Cannabinoid use

disorders and their

management
BY WANG DAVOU LUKA
UJ/2011/MD/O154
OUTLINE
Introduction
Cannabinoids and receptors
Cannabis preparation and epidemiology
Pathophysiology
Dependence
Intoxication
Withdrawal
Other cannabis induced disorders
Unspecified cannabis related disorders
Management
Medical use of marijuana
Conclusion.
introduction
Cannabis is the most widely used illegal drug in the world
It has become a common part of youth culture in most developed societies, with first use now
occurring in the mid to late teenage years
Cannabis use disorder is the continued use of cannabis despite clinically significant distress or
impairment
Cannabinoids and receptors
A cannabinoid is one of a class of diverse chemical compounds that acts on cannabinoid
receptors in cells that alter neurotransmitter release in the brain
They are ligands for their receptors and they include
◦ Endocannabinoids e.g. anandamide, 2-arachidonoylglycerol, noladin ether etc. they are involved in
retrograde signaling, permitting the postsynaptic cell to control its own incoming synaptic traffic
◦ Phytocannabinoids e.g. ∆9 /∆8 THC (Tetrahydrocannabinol), Cannabidiol, Cannabigerol etc. found in
plants like Cannabis sp, Echinacea sp etc. THC is the primary psychoactive component of the Cannabis
plant. Cannabidiol(CBD) on the other hand is non psychotropic and it has been shown to counteract
cognitive impairment, it is the main cannabinoid in CBD dominant cannabis and has medicinal value
◦ Synthetic cannabinoids: Cannabinoids synthesized in the lab. When synthetic cannabinoids are used
recreationally, they present significant health dangers to users.
Cannabinoids and receptors
There are two known types of cannabinoid receptors, termed CB1 and CB2
There are mounting evidence of more
These receptors are diffused with respect to location in the human body
CB1 is found in brain more specifically in the basal ganglia, limbic system, hippocampus,
cerebellum, reproductive system, eye. Absent in medulla oblongata
CB2 is found predominantly in the immune system. CB2 appear to be responsible for the anti-
inflammatory and possibly other therapeutic effects of cannabis
Cannabis preparations
Cannabis preparations are obtained from the plant Cannabis sativa. The plant occurs in male
and female forms. The female plant contains a higher concentrations of cannabinoids.
The most potent forms of cannabis comes from the flowering tops of the plants or from the
dried, black brown resinous exudate from the leave (hashish)
The cannabis plant is usually cut, dried, chopped and rolled into cigarettes which are then
smoked
The common names for cannabis are marijuana, grass, pot, weed, tea and mary jane
hashish
epidemiology
Cannabis is the most commonly used illicit drug globally
The risk of developing dependence among those who have ever used cannabis was estimated at 9% in the USA in the early 1990s
Approximately 13.1 million people are cannabis dependent globally (Degenhardt et al, 2013)
pathophysiology
∆9 THC is recognized as the major psychoactive component of cannabis. THC potently activates the
G-protein-coupled cannabinoid receptor CB1 and modulates the cannabinoid receptor CB2
Smoking is the most common and efficient means of ingestion, with the dose being titrated by the
user through varying the depth and frequency of inhalation. About 2-3 times as much cannabis
must be taken orally to be as potent as smoked cannabis
After intake, THC undergoes metabolism to 11-hydroxy ∆ 9 THC , the metabolite that is active in the
CNS. The half life of THC is approximately 4 hours. The long life of the active metabolite is
explained by the incorporation of the compound in lipid storage depots and similar storage sites in
muscle tissues. 30-60% of THC, in all forms, is excreted in feces; the remaining amount is excreted
in urine
The active metabolite is believed to exert all of its effects on the brain via the CB1 receptor. Since
CB1 receptors are absent on the brainstem nuclei, respiratory and cardiac functions are preserved
pathophysiology
Cannabinoids affect the monoamine and GABA neurons. E.g. causes monoamine and amino acid
neurotransmitters to be released
Tolerance to cannabis does develop, however , and psychological dependence has been found,
although the evidence for physiological dependence is not strong.
When cannabis is smoked, the euphoric effects appear within minutes, peak in about 30
minutes, and last 2-4 hours. Some motor and cognitive effects last 5-12 hours
Diagnosis and clinical features
DSM 5 recognizes the following 5 cannabis associated disorders
◦ Cannabis use disorder
◦ Cannabis intoxication
◦ Cannabis withdrawal
◦ Other cannabis induced disorders
◦ Unspecified cannabis related disorders
Case study
Mr. Red, a 19 year old single male presents, complaining of apathy, lack of motivation, and an
increasing sense of social isolation. He tried marijuana for the first time at age 15, when he was a
junior in high school, and quickly started smoking on a daily basis. He would spend nights and
then days with friends, getting “stoned”, experiencing the “giggles” and relishing the inevitable
“munchies”. He quickly noticed that smoking marijuana seem to quell feeling of anxiety he
experienced in social settings. Having graduated from high school a year earlier, he describes
unfulfilled plans to attend college, which were foiled by his inability to submit the requisite
applications. He describes half hearted attempts to secure employment and now resides in the
basement of his parents house, supported by them. He describes a typical day in the following
fashion
upon waking, usually in the late morning, he invariably takes a bong hit or smokes a
joint, to “get going”. Then he spends a significant amount of time preparing breakfast- he feels
the marijuana heightens his culinary senses and he takes great joy in cooking and preparing a
large meal.
Case study
Following breakfast, he retires back to his room in the basement and spends the next several
hours playing video games online. When he senses that he is slowing down and feeling sleepy, he
will smoke more marijuana because it gives him more energy and improves his mood. He will
typically break form his immersion in the online gaming world for a late lunch, repeating his
earlier efforts associated with breakfast. Occasionally, he will go to the local park to play
basketball with the kids that are still in high school. Previously a successful athlete in high school,
he feels like he has lost a step and his reflexes in the in the court are not as quick as they used to
be
He has taken to selling a baseball card collection he painstakingly acquired when he was younger
to raise money to pay for his marijuana, and that collection has dwindled, he has started to grow
marijuana in his basement. He describes his first effort as generating a meager plant that bears a
resemblance to the sad Christmas tree from Charlie Brown.
Case study
He does not understand why he no longer has a girlfriend or why it has become difficult to meet
new girls. He seems perplexed by his last girlfriend’s complaints that he had become boring and it
seemed like he was “letting life pass him by”. He reports that his parents seem to be growing
increasingly frustrated with him and reports arguing with them over his marijuana use- they
identified it as a problem, he disagrees. He no longer goes out at night and instead spends most
of his time smoking and playing video games alone in his room in the basement.
He denies any difficulty sleeping. Although he does not remember dreaming anymore and cannot
remember the last dream he had. He report some cognitive difficulties associated with decreased
ability to concentrate and some short term memory problems. He reports feeling occasionally
irritable when too much time passes in between smoking and feels that marijuana makes him
less irritable. He is interested in being more social, more engaged, and feeling like he is achieving
his goals seems to be unable to explain why he cannot accomplish what he sets out to do
Case study
He does not seem appreciate that his heavy and chronic marijuana use is a significant cause of
his symptoms. He indicates that overall he enjoys smoking marijuana and believes it makes it
easier for him to enjoy his days, which have become more difficult lately as he appreciates the
stark differences between the quality of life he is enjoying compared with his peers who are now
working or attending college
Cannabis use disorder
Also known as cannabis dependence
Risk of developing dependence is about 9% for anyone who uses cannabis. The earlier the age at
first use, the more often cannabis has been used, and the longer it has been used, the higher
the risk of dependence
Cannabis use disorder is defined in DSM 5 as the continued use of cannabis despite clinically
significant impairment, ranging from mild to severe
People who are cannabis dependent will continue to use it even though they perceive their use
as problematic
Cannabis use is associated with comorbid mental health problems, such as mood and anxiety
disorders and discontinuing cannabis is difficult for some users
Tolerance develop due to increased elimination of the drug with increased use
Cannabis use disorder
Young people are at greater risk of developing cannabis dependence because of the association
between early initiation into substance use and dependence subsequently
There is evidence that cannabis use during adolescence, at a time when the brain is still
developing, may have deleterious effects on neural development and later cognitive functioning
DSM 5 and ICD 10 includes the diagnostic criteria for cannabis use disorder
Case study
Mr. M was an unemployed 20-year-old man who lived with his parents. He was brought to a
hospital by some friends in a state of anxiety and agitation. He had been out for the evening with
some friends at a restaurant, and after a couple of beers, he decided to have some cannabis. He
had smoked cannabis on previous occa­sions; however, this time he ate a lump of cannabis
despite warnings from his friends . After about half an hour, Mr. M appeared tense and anxious
and complained that everything was changing . He could see the faces of his friends increasing to
about three times their natural size. The room became distorted, and its proportions and colors
kept altering. He felt that the other guests in the restaurant were talking about him and his
friends in a menacing way, so he suddenly rushed outside because he felt that he was in danger.
He became increasingly agitated and started running down the middle of the street, dodging in
and out among the traffic.
Case study
Eventually, his friends were able to catch him. They were unable to quiet his anxiety, however,
and had a hard time persuading him to go with them to the hospital. On examination Mr. M
appeared tense and apprehensive, look­ing around the room as if he felt uneasy with the
surroundings, but he denied perceptual symptoms and did not really believe that he was the
subject of persecution. He was fully aware of his surround­ings, but his attention was fleeting, and
he did not always answer questions. There was no marked impairment of memory, and he was
fully oriented. Physical examination revealed conjunctival injection and an increased pulse rate of
120 beats per minute, but otherwise no abnormalities were found. Neurological examination also
revealed no abnormalities. In the course of a few hours, he quieted down. When he felt
recovered, he left the hospital with his friends.
Cannabis intoxication
Marijuana intoxication is the euphoria, relaxation and undesirable side effects that occur with
marijuana use
Cannabis intoxication commonly heightens user’s sensitivities to external stimuli, reveals new
details, makes colours seem brighter and richer and subjectively slows the appreciation of time.
In high doses, users may experience depersonalization & derealization. Motor skills are impaired
by cannabis use, and the impairment in motor skills remains after the subjective, euphoriant
effects have resolve.
The delirium associated with cannabis intoxication is characterized by marked impairment on
cognition and performance tasks. Even modest doses of cannabis impair memory, reaction time,
perception, motor coordination and attention.
Cannabis withdrawal
Cessation in daily cannabis users leads to withdrawal symptoms
These include irritability, cannabis cravings, nervousness, anxiety, insomnia, disturbed or vivid
dreaming, decreased appetite, weight loss, depressed mood, restlessness, headache, chills,
stomach pain, sweating and tremors.
Cannabis induced psychotic disorder
This is rare
Cannabis induced psychosis
Transient paranoid ideation is more common
The psychotic episodes are sometimes referred to as “hemp insanity”
Case study
A 35-year-old white married male who was naive to cannabis use was given two "joints" by a
friend. He smoked the first of the two in the same manner that he normally smoked a cigarette
(in about 3 to 5 minutes). Noting no major effects, he proceeded imme­diately to smoke the
second in the same amount of time . Within 30 minutes, he began to experience rapid
heartbeat, dry mouth, mounting anxiety and the delusional belief that his throat was clos­ing up
and that he was going to die. That belief induced further panic and the patient was brought to
the emergency room in the midst of the experience. Reassurance that he would not die had no
effect. He was sedated with diazepam and some of his anxiety diminished. He eventually went
to sleep and on awakening in about 5 hours he was asymptomatic with full recall of previous
events.
Cannabis induced anxiety disorder
Cannabis induced anxiety disorder is a common diagnosis for acute cannabis intoxication
Which in many persons induces short lived anxiety states often provoked by paranoid thoughts.
In such circumstances, panic attacks may be induced, based on ill defined and disorganized
fears. The appearance of anxiety symptoms is correlated with the dose and is the most frequent
adverse reaction to the moderate use of smoked cannabis.
Inexperienced users are more likely to experience anxiety symptoms than are experienced users
Unspecified cannabis-related disorders
Cannabis disorders that cannot be classified as the others discussed
Cannabis intoxication can be associated with depressive symptoms, although such symptoms
may suggest long-term cannabis use
Hypomania, however, is a common symptom in cannabis intoxication
When either sleep disorder or sexual dysfunction symptoms are related to cannabis use, they
almost always resolve within days or a week after cessation
TREATMENT AND
REHABILITATION
Principle of treatment is abstinence and support
Abstinence may be achieved through direct interventions, such as hospitalization, or through
careful monitoring on an outpatient basis by the use of urine drug screens
Support can be achieved through the use of individuals, family, and group psychotherapies.
Education should be a cornerstone for both abstinence and support programs
For some patients, an anti-anxiety drug may be useful for short term relief of withdrawal
symptoms
For other patients, cannabis use may be related to an underlying depressive disorder that may
respond to specific antidepressant treatment.
MEDICAL USES OF MARIJUANA
Marijuana has been used as a medicinal herb for centuries, and cannabis was listed in the US
pharmacopeia until the end of the 19th century as a remedy for anxiety, depression and GI
disorders among others.
It is used to treat various disorders such as nausea secondary to chemotherapy, multiple
sclerosis, chronic pain, AIDS, epilepsy and glaucoma
In a strongly worded editorial, the new England journal of medicine urged that “Federal
authorities should rescind their prohibition of the medical use of marijuana for seriously ill
patients and allow physicians to decide which patient to treat”.
Medications containing natural or synthetic cannabinoids analogs includes: Dronabinol,
Nabilone, Rimonabant etc.
CONCLUSION
Cannabis contains psychoactive substances known as cannabinoids.
Cannabinoids binds to their receptors in the brain and elsewhere to alter the release of
neurotransmitters responsible for the brain functioning, therefore altering the brain function
Use is associated with dependence, intoxication, withdrawal symptoms, other disorders and
unspecified cannabis related disorders
Principle of treatment is abstinence and support.