Average
Syndrome, cannabinoids represent an alternative
to antipsychotic and amphetamine-based
medications.
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Myles Walker, Connecticut
“ I am the “King of Tourettes”. I was originally born in Hartford, Connecticut. I took

myself off medication at 15 years old, in the 90s. I was living in Nashville, Tennessee
first time I smoked weed, which was age 14.
Cannabis is better for Tourettes. I wrote a book “Me & My Tourettes, Motivated By
God”. I talk about how smoking cannabis helps me in there!
Trust me when I tell you their are A LOT of people all over the world as well as
different cities towns places I’ve lived know about me smoking. Know my story.
I’m a Tourettes advocate. I keep it real. I don’t that fake shit. It makes my Tourettes
go away.
”
All strains seem to have the same, great effect, to be honest.
Cannabis and Trigeminal Neuralgia (TN)
General
The trigeminal nerve is the nerve responsible for sensation in the face and motor
functions such as biting and chewing. It is the largest cranial nerve. Trigeminal
neuralgia (TN) is a chronic pain disorder affecting this nerve, and it is thought that the
cause is a loss of myelin around the nerve. Blood vessel compression may also be a
cause, and TCIs, multiple sclerosis (MS), stroke and brain injuries may also cause TN.302
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TN is also known as tic douloureux, prosopalgia, Fothergill’s disease (after John

Fothergill’s description of TN in 1773) and “suicide disease”, due to the high number of
people who commit suicide due to TN, much in the same way that cluster headaches
are sometimes called “suicide headaches”. 25% of people who suffer from TN commit
suicide.303 The pain is excruciating, and is comparable to severe burns, giving birth and
the bite of a bullet ant. Typically, the pain starts on one side of the face and moves to
another, and can last anything from a few seconds to a few hours.
Kathy Bolivar
“ I started using cannabis about 5 years ago, because I suffer from something called
Trigeminal Neuralgia. It’s a problem with the nerves that control things like the eye
and jaw, and it affects my hearing. It’s also a really painful condition. Around the
age of 9, I was physically abused. I was hit in the head one day and that’s when my
headaches started.
They disappeared after a year, but came back in 2005. Then, it came back with a
vengeance. The doctor looked at me, and told me I had TN. He also said that there
were so few cases of it that no one knows what causes it, or how to treat it. All he
could do was give me medication to treat the pain and seizures. It’s kinda like being
stabbed in the face with electricity.
I had been on medications for awhile, when a man recommended I try cannabis
after overhearing me talk about the TN. I thought it wouldn’t hurt to just give it one
shot. It worked! I told him, “This is amazing, you have no clue how much easier you
”
have made my life.
LeafWell
Medications usually prescribed for TN include antiepileptics/anticonvulsants such as

carbamazepine, lamotrigine and oxcarbazepine (benzodiazepines),304 GABA agonists
such as baclofen, and anticonvulsants such as gabapentin. Antipsychotics such as
pimozide may also be used. Serotonin-norepinephrine reuptake inhibitors (SNRIs) such
as amitriptyline may also be used. Opioids are not recommended for TN and, as with
many other types of nerve pain, will have little-to-no effect on reducing pain. Surgery
is also an option, as is botox treatment. An estimated 1 in 8,000 people develop TN in a
given year, with onset usually beginning after 50 years old. Those with conditions such
as MS, AIDS/HIV and diabetes are more likely to develop TN.305
POSITIVES NEGATIVES
• Many of the medications prescribed for the pain • Too much THC may increase anxiety and
of TN have some seriously negative side-effects, therefore exacerbate pain.
such as nausea, vomiting, dizziness, headaches,
sleepiness, trouble with coordination, • Like with many conditions, no definitive
kidney problems, aggressive behavior, and evidence as of yet that cannabis helps for TN
an increased risk of suicide. Cannabinoid- due to lack of clinical trials.
terpenoid based medications could have far
fewer deleterious effects and beat the pain of
TN as well.306
TREATMENT
• Many of the medications prescribed for TN may
interact negatively with each other, making TN CBD could be of immense use for TN, but for
treatment a fine balancing act, lest the chances a condition as complex and ill-understood as
of overdose increase. Cannabinoid-based trigeminal neuralgia, we do not know precisely
medications could avoid this by replacing many what set of cannabinoids and terpenoids may be
different pills. best. Utilizing the entourage effect may be best
• Cannabinoids can be used to improve mood, for TN.
sleep and appetite.
• CBD may act as a neuroprotectant.
VALUE OF MMJ
Just as CBD shows promise as a neuroprotective and BASED ON CURRENT EVIDENCE
Average
anticonvulsant for use with MS and epilepsy, it could be
used similarly for TN. Other terpenoids like pinene and
limonene can lift the mood. Terpenes like humulene,
bisabolol and linalool can act as anxiolytics, analgesics
and sedatives. THC may help beat or distract from the
pain of TN.
LeafWell
3
CHAPTER
DOSAGE
AND
USAGE
176 DOSAGE AND USAGE
A Guide to Dosing/Titration
PROS CONS
Potentially harmful to health.
Immediate effect. Loss of some medically beneficial

Smoking Easy.
cannabinoids (i.e THCa)
Not ideal for the

immunocompromised.
Immediate effects. Can be exposed to harmful particles

when using poor quality vaporizers.
No smoke.
Vaporizing Quite efficient.
Little study on the long-term effects.
Flavored cartridges may be

Better temperature control. carcinogenic.
Long-lasting effects. Effects are not immediate, so there

Discreet. is a danger of overdosing.
May contain less cannabinoids than

Edibles No health risk from breathing
burning matter. stated
Smaller amounts of cannabinoids Can contain high levels of refined

(THC in particular) needed. sugar.
Consistent dosage.
Short duration of effects.
Inhalers Immediate effects.

Is not an ideal for all conditions.
No smoking or vaporization
Bioavailability is variable.
required.
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DOSAGE AND USAGE 177
PROS CONS
Long effect duration. May not contain the amount
cannabinoids they say they state.
Felt in 15 - 30 minutes.
Can contain harmful chemicals and
Tinctures Easier to control dosage. pathogens.
Often whole plant extracts of May only contain THCa and CBDa, not
specific strains. THC or CBD.
Good for skin conditions (e.g.

eczema, acne).
Salves/ May only work for skin conditions.
No psychoactive effect.
Topicals Absorption can be quite slow.
Non-invasive.
Sustained levels of cannabinoids

over a long period of time.
Can take a long time to take effect.
Patches/ High rate of absorption into the
Not widely available.
bloodstream.
Transdermals
Can provide long-lasting relief.
Easily absorbed into the

Could be uncomfortable for some.
Suppositories bloodstream.
Not widely available.
Little-to-no psychoactive effect.
Easy to take. Slow absorption rate.
Low bioavailability.
Tablets/Pills Slow-release of cannabinoids.
Can be formulated to protect Unpredictable absorption.

cannabinoids from digestion. Limited supply.
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Frankly, there is not much scientific research about appropriate cannabis dosing. We
will quote Mara Gordon, Co-founder and Chief Process Engineer of Aunt Zelda’s, who is
also one of our contributors, and say, “With cannabis dosing, it seems that there is more
than one way to skin a cat”. Currently, there are two schools of thought on this issue:
1 Throw all the cannabinoids and terpenoids you can at whatever condition
it may be (which is usually the advice given for treating cancer, which is
sometimes known as the Rick Simpson Method. However, even for cancer,
specific cannabinoid profiles may be needed. Also, this is probably not wise for
all conditions, where some effects of cannabis can be detrimental);
2 Specific conditions require specific cannabinoid and terpenoid profiles.
Of course, the answer could be a little of both, and a combination of answers 1 and 2
might be the most effective treatment for certain conditions. Also, it seems that the
same cannabinoid-terpenoid profile may have a different effect on different people,
even if they suffer from the same condition. This could either mean that for effective
treatment they might need to take an entirely different cannabinoid-terpenoid profile,
or the same profile at either a higher or lower dosage.
Moreover, cannabinoids can be biphasic, meaning they can have two completely
different effects when taken at a certain dosage. Cannabis is typically an antiemetic, but
moderate doses of CBG, being an inverse agonist of the CB1 receptors, may have the
opposite effect and induce vomiting. THCV is perhaps the better example, where low
doses act as a CB1 antagonist, and high doses act as a CB1 agonist.
To make matters more complicated still, different ingestion methods can have different
effects as well. Cannabinoids behave differently if they are vaporized, as opposed to
eaten (significantly more THC is converted into 11-hydroxy-THC when eaten) . Even
with cannabis tinctures, cannabinoids infused into different kinds of oils may well have
different effects. A coconut oil-based tincture may well have different effects to an olive
oil- based tincture. The manner in which the cannabinoids were derived has an effect
as well, so a CO2 extracted concentrate will likely have different effects from an ethanol
extract. As different companies work with different plants, different growing mediums
and different extraction methods, even what appears to be the same cannabinoid
profile may have different effects. This makes giving any generalizations extremely
difficult.
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Some conditions, like acne, eczema or psoriasis, may be helped more by cannabinoid-
based topical creams and salves that you put directly onto the skin. Other conditions
may be best treated with suppositories (e.g. irritable bowel diseases, bowel cancer,
endometriosis). Edibles and other forms of ingesting cannabis can take a long time to
take effect, whereas Sativex is utilized via inhaler, meaning it can give fast-acting relief
for spasms.
The best advice that I feel comfortable giving a new patient regarding cannabis dosing
is, “take it slow, do not take too much at once, and try a little bit of everything to see
what works best for you. Utilize a wide variety of ingestion methods, and if you are using
edibles, be sure to microdose.” Anecdotally, many patients seem to use 1 gram or less of
cannabis per day. This suggests that huge quantities of cannabis may not be needed,
except for specific conditions like cancer, although economic factors could also play a
part in this (i.e. not everyone can afford the amount they really need).
Now, to note: 1 gram of cannabis can be a lot, with cannabinoid concentrations as high
as 850 mg! Many patients may see experienced users use 1 gram in one sitting, but
they are likely to have developed some tolerance to the cannabinoids. Also, the method
of ingestion makes a huge difference. Eating 1 gram of cannabis is very different from
smoking 1 gram of cannabis. Some patients may also use vaporizers that can give a
more controlled dosage, where a “hit” or a “puff” on the vaporizer is equal to a few
milligrams of cannabinoid intake. Most patients only seem to need small quantities of
cannabinoids for therapeutic effect, so “a gram a day keeps the doctor at bay” could
even be “a few milligrams a day keeps the doctor away”!
Perhaps due to the ease of application, the lack of smoke and the easily-measured
dosing, many medically-minded companies tend to produce a range of tinctures with
different cannabinoid profiles. The most common tinctures, as far as we have seen,
include THC:CBD/CBD:THC ratios of 1:1, 2:1, 3:1, 5:2 and 1:0, as well as CBD:THC ratios of
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30:1, 20:1 and 18:1. Generally, these tinctures come in bottles with droppers that contain
measurement in millilitres (ml) on them. These droppers usually measure up to 1 ml,
and the usual starting dosage is 0.25 ml, then waiting 15 - 30 minutes to see how it
affects you (although in some instances, tinctures may not take any effect for 1 - 2 hours
until after ingestion). The effects usually last between 2 - 8 hours, depending upon
your metabolism and the amount taken. More can then be taken if necessary. Using a
maximum of 3 mg of cannabinoids - or around 2.5 mg - per dose is perhaps the best
way for new patients to start taking cannabis. Tinctures can also be used to make
topicals as well.
Patients may also find it helpful to use different cannabinoid profiles for different times
of day. For example, a patient may use a CBD:THC ratio of 3:1 during the day, and a 1:3
ratio at night, so that the psychoactive effects are not felt during the day when the
person may be working, looking after their children and generally busy with life. This
also means that, overall, the person has a CBD:THC ratio of 1:1 over the course of the day.
CBD may also help a person feel more “awake”, so it is perhaps best to utilize high CBD
concentrations during daytimes, and higher THC concentrations at night to aid sleep.
Using cannabinoid-based medications this manner is sensible to start. Many who know
cannabis and cannabinoids’ effects usually recommend to start off with one ratio, and
then try another ratio to “attenuate” the effects. Unlike many other pharmaceutical
drugs, cannabinoids seem to work “gradually” or in “degrees”, letting patients control
the effects they have to a certain extent. So, for example, you could try microdosing a
small amount of CBD:THC 3:1, and then use a small amount of the CBD:THC 1:3 ratio, in
order to see which ratio treats you best if the CBD:THC 3:1 is not working for you.
This method may produce more reliable results if you are trying to see which profile
works best for you. Of course, it is difficult to know if both the 1:3 and 3:1 products are
exactly the same, with the same terpene profiles, because not all companies extract
their cannabinoids in the same way, and even the same strains of cannabis can have
different profiles if they are grown even slightly differently or are grown in a different
environment.
We don’t yet know exactly which cannabinoid-terpenoid profiles are preferable for
different conditions; and, although there is more anecdotal evidence everyday, there
is much less scientific evidence available - for now, at least. For example, it seems that
those suffering from epilepsy require a high CBD profile (20:1 CBD:THC), whilst those
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who suffer from chronic pain appear to need a greater amount of THC. The medication,
Sativex, is a 1:1 THC:CBD ratio. Those using cannabis to treat cancer may need high
amounts of a variety of THC and other cannabinoids, whilst those suffering from anxiety
may need a few milligrams of THC at most to avoid it exacerbating symptoms.
If you decide to eat cannabis, then it is highly recommended to try microdosing. Eating
no more than 5 mg of THC at a time (preferably less, such as 3 mg), and wait at least
1 - 2 hours before your next dose. Even small amounts of THC can be therapeutic, and
a psychoactive state does not need to be achieved for the therapeutic and medicinal
benefits cannabis can provide. This is perhaps best seen in the documentary, The
Scientist, which looks at the work of Raphael Mechoulam, where the following exchange
takes place:
INTERVIEWER
So in 1995, you had an idea of testing THC on children.
RAPHAEL MECHOULAM (RM)

It has been known for many years that cannabis can lower the [negative] effects of
anti-cancer drugs. Anti-cancer drugs, many of them, cause terrible side-effects. And in
children, unfortunately children get cancer as well, children vomit and want to vomit,
nausea, they’re really in bad shape, and they cry all the time and their parents are in a
bad shape. Luckily, most of the children can be cured of the cancer, but the treatment is
absolutely difficult.
We wanted to do a clinical trial on children. We did that with Professor Avramov, Aya
Avramov. She was head of department of pediatric oncology in one of the Jerusalem
hospitals, and we did a major study with THC given in oily drops under the tongues of
children. Obviously, children cannot smoke, we had children who were not even one year
old. We dropped, or she dropped, THC in olive oil under the tongue two or three times a
day, small doses, during the anti-cancer treatment.
In the beginning, we wanted to do a double-blind study. Some of the children got the
THC, some of the children got only the olive oil. After a week, she told me: “I’m not going
ahead with that. I know who exactly is getting the THC, I know who is not getting it.”
There was a complete separation. Those that didn’t get it continued to vomit, so she went
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ahead doing an open study, and she gave THC, pure THC, under the tongue, about 400
times, which means that those that were involved in the experiment got it every time
they were treated with whatever they were being treated, and at the end we saw that
we had a complete, complete block of vomiting, a complete block of nausea by a small
amount of THC that did not cause any psychoactivity, nothing.
So here we had a complete therapeutic effect and we published that307 and again,
essentially nothing happened. Finito, that was it. It’s still not being used in children.
INTERVIEWER
And you think it’s a good idea to use it for children?
RM
Well, I believe it’s an excellent idea because we help those children that suffer, but … I
have no influence on oncologists.”308
There are various ingestion methods you can try to utilize cannabis as a medicine.
For example, using a small amount of tincture or edible may be helpful for long-
term relief of pain or anxiety, whilst using a vaporizer may be better when immediate
relief is needed, for example, where the pain is immensely strong, or if the person is
having a panic or anxiety attack. Sativex for instance is a spray that takes effect almost
immediately, which is designed to stop the sudden muscle spasms associated with
MS. For conditions like endometriosis or rectal cancer, a combination of ingestion and
suppositories may be ideal.
One huge factor that comes into play for the majority of traditional pharmaceutical
medications is weight. For instance, a person weighing 200 lbs will likely need a
different amount of painkillers to a person weighing 120 lbs. Cannabinoids, however, do
not seem to behave in the same way, and the weight of the individual does not seem
to determine the effect a particular cannabinoid-terpenoid profile and concentration
will have on them. However, those with higher amounts of fat may retain higher
amounts of THC, because it is lipophilic. The effect cannabis seems to depend very
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much on an individual’s overall metabolism, rather than just one factor. This means
a lighter person may well be able to tolerate a higher amount of THC than a heavier
person, although again this is dependent upon several factors. We do not yet know
precisely why this is, but it could be because cannabinoids work on the body’s and
brain’s receptors, which are not affected by how much the person weighs. Therefore,
receptor saturation may be what determines the effect cannabinoids and terpenoids
will have, as opposed to weight alone. There may also be some differences between
the dosing needed for men and women, due to hormones and the different amounts
of fat stored in the body.
There could be several factors that could affect how cannabinoids behave in the body,
including: body fat (body-mass index, or BMI); sex, (with women appearing to be more
sensitive to THC, but also quickly developing a higher tolerance to it, although this has
yet to be proven in human trials)309; age (children and adolescents seem to be more
sensitive to THC, with this sensitivity may fluctuating over their lifetime); diet; exercise;
genetics (e.g. the presence of certain genes, or how fast one’s natural metabolism is);
and of course whether or not the person suffers from any particular injury, ailment or
disease. It has been speculated that some treatment-resistant diseases may be due to
an endocannabinoid deficiency, therefore, it is arguable that phytocannabinoids act
like “vitamins”, and could be used as a form of “preventative medication”. The evidence
needed to prove “preventative medicine” is quite high, so this is still speculative at this
point.
Another piece of advice would be to look out for companies who take scientific tests
seriously. This means regular testing for cannabinoid-terpenoid profiles, heavy metals,
pesticides and other pollutants, and patient feedback wherever possible. To be fair
to the companies making these product and the labs testing them, extracting and
accurately measuring for cannabinoids and terpenoids is very difficult. However, it is
advisable to be wary of anyone who claims to have all the answers - cannabis is not a
panacea, and like any other medicine, it deserves to be treated with respect, and to be
used carefully.
Another big issue with dosing are the cannabinoids and terpenoids beyond just
THC and CBD, like CBDa, CBDV, THCV, THCa, CBC and so on. Sadly, these often get
forgotten about, but for some conditions they may be just as important as THC and
CBD. They often work in tandem with one another, which is called the “entourage
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effect”, and can be more effective in combination, or even produce different results.
Acidic cannabinoids are also non-psychoactive, but appear to work with other
cannabinoids to create a whole that’s greater than the sum of its parts. There is some
evidence suggesting that THCa and CBDa work with THC and CBD to produce greater
painkilling and antiemetic effects.
Developing a tolerance to cannabinoids may also be an issue for patients in the

long-term, although it should also be noted that building some tolerance can be
useful, in order to reduce any overwhelming and negative effects. Some people
take “tolerance” breaks, as the body breaks down cannabinoids over time, and a
person can reduce their tolerance by taking a few weeks break from medicating
with cannabinoids. Another idea is to “switch strains”, where the idea is to change
the cannabinoid-terpenoid profile - one which the body has not grown tolerant to.
Yet, some people may require a specific profile, so this may not be ideal for everyone.
When using extracts or products that utilize extracted cannabinoids, the method
in which the cannabinoids and terpenoids are extracted matters. Cannabinoids
derived using ethanol extraction techniques (e.g. Rick Simpson Oil) seem to retain
the chemical bonds in between cannabinoids better. Anecdotally, some patients
using cannabinoids extracted using other methods, where chemical bonds between
cannabinoids are broken (e.g. CO2 extraction), have reported gaining a tolerance to
cannabinoids more quickly. Whilst in some instances, developing tolerance may be a
positive as the psychoactive effects become less uncomfortable, in others it may prove
to be negative as higher doses are needed, which is more expensive and potentially
more dangerous.
As for terpenoids, it is perhaps best to go with a broader range of profiles. Do not think
that any one terpene will be the most effective medicine for you. Instead, you will more
than likely find something that works better for you by trying a range of cannabinoid
and terpenoid profiles, and finding the specific ones that help you. Interestingly, many
patients that we surveyed tended to prefer strains with varied terpene profiles that hit
the right balance, like Blue Dream and OG Kush. Whether this is just because these
strains are more popular and available, or if there is a genuine reason for this in the way
the terpenes are working in concert, we do not know.
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Mara Gordon - Process Engineer & Founder of Aunt Zelda’s. Aunt Zelda’s is working
on an extensive number of pre-clinical and clinical trial for the use of cannabinoids
and terpenoids for many different conditions.
Hello Mara. Nice speaking to you again. We have lots of contributors in this
book, and we thought to ask you to contribute as we want more than just
preclinical data - we want to see how cannabis works in real life, not just in
the lab. We have such little clinical data …
… Which is so frustrating. You know about my company, Zelda Therapeutics. We do

both preclinical and clinical trials, so I’m speaking from first-hand experience on
the differences between the lab and reality. Rodents and petri dishes don’t always
translate to humans. Because how many mice are we thinking of treating for breast
cancer? We’ve just started doing double-blind clinical trials on insomnia, and to be
doing such scientific inquiries into patient usage on this is such a phenomenal and
huge undertaking. And, I should say, the research we do on preclinical will give us
enough information - and it looks like it so far - to justify the more exhaustive and
expensive clinical studies.
Have you found anything particularly interesting, then? Is there a

cannabinoid-terpenoid profile that works better for insomnia?
Oh, yeah. We’ve actually filed patents on them already. We’ve been treating insomnia
for over 7 years, and it’s the formulation that we use for our insomnia product that
we’re using for a clinical trial by Zelda Therapeutics. Which is great, because we know
it works, but we want to see it on a larger scale!
Do you mind telling us which product this is?
This is our Nighttime Formula. I mean, because it’s cannabis, we can’t make claims
on our products. We can’t say it’s our “Insomnia Formula”, but we can call it our
“Nighttime Formula”. There are a lot of ways of creating a sleep formula, and you
might be surprised by what cannabinoids are in it. Some people think, “Oh, if it
doesn’t have this in it, it won’t work. I’m able to fall asleep with x, so you’re wrong ”. So
I say, “Well, there’s more than one way to skin a cat.” THC, CBN, myrcene and linalool
are the primary components. There’s no CBD in there, which surprises a lot of people.
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That doesn’t surprise me very much, as people have reported that CBD can
help keep them awake …
My husband, interestingly enough, uses CBD every night to go to bed. He doesn’t

use THC every night, but he smokes THC through the evening, so he might as well
be because of the way it peaks and comes back down, I think it’s adding to his
sleepiness. But certain people, and I have a pretty good profile of who they are,
who get sleepy when they use CBD, and others like me feel more “activated”. On
the other hand, it also depends on the source of the CBD and the entourage effect,
which may determine whether the CBD will be “sleepy” or “invigorating” as well. But
on its own, for me, CBD makes me too wired and unable to sleep. So the same thing
can treat two people exactly the opposite.
Yes, this is partly what makes cannabinoids so interesting - the way they
have highly individualized effects. I suppose a lot of doctors and scientists
have been looking for highly tailored medications for specific people …
Yes, if you think about it in terms of a “compounding pharmacist”. One of the things
we do with all of our products, and these are things that we’ve done all along, is we
have purposefully blended not to create ratios in our products. You go to a website
that is for a more commercial product, and they’re going to have ratios of 1:1, 1:2:, 1:4
and so on, whatever those ratios mean. What we’ve done is keep ratios extremely
high, so 1:20 or 1:30 and vice-versa. This allows the patient to mix it and find the ratio
they need on the spot. So, in the morning they may need a 1:1 ratio, but at night they
may need a 30:1. Once you mix the ingredients, you can’t unmix them. We want
people to have the freedom to customize to their needs.
In the preclinical work we’re doing on breast cancer and the three major breast
cancer groups, with particular emphasis on HER2+ and triple negative as they’re
the most difficult to treat, we’re finding tremendous results. In fact, I presented at
Harvard Medical School some of our preliminary results this time last year. We’ve had
even more positive results since then, and we’ve submitted to speak at CannMed in
October.
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I’ve been talking to Dr. Michael Masterman-Smith, and he mentioned similarly

about letting patients mix their ratios to find what’s best for them …
Well, good. I feel, in a lot of ways, that we’ve been saying this for years and the
industry goes running around all over the place, and then they catch up eventually.
Because what you may feel has a therapeutic effect at one point, may not be so at
another point. Having the freedom of customization is very important.
So, could you tell us more about the patterns you’re seeing with regards to
specific cannabinoid-terpenoid profiles for specific conditions?
We’ve been seeing patterns and have a pretty good idea as to what profiles work for
which conditions. The challenge that we all have is that what works for one person
may not be exactly the same in terms of dosing. So you have to take other things
into consideration other than just the primary diagnosis and the dose. I can have
10 people standing here with the exact same diagnosis, and they’ll need slightly
different or even extremely different doses. The chances are, though, that they’ll be
on the same profiles, but may need different dosages. One person might need 2 mg
to get to sleep, another 13 mg, but it’ll be the same profile that knocks them both
out.
We find that older people generally need less than younger people. The younger the
person, the higher the dose. Another thing is that women tend to use a lower dose
than men, for a number of reasons. Also, it’s extremely important to understand the
comorbidities. Rarely does someone come to us with a serious diagnosis that also
doesn’t come with other things that need to be addressed. For example, someone
could come to us and say “I’ve got horrible back pain.”, and as we are finishing
the interview and telling them what might be useful for them, they mention that
they have hepatitis C, high blood pressure, diabetes or whatever else! That is a very
common problem, and is quite frankly the problem with a lot of medicine. It’s not
unique to cannabis at all.
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In some ways, I find this fascinating. The way we treat cannabis is almost
like a microscope for how we treat medicine in general and the philosophy
behind medicine …
… Absolutely. I agree. You have doctors who are trying to figure out how to
recommend cannabis, and it cracks me up because they don’t necessarily
understand who to prescribe any medicine! They go to a guidebook that says “If you
have x diagnosis, are y years old and weigh z amount, then you need a particular
medicine at a particular dosage because that’s what it says on a chart. So it’s not like
they’re thinking, “Well, if we do this, we’re affecting that system in the body.” Most
doctors are more tradesmen than scientists. So it takes a particular kind of doctor,
who’s a scientist and not a tradesman. Doctors spend moments with a patient, and
the rest of it is autogenerated.
Doctors seem to be waking up to this manner of prescribing drugs …
Yep. This is how it was before Bayer Aspirin. So thank you very much Bayer Aspirin for
the single molecule that has destroyed modern medicine!
I guess this is one reason why we also have over-prescription of opioids as

well, I suppose?
Absolutely. When you take an opioid or any pharmaceutical - anything that was
originally meant as a plant medicine … I heard something recently that made a lot
of sense to me, and that is, if you take whole plant medicines, you get sick if you
take too much, so you stop taking too much. The problem with a lot of modern
pharmaceuticals is that they don’t necessarily make you feel sick when you’ve taken
too much. So you keep taking more, which leads to problems. I could take a bunch of
aspirin, and it would burn a hole in my stomach and potentially kill me as it’s thinned
the blood so much. But I could eat willow bark as well, and it would likely make me
sick long before I reached that point.
It’s the natural checks and balances of plant medicine …
Exactly. And you know, things are going back very rapidly to whole plant medicines.
Doctors are looking more and more out-of-the-box, because we’re living longer but
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not necessarily better.
Could you tell us more about the process the patient has to go through to get
their ideal medication?
We’ve identified 6 main questions that need to be answered before we begin our
first attempt at a therapeutic dose for a patient. Those 6 things are:
1. The age of the patient.

2. The diagnosis.
3. The current and previous pharmaceuticals and treatments they’re going
through.
4. Their previous and current cannabis experience, if any.
5. What their objective is with cannabis.
6. Any comorbidities.
Once we have this information, we can get a pretty good grasp on what the patient
might need. So we ask those questions, and they come back to us and say “I want
to kill the cancer” or something similar. That will be a different approach, and
that is why we ask them their objective with cannabis. They come to us saying, “I
can’t sleep” or “my bones hurt from the chemotherapy” or “I need to increase my
appetite” and so on. This means we’re going to treat it very differently, as it’s up to
the patient to drive that conversation - it’s not up to us to impose upon them how
and why to use cannabis. Cannabis has a very special place in medicine, because you
can control the dosage.
With everything else, you have to have the correct dosage or it doesn’t work - it’s
an all-or-nothing sort of thing. For instance, if a doctor gives you prozac, if it works,
you won’t be depressed. However, if you don’t get enough of a dose, you’ll still be
depressed. you’re not going to be a little less depressed. The prozac either works or it
doesn’t.
So cannabinoids work in a matter of “degrees” or a “graduated” way?
I think this is because cannabinoids work through the ECS, where one of its main
functions is to promote homeostasis in the body. So it’s like a chuckle vs. a belly
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laugh. Because cannabinoids don’t target the same way pharmaceuticals do. So if a
person comes to me saying, “I only want to target the CB2 receptors”, I ask “Do you
think there’s a way of doing that, and do you think this is truly ideal? If you can find
a way of doing this, let me know!”
You mentioned comorbidity. One of the biggest areas of comorbidity we

came across in our study was anxiety and depression. People who suffer
from these conditions would often prefer vastly different strains, but yet
many suffer from both. How would a patient go about treating a comorbid
diagnosis of anxiety and depression?
I would approach such a comorbidity by microdosing to begin. And then I would

probably use some form of vaporization for immediate, short-term treatment of
symptoms. Use as small amount of THC as possible so the anxiety isn’t exacerbated.
I would also be careful of the profile of the medicine selected, so there aren’t any
terpenes in there that could exacerbate their anxiety. Some people find alpha- and
beta- pinene to exacerbate their anxiety, for example.
The other thing is to find out whether or not the person is using another
pharmaceutical to deal with their issue. So you have to take them into consideration.
We would probably not treat anxiety and depression too differently, other than the
fact that with the anxiety you will likely need a quick-responding medicine to get
them over the humps when they’re having anxiety attacks or in stressful situations.
We have a guy, for example, who’s so painfully shy that he has major difficulty
with interacting with other people. What he does for a living requires him to go
to customers’ homes. He was smoking all day long before we started treating
him. He would go out to his truck, take out a pipe or a joint every 1-2 hours, and
obviously having to do this all the time isn’t incredibly efficient. So we started him
on microdosing with a sublingual tincture on a ratio of 1:3 THC:CBD in small doses
(<5mg), and he would work for up to 8 hours without any major panic attacks. Now,
every once in a while, it gets on top of him, in which case he has a vaporizer pen
which he can take one puff from, and that’s enough to bring him down and remain
functional.
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So a multimodal medication, basically!
Absolutely. I’m giving a talk on various methods of ingestion and when it’s
appropriate to use each one and when it’s appropriate to combine different
methods. You know, I get up every morning and take my medicine sublingually
and go about my day. But today, I had a meeting and have a headache. So I went
ahead and took a puff off of our Grand Daddy Purple (GDP)-Platinum Kush, and
it was enough to get me over the hump of not feeling well and unmotivated,
and successfully carry on with the meeting. Now, before I go to bed, I’ll take the
nighttime formula and vaporize the same formula so I can get to sleep right away.
The sublingual will take effect while I’m asleep, and I’ll be able to get a full 8 hours
sleep. I’ll wake up feeling fine because it will have worn off by then. So it’s always a
combination. I also use topicals throughout the day.
We’ve spoken about this before, but could you tell us more about any
negative interactions between cannabis and other drugs?
Many drugs are metabolized by the liver enzyme, cytochrome P450 (CY P450)
and others. So, for starters, it’s just so much more complex than just opioids and
benzodiazepines. So, if you look at the pharmacopeia, which we’ve done, CBD is
much more problematic with this than THC. For the most part, the thing we have
to be most careful about is the dosing. We have to adjust the dosage according to
other medications, and the adjustment might have to be on the pharmaceutical
side rather than the cannabinoid side. The same people will use opioids and, as
soon as they add cannabinoids, they’re able to reduce their opioid intake by 50%
immediately. Some of this is because the cannabinoids are providing relief, but
some of it is also because of CBD’s effects opioid metabolization.
There’s other things as well. Immunotherapies are very popular now for firstline
treatment for a lot of cancers. So, with immunotherapies, we’re telling people to
hold off on cannabinoids until they’ve completed their immunotherapy.
And how about immunosuppressants?
That’s a different thing entirely. We’ve had tremendous success with patients
who’ve had organ transplants. We’ve had patients reduce their intake of steroids
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and anti-rejection treatments. The side-effects of these medications are lessened,

and costs are reduced as such medications are expensive. Cannabinoids can also
help with the wear and tear of the organs and prevent inflammation.
One example is a young man with a liver transplant. He had a diagnosis of

hepatocellular carcinoma. When he came to us post liver transplant - and the
cancer had returned in his lungs, they wished to use cannabis with needed
chemotherapy treatments. Because there were delays in beginning his
chemotherapy, he was only using the cannabis for three weeks. He went in for
the blood work before the chemotherapy, and the doctor called the mother back
telling her that her son’s blood numbers were all normal. He still has not had
chemotherapy three years later.
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@erik.nugshots
LeafWell
On Hemp-Based Products
A lot of people think that they can get the cannabinoids they need from hemp.
However, there are some significant issues with hemp products. Yes, there could very
well be some very good hemp-based products out there, and we certainly need to do
more research on the possibilities of using hemp for their cannabinoids. Indeed, for
some people, there may even be some benefit in using hemp-based CBD. Yet, there are
some major issues with hemp-based products, including:
• Hemp is grown for its fiber, not its cannabinoid content. This makes hemp an
unreliable source of cannabinoids, as it doesn’t contain the same amount of
trichomes cannabis grown for medical purposes has.
• This means that, rather than cannabinoids, we’re likely to get plant fats and waxes
rather than the cannabinoids we desire.
• Furthermore, due to the comparatively fewer cannabinoids found in hemp, harsher
extraction methods may be used to get a hold of them. This means industrial
chemicals may be more likely to make their way into the final product.
• This means that many hemp-based products may cause potential health
complications, including urinary tract and bowel infections, especially when used
regularly and in high doses.
• Hemp-based cannabinoid products from Europe (and particularly the UK, where
hemp-based cannabinoid products are treated as medicinal) are generally of
better quality due to testing requirements and regulations. Yet, some of the above
problems are still a concern.
Other issues include the product not containing the levels of cannabinoids they claim
to have, and bad quality products with high amounts of pesticides, heavy metals and
pathogens found to still be in the end product (usually a tincture).
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Synthetic Cannabinoids (SCBs)
As you may have already discovered, there are a lot of “legal” or “semi-legal” products
out there that use analogues of cannabinoids that are not necessarily covered by
the law. In recent years, this has lead to a deluge of “cannabis alternatives” (aka
“designer marijuana” or “synthetic marijuana”), where synthetic cannabinoids such
as cannabicyclohexanol, HU-210, JWH-018 and JW-073 are sprayed onto inert plant
material.
These products are often sold and marketed as “incense” or “herbal blends”. Perhaps
the most well-known products are K2 and Spice, both of which have received significant
media attention, which led to such products becoming illegal in many countries (they
are now Schedule I substances in the US). Other common names include Black Mamba,
Bombay Blue, Zohai, Bliss and probably more than can be listed here. One thing that
is most notable about these products is that they seem to be more dangerous than
natural cannabis. To quote from ‘Synthetic Pot: Not Your Grandfather’s Marijuana’:
“SCBs are a large collection of man-made chemicals, reported in the scientific literature
over decades of research to have affinity for CB1 and CB2 cannabinoid receptors.
Products known as K2 or Spice contain a mixture of SCBs that have been illicitly
synthesized and sprayed onto inert plant material, to mimic the appearance and
psychotropic effects of Δ9-THC in marijuana.
K2/Spice products are falsely marketed to adolescent and other vulnerable populations
as ‘safe’ and/or ‘legal’ alternatives to marijuana, and are widely known to avoid detection
in standard drug screens due to their lack of structural similarity to Δ9-THC.
SCBs present in K2/Spice products produce a variety of dangerous acute and chronic
adverse effects, including psychosis, seizures, tolerance, dependence, and death, with a
greater severity and frequency than observed following marijuana use.
Very little is known about the mechanisms underlying the distinct toxic effects of SCBs
compared to Δ9-THC, but it is likely that they result from actions at both CB1 and non-
CB1 cannabinoid receptor targets.”310
We do not yet know enough about the endocannabinoid system (ECS) to be able
to start messing around with synthetic, experimental analogues of delta-9 THC and
other cannabinoids. The ECS is an extremely powerful system, intimately involved in
homeostasis, brain development and even reproduction. Unwittingly shutting down or
desensitizing one part of the ECS, or the endogenous cannabinoids it produces, could
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prove to be extremely dangerous. Essentially, the message here is: do not take these
substances. They are not the same as well-grown, natural cannabis.
Why are synthetic cannabinoids so much more dangerous than natural cannabis?
Just because a compound may be somewhat structurally similar to THC, CBD etc., it
doesn’t mean that it won’t have significantly different effects at a molecule level. We
do not know exactly how synthetic cannabinoids affect the body and the mechanisms
by which they work. Another problem with synthetic cannabinoids is that they lack the
“entourage effect”. Without the whole gamut of cannabinoids and terpenoids that are
present in the natural cannabis plant, synthetic cannabinoids do not have the same
system of checks and balances, in some ways limiting their usefulness as medicine, and
potentially accentuating their harmful effects.
Yet, when it comes to synthetic cannabinoids, we should not necessarily be too hasty
in writing them off completely in clinical settings. Nabilone (brand name Cesamet)
is a synthetic version of THC that has been used since 1981 as an antiemetic and to
manage pain for patients with cancer, Parkinson’s disease, ulcerative colitis, multiple
sclerosis (MS) and fibromyalgia. Dronabinol (brand name Marinol) is another synthetic
form of THC that is used for chronic pain and as an antiemetic for cancer and AIDS/HIV
patients. Interestingly, nabilone is listed as a schedule II drug, and dronabinol is listed as
a schedule III drug.
Why naturally-occurring cannabinoids are treated so differently, we do not know, but

there does seem to be glaring contradictions in the ways in which authorities schedule
substances. Many of these synthetic, “purified” cannabinoid-based medications are
often not as well-tolerated by patients and, as mentioned previously, may in fact be
less effective, due to the lack of “entourage effect”. Having other cannabinoids and
terpenoids “in the mix” may well increase the therapeutic value of THC, and taking these
away may detract from the value of cannabinoids as medicine.
The CBD-based Epidiolex medicine developed by GW Pharmaceuticals is undergoing

Phase III FDA-authorized clinical trials. The mouth spray Sativex (generic name
naboximols), a 1:1 CBD:THC medication used primarily for MS, is another GW
Pharmaceuticals product that’s available on prescription in many countries outside of
the US. GW Pharmaceuticals seems to focus mostly on plant-derived cannabinoids as
opposed to synthetic versions, so do not necessarily fall under the rubric of “synthetic
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cannabinoid medications”. There are many other whole-plant extracts out there on
the market today, many of which purport to contain many other cannabinoids such as
THCA, CBG, CBC, CBDA and so on. Whether or not the companies making such extracts
all achieve consistent results with regards to their cannabinoid-terpenoid profiles is not
certain, but I hope that this eventually becomes the case. GW Pharmaceuticals, who
have the technical know-how and the licensing to do so, may well have a slightly easier
time than others who are still working “in-between” the legal and illegal worlds, where
government approval is not so easy to come by.
There are other potentially positive aspects to developing and potentially utilizing
synthetic or semi-synthetic cannabinoids. Many cannabinoids are very “unstable” when
out in the open and exposed to air, light, changes in temperature and so on.311 They
start to degrade and change over time, and can end up having entirely different effects.
Moreover, different cannabinoids will have different degradation points.312 There is little
data in this area, but we can definitely be sure that the method of preparation matters.313
Cannabinoids are lipophilic, meaning they love to attach themselves to lipids such as
those found in coconut oil, olive oil, butter etc. Yet, even using different lipids will affect
cannabinoid-terpenoid profiles, as well as how they behave when in the body. There is
still a lot of research needing to be done in this area, but it does seem that oils are one
of the better ways of keeping cannabinoids stable over a longer period of time. Yet, how
stable they are depends on a lot of factors, and there is still much study to be done in
this area.
To add further complications, cannabinoids like CBDA, THCA and many of the acidic
cannabinoids are notoriously difficult to keep stable. Even delta-9 THC is difficult to keep
stable, and so is delta-8-THC, which is less psychotropic and expensive to prepare314 but
has similar medical properties as THC. However, as such compounds are often not found
in huge abundance, they can become very difficult to extract.
In order to get around such difficulties, synthetic and semi-synthetic cannabinoids

may be a simpler and more efficient way of doing things. Adding a compound to a
natural cannabinoid in order to make it more stable could be the only way of ensuring
consistent dosage of CBDA, CBC and so on. Alternatively, finding out all we can about
a natural cannabinoid and then creating a synthetic, well-tolerated, safe and clinically-
tested “mimic” may in some instances be the only solution to getting the amount of
cannabinoids we need for specific medical and therapeutic uses.
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Naturally-derived cannabinoids and terpenoids seem to be better tolerated by

most patients, but this does not mean we should completely discount all synthetic
cannabinoid-based medications. Eventually synthetic cannabinoids that are developed
may actually help with reducing the negative side effects of natural cannabis. For
example, THC could be useful for someone with MS and/or chronic pain, but someone
with schizophrenia should probably avoid it, but scientists may be able to isolate what
component of THC badly affects schizophrenic patients. It also appears that different
cannabinoids can help or harm different forms of cancer (although to what extent this
is the case is not actually known315).
We ought not to be scared of the word “synthetic” when it comes to cannabinoids,

as it could mean something completely different when used in a medical and
pharmaceutical setting - it is the untested synthetic cannabinoids that are marketed to
recreational users that are of concern. One of the main positives of legalization is that it
will bring with it proper regulations, which will stop harmful synthetics from entering
the market.
In summary, synthetic and semi-synthetic cannabinoids and terpenoids that have been
tested for safety and efficacy have a part to play in making new and better medications.
In the meantime, naturally-derived cannabinoids and whole-plant extracts are
generally well-tolerated by patients. In addition, it seems that the ‘entourage effect’ is
hugely important, and may well “buffer” the negative effects of other cannabinoids. At
the same time, not every condition necessarily needs all the cannabinoids and terpenes
found in the cannabis plant.
This means that some “engineering” is required in order to get the profiles we need,
whether this is through creating SCBs or genetically manipulating the plant, as we do
with many fruits and vegetables. In some instances, we may need to stabilize a natural
cannabinoid using semi-synthetic methods. Finally, we should not be afraid of the word
“synthetic” - we should be afraid of untested, harmful substances arising from the lack
of regulations being released onto the market.
LeafWell
4
CHAPTER
MEDICATION
AND SIDE
EFFECTS
202 MEDICATION AND SIDE EFFECTS
Cannabis vs. Other Medications
From a practical standpoint, it is imperative that we adequately investigate

cannabinoid-terpenoid profiles as many can potentially be used to “approximate”
or “mimic” the effects of other drugs, but without the dangerous and negative side
effects. If it is true that cannabinoids may have “Indirect effects on opiate, serotonin,
NMDA, and γ-aminobutyric acid receptors which allow endocannabinoids to modulate
other networks”,316 then we must see in which ways they interact with other drugs that
work on the same receptors. In this way, cannabis may be a real answer to the opioid
epidemic that is devastating the U.S. and many parts of the world, as we may be able to
achieve opioid-like effects without having to use opioids.
Cannabinoids (in particular THC) may be able to affect opioid receptors, but via the
endocannabinoid system, rather than by going straight through to the opioid receptors.
THC may be the master key to a number of different locks, or receptors. Antiepileptic
drugs (AEDs), many of which work by controlling cells’ calcium ion channels, may
be approximated by CBD. Antidepressants, which work mostly on serotonin and/
or norepinephrine receptors, may be also be affected by CBD. Working out what
cannabinoid-terpenoid profiles work on which receptors, in what ways, and for which
specific conditions, could help us create unique, safe medications with both broad
spectrum and tailored medical applications. I like where this is going. Pain relief,
decreased seizures and anxiety without potentially fatal side effects?
Of course, due to these physiological effects, we must take care to ensure there is not
any negative interaction between cannabinoid-terpenoid-based medications and
other, potentially life-saving medications. For example, taking CBD in combination with
benzodiazepine-based AEDs may make overdose on AEDs more likely. Similarly, as CBD
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MEDICATION AND SIDE EFFECTS 203
may affect immune response, we must also be careful of any potential interaction with
immunosuppressants, antivirals, antifungals, antibiotics and so on. Those undergoing
immunotherapy for cancer may also want to be careful of cannabinoids, especially CBD.
This is because many drugs are processed by the liver enzyme, cytochrome P450
(CYP450). CBD in particular “desensitizes” this enzyme, meaning other drugs cannot
be processed as easily. Conversely, this also potentially means that lower doses of other
drugs and medications may be needed. According to Drugs.com, cannabis interacts
with a total of 603 drugs, with 129 being major interactions and 474 having moderate
interactions, as well as a moderate interaction with alcohol.317 Without having to list
them all, many of the interactions seem to be with benzodiazepines (e.g. diazepam,
lorazepam, alprazolam), non-benzodiazepines (e.g. zolpidem), opioids (e.g. morphine,
tramadol, hydrocodone) and some types of antidepressants (e.g. sertaline).
Another problem that arises when looking at cannabis as medicine is trying to gauge
its efficacy while controlling for other variables. For example, cannabis is often used to
treat the side-effects of chemotherapy, but many claim that cannabinoids may be used
to actually combat the cancer as well. However, a cannabinoid-only treatment method
for cancer is an experiment that it is unlikely anyone would attempt, for obvious reasons.
So for the foreseeable future, cannabis will continue to be a valuable tool, used mainly to
treat the side-effects of traditional chemotherapy and radiotherapy treatments. If it does
help decrease the proliferation of cancer cell, it will be an uncredited actor for now.
So far, the evidence shows that cannabis is relatively safe in comparison to many
drugs, prescribed or not. Moreover, in some cases, cannabis may even be more
effective at managing pain and inflammation than many prescription drugs, especially
anticonvulsants/antiepileptic drugs (AEDs), opioids and upper spectrum NSAIDs.318
Another advantage is that you cannot overdose on natural cannabinoids alone, or at
least the chances of overdose are theoretical. To quote Judge Francis L. Young:
“At present it is estimated that marijuana’s LD-50 is around 1:20,000 or 1:40,000. In

layman terms this means that in order to induce death a marijuana smoker would have
to consume 20,000 to 40,000 times as much marijuana as is contained in one marijuana
cigarette. NIDA-supplied marijuana cigarettes weigh approximately .9 grams. A smoker
would theoretically have to consume nearly 1,500 pounds of marijuana within about
fifteen minutes to induce a lethal response …
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In strict medical terms, marijuana is far safer than many foods we commonly consume.
For example, eating 10 raw potatoes can result in a toxic response. By comparison, it is
physically impossible to eat enough marijuana to induce death. Marijuana, in its natural
form, is one of the safest therapeutically active substances known to man. By any
measure of rational analysis marijuana can be safely used within the supervised routine
of medical care.”
The reason for this? It seems that the human body breaks down the natural
cannabinoids found in cannabis very quickly, meaning a toxic level is next-to impossible
to meet. After all, consuming the supposed fatal dosage of cannabis - 1,500 pounds of
anything in 15 minutes - would kill anyone. Another reason, is that cannabinoids seem
to work on the allosteric sites of the cell, meaning they influence cells to behave in a
certain manner “indirectly” or “semi-directly”. Cannabinoids also seem to influence
other compounds that work on the orthosteric sites, without having to “overload” the
main or “orthosteric” site of the cell. The endocannabinoid system is a G protein-coupled
receptor, meaning it does not have the specialized properties other receptors such as
dopamine and opioid receptors have. This means that overdose on phytocannabinoids
is difficult to achieve, although using synthetic cannabinoids may have more harmful
effects due to the relationship between the ECS and the other receptors in the system.
Now, this is not to say that cannabis is completely harmless. We will never discover
how phytocannabinoids affect our bodies, for the good or bad, until the federal
government legalizes and down-classifies cannabis, or at least gets rid of the obstructive
regulations that limit its research. The rules and regulations as they stand have lead
to the development of synthetic cannabinoids (SCBs), which are untested and have
very extreme effects, which natural phytocannabinoids do not seem to. Synthetic
cannabinoids are potentially very dangerous. The ECS is a very sensitive system that
affects homeostasis - shutting off or desensitizing a part of it could prove to be very
dangerous, and it seems that these SCBs may do just that.
If research proves that cannabis is harmful, we need to know that, and act accordingly.
The question of treating disease with cannabis should not rely upon an administrator
with no scientific training or an elected official with a political agenda. Hopefully, that
day will come soon.
LeafWell
Effects on the Brain
There is no evidence that cannabis use causes a loss of grey matter or white matter.
However, there may be some reductions in hippocampal volume. This is what may
cause the impairment of short-term memory after using cannabis. Yet, for older people,
a little bit of cannabis may boost the brain319 rather than dull it. CBD may also have
neuroprotective effects, protecting the brain from stroke and other traumatic brain
injuries (TBIs) as well as diseases that affect the nervous system. The main negative
effects on the brain seem to occur if the user is very young and not using a medically-
controlled dosage. Children, teenagers and those under 25 should ideally avoid cannabis
use unless medically necessary.
Cardiac Problems
Using cannabis seems to cause an increase in heart rate and blood pressure whilst
sitting down, and a decrease in blood pressure when standing up. In the short-term, this
may increase the risk of heart attack. However, THC is a vasodilator, meaning that it can
widen the arteries and lower blood pressure overall.
Many of the cardiac problems to do with cannabis may be due to it being smoked
rather as opposed to anything about the cannabinoids themselves. Smoking cannabis
may increase the likelihood of myocardial infarction (heart attack) and stroke, as well
as decrease exercise tolerance. Of course, when it comes to using medical marijuana,
it is perhaps better to find alternatives to smoking it wherever possible in order to take
advantage of its health benefits.
Whilst using cannabis may cause some cardiac problems in some people, it is arguable
that these can be mitigated to some extent by not smoking cannabis. Now, whilst
cannabis smoke may not necessarily be as carcinogenic as tobacco smoke,320 it makes
sense intuitively that inhaling any type of burning matter into your lungs may cause
cardiovascular problems.
So, how does cannabis compare with other prescription medications in this area?
Pharmaceuticals aren’t smoked, obviously, so there is one advantage there. Yet,
the advantages may end there, depending on the pharmaceutical we’re talking
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about. Opioids, benzodiazepines and barbiturates are central nervous system (CNS)
depressants, and so slow down heart and breathing rate, causing a loss of consciousness
and potentially being fatal. The chances of a fatal overdose are increased if opioids and
benzodiazepines are being used in conjunction with one another, and/or with alcohol.
Cancer
There is, so far, no definitive evidence found linking cannabis use and cancer, although
there may be some. To quote from “Medical Consequences of Marijuana Use: A Review
of Current Literature”:
“[T]here does appear to be an increased risk of cancer (particularly head and neck, lung,
and bladder cancer) for those who use marijuana over a period of time, although what
length of time that this risk increases is uncertain.”321
The same study also states:
“Unfortunately, methodological limitations in many of the reviewed studies, including

selection bias, small sample size, limited generalizability, and lack of adjustment for
tobacco smoking, may limit the ability to attribute cancer risk solely to marijuana use.”
Of course, there’s a lot of research out there regarding cannabis’s ability to treat cancer,
and cannabinoids may potentially be used to kill cancer cells. As such, it may well be
the smoke that’s carcinogenic, not necessarily the cannabinoids themselves. However,
more research on cannabinoids needs to be done before we can say that they are non-
carcinogenic (or even anti-carcinogenic), and certain cancers may proliferate rather than
be destroyed if the right cannabinoids aren’t used.
Properly researched, cannabinoids may well be a form of “phytochemical therapy” to

be used in conjunction with other methods of cancer treatment. This is on top of the
antiemetic and pain killing effects cannabis may have. This multi-pronged effect means
that cannabis may be the ideal replacement for the opioids usually prescribed cancer
patients to kill their pain.
Cannabis contains polycyclic aromatic hydrocarbons (PAHs), and burning these and
inhaling the smoke can potentially be a cause of many different kinds of cancer. This is
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no different from inhaling the smoke of burning matter of any kind, and it is arguable
that 1) cannabis smoke is not necessarily as carcinogenic as other kinds of smoke (in
particular tobacco smoke); and 2) the cannabinoids provide some form of protection
against the damage caused by smoking. However, it is safe to say that inhaling the
smoke of burning matter of any kind is usually less than ideal, and this applies to
cannabis, too.
LeafWell
5
CHAPTER
THE BIOLOGY
OF THE
CANNABIS
PLANT
210 THE BIOLOGY OF THE CANNABIS PLANT
The Basics
There are 1,200 known compounds in the cannabis plant, with 144 of these being
cannabinoids and over 200 terpenes (some approximate about 212). There may well be
many more compounds in cannabis that we have not discovered as of yet. Of course,
not every plant will contain every single cannabinoid or terpene - this depends very
much upon strain, environment and the growth medium, as well as length of flowering
period.
Sativa
Narrow leaves
Spread out branches
Taller
Produces fewer flowers

Effects:
Spring green, red or golden buds More uplifting
and energetic
Indica
Broad leaves
Closer branches
Shorter and bushier
Produces more dense flowers

Effects:
Dark olive green, purple buds More relaxing
and sleepy
Ruderalis
Different sized leaves
Smaller in size
Scrawny branches
Auto-flowering, often hybridized

Effects:
with indicas or sativas Not psychoactive, but
has therapeutic CBDs
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THE BIOLOGY OF THE CANNABIS PLANT 211
Cannabis sativa is an annual, and completes its entire life cycle from seed to
germination within one year and dies. It is also herbaceous, meaning that the plants
that have no persistent woody stem above the ground, and dioecious, with both male
and female plants, and usually an inability to pollinate themselves). It is a flowering plant
that needs less that 12 hours of sunlight per day. There are three distinct subspecies:
Cannabis sativa, Cannabis indica and Cannabis ruderalis. Each of these subspecies can
all be “crossed” and hybridized. Cannabis sativa usually grows tall and has long, spindly
leaves. Cannabis indica usually grows short, with broader leaves. Cannabis ruderalis has
broad leaves, and rarely grows above 2 feet tall. Interestingly, C.ruderalis is rarely seen in
the U.S. but its leaves resemble the classic depiction of ‘pot’ in graphic art. Psychoactive
cannabis may also be crossed with non-psychoactive hemp plants. Cannabis sativa hails
from the Cannabaceae family, which includes other genera such as Humulus (hops) and
Celtis (hackberries), just in case you are interested.
Male cannabis plants are sometimes called staminates, and are usually taller and less
robust than female (aka pistillate) cannabis plants. Cannabis also has hermaphrodite
plants, meaning they can present both male and female flowers in times of
environmental stress.
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Cannabis leaves have a “hand”-like shape, with serrated “fingers”, which usually
grow in 1, 3, 5, 7 and 9. The number of “fingers” a cannabis plant has is determined by
environment and genetics. Some have postulated that inhalation of the five fingered
plant led to the term ‘high five’, but this seems a bit of a stretch.
When it comes to cannabis, you will often hear or read about genotypes and
phenotypes. Genotype refers to the genetic constitution of an organism at the tiniest
level, whereas phenotype refers to what the organism looks like. An organism’s
genotype can be affected by the environment it is in. For example, if cannabis grows at
high altitudes, low oxygen levels can cause its genes to express traits that will allow it to
thrive in that environment. In relation to cannabis, this means that two cannabis plants
of the same genotype can display different characteristics when grown in different
environments.
When it comes to medical marijuana, female cannabis plants are often the most
desired, as they produce the pistillate flowers (aka “buds”) that people utilize for their
physiological effects. However, male plants can be desirable for their genetics, as
they can be used to fertilize females and create variation in the gene pool, carry on a
specific genetic line and make new crosses. Male plants also have unique cannabinoid-
terpenoid profiles of their own.
LeafWell
As with most plants and living organisms, the germination of cannabis seeds is
triggered by darkness, moisture and warmth. Germination can take between 12 hours
and 7 days to occur, with older seeds usually taking longer to germinate as the seed
shell is tougher to break through. When the right conditions are met, and the seed
shell has been broken through, the plant emerges as two round leaves and a single root
tendril. Kept appropriately, cannabis seeds can lay dormant for many years, perhaps
decades, although the longer the cannabis seed has laid dormant for, the lower the
germination rate.
@erik.nugshots
LeafWell
Cannabis grows favorably under the following conditions:
1. Seed & Grow Space
Start with an easy-to-grow indica-sativa hybrid, such as Skunk #1,

or an autoflowering plant.
Only grow 2 - 6 female plants.
Good seeds should be brown-coloured, not green.
Set up your grow space, growing inside is more discreet. Keep

@bcbubbleman
things simple by using soil, as it contains all the nutrients you

need.
Cannabis plants thrive in clean, dry and warm environments.

Consistent temperatures lead to better grows.
2. Germination
1) Line plates with a few layers of dampened kitchen towels, then

put the seeds on top;
2) Cover the seed with another few layers, draining off any excess
water;
3) Cover your seeds with another plate;
4) Leave the seeds in a warm, dark place away from direct sunlight.
It will take between 24 hours and 7 days for the seeds to sprout.
5) Once the seed has sprouted, it’s ready to be “potted”. Place the
@bcbubbleman
plant root-first into the soil, approximately 1 ¼ inch below the

surface. Lightly cover with soil, and put in a well-lit area.
6) Once the seedlings start sprouting leaves, give it as much sunlight

as possible for 1 - 4 weeks. Do not overwater the plant, and watch
out for mold and mildew.
LeafWell
3. Vegetation
After 6 - 7 days re-plant into a larger container. It will need between

13 and 24 hours (18 hours is the usual amount) of sunlight per day.
For indoor plants, artificial lights should be 100-120 watts. The

ideal temperature is between 68 to 77 fahrenheit. Keep fresh air
circulating in the room with a fan.
Remember, your plant needs both light and dark. Cannabis grows in
cycles of 18 hours of light and 6 hours of dark during the vegetative
period. Water closer to the stalk to start, but move further away
from the stalk as it grows bigger and the roots grow outward to
@bcbubbleman
reach the root tips.
Start “topping” your plants, where you cut in-between the nodes at
the top of the plant, in order to produce new branches, each with a
“cola” of cannabis.
4. Flowering
To flower, the plant needs 12 hours of light and 12 hours of darkness

a day. Keep watering to hours when it is light. Lights as low as 200
watts can trigger flowering, but 400 watt - 600 watt lights are best.
Make sure your lights don’t raise the temperature. Having fans will
help with keep your grow room cool, as well as strengthening the
plant’s stems.
The ideal temperature for cannabis at this stage is between 77 and

82.4 degrees fahrenheit during the daytime, with a nighttime drop
in temperature of 5 degrees, to 68 - 73.4 degrees fahrenheit.
Your plant needs to be staked and trellised at this point (bamboo

sticks are a popular choice) in order to support the buds it will
produce.
Do not prune the plant for 2 weeks into the flowering stage - doing
@bcbubbleman
so may upset the plant’s hormone cycle.
“Flush” the cannabis with rain or distilled water, and do not add
any extra nutrients to the soil in the last 2 weeks of flowering pre-
harvest.
LeafWell
5. Harvesting and Drying
Check if you cannabis flowers are ready by seeing if the hairs on the
flowering buds have turned to a different colour, such as red, pink,
yellow or purple.
To harvest, cut the plant at the stem, remove the leaves and hang it
to dry. This usually takes 7 - 10 days in a clean, dry, dark room.
@bcbubbleman
As well as the buds, keep leaves with lots of trichomes on them to

make concentrates, oils and homemade tinctures.
It is recommended that you ‘cure’ the cannabis buds in a mason jar

for at least 2 weeks, preferably 4.
6. Storing
Store in mason jars no more than two-thirds full, out of direct

sunlight, in dry conditions.
Well-dried, well-cured and well-stored cannabis can keep for up to

2 years in mason jars, peaking in potency between 2 and 6 months.
Potency usually reduces after the 6 - 8 month mark.
The ideal conditions and growth pattern vary between different varieties, or “strains”,
of cannabis. Sativa-dominant varieties usually take longer to flower (10 weeks +) and
require more light and acidic soil, whereas indica-dominant varieties are quicker to
flower (between 6 and 10 weeks) and do not require as much light or as acidic a soil.
Sativas tend to have a shorter vegetative stage as well, lasting around 2-3 weeks,
in comparison to indicas’ 1 - 2 months. Ruderalis (autoflowering) varieties enter the
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flowering stage based upon the maturity of the plant rather than the light cycle. This
makes sense when looking at the environment each type of cannabis grows in. Sativas
usually grow in hot, equatorial climates with lots of sun and rain. Indicas usually grow in
colder climates and high altitudes. Ruderalis is a species of cannabis native to Central
and Eastern Europe and Russia and thrives in a colder, more dictatorial climates.
However, due to hybridization on top of the already complex genetics of the cannabis
plant, differences in environment and nutrition can cause certain genes to switch
“on” or “off”. This means that a sativa-dominant cannabis plant may display indica
characteristics under certain conditions, and vice-versa. Cannabis ruderalis, on the
other hand, does not seem to have such characteristics if they have not been crossed
with any other type of cannabis plant; it is the lone wolf of the cannabis subspecies.
Some have suggested that these factors make Cannabis ruderalis a separate species
from Cannabis sativa, although others argue that the structure and phytochemical
composition of Cannabis ruderalis are similar enough to warrant inclusion into the same
family. Moreover, ruderalis can be hybridized with sativa and indica strains, suggesting
a relationship on a deeper level. In botany, there are often multiple answers to every
question.
Jeff Raber
Why is cannabis medicine, and why does it seem to work for so many
conditions?
Well, what’s your definition of medicine? Cannabis does provide a very positive
physiological response. As to why cannabis works the way it does, I think that
speaks to the endocannabinoid system (ECS) and how it works - that is a network
of receptors and molecules that interact with those receptors that generate
physiological responses.
How much should I take, and is there a strain or cannabinoid profile that’s
best for my condition?
How much you should take should be the minimum effective dose. Basically you
want to use as little as possible to generate the best therapeutic response.
LeafWell
Concerning which type of cannabis composition is best for you is an exceptionally

complex question. I don’t think we can recommend this based on any type of strain
names. We’re still trying to learn which compositions are best for what; and what we
have recently learned is that it really relates to a whole plant cannabis composition.
How many molecules can we look at, and how many can we standardize, control
and deliver in a consistent fashion? The end consumer then needs to standardize
their use at home or their preferred setting as well.
Have you noticed any particular profiles to be useful for specific conditions?
I have, but it’s very general and anecdotal. It does seem to be that there are a lot of
positive responses from combinations of cannabinoids. As for which terpenes elicit
which responses is pretty much still misunderstood and not at all well understood
I would say. That’s a difficult part to standardize. You have pain relief for people
who are taking both THC and CBD. Cannabinoid acids are starting to become
more interesting for their utility, but I don’t know if there is one simple answer for
everybody, it’s a very individualized approach, depending upon what is your exact
ailment. Someone will say the broad-based word “pain”, but which type of pain?
Neuropathic pain? Inflammatory-driven pain? Where is the pain? All of those things
might really be important in understanding which type of chemical composition is
given, and in which form.
Is there a method of ingestion that is best or is better than another?
That’s an individualized preference, in some respects. Inhalation can be rapid.

Sublingual delivery can give you similar molecules in a slightly slower fashion.
But oral consumption will give you very different molecules in the blood. It can
mean a significantly different effect. Some people prefer oral-only, and others will
swear by “only inhalables”. I don’t think there’s really a best answer on that one. It
might just be your individual preference. Sometimes, it’s a mixture of consumption
methods, because you might need a really rapid response if you’re in extreme pain
or anxiety where you might not be able to wait two hours, but you want the effects
to last a prolonged period of time so you don’t have to inhale every ten minutes. So
sometimes, you may need both.
LeafWell
Does the oil base affect the effect cannabinoids and terpenoids have? I.e. will
a product based on olive oil differ from one based on coconut oil?
Marinol, from my understanding, is based on sesame seed oil and is about 40%
available. But in a general sense, you might have very different absorption rates
depending upon the method used to extract the cannabinoids. MCT oil seems to
be a little bit more effective for absorption, but again that could be for various other
reasons. Was there something else in that cannabis oil, like terpenes or cannabinoids
that improved that absorption? We just don’t know that very well, and that is why
patients need to titrate themselves with a specific product that is standardized. That
would be the best approach for a new patient. Start low and work your way up to the
therapeutic amount.
Has there been an improvement in how well standardized many cannabinoid-

based products are?
No, not really. I think there is a little bit more standardization going on, but it’s still
gravely, gravely lacking. Very, very few products on the market are standardized in a
broad-based system.
@bcbubbleman
LeafWell
A Brief Guide to Some of the Most Popular

Cannabis Strains
There is a lot of politics in the world of cannabis breeding, with clashes over who created
what, as well as who makes the best strains, and most stable seeds. In the interest of
science, breeder/growers should check their egos at the door, and rally behind the cause
of medical marijuana by breeding cannabis strains with specific cannabinoid-terpenoid
profiles with the treatment of medical conditions in mind.
In the past, increasing the THC concentration of a particular strain was what every
grower/breeder strove for. For obvious reasons, producers sought maximal yield, size and
potency from a given crop, which led to hybrids with ever-increasing amounts of THC,
with little or no CBD to counteract it. However, as more scientists started to discover the
health benefits of various other phytocannabinoids, terpenoids and flavor profiles, the
cannabis-growing community took notice. Interesting hybrids started developing, and
breeders began to look at the things they may have lost during hybridization. Now there
is an effort to rediscover these rarer phytocannabinoids and terpenoids, and get them
back in the current gene pool. Those who decided to keep the strains of yesteryear due
to their uniqueness may have done the medical world a huge favor by saving genetics
that may have otherwise been lost.
LeafWell
When it comes to the question of “What should I choose? Indica or sativa?”, there’s
probably no better answer given so far than by Dr. Ethan Russo, neurologist and
medical scientist specializing in cannabis:
Dr. Russo
There are biochemically distinct strains of Cannabis, but the sativa/indica distinction
as commonly applied in the lay literature is total nonsense and an exercise in
futility. One cannot in any way currently guess the biochemical content of a given
Cannabis plant based on its height, branching, or leaf morphology. The degree of
interbreeding/hybridization is such that only a biochemical assay tells a potential
consumer or scientist what is really in the plant. It is essential that future commerce
allows complete and accurate cannabinoid and terpenoid profiles to be available.
CCR
Sativa is often described as being uplifting and energetic, whereas indicas are
described as being relaxing and calming. Can you speculate on what could be the
basis for these perceived differences?
Dr. Russo
We would all prefer simple nostrums to explain complex systems, but this is futile
and even potentially dangerous in the context of a psychoactive drug such as
Cannabis. Once again, it is necessary to quantify the biochemical components of a
given Cannabis strain and correlate these with the observed effects in real patients.
Beyond the increasing number of CBD predominant strains in recent years, almost all
Cannabis on the market has been from high-THC strains. The differences in observed
effects in Cannabis are then due to their terpenoid content, which is rarely assayed,
let alone reported to potential consumers. The sedation of the so-called indica strains
is falsely attributed to CBD content when, in fact, CBD is stimulating in low and
moderate doses! Rather, sedation in most common Cannabis strains is attributable
to their myrcene content, a monoterpene with a strongly sedative couch-lock effect
that resembles a narcotic. In contrast, a high limonene content (common to citrus
peels) will be uplifting on mood, while the presence of the relatively rare terpene in
Cannabis, alpha-pinene, can effectively reduce or eliminate the short-term memory
impairment classically induced by THC.” 332
LeafWell
Are there breeders and growers that are “better” than others? Surely, but we cannot say
for sure who is the “best”. However, I can say with confidence, this type of competition is
one that benefits us all. Many of the best breeders and growers are likely to be working
outside of the spotlight, probably developing cannabis varietals rarely seen in the
mainstream. Yet, this is not to say that some of the big breeders and growers haven’t
contributed in a major way to the way cannabis looks today. Sam the Skunkman,
Shantibaba, Ed Rosenthal, Jorge Cervantes, DJ Short, Swerve, TGA Subcool, Nevil
Schoenmakers, the Greenhouse Seeds team, The Sensi Seedbank, Soma, Reeferman,
Kyle Kushman, Underground Originals … The list of legendary names and brands
goes on. Finding the “best” might be a case of personal preferences, as well as growth
medium and environment. Many of the “best” strains are likely to be grown by specialist
growers, who do not necessarily even have names for their strains.
Here are some of the most popular cannabis strains available today. We have used
test results by Digamma Labs and reports from Leafly to try and determine their
cannabinoid and terpenoid profiles, but there may be compounds that are missed. We
would love to see repeated cannabinoid-terpenoid test results of these strains when
grown in different environments, but alas, it is difficult to get such information without
growing thousands of plants, which we can assure you is illegal for us and most citizens
of the world.
@erik.nugshots
LeafWell
Please note: different expressions of the same genetic will have different cannabinoid-terpenoid profiles. Additionally, different
environments and growing mediums will also affect which cannabinoids and terpenoids the plant develops. The effect a particular
variety of cannabis has may differ from individual-to-individual.
Type Most Prominent Cannabinoids and Effect (Note: May Differ from Per-
Strain (Sativa/Indica/Hybrid) Terpenoids (Possibly) son-to-Person and Phenotype to Phenotype)
Blue Dream Hybrid - Sativa THC, CBD, CBG, THCV, CBC. The broad terpene profile of Blue
Dominant (Blueberry Particularly high in alpha- and beta- Dream suggests that it will have
x Super Silver Haze) pinene,caryophyllene and linalool. a range of effects, depending on
Myrcene is also commonly found in high whether it leans more on the sativa
concentrations, but occasionally is not or indica side. The caryophyllene
present or has little presence, especially may help create some of the more
if there is a lot of caryophyllene in it. Has “spicy” flavors (redolent of many
a broad and varied terpene profile that haze varieties) as well as “up” effects.
includes trace amounts of limonene The myrcene may counteract this to
and humulene as well. Nerolidol is often some extent, and the low amounts
found, as well as small amounts of of limonene may mean this strain
limonene. doesn’t ten to get too overwhelming.
Blue Dream is very popular, and this
broad range of effects might be one
of the reasons why. Those suffering
from anxiety and depression praise
Blue Dream.
OG Kush Hybrid (Chemdawg x THC, CBD, CBG; trace amounts of CBN, The terpene profile of OG Kush
[Lemon Thai x Hindu THCV, CBC and CBL. Limonene and suggests that it would have a
Kush]) myrcene are the main terpenes found balanced head-body effect. Some
in OG Kush, as well as pinene and have noted OG Kush’s ability to help
caryophyllene. with their pain.
Gorilla Glue Hybrid - Indica Plenty of THC and CBG. Some CBN. Has May be great for sleep and pain.
No.1 (GG No. 1) Dominant ([Sour some CBD, but not huge amounts. High
Dubb x Chem Sister] in pinene. May also contain plenty of
x Chocolate Diesel) myrcene.
Gorilla Glue Hybrid - Indica As GG No. 1 and GG. No. 4 come from As above.
No. 4 (GG Dominant, although the same stock, they may have similar
No. 4) maybe slightly more effects. However, GG No. 1 is said to
sativa-leaning than be more “piney”, so there may be
GG No. 1 ([Sour Dubb some slight differences between each
x Chem Sister] x cannabinoid-terpenoid profile.
Chocolate Diesel)
Sour Diesel Sativa Dominant THC, CBD, CBG, CBC, CBL and trace Energetic, with some body effect due
(Chemdawg ‘91 x amounts of THCV. Myrcene and to the myrcene. May be good for pain
Super Skunk) limonene may be the main terpenoids, and depression.
with small amounts of pinene and
caryophyllene.
LeafWell
Strain (Sativa/Indica/Hybrid) Terpenoids (Possibly) son-to-Person and Phenotype to Phenotype) Stra
Blackberry Indica (Afghani x THC, CBD. May contain high amounts Relaxed, body effect. May be good for Seq
Kush Blackberry) of CBD. Linalool and pinene may be pain, insomnia and headaches. Stra
present in high amounts.
Skunk No. 1 Hybrid (Afghani x THC, with some CBD. Skunk No. 1 Likely a mixed mind-body effect.
Acapulco Gold x has wide parentage, and so may Uplifted yet relaxed. Could be great
Columbia Gold) display a wide range of cannabinoids for increasing appetite and reducing
and terpenoids. Limonene, myrcene stress and anxiety. Juic
and pinene may be the most
common terpenoids, alongside some
caryophyllene.
Northern Indica (Afghani), THC, CBD, CBG. May contain high A relaxed, body effect thanks to the Gra
Lights (NL) although some amounts of CBD. A myrcene- myrcene, humulene and linalool. Pur
contemporary heavy strain. Nerolidol, humulene, However, due to the presence of
varieties may contain caryophyllene, linalool and pinene can terpenoids like caryophyllene may
some sativa genetics also be found. Northern Lights may also prevent some of the “couchlock” effect
crossed into it in contain trace amounts of ocimene. in some. May be good for pain and
order to improve insomnia. The CBD may help with
vigor. inflammation.
Aca
Chemdawg Hybrid - Sativa THC, CBD. A very limonene-heavy strain. Energizing, although some body Gold
Dominant (Unknown Also contains nerolidol, humulene, effect is likely due to the humulene,
origin, possibly Thai) caryophyllene, linalool, myrcene and linalool and myrcene.
pinene.
Girl Scout Hybrid - Sativa THC, THCv, CBG, CBN, CBC and CBL. Energizing and perhaps even appetite
Cookies (GSC) Dominant (OG Kush Low in CBD. High in limonene and suppressing. Could be great for
x Durban Poison) caryophyllene, with some myrcene and diabetics and those suffering from
pinene. depression. However, those suffering
from anxiety may wish to avoid such
a strain - something to bear in mind Che
when strains come with high amounts
of limonene and caryophyllene.
Cheese Hybrid (Skunk No. 1 THC, CBD, CBN, CBG. A very myrcene- Sleepy, relaxed and perhaps hungry.
phenotype) heavy strain, with some nerolidol, Some have noted some uplifting,
humulene, caryophyllene, limonene and energizing effects, suggesting there
pinene. may be some significant sativa Tan
influence in certain phenotypes. Could Pow
be great for pain and insomnia.
Platinum Blue Hybrid - Indica THC, CBD, CBG, CBN. Plenty of pinene Relaxed, yet perhaps not necessarily
Dream Dominant (Blueberry - both alpha and beta - in Platinum as “couchlocked” as usual due to
Kush x Haze) Blue Dream. Myrcene, nerolidol and some haze influence. Not as high in
caryophyllene are also commonly found myrcene as some other indicas. Could
in this strain. Some linalool, limonene be useful for pain and anxiety.
and humulene is also present.
LeafWell
Strain (Sativa/Indica/Hybrid) Terpenoids (Possibly) son-to-Person and Phenotype to Phenotype)
Sequoia Sativa (White THC, CBN. Caryophyllene and limonene Likely to be uplifting and energizing.
Strawberry Strawberry x White are the main terpenes in Sequoia Perhaps not great for those prone to
Nightmare) Strawberry, with humulene, linalool, anxiety, but those with ADD/ADHD
myrcene and pinene also being present. and/or depression may possibly find
Trace amounts of nerolidol may be this strain helpful.
present on occasion.
Juicy Fruit Hybrid (Afghani x THC, CBD. High in terpinene, as well as Focused and uplifted. Possibly very
Thai) caryophyllene, limonene and ocimene. good for depression and ADD/ADHD.
Also contains linalool, nerolidol,
humulene and pinene.
Grand Daddy Indica (Purple Urkle x THC, CBD, CBC. Myrcene, linalool and Relaxed and sleepy. Could be great for
Purple (GDP) Big Bud) caryophyllene seem to be the main pain, depression and insomnia.
terpenes in GDP. Limonene and nerolidol
amounts can range from small to high
as well, and humulene and pinene are
also present. May contain trace amounts
of ocimene on occasion
Acapulco Sativa (Landrace THC, THCv. A very caryophyllene-heavy Uplifting, energizing and focused, but
Gold Strain) strain. Also tends to contain lots of relaxed. Perhaps not great for those
myrcene and a little pinene, but not in all prone to anxiety, but could be great
cases. Interestingly, when Acapulco Gold for pain, fatigue and depression.
contains lots of beta-pinene, it contains
little or no myrcene, and when there’s
plenty of myrcene, there’s little pinene.
Limonene, humulene and linalool are
also common terpenes in Acapulco Gold.
May contain trace amounts of nerolidol.
Cherry Diesel Hybrid (Cherry OG x THC, some CBD. Plenty of terpinene, Euphoric and relaxed, yet uplifted. A
Turbo Diesel) with limonene, myrcene, caryophyllene, balanced mind-body effect. Could be
ocimene, linalool and pinene following. great for fatigue, stress, headaches
May contain some humulene and and pain.
nerolidol, and is sometimes low in
ocimene.
Tangerine Hybrid - Sativa THC, CBD. A terpinene-heavy strain, with Focused and uplifted. Could be great
Power Dominant (Agent myrcene being the next most abundant. for stress, depression and the CBD
Orange x Blue Also contains some nerolidol, humulene, may make this strain helpful for
Power) caryophyllene, linalool, limonene, inflammation as well.
ocimene and pinene.
LeafWell
Strain (Sativa/Indica/Hybrid) Terpenoids (Possibly) son-to-Person and Phenotype to Phenotype) Stra
Blue Power Indica (Power x THC, CBD, CBN. A limonene-heavy strain, A body effect. Relaxed, euphoric and Wh
White Moonshine) with plenty of linalool and caryophyllene maybe even hungry. Could be useful
as well. Nerolidol, humulene, myrcene for stress, insomnia and depression.
and pinene are also present, as well
as trace amounts of ocimene and
terpinene.
Wh
Bubba Kush Indica (OG Kush x THC, CBD, CBC, CBDa. Limonene and Relaxed and sleepy. Bubba Kush could aka
[West Coast Dawg caryophyllene are the main terpenoids in be great for pain and insomnia. Man
x Old World Kush]); Bubba Kush, and occasionally contains
Pre-98 Bubba high amounts of nerolidol as well.
Kush is an indica of Linalool, pinene, myrcene and humulene
Hindu Kush lineage, are also present.
possibly crossed with Dur
Bubblegum Pois
Skywalker OG Hybrid - Indica High in THC. CBD, CBG, THCv, CBC, Sleepy, relaxing effects. Likely to be
Dominant (OG Kush CBL and CBN. High in myrcene and useful for stress, pain and insomnia.
x Skywalker) limonene, with some linalool, pinene and
caryophyllene.
Dut
Strawberry Sativa (Strawberry High in THC. Some THCv. Contains Happy, uplifted, euphoric and
Cough Fields x Haze) linalool and caryophyllene, as well as energetic. Could be useful for pain,
some pinene. fatigue and lack of appetite.
ACDC Hybrid - Sativa A high CBD strain, with little to no Little to no psychoactive effect,
Dominant psychoactive effect. ACDC may contain although there is some physiological
(Cannatonic extremely high amounts of CBD, with effect. May be useful for treating
Phenotype) a THC:CBD ratio going as high as 1:20. chronic pain, epilepsy, inflammation,
Also contains some CBG and CBC. May anxiety and the negative side-effects
contain THCv and CBL in trace amounts of chemotherapy.
on occasion. Myrcene is the most
common terpenoid in ACDC, although
occasionally small amounts of linalool,
pinene, limonene and caryophyllene
may be found.
Cannatonic Hybrid (MK Ultra x A CBD-rich strain. The first strain to be Little to no psychoactive effect,
G13 Haze) purposefully bred for CBD. May contain although some phenotypes may
THC:CBD ratios ranging from 2:1, 1:1 have some psychoactive effect. Could
and 1:2, with a THC content that rarely be useful for treating chronic pain,
goes above 6%. Also may contain small inflammation, epilepsy, headaches
amounts of CBN, CBG, THCv and CBC. and MS.
Contains some myrcene, linalool, pinene,
limonene and caryophyllene.
LeafWell
e) Strain (Sativa/Indica/Hybrid) Terpenoids (Possibly) son-to-Person and Phenotype to Phenotype)
White Widow Hybrid (Brazilian Very high in THC. May contain small Relaxed, energetic, stimulated and
Sativa x South Indian amounts of CBD. A limonene and uplifted. Could be great for depression,
Indica) pinene- rich strain. Contains some stimulating the appetite and fatigue.
humulene, myrcene and linalool as well. Perhaps not ideal for those of a
nervous disposition.
White Rhino Hybrid - Indica A wide cannabinoid profile. High THC Relaxed, sleepy. Could be great as an
d aka Medicine Dominant (White and CBD content. Also may contain CBG, antiemetic. May be useful for pain,
Man Widow x Afghani) CBN, CBC, CBDA and CBL. Myrcene, insomnia, inflammation, muscle
pinene and linalool are likely to be spasms and headaches.
found in White Rhino, as well as some
caryophyllene.
Durban Sativa (Landrace THC, THCV, CBG. May contain some Stimulated, focused and energetic.
Poison Strain) CBN, CBC and CBL on occasion. Little to Could be particularly useful for
no CBD. High in limonene, with some depression, ADD/ADHD, diabetes, CFS
myrcene. May also contain pinene and and muscle spasms.
caryophyllene, and occasionally traces
of linalool.
Dutch Treat Hybrid (Unknown THC, with some CBD. Pinene, Uplifted, euphoric, relaxed. Could be
Sativa x Unknown caryophyllene and linalool may be the great for beating stress, fatigue and
Indica) most often-found terpenoids in Dutch headaches.
Treat.
@erik.nugshots
LeafWell
CONCLUSION
230
Conclusion
It is only relatively recently that cannabis was made illegal the world over. This comes
from prohibition and “The War on Drugs”, which started in the early 1910s, although
there were local laws prohibiting drug and alcohol use in the US in the 1860s. To be fair
to the policies surrounding drugs and medications in the early 1900s, many “medicines”
at that time did not have to list all their ingredients, subjecting unwitting patients to
snakeoil, or even outright poison. Drug restrictions in the US intensified in the 1930s
with the establishment of Federal Bureau of Narcotics (1930), and Franklin D. Roosevelt
supported the Uniform State Narcotic Drug Act (1935) and the cannabis Transfer Tax
Act (1937). Overbroad regulations led to cannabis being paired with more harmful
substances, which is what perhaps led to it being unfairly maligned and kept out of the
view of genuine scientific discovery.
The Drive for Legalization

The pressure to make cannabis legal for medical use throughout the United States (and
the world) has been growing. This move towards legalized medical use has also often
bought with it a move towards legalization for recreational use (as PROP 64 shows) and,
as many of us know, where the US goes on drug policy, the rest of the world follows. Also,
as more and more scientific evidence comes out on cannabis’s medical applications, the
question needs to be be asked: how can we ethically deny people medicine that could
potentially help them and, moreover, help them far more safely and effectively than
many other medications that are legal?
LeafWell
231
What does this mean for medical cannabis in the present and future?
One of the biggest benefits of legalized medical cannabis is the removal of barriers to
research into the medical applications of various unique cannabinoids and terpenoids
found in the cannabis plant. Other benefits include safer, higher quality produce.
Legalized “recreational” use arguably helps to some extent in this regard, too, as those
who would prefer to work in a “recreational” market no longer have to label their
product “medicine” in order to legally operate. Meanwhile, those who would like to see
safe, standardized medicine developed from cannabis plants can focus on developing
more appropriate products for patients.
For several years now, there have been various concerns with the state of the cannabis
industry as it stands, perhaps the main ones being “safety” and “consistency”. Yes, there
is plenty of evidence suggesting that cannabis has medical use. The problem is, how
do we measure how effective cannabis is, if we don’t have any standardized way of
measuring its efficacy? What conditions cannabis can be used for, and what specific
cannabinoid-terpenoid interactions are helpful (or even harmful)? What about testing
for pathogens (viruses, bacteria, mold, mildew etc.) and pollutants (heavy metals,
pesticides, herbicides etc.), or other medications could cannabis interact with negatively,
or enhance its effects? And the most burning of questions: how can something which
has not been tested properly for all of these things be called “medicine”?
For now, we have in vitro and in vivo studies, animal studies (mostly mice and rats), a
substantial amount of anecdotal evidence and, yes, some clinical trials at various phases.
When taken as a whole, the body of evidence so far suggests that there is definitely
something to be said for the notion that “cannabis is medicine - we just haven’t
discovered precisely how, why, and to what extent”. There are few if any medications
out there with the same safety profile various cannabinoids and terpenoids have (i.e.
you cannot overdose on cannabis alone, at least not life-threateningly so). If we look
at the sheer number of health conditions cannabinoid-terpenoid-based medications
could potentially help with, then it is frankly almost criminal that this plant has been so
difficult to study scientifically for so many years, due to arbitrary laws. Even if we only
use cannabis to replace opioids for the treatment of long-term, chronic pain, we can say
that it definitely has some medical application. However, the concept of cannabis as
medicine seems to go further than this, and it does look like it is a plant with a multitude
of medical applications.
LeafWell
232
There are, of course, many other positives to cannabis legalization. The methods and
efficiency of growing mediums is also likely to improve hugely, as people work out how
to grow larger amounts of high-quality cannabis in smaller spaces, using less energy.
In fact, this has been occurring since the explosion of homegrown cannabis in the 60s
and 70s, which was made all the better ever since Skunk, Haze and Northern Lights
genetics were stabilized in the 1980s and 1990s! This is around the same time as medical
marijuana underwent greater amounts of research, and the Netherlands relaxed laws
on the possession and sale of small quantities of cannabis.
If anything, the move towards legal medical cannabis has led to the realization that
cannabis has much more to offer than just the psychoactive effects of THC. The
discovery of multiple phytocannabinoids, terpenes and flavonoids has spearheaded the
drive to create new CBD-rich strains. For example, Resin Seeds introduced Cannatonic,
a hybrid strain bred specifically for its low THC content and high CBD content. Growers
now realize that previously unexplored cannabis strains actually have unique properties,
promising untapped applications for different disease processes. If you take anything
from this book, let it be that we do not know enough about cannabis, good or bad. We
need more research that can elevate cannabis to true medicinal status. The potential for
this is on the horizon. Ultimately, we need the politicians to step aside and let scientists
and patients lead the way.
LeafWell
@bcbubbleman
LeafWell
233
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LeafWell
FURTHER READING 245
Cervantes, Jorge, Marijuana Horticulture (2011) and The Cannabis Encyclopedia: The Definitive Guide to Cultivation & Consumption of Medical
Marijuana (2015).
Herer, Jack, The Emperor Wears No Clothes (1985).
Rosenthal, Ed, Beyond Buds: Marijuana Extracts, Hash, Vaping, Dabbing, Edibles & Medicines (2014).
Clarke, Robert C., and Merlin, Mark D., Cannabis: Evolution and Ethnobotany (2013); Clarke, Robert C., Marijuana Botany (1981) - HortaPharm.
Backes, Michael and Weil, Andrew, Cannabis Pharmacy: The Practical Guide to Medical Marijuana (2017).
Grinspoon, Lester, Marihuana Reconsidered (1971, updated 1977).
Ivker, Rav, Cannabis for Chronic Pain (2017).
Blesching, Uwe, The Cannabis Health Index: Combining the Science of Medical Marijuana with Mindfulness Techniques to Heal 100 Chronic Symp-
toms and Diseases (2015).
Holland, Julie, The Pot Book (2010).
King, Jason, The Cannabible (2001).
Pertwee, Roger G. (ed.), Handbook of Cannabis (2014).
DeAngelo, Steve, The Cannabis Manifesto: A New Paradigm for Wellness (2015).
Booth, Martin, Cannabis: A History (2003).
Stark, Michael, Marijuana Potency - How Marijuana Works (1977).
Russo, Ethan, Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential (2002).
Sam, Martin, The Leafly Guide to Cannabis: A Handbook for the Modern Consumer (2017).
Goldstein, Bonni, Cannabis Revealed: How the World’s Most Misunderstood Plant is Healing Everything from Chronic Pain to Epilepsy (2016).
Bakalar, James B. and Grinspoon, Lester, Marihuana, the Forbidden Medicine (1993).
WEBSITES OF INTEREST
Erowid - https://www.erowid.org/
Multidisciplinary Association for Psychedelic Studies (MAPS) - http://www.maps.org/
Leafly - https://www.leafly.com/
Seedfinder - https://en.seedfinder.eu/
National Organization for the Reform of Marijuana Laws (NORML) - http://norml.org/
Marijuana Policy Project (MPP) - https://www.mpp.org/
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246 APPENDIX
A. List of Endocannabinoids
Endocannabinoid and Other

Chemicals Important in the ECS Function
Anandamide, aka N-arachi- A fatty acid neurotransmitter. Degraded by the fatty acid amide hydrolase (FAAH)
donoylethanolamine, AEA enzyme, converting anandamide into ethanolamine and arachidonic acid. FAAH
(C22H37NO2) inhibitors lead to elevated anandamide levels. Anandamide’s effects can occur in
either the central nervous system (CNS) or the peripheral nervous system (PNS).
Anandamide is said to be analogous to THC. Anandamide plays a role in memory,
the regulation of feeding behavior, reward, motivation and implantation of the
early stage embryo in its blastocyst form into the uterus. Modulating anandamide
also may inhibit the growth of breast cancer cells.330 Anandamide can also be
found in dark chocolate.
2-Arachidonoylglycerol, aka 2-AG is an endogenous agonist of the CB1 receptor and the primary endogenous
2-AG (C23H38O4) ligand 331 for the CB2 receptor. Like other cannabinoid receptors, 2-AG has
more than one endogenous ligand. 2-AG is an ester formed from glycerol and
the omega-6 fatty acid, arachidonic acid. Unlike anandamide, 2-AG is found
in relatively high concentrations in the CNS. Formation of 2-AG is dependent
on calcium and is mediated by the activities of phospholipase C (PLC) and
diacylglycerol lipase (DAGL) - both key enzymes in the biosynthesis of 2-AG. 2-AG
was discovered by Raphael Mechoulam and Shimon Ben-Shabat. 2-AG is degraded
by monoacylglycerol lipase (MAGL), FAAH and some other unknown enzymes that
haven’t been properly characterized as of yet. 2-AG is formed in a similar way to
anandamide, except it requires glycerol rather than a free amine.
2-AG can be found in maternal human and bovine milk. 2-AG plays a role in
immune response, appetite regulation, inflammation and pain. 332 2-AG is the
most abundant endocannabinoid in the human body. 2-AG may also play a
role in inhibiting cancer cell growth. 2-AG potentiates GABAA receptors at low
concentrations of GABA.333 Using CBD may boost the body’s levels of 2-AG.
Arachidonic Acid, aka AA AA is a polyunsaturated omega-6 fatty acid, and is related to the saturated
(C20H32O2) arachidic acid, found in cupuassu butter. AA is a carboxylic acid with a 20-carbon
chain and four cis-double bonds. AA is present in the phospholipids of the
membranes of the body’s cells. AA is found in particularly high concentrations
in the brain, muscles and liver. Skeletal muscle is an especially active site for AA
retention, and AA is very important in promoting the growth and repair of skeletal
muscle tissue. This makes AA of great interest to those suffering from various kinds
of muscle and bone injuries, and athletes may also potentially use AA to build and
rebuild muscle. AA concentration in the body may also be associated with the
onset of Alzheimer’s disease - cannabinoids may be able to control the amount of
AA the body produces and mitigate inflammation.334
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APPENDIX 247

N-Arachidonoyl Dopamine, NADA is a CB1 receptor and TRPV1 agonist. Although NADA has been found to possess
aka NADA (C28H41NO3) immunomodulatory activity in humans (NADA controls inflammatory response), most
of its effects have been studied in rodents.335 NADA plays a regulatory role in both the
CNS and PNS, and is found in high concentrations in the hippocampus, cerebellum
and striatum. NADA may also be involved in smooth muscle contraction, vasorelaxation
in blood vessels, immune response and inflammation, and may have antioxidant and
neuroprotective properties.336 337 NADA and anandamide may have some opposing
effects. 338
Arachidonoyl Serotonin, aka AA-5-HT is an inhibitor of FAAH, and is an antagonist of the TRPV1 receptor. AA-5-HT
AA-5-HT (C30H42N2O2) is present in the ileum and jejunum of the gastrointestinal tract. May have analgesic
properties, and may be effective against both acute and chronic peripheral pain.339
2-Arachidonyl glyceryl ether CB1 and CB2 agonist. Partial agonist for the heat-detecting protein, transient receptor
aka 2-AGE, Noladin Ether potential V1 (TRPV1). Regulates calcium uptake and gamma-aminobutyric acid (GABA),
(C23H40O3) which regulates neuronal excitability.340 2-AGE also lowers intraocular pressure. There is
still some debate as to the extent 2-AGE occurs in the human body.
N-Arachidonylglycine, aka NAGyl is a carboxylic analog of anandamide. NAGyl has a wide range of signalling
NAGyl (C22H35NO3) targets in the brain and immune system.341 NAGyl binds to the abnormal cannabinoid
receptor, and is found in high concentrations throughout the body. How NAGyl is
biosynthesized is not fully understood, but there are two theories. 1) NAGyl could be
the enzymatically regulated conjugation of arachidonic acid and glycine; or 2) NAGyl
could be developed by the enzyme alcohol dehydrogenase, catalyzing the oxidation of
anandamide into NAGyl.
NAGyl may suppress pain, and could be especially useful for treating neuropathic pain.
342 343
NAGyl may also induce cell migration. Both THC and NAGyl are full GPR18 agonists
and induce migration in human endometrial HEC-1B cells. This means NAGyl may be
useful in treating endometriosis.344 345
Docosatetraenoylethanola- DEA has a similar structure to anandamide (only containing docosatetraenoic acid
mide, aka DEA (C24H41NO2) instead of arachidonic acid), and acts on CB1 receptors. 346 However, DEA does not
seem to bind to CB1 receptors to the same extent as anandamide. DEA’s role as a
neurotransmitter is not understood.
N -Acyl-Phosphatidylethanol- NAPEs are hormones released by the small intestine into the bloodstream when
amine, aka NAPE it processes fat. They are formed from phosphatidylethanolamines (a group
of phospholipids that plays a role in membrane fusion and curvature). When
phospholipases cleave NAPEs, they can be transformed into N-acylethanolamines,
including anandamide. NAPEs affect the hypothalamus in the brain, and can suppress
appetite. This could be one reason why cannabinoids may be used to treat obesity.
NAPEs are not endocannabinoids per se, but are important intermediaries in the
biosynthesis of cannabinoids.
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248 APPENDIX

NAPE-specific phospholipase The enzyme that catalyzes the release of N-acylethanolamine from NAPE. This enzyme
D aka NAPE-PLD is a major part of the process that converts lipids into chemical signals like anandamide
and oleoylethanolamine, 347 and may even play a part in the detection and reduction of
bile acid. 348
Monoacylglycerol Lipase aka A key enzyme in the hydrolysis of 2-AG by converting monoacylglycerols into fatty
MGL acid and glycerol. Works together with hormone-sensitive lipase (LIPE) to hydrolyze
intracellular triglyceride stores. Chronic inactivation of MAGL results in massive
elevations of 2-AG and downregulation of CB1 receptors in the brains of mice. 349
Lysophosphatidylinostol, aka LPI is an endogenous lysophospholipid and endocannabinoid neurotransmitter

LPI, L-α-lysophosphatidylin- has been proposed to be one of the endogenous ligands of the protein, GPR55. This
ositol (C25H49O12P) suggests that cannabinoids have a role to play in obesity350 and a variety of other
metabolic diseases.351
Oleamide (C18H35NO) Oleamide is an amide derived from oleic acid. Oleamide is biosynthesized from
N-oleoylglycine. Oleamide accumulates in cerebrospinal fluid during sleep deprivation,
and induces sleep in mammals.352
Oleoylethanolamide, aka OEA OEA is the monounsaturated analog of anandamide, but acts independently of the
(C20H39NO2) cannabinoid pathway, but does bind to the cannabinoid receptor GPR119. OEA is
produced by the small intestine. OEA regulates feeding and body weight in vertebrates.
OEA is not a strict endocannabinoid as it lacks affinity for CB1 and CB2 receptors. OEA
may be involved in neural responses to food stimuli.353
Palmitoylethanolamide, aka As with OEA above, PEA cannot be considered an endocannabinoid as it does not
PEA (C18H37NO2) show an affinity for the CB1 or CB2 receptors. PEA does, however, have an affinity for the
cannabinoid-like G-coupled receptors, GPR55 and GPR119. PEA enhances anandamide
activity, and an imbalance in the endocannabinoid system and alterations of the levels
of PEA occurs during chronic inflammation. PEA has analgesic, neuroprotective and
anticonvulsant properties. 354
RVD-Hpa RVD-Hpa is a selective agonist for the CB1 receptor.355 May be involved in the integration
of signals from both lipid- and peptide- derived signalling molecules.
Fatty acid amide hydrolase FAAH is a member of the serine hydrolase family of enzymes, meaning that they
aka FAAH contain nucleophilic serine (an amino acid) in their active sites, and are hugely
important for the hydrolysis of substrates such as fatty acids. FAAH hydrolyses
anandamide, N-acylethanolamines, oleamide and N-acyltaurines, which are TRP
agonists. FAAH may be a target for pain relief and a treatment for anxiety disorders. 356 357
Stearoylethanolamide (SEA) Stearoylethanolamide is an endocannabinoid neurotransmitter that may downregulate

liver enzymes.358 SEA may also work in combination with AEA to produce an “entourage
effect”. 359
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Virodhamine, aka O-arachi- O-AEA is an endocannabinoid and nonclassic eicosanoid (a signalling molecule made
donoyl ethanolamine; O-AEA by the oxidation of arachidonic acid or any other polyunsaturated fat. Virodhamine
(C22H37NO2) may regulate body temperature. O-AEA is a CB1 receptor antagonist or partial agonist
and a potential CB2 receptor agonist. O-AEA may be involved in the regulation of body
temperature360 and the relaxing of arteries.361
B. List of Phytocannabinoids
Cannabinoid Use/Effect
Delta-9 The main “psychoactive” cannabinoid found in cannabis.
Tetrahydrocannabinol (THC) - THC may be especially effective for pain, addiction, nausea,362 tumors 363 and ADHD.364
C21H30O2 THC may also be a potential bronchodilator,365 and could be of use for asthmatics. In
most varieties of psychoactive cannabis, THC/THCa (see below) is the most commonly
found cannabinoid. THC is a partial agonist of the CB1 and CB2 receptors. After cannabis
is consumed, it is converted by the body into 11-Hydroxy-THC (11-OH-THC). The body
further metabolizes 11-OH-THC into 11-nor-9-hydroxy-THC (11-COOH-THC). 11-OH-THC
may be more readily absorbed by the brain than THC. When cannabis is eaten as
opposed to vaporized or smoked, it is believed that the body converts a greater amount
of THC into 11-OH-THC, and this is released over a longer period of time - hence the more
potent effects. In comparison to the body’s own endogenous endocannabinoids, THC
targets endocannabinoid receptors less selectively, and has relatively low cannabinoid
receptor affinity and efficacy. THC appears to result in downregulation of cannabinoid
receptors rather rapidly. Tolerance to THC may develop, but irregularly and sensitivity
to THC may return after a short period of withdrawal. THC also contains phenol groups,
and thus has antioxidative properties, sufficient enough to protect against oxidative
stress, such as glutamate-induced excitotoxicity (e.g. after experiencing stroke).
Mu-opioid receptors may also modulate THC’s rewarding effects, 366 which may help
explain why it can potentially act as a replacement for opioids and even prevent
“cravings” for those who are addicted to such types of painkiller. THC effects mostly the
CB1 receptors. Delta-8 THC is structurally similar to delta-9 THC, differing only by a few
atomic bonds, and found in much less quantities in the cannabis plant. Delta-8 THC is
also a partial agonist of CB1 and CB2 receptors.
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250 APPENDIX
Delta-1 Tetrahydrocannab- THCa is the precursor to THC. THCa is a potential anti-inflammatory. THCa may also
inolic Acid (THCa/THCA) - encourage appetite, combat insomnia, is anti-tumor and act as an anticonvulsant. 367
C22H30O4 THCa converts into delta-9 THC when it is decarboxylated to a temperature of 220°F
(104.444°C), as well as when fresh cannabis plants are harvested and left to dry. THCa
is not psychoactive, and very little THCa is converted into THC in the body if ingested
without heating THCa first.
Delta-9 Tetrahydrocan- Has no known effect, but may have some uses for diabetes. THCV may be somewhat
nabivarin (THCv/THCV) - psychoactive, although to what extent it is not known, and may shorten THC’s effect
C19H26O2 duration. African landrace strains may have higher concentrations of THCV than
strains of cannabis from other parts of the world, but this needs to be tested. THCv is
thought to be one of the main reasons why such strains have “buzzy”, “racy” effects.
THCV also seems to “break down” THC, and this may help explain why strains high
in THCV seem to have a shorter duration of effects. The dosage of THCV affects the
duration of the effect of THC. This means that THCv may be a CB1 receptor antagonist
at low doses, and a CB1 receptor agonist at high doses. THCv is a partial agonist of the
CB2 receptor.
Cannabidiol (CBD) - The other main cannabinoid found in marijuana, alongside THC. CBD is thought to be
C21H30O2 non-psychoactive, although there are some reports of slight psychoactivity by some
users.368 CBD works in combination with THC and other cannabinoids, psychoactive
or otherwise. As CBD has physiological effects, it could be said to be psychoactive to
some degree, even if it’s not to the same extent as THC. CBD also inhibits the enzyme
cytochrome P450 (CYP450),369 which is an enzyme that is essential for the elimination of
toxins and other foreign compounds from the body. CYP450 is found mostly in the liver,
although it is found in smaller amounts throughout the body. CBD has broad spectrum
use, and can be used for pain370, stress, asthma, seizure disorders such as MS371 and
epilepsy,372 and lowering blood sugar levels for diabetes.373 CBD is also potentially an anti-
inflammatory and cancer-killing cannabinoid.374 CBD may also be an antipsychotic.375 CBD
also may have an effect on the immune system.376 CBD may also promote neurogenesis.377
CBD is thought to have a low affinity for CB1 and CB2 receptors, acting as an indirect
antagonist of these receptors. CBD may extend the effects of THC, as well as act as a
“buffer” to some of its psychoactive effects, although CBD may also potentially extend the
duration of cannabis’ psychoactive effects. In most varieties of cannabis, CBD is the second
most common cannabinoid in cannabis, although some types of cannabis may contain
large, equal or even greater amounts of CBD than THC. There are also many strains being
developed today that have high CBD, with low or equal THC ratios. The lack of CBD in
many sativa varieties of cannabis is one reason given as to why sativas’ effects may be so
overwhelming for many, as well as why their effects tend to last a short duration of time.
CBD may also possess antioxidant activity and protect against oxidative stress. CBD
has been touted as a potential protective against the effects of traumatic brain injuries
(TBIs). CBD, like CBG, CBG, CBGV and THCV, may stimulate and desensitize human
TRPV1. CBD may also inhibit FAAH. This may be one of the many reasons why CBD has
anti-cancer, anti-inflammatory and analgesic effects.378
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APPENDIX 251
Cannabidiolic Acid (CBDa/ CBDa has anti-inflammatory379 380, antiemetic and anti-tumor properties. Until recently,
CBDA) - C22H29O4 found mostly in Cannabis ruderalis, which is the type of cannabis used to create
auto-flowering strains. Strains such as Cannatonic and ACDC have been developed to
produce more CBD/CBDa than THC/THCa.
Cannabidivarin (CBDv/ Non-psychoactive. CBDv is a homolog of CBD, meaning they share many of the same
CBDV) - properties as each other.
C19H26O2 The difference between CBDv and CBD is that in CBDv the side chain is shortened by
two methylene bridges. CBDv may also have anti-epileptic effects, and is being looked
at by GW Pharmaceuticals for its therapeutic potential for epilepsy as well.381
Cannabichromene (CBC) - CBC is non-psychoactive. CBC may be hugely beneficial for treating stress and anxiety.
C21H30O2 CBC has antiviral and anti-tumor properties, 382 and has been shown to stimulate the
growth of bone tissue. 383 CBC is an agonist of both the CB1 and CB2 receptors, and
inhibits AEA uptake.
Cannabigerol (CBG) - Non-psychoactive. Stimulates bone growth and brain cell growth. Combats insomnia
C21H32O2 and depression384. Antibacterial and anti-tumor. CBG is a neurogenic compound, and
as such could be very useful in the treatment of nerve pain. Of particular interest to MS,
ME, ALS, head/brain trauma, diabetes, cancer and HIV/AIDS sufferers, or indeed any
condition where neuropathic pain is a distinct possibility. Psoriasis and IBS sufferers may
find benefit in CBG as well.
CBG is one of the few genuinely neurogenic compounds available in nature, and is
rarely found in any other plants or substances. The particular derivative of CBG that
is said to be neuroprotective is VCE-003.2.385 CBG is a partial agonist of the CB1 and
CB2 receptors, and inhibits AEA uptake. Moderate doses of CBG may also be a CB1
antagonist and may oppose the antiemetic effects of CBD at the 5-HT1A receptor.386
CBG may activate the alpha-2 adrenoreceptor and block the 5-HT1A receptor. 387
Cannabigerovarin (CBGV) - CBGV, like many of the cannabinoid acids, seem to have some interesting properties.
C19H28O2 We have stated that the cannabis plant has a system of “checks and balances”, and the
plant seems to produce acids such as CBGV as an insecticidal and to help the plant
ward off diseases. CBGV has been found in higher concentrations in some landrace
indica strains.388 As CBGV is part of the CBG group of cannabinoids, it may be especially
useful for psoriasis, irritable bowel disease and as an antibacterial agent.389 CBGV is not
psychoactive.
Cannabinol (CBN) - C21H26O2 Cannabinol is a byproduct of oxidized THC, and normally forms after THC is exposed
to oxygen or heat. Older cannabis that’s been exposed to air also shows a slightly
higher level of CBN, as THC breaks down to CBN. CBN may be slightly psychoactive
and a medium to strong sedative.390 Useful as an antiemetic, anticonvulsant and in the
treatment of insomnia.391 CBN may have a higher affinity for CB2 receptors, and thus
may play a role in immune response.392 Any cannabis containing THC is likely to contain
at least trace amounts of CBN. CBN is a CB1 and CB2 receptor agonist, as well as an
inverse agonist of the CB2 receptor at high dosages.
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252 APPENDIX
Cannabicyclol (CBL) Cannabicyclol is converted into CBC by light. CBL is a degradative product, like
C21H30O2 CBN. Little is known about CBL, although it was looked at for possible effects on the
biosynthesis of prostaglandins (a lipid compound with hormone-like effects, acting as
vasodilators and inhibiting the aggregation of blood platelets). 393
Cannabielsoin (CBE) CBE is a metabolite of CBD, and is formed from a metabolic process of CBD. 394
C21H30O3
Beta-Caryophyllene - C15H24 Beta-Caryophyllene is found in black pepper, cloves, black caraway and cinnamon.
Beta-caryophyllene no psychoactive effect, but does seem to affect the CB2 receptors.
395
Due to this effect, beta-caryophyllene is often seen as a cannabinoid, but is popularly
considered a terpene as well. Could be useful as an anti-inflammatory. Caryophyllene
has use as an antinociceptive (pain blocker), neuroprotective, treatment for addiction,
anxiolytic, antidepressant and anti-cancer treatment.396 397 398
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APPENDIX 253
C.
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254 APPENDIX
D. List of Terpenes
Terpenoid Effect
Alpha- and Beta - Pinene - This is what gives some cannabis its “pine” like smell. Pinene is also found in pine
C10H16 needles, dill, parsley, rosemary and basil. Pinene has two structural isomers - alpha and
beta. Alpha-pinene is said to be responsible for more “rosemary”- like smells, whereas
beta- pinene is said to be responsible for more “dill”- like smells. Effects include alertness
and memory retention, but may also induce sleep and relaxation in higher doses. Useful
for asthmatics and as an antiseptic and antimicrobial. 399 400
Myrcene - C10H16 Myrcene is a mild-to-moderate antioxidant, anticarcinogenic, anti-inflammatory and

antidepressant.401 402 403 Myrcene may work particularly well for sleeplessness and muscle
tension, too. Myrcene may work in combination with CBD and/or THC in order to
produce a “couchlock” effect.
Limonene - C10H16 Limonene is responsible for the “citrus” or “lemony” aroma and taste found in some
strains of cannabis. Limonene is found in fruit rinds, juniper berries, peppermint and
rosemary. Limonene may elevate mood and provide stress relief. Limonene may also
help battle cancer. 404 405
Beta-Caryophyllene - C15H24 Beta-Caryophyllene is found in black pepper, cloves, black caraway and cinnamon.
Beta-caryophyllene no psychoactive effect, but does seem to affect the CB2 receptors.406
Due to this effect, beta-caryophyllene is often seen as a cannabinoid as well. Could
be useful as an anti-inflammatory. Caryophyllene has use as an antinociceptive (pain
blocker), neuroprotective, treatment for addiction, anxiolytic, antidepressant and anti-
cancer treatment. 407 408 409
Linalool - C10H18O Linalool is a terpene also found in lavender and jasmine.

Linalool, along with myrcene, could be useful for anxiety relief and sedation,410 and also
has anticonvulsant, antimicrobial, antidepressant and anti-acne properties. 411 412
Humulene - C15H24 Humulene occurs naturally in clove, basil and hops. Earthy, woody, spicy aromas and
flavors are usually associated with humulene. Humulene is an antibacterial, antitumoral
and anti-inflammatory.413 414 415
Bisabolol - C15H26O Bisabolol is another flowery-smelling terpene found in cannabis, and has been used
in cosmetics for a number of years now. Chamomile and candeia trees contain high
quantities of bisabolol. Bisabolol has low-psychoactivity.
Bisabolol has anti-inflammatory, anti-irritant, antioxidant, antimicrobial and analgesic
properties.416 417 Bisabolol may also be an effective treatment for leukemia. 418
Trans-Nerolidol - C15H26O This terpene is most often found in tea tree, jasmine tea and lemongrass, and is
thought to contribute to cannabis’s sedative effects. There are also suggestions that
trans-nerolidol has antiparasitic, antifungal and antimicrobial properties, and could well
inhibit the growth of leishmaniasis - a disease caused by protozoan parasites spread by
sandfly bites. 419 420
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APPENDIX 255
D. List of Terpenes
Terpenoid Effect
Delta-3 Carene/Carene - Delta-3 carene is another piney-/earthy-/lemony- smelling terpene found in cannabis,
C10H16 and may help stimulate bone growth.421 Carene may also have use as an anti-fungal,
anti-inflammatory and antihistamine.422 423 Carene is thought to be the main terpenoid
responsible for “dry mouth”.424
Borneol - C10H18O Borneol may be an analgesic, antiseptic and a bronchodilator.425 426 Borneol may also
help induce sleep, and could be one of several terpenoids found in cannabis that’s of
interest for insomniacs. Borneol has a “minty”, “camphor” smell.
Eucalyptol (aka Cineol) - Eucalyptol may have potential use as a cough suppressant and antiseptic.427 Eucalyptol
C10H18O is sometimes used in small amounts as a flavoring in mouthwash. Eucalyptol may
also ease pain and lower blood pressure. Eucalyptol may also be useful in treating
Alzheimer’s disease by mitigating inflammation in amyloid beta toxicated PC12 cells.428
Camphene - C10H16 Camphene may be a potent anti-inflammatory and antibiotic. 429 430 Camphene has a
“fuel”-like smell.
Terpineol - C10H18O Terpineol may have antioxidant, analgesic and painkilling properties. 431 The area
where terpineol seems to shine is in the immune system: terpineol may have anti-
inflammatory, antibacterial and antiviral properties, and stimulates the immune
system.432 Terpineol has a pleasant smell, and can be found in lilacs.
Gingerol - C17H26O4 Gingerol may have antiemetic, anti-cancer and anti-inflammatory effects. 433 434 Gingerol
is closely related to piperine (C17H19NO3) and Zingiberene (C15H24), and all three are
compounds that are often found in ginger, capsaicin, chili and black pepper.
Ocimene - C10H16 Ocimene is related to myrcene, and is a common terpene found in many plants and
fruits. Ocimene has a pleasant, fruity, floral smell and is found in mint, parsley, pepper,
basil, kumquats, mangoes and orchids. Ocimene may have antiviral and antifungal
properties. 435 436
Terpinene - C10H16 Terpinene is a turpentine-smelling terpenoid that can be found in cardamom and
marjoram oils, cumin, apple and tea. Terpinene may have antimicrobial properties, as
well as antioxidant, anti-inflammatory and antiproliferative properties.437 438 439 Other
terpenes that are found in cannabis (as well as thyme), such as thymol and carvacrol,
also have similar antiproliferative properties. 440
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256 APPENDIX
E.
F.
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APPENDIX 257
G. List of Nutrients Needed By the Cannabis Plant
Major, Secondary
Terpenoid or Micro Nutrient Function
Nitrogen (N) Major Major component of chlorophyll, which plants need for photosynthesis.
Symptoms of shortage include poor plant growth and yellowing leaves
(“chlorosis”), as the plant is unable to make enough chlorophyll.
Phosphorus (P) Major Needed for normal growth and maturity. Plays a role in photosynthesis,
respiration, cell division, cell enlargement, and energy storage and
transfer. Phosphorus deficiencies in plants can be difficult to detect,
due to no obvious outward symptoms, with the exception of some
stunted growth. Other signs include dark green leaves and purple/red
pigmentation, but these can be caused by other environmental factors
as well. Phosphorus deficiency can cause plants to mature at a much
slower rate, and make them more susceptible to diseases.
Potassium (K) Major Regulates the opening and closing of stomata, meaning it controls
CO2 uptake. Potassium is essential for the production of adenosine
triphosphate (ATP) - the “powerhouse” of cells, necessary for intracellular
energy transfer. Potassium deficiency essentially affects all areas of plant
growth, including root, seed and fruit development. Leaves are also
more prone to scorching and discoloration.
Calcium (Ca) Secondary Holding together cell walls, preventing improper growth. Calcium
deficiency in plants causes localized tissue necrosis, and leads to
eventual death of plant roots and tips.
Magnesium (Mg) Secondary One of the building blocks of chlorophyll and plays a major role in
photosynthesis. Magnesium deficiency causes chlorophyll degradation.
Sulfur (S) Secondary Acts as a soil conditioner and reduces the sodium content (the
“saltiness”) of soil. Signs of sulfur deficiency include the leaves
undergoing chlorosis and stunting of the plant’s.
Iron (Fe) Micro Necessary for enzyme function; plays a role in photosynthesis. Iron
deficiency is also known as “iron chlorosis”, and essentially stunts the
growth of the plant by inhibiting leaf growth. Leaves yellow, then turn
white, and the whole plant eventually stops growing.
Boron (B) Micro Affects vegetative and reproductive growth of plants, and is important
for cell expansion, keeping meristem (undifferentiated cells that cluster
around new growth sites on the plant) healthy and plant fertility. Boron
deficiency causes plants to “abort” at the growing point, leading to
branch proliferation. The new branches end up growing improperly, and
their leaves display signs of chlorosis.
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258 APPENDIX
G. List of Nutrients Needed By the Cannabis Plant
Major, Secondary
Terpenoid or Micro Nutrient Function
Chlorine (Cl) Micro Balances potassium ion concentration during the opening and closing
of stomata. Too little chlorine can cause wilting in roots and leaves. Excess
chlorine can be toxic to plants, and cause the leaves to “scorch” and
brown.
Manganese (Mn) Micro Important for photosynthesis, respiration and nitrogen assimilation.
Manganese deficiency can look similar to iron deficiency, with leaf
discoloration and general stunted growth. Some slight differences
in symptoms may include sunken spots in areas that contain lots of
chlorophyll (i.e. leaf areas) and a more green-yellow “marbled” leaf
appearance.
Copper (Cu) Micro Assists in metabolizing carbohydrates and proteins; essential in plant
respiration. Copper deficiency can cause chlorosis and weaken stems
and twigs.
Zinc (Zn) Micro Plays a key role in growth hormone production and internode elongation.
Zinc deficiency can cause a bronzing of leaves and necrotic spots on leaf
tissue.
Molybdenum (Mo) Micro Needed by symbiotic nitrogen fixing bacteria in the plant’s roots to
fix atmospheric nitrogen. Essential for converting nitrate to nitrite
to ammonia in order to synthesize amino acids within the plant.
Molybdenum deficiency displays itself as chlorosis on the margins of the
plant’s leaves, and eventual leaf necrosis.
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GLOSSARY 259
Agonist
The opposite of a receptor antagonist. An agonist is a chemical that promotes a biological re-
sponse by binding to a receptor.
Cannabidiol (CBD)
A major phytocannabinoid with lots of potential health benefits, and for most people none of the
psychoactive effects. Accounts for up to 40% of the cannabis plant’s extracts, and after THC is the
cannabinoid often found in largest amounts. Also seems to “balance out” the effects of THC, re-
ducing its negative side-effects. Some suggest that CBD also “extends” the psychoactive effects
of cannabis to some extent.
Cannabinoid
A chemical compound that acts on cannabinoid receptors.
CB1 Receptor
A cannabinoid receptor that is located primarily in the central and peripheral nervous system.
CB2 Receptor
A cannabinoid receptor that is located throughout the body, including the brain and immune
system.
Decarboxylate/Decarboxylated/Decarboxylation/Decarb/Decarbed
The chemical reaction that removes a carboxyl group and releases CO2, i.e. removing a carbon
atom from a carbon chain. Usually used in relation to applying heat to cannabis, whether in
terms of smoking, vaporizing or cooking.
Endocannabinoid
Cannabinoids produced naturally by the human body.
Endocannabinoid System (ECS)

The name given to the groups of cannabinoid receptors found within the brain and throughout
the body. The ECS was discovered in 1990, and is now believed to be the key to modulating sleep,
appetite, mood, memory and the motivation and reward center. The ECS is intimately linked with
homeostasis.
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260 GLOSSARY
Entourage Effect
Used to describe the effect cannabinoids and terpenoids have when working in concert with
each other, giving different cannabis plants their unique effects. Another word that could be
used is “synergy” - a term used for when the whole effect is greater than the sum of its parts.
Homeostasis
The maintenance of a constant internal environment. The ECS, hormones and the nervous
system are responsible for this.
Ligand
A substance that forms a complex with a biomolecule to serve a biological purpose.
Neurotransmitter
Chemicals that enable neurotransmission (aka synaptic transmission) - the process by which
signalling molecules are released by a neuron - and transmits messages across the synapse.
Phytocannabinoid
Cannabinoids that occur naturally in the cannabis plant. There are hundreds of different types
of phytocannabinoids, of which the main two are THC and CBD.
Receptor Antagonist
A type of receptor ligand that blocks or dampens a biological response by binding to a receptor.
Synapse (aka “Chemical Synapse”)

Biological junctions through which neurons’ signals can be exchanged to each other. Non-neu-
ronal cells found in muscles and glands can also receive messages via synapses.
Terpene/Terpenoid
The organic chemicals that give plants their unique smell and flavor. Examples of terpenes
found in cannabis include myrcene, pinene and linalool. The term “terpenoid” refers to a ter-
pene that has been oxidized, usually via drying and curing.
Tetrahydrocannabinol (THC)
The principal psychoactive constituent of cannabis. In its non decarboxylated form, THC is
known as tetrahydrocannabinolic acid (THCa), and is non-psychoactive.
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GLOSSARY 261
Titrate
The measurement and balancing of a dose of medicine.
Vaporization/Vaporize
A phase change, e.g. a solid turning into liquid. Ice, for example, is still water, even though it’s
solid. To “vaporize” marijuana means to use it without combustion (see “decarboxylation”). You
are essentially turning matter into vapor by heating the cannabis when you are vaporizing, to
put it simply.
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262 FOOTNOTES
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169 Smith, Ellen Lenox, ‘An Evaluation of the Use of Cannabis in EDS with
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158 Støving RK, Andries A, Brixen K, Flyvbjerg A, Hørder K, Frystyk J., ‘Leptin,
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159 ‘Adult Obesity Facts’, Center for Disease Control and Prevention (CDC), 178 Whalley, B and Jones, N., ‘CBD-V As a Treatment for Epilepsy?’, Project
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180 Ibid., p. 74 (ref. 117)
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202 Ibid., p. 128 (ref. 198)
185 Cunha, J.M. et al. ‘Chronic administration of cannabidiol to healthy volun-
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375 Ibid. p. 63 (ref. 85)
LeafWell
272 FOOTNOTES
376 Ibid., p. 94 (ref. 150)
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LeafWell
Contributors List
Dr. Lumír Ondřej Hanuš - School of Pharmacy, Ein Kerem Campus, Hebrew
University of Jerusalem · Institute of Drug Research.
Professor Roger Pertwee - Emeritus Professor, School of Medical Science,

Aberdeen University.
Dr. Michael-Masterman Smith - Chief Scientific Officer, CA Labs, Inc.; cancer

biologist and pharmacologist.
Mara Gordon - Chief Process Engineer & Co-Founder of Aunt Zelda’s.
Jeff Raber, Ph.D. - Specialist in organic chemistry; President & Co-Founder of

The Werc Shop.
Eben Britton - Former Offensive Tackle for the Jacksonville Jaguars and
Chicago Bears; cannabis advocate with Athletes for Care and the Gridiron
Cannabis Coalition (GCC)
Marco Troiani - Digamma Labs; former Chief Scientist at DB Labs.
Savino Sguera - Digamma Labs; former Advisor for Division of Public and
Behavioral Health (DPBH) and Department of Administration for Nevada.
Photographers
Erik Nugshots @erik.nugshots
Marcus “Bubbleman” Richardson @bcbubbleman
Curtis Taylor @curt_ice and John Bayes (Green Bodhi)
Morgan English @ThisCannabislife
Patients
Sean Major
Jason and Jayden David
Robert Hokum
Ian Frizzle
Tracy Sirrine
Jeff Breier
Colin Wells
Matthew Falk
Tamara Ritchon
A book by
What makes cannabis medicine?
LeafWell
Medical Cannabis presents huge potential for personalized medicine due to the
unique way it interacts with our individual endocannabinoid system (ECS). Moreover,
due to the way in which the ECS works, cannabinoids and terpenoids derived from
the cannabis plant could help us develop some of the safest, most well-tolerated
medications available for otherwise hard-to-treat conditions, as well as preventatives
for optimal health.
Why Cannabis is Medicine

This book takes a look existing medical evidence and patient testimonies to
understand what conditions cannabis could be useful for and why. It provides
information on dosing, explains how the endocannabinoid system works and the
fundamental role it plays in homeostasis. We ask some of the leading experts in the
ﬁeld of pharmacology, medicine and cannabinoid science to discuss their experience
regarding the plant’s medical potential.
This book is for patients, scientists, doctors and even just the plain curious who wish
to
understand more about the medicinal applications of this plant and what it means
for the future of medicine. This is an area of cutting-edge research, and we hope this
book provides a step towards change and a greater understanding of drugs and
pharmacology as a whole.
About Leafwell
Leafwell is an organization dedicated to ﬁnding out about the pros and cons of
medical cannabis in an objective manner. We want patients and healthcare
practitioners to understand more about the effects of cannabis, cannabinoids and
the endocannabinoid system and how to approach cannabis as medicine. We hope
you enjoy this book. Check out Leafwell.co if you’d like to learn more about the
medical cannabis and what cannabinoids could mean for the future of medicine and
the development of drugs.
A book by
LeafWell
LeafWell

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Why

A book by With contributions by

12 Conversation with Dr. Lumir Hanus

17 History of Medical Cannabis

28 Chapter 1: The Endocannabinoid System

34 The ECS and Its Parts

36 What Other Receptors Do Cannabinoids Affect?

40 Conversation with Prof. Roger Pertwee

52 Chapter 2: Cannabis and Conditions

56 Cannabis and Addiction Treatment

60 Cannabis and Alzheimer’s Disease

63 Cannabis and Amyotrophic Lateral Sclerosis (ALS) / Lou Gehrig’s Disease

65 Cannabis and Anterior Cruciate Ligament (ACL) Reconstruction

67 Cannabis and Anxiety

69 Cannabis and Arthritis

71 Cannabis and Attention Deficit Hyperactivity Disorder/Attention Deficit Disorder (ADHD/ADD)

73 Cannabis and Asthma

76 Cannabis and Autism/Asperger Syndrome

78 Cannabis and Autoimmune Disorders

80 Cannabis and Bipolar Disorder

83 Cannabis and Cardiovascular Diseases (CVDs)

88 Cannabis and Cancer

95 Conversation with Dr. Michael Masterman-Smith

101 Cannabis and Chronic Pain/Muscle Pain

104 Cannabis and Cystic Fibrosis (CF)

106 Cannabis and Diabetes

109 Cannabis and Depression

112 Cannabis and Eating Disorders

114 Cannabis and Eczema and Psoriasis

116 Cannabis and Ehlers-Danlos Syndrome (EDS)

119 Cannabis and Endometriosis

121 Cannabis and Epilepsy

125 Cannabis and Fibromyalgia

127 Cannabis and Glaucoma

130 Cannabis and HIV/AIDS

132 Cannabis and Huntington’s Disease (HD) aka Huntington’s Chorea

138 Cannabis and Insomnia

141 Cannabis and Kidney Disease/Kidney Failure

143 Cannabis and Migraine/Headache

147 Cannabis and Multiple Sclerosis (MS)

149 Cannabis and Liver Diseases

151 Cannabis and Nausea Mitigation

154 Cannabis and Peripheral Neuropathy (PN)

156 Cannabis and Parkinson’s Disease (PD)

158 Cannabis and Premenstrual Syndrome (PMS)

162 Cannabis and Spinal Cord Injuries (SCIs)

164 Cannabis and Sickle Cell Diseases (SCDs)

166 Cannabis and Stroke/Traumatic Brain Injury (TBI)

168 Cannabis and Tourette Syndrome (TS, Tourette’s)

171 Cannabis and Trigeminal Neuralgia (TN)

174 Chapter 3: Dosage and Usage

185 Conversation with Mara Gordon

194 On Hemp-Based Products

195 Synthetic Cannabinoids (SCBs)

200 Chapter 4: Medication and Side-Effects

205 Effects on the Brain and Cardiac Problems

208 Chapter 5: The Biology of the Cannabis Plant

214 The Growth Cycle

217 Conversation with Jeff Raber

220 A Brief Guide to Some of the Most Popular Strains

228 Chapter 6: Conclusion

We understand that this is a complex area of research that can be difficult to

This is by no means a be-all-and-end-all look at the cannabis plant as medicine.