3.

2: Cannabis
 Marijuana
• few other drugs have been so politicized
in the history of the twentieth century
• the marijuana plant: a scrawny weed
with an attitude
“Its roots gobble up
all the nutrients in the
soil, and like a
vampire it sucks the
life blood from the
earth.”
-Ernest Abel
 Rescheduling?

In Canada, cannabis was

Drug Enforcement
removed from Schedule II of
Administration’s (DEA):
the Controlled Drugs and
Schedule 1
Substances Act, 1996
• “high potential for abuse,” • Cannabis Act (2018)
“no currently accepted
medical use” and a “lack of
accepted safety”
Scheduling
 Pharmacological
Classification
• Marijuana is associated with an odd
assortment of unconnected
properties
– makes it difficult to place it within
a traditional classification of
psychoactive drugs
• Marijuana is commonly referred to as
a synonym for cannabis

– Cannabis is the shortened botanical

term for the hemp plant
• oldest cultivated plant not used
for food?

– Marijuana is obtained not from the

stalks of the cannabis plant but
from its serrated leaves
• In a cool, humid climate
– less resin is produced
– fiber is stronger and more durable

• In a warmer, less humid climate

– fiber content is weak
– but much resin is produced
• Marijuana (alternately spelled “marihuana”) is
produced from the flowering hemp, a weed-like plant
given the botanical name Cannabis sativa by Linnaeus
in 1753
• Cannabis sativa
• Cannabis indica
• Cannabis ruderalis
• 70 unique compounds that are
collectively known as
phytocannabinoids
• as well as more than 400 other
identified compounds
• flowers and
leaves of
cannabis
plants contain
trichomes
• Phytocannabinoids include
cannabis’s key psychoactive
ingredient: 𝚫9-
tetrahydrocannabinol (𝚫9-THC)
– as well as other compounds such
as Δ8-tetrahydrocannabinol (Δ8-
THC), cannabidiol (CBD),
cannabinol, N-alklamide, and B-
caryophyllene
• Cannabis sativa plants contain the
greatest concentrations of Δ9-THC
• Cannabis indica tends to have a
relatively greater concentration of
cannabidiol (CBD)
• Cannabis indica plant named in
the 1780s by Jean-Baptiste
Lamarck who first differentiated
Cannabis sativa and Cannabis
indica varieties
– distinction may be more pop
culture myth than scientific
fact
 • Terpenes are aroma
compounds found in
all plants, and there's
growing evidence that
pot's terpenes play a
big role in psycho-
Terpenes activity
– Alpha-pinene
– Limonene

• the entourage effect

 Hemp

• hemp plants contain no more

than 0.3 percent (by dry weight)
of THC
• marijuana typically contains 5 to
20 percent THC
 Consumption

• Cannabis can be obtained in a number of

different forms for the purpose of
consumption
• The most familiar to us is marijuana,
which is derived from the Mexican word
maraguanquo, meaning “an intoxicating
plant”
• marijuana and tobacco can be
consumed together in “blunts” or in
“spliffs”
• Marijuana potency in terms of THC
content varies
• One method is to prevent pollination
and hence seed production by the
female plants
– sinsemilla (meaning “without seeds”)
typical THC concentration
was about 1 to 2 percent

1960s and 1970s

early 1990s

concentrations have steadily

risen to about 10 percent
• Cannabis plant material can also be
processed using methods that
concentrate its psychoactive ingredients
– cannabis extract called hashish
• provides a higher concentration of Δ9-
THC
• Even higher concentrations occur in oil
extracted from hashish
– as high as 65 percent
• there is a recent trend toward a new
form of high-potency cannabis
consumption called dabbing
• extraction of cannabis with butane
followed by evaporation of the solvent
• “dabs,” “earwax,” “butter,” “shatter,” “honey
oil,” and “butane hash oil”
 • Cannabis is believed to have
originated in central Asia,
probably in China
• Medical and religious use of
cannabis can be traced back
History of to ancient China, India, and
the Middle East
Cannabis • spread to the Arab world,
where the consumption of
hashish became
commonplace
• Western interest did not
begin until the early to mid-
nineteenth century
• French physician Jacques-Joseph
Moreau established Le Club des
Haschischins (“club of the hashish
eaters”)
• history of cannabis in the United States
dates back to the colonial era
• hemp growers had little awareness of
the plant’s intoxicating properties
the social practice of consuming
cannabis was brought into the
United States in the early 1900s
by Mexican immigrants

1920s

early 1900s

marijuana smoking began

to be a social
phenomenon
• Recreational
use was taken
up primarily
by jazz
musicians and
people in
show business
 Killer Weed
• In the culture of the time,
marijuana was not considered a
threat at all
• but in the 1930s Harry Anslinger
spearheaded a public relations
campaign
• marijuana was portrayed as a
social menace capable of
destroying the youth of America
• The sprawled body of a young girl lay crushed on
the sidewalk the other day after a plunge from the
fifth story of a Chicago apartment house. Everyone
called it suicide, but actually it was murder. The
killer was a narcotic known to America as
marijuana, and to history as hashish. It is a narcotic
used in the form of cigarettes, comparatively new
to the United States and as dangerous as a coiled
rattlesnake. . . . How many murders, suicides,
robberies, criminal assaults, holdups, burglaries,
and deeds of maniacal insanity it causes each year,
especially among the young, can be only
conjectured. . . . That youth has been selected by
the peddlers of this poison as an especially fertile
filed makes it a problem of serious concern to
every man and woman in America.
– Harry J. Anslinger, Commissioner, Federal Bureau of
Narcotics, in the opening of an article in the widely-read
periodical, The American Magazine, published in July 1937.
•Marihuana Tax Act
of 1937

•A Bill to End the

War on Drugs, 2021
•https://www.psychiatrictim
es.com/view/a-bill-to-end-t
he-war-on-drugs

•https://www.hrw.org/news
/2022/10/28/biden-admini
stration-takes-steps-marijua
na-justice-reform
 • long-term study of drug use
shows a developmental
sequence of involvement
(stages of progression) in
The Gateway drug-taking behavior
Hypothesis • But the overwhelming
proportion of young
marijuana smokers do not
go on to use other illicit
drugs
• “…millions of baby boomers once did, indeed, inhale.
They later went into business, not cocaine or heroin.”

• “The cannabis experience has greatly improved my

appreciation for many human frontiers. … When I’m
high I can penetrate into the past, recall childhood
memories, friends, relatives, playthings, streets,
smells, sounds, and tastes from a vanished era. … The
heightened sensitivity in all areas gives me a feeling of
communion with my surroundings, both animate and
inanimate.” – Carl Sagan
• marijuana smokers are
several times more
likely to consume illicit
drugs such as cocaine
and heroin during their
lifetimes than are
people who never
smoked marijuana
• The strongest form of the gateway hypothesis
relates to the possibility of a causal link
between marijuana smoking and the use of
other illicit drugs
• two schools of thought here: the intrinsic
argument and the sociocultural argument
• 1) the pleasurable sensations induced by
marijuana create a biological urge to
consume more potent substances
• 2) relationship exists because of the
activities, friends, and acquaintances that
are associated with marijuana smoking
• The consensus is that any early exposure to
psychoactive substances in general
represents a “deviance-prone pattern of
behavior”
• marijuana smokers show a greater
inclination toward risk-taking behavior and
are more unconventional with regard to
social norms
 McGlothlin and West
(1968) first proposed an
amotivational syndrome
occurring in cannabis
Amotivational users
Syndrome a failure to follow through on long-
term plans, an indulgence in
childlike thinking, and an
engagement in introversive
behavior
• 2022 Study
• https://academic.oup.com/ijnp/advance-articl
e/doi/10.1093/ijnp/pyac056/6674260
 Pharmocokinetics

burning of marijuana causes THC to

vaporize and enter the smoker’s lungs in
small particles
• 50% from lit cannabis; up to 80% from vaping

Effects occur within seconds for inhalation

• Orally, effects first occur between 30
minutes and 2 hours, but slower absorption
leads to a prolonged duration of effects
compared to inhalation
– 25 to 30 percent reaches bloodstream
– reduced bioavailability
• Δ9-THC metabolized in the liver by P450
enzymes
• primary metabolite of Δ9-THC is 11-hydroxy-
Δ9-THC
• Δ9-THC exhibits high lipid solubility, leading to
rapid distribution into tissues in the body,
including the brain, as well as an accumulation
in fat
• complete elimination from the body is much
slower because of persistence of the drug
in fat tissue
• elimination half-life of THC is generally
estimated at about 20 to 30 hours
• makes Δ9-THC detectable for as long as 30
days after ceasing repeated use
 Pharmocodynamics
Modern cannabinoid
pharmacology began in
1964
• THC identified as the
major active ingredient

1988

1964

Researchers identified
the human body’s
endocannabinoid
system (ECS)
• Sea squirts, newts, rodents, and all
vertebrate species share the
endocannabinoid system (ECS) as an
essential part of life and adaptation to
environmental changes
• evolved in primitive animals over 600
million years ago
– cannabis plant evolved 34 million years
ago
 The endocannabinoid system
(ECS)
The ECS is comprised of cannabinoid receptors, endogenous
cannabinoids (endocannabinoids), and the enzymes
responsible for the synthesis and degradation of the
endocannabinoids

the ECS has been described as the most complicated and

most ubiquitous signaling system in our bodies

a vital molecular system for helping maintain homeostasis

Helps cells stay in their Goldilocks zone

 Receptors
Two major cannabinoid receptors:
• CB1 receptors are one of the most abundant receptor
types in the brain
• CB2 receptors are more abundant outside of the
nervous system, in places like the immune system

Endocannabinoids are molecules that, like

the plant cannabinoid THC, bind to and
activate cannabinoid receptors
 Endocannabinoids

• There are two major endocannabinoids:

– Arachidonoylethanolamide (anandamide)
• Ananda - ‘inner bliss’

– 2-arachidonoylglycerol (2-AG)
• Endocannabinoids are made from fat-like
molecules within cell membranes, and are
synthesized on-demand
• They are made and used exactly when they’re
needed
– Not packaged and stored for later use
• Their enzymes ensure they are used when
needed but not for longer than necessary
 • EC system communicates its
messages in a different way
because it works “backward”
• Retrograde (not anterograde)
signaling
Retrograde
• cannabinoids function like a
signaling “dimmer switch” for
presynaptic neurons
• THC overwhelms the EC
system which can throw the
entire system off balance
 Phyto

Endo
 • Immediate physiological
effects after smoking
marijuana are relatively
minor
• there is a dose-related
Acute increase in heart rate
• Hypotension
Effects • Cannabis produces a
reddening of
conjunctivae, the
membrane covering the
front of the eye and
lining the inside of the
eyelids
• “I’m not
baked, it’s
allergies”

treatment for
glaucoma
 Munchies
• Cannabis use
produces an increase
in appetite
• observed in Hydra
and in rats,
administration of
anandamide leads to
increased overnight
food intake
After fat cells release leptin, lower endocannabinoid levels
leptin reduces anandamide reduce food intake and
and 2-AG concentrations in greater endocannabinoid
the hypothalamus levels increase food intake
endocannabinoid signaling in the gut
drives the overeating characteristic of
Western diets

From an evolutionary perspective,

having a positive feedback mechanism
for fat intake makes sense
 it is common for a first-time smoker
to feel no discernible effects at all

The marijuana high, as the name

implies, is a feeling of euphoria and
well-being
Subjective mundane ideas can seem filled
Effects with profound implications
time seems to pass more slowly

Sleepy and dreamy

 TEMPORAL MENTAL THE INDIVIDUAL HAS
DIFFICULTY IN RETAINING,
DISINTEGRATION INCOORDINATION COORDINATING, AND SERIALLY
INDEXING THOSE MEMORIES,
PERCEPTIONS, AND
EXPECTATIONS THAT ARE
RELEVANT TO THE GOAL HE IS
PURSUING
 “But I drive more carefully when I’m
stoned!”

complex motor tasks such as driving an

automobile are more poorly performed
• Acute psychological
reactions such as
paranoia and increased
anxiety can occur with
marijuana use
• Repeated cannabis use
during adolescence is a
risk factor for
schizophrenia
 Synthetic
Cannabinoids
• John W. Huffman
initially developed
synthetic cannabinoids
in the 1990s
• By 2008, underground
drug manufacturers
were replicating his
work on synthetic
cannabinoids and selling
it under the name Spice
• https://www.healthycan
adians.gc.ca/recall-alert-
rappel-avis/hc-sc/2013/
• Health Canada assigns a drug identification
number (DIN) to all drug products evaluated
and authorized for sale in this country
– Nabilone (Cesamet)
– Sativex
• FDA
– Epidiolex
– Marinol
• Dronabinol
• No CBD-specific product has a DIN
• most commonly sold as oil, has been
promoted as a natural cure for pain, anxiety
and insomnia, despite limited medical
research
• Medical marijuana may offer an alternative
to addictive opioids
• https://norml.org/marijuana/fact-sheets/relationship-
between-marijuana-and-opioids/