Week 7: Cannabis (only in exam) Flashcards
Cannabis Sativa History
Indigenous to Central and Southern Asia
Use dates back to 3000 BCE
Two main varieties
- One is cultivated for its fibers, and has relatively low active ingredients (hemp)
- One is cultivated for intoxicating properties, and has high active ingredients
The Cannabinoids
The word cannabinoid refers to every chemical substance, regardless of structure or origin, that joins the cannabinoid receptors of the body and brain and that have similar effects to those produced by the Cannabis Sativa plant.
In sativa’s the main active ingredient is delta-9-tetrahydrocannabinol (THC)
A large class of chemical compounds, called cannabinoids, are found exclusively in cannabis and contribute to the behavioural effects of the plant
To date, 85 cannabinoids have been identified
Their role in behavioural effects is difficult to specify
Depends on method of preparation, route of administration etc…
Content of cannabinoids in marijuana changes over time
Neuropharmacology of Cannabis and cannabinoid receptors
Cannabinoid receptors were identified in the late 1980s
Two types – coupled to cyclic AMP second-messenger systems (GPCR)
CB1 – present in CNS; cortex, hippocampus, cerebellum, substantia nigra, hypothalamus, brainstem, and spinal cord
CB2 – present mostly outside of the CNS; spleen and immune system
Action of cannabinoids in the synapse
In neurotransmission a NT is released from the presynaptic cell onto the postsynaptic cell.
When this occurs, cannabinoids can be released by the post-synaptic cell, to act on the presynaptic cell cannabinoid receptors.
When this occurs you can get either;
DSI- Depolarisation induced suppression of inhibition
DSE-Depolarisation induced suppression of excitation
This isn’t the only way cannabinoids act in the brain but is one of them
CB1 Receptor and Dopamine
CB1 receptor activation increases dopamine levels in the NAc, although the mechanism is unclear
But recreational doses of THC don’t increase DA in humans, so reinforcing mechanism is unclear
The endocannabinoid system seems particularly involved in stress recovery
“relax, eat, sleep, forget, and protect” seem to be mediated by endocannabinoids
Effects of cannabis on the body
Effects on the body
Subjective effects
Alterations in perception
Euphoria
Feelings of well-being
Increased appreciation of humor
Eyes:
- redenning
- decreased intra-ocular pressure
Mouth
- dryness
Skin
-Sensation of heat or cold
Heart
- increased heart rate
Muscles
- Relaxation
Effects on sleep from cannabis
Causes drowsiness and increases sleeping time
Higher doses can interfere with sleep
Restlessness and insomnia
Some evidence that lower doses cause changes in sleep-stage patterns
Higher doses impair sleep
No effect of marijuana discontinuation on sleep (no withdrawal effect)
Medically useful effects of cannabis
Are widespread
- eg. alzheimers, ALS, chronic pain, gliomas, depression, dystonia, fibromyalgia, GI disorders, Hep C, HIV, Hypertension, Incontinence, Anitbiotic resistance, MS, Muscle relaxer, osteoporosis, Arthritis, sleep apnea, tourettes
This has resulted in a lot of political pressure to create policy to allow this. But also on pharma companies to produce ways to have medical marajuana without getting high
Effects on behaviour and performance of humans
Theophile Gautier (a member of the club of hacichins) – first European author to write about the subjective effects of cannabis
Hallucinogenic effects of high doses
Not entirely accurate and highly embellished
Has shaped the expectancies and prejudices of users
Mood changes and getting high
Mood changes and getting high
A feeling of well being and joyfulness
Occasionally feelings of anxiety and foreboding
Frequent laughing and good humor
Perceptual heightening; mundane thoughts and insight take on great significance; creativity is enhanced
(watched a video showing perceptual heightening - double rainbow clip)
In spite of consistent reports of elevated mood from users, systematic measurement yields conflicting results
Both positive and negative mood changes have been reported
Unique patterns of responding to mood scales across studies
Increase in scales of stimulation and sedation simultaneously
Environment impacts how drug changes mood
People become more susceptible to being influenced by the mood of others
People who report having a positive initial experience were more likely to use marijuana in the future
Perception and Cannabis
One of the common subjective effects is increased sensory sensitivity
Empirical tests have found decreases or no change in sensory thresholds
Loss of sensitivity to pain
Increases in subjective time – time slows
Memory and Cannabis
No effect on recall of previously learned material; does disrupt ability to recall words or narrative material
Biggest impact is on short-term memory
Temporal disintegration – lose the ability to retain and coordinate information for a purpose (loss of temporal ordering - stories get jumbled)
Likely has something to do with the effect of cannabinoids on limbic system function as this is key for stm function
Cannabis and Creativity
Widely reported subjective effect is enhanced creativity
Objective research does not support this assertion
Cannabis and Performance
High doses of cannabis impair certain tasks
Incredible variability in effects on performance
Very difficult to reach specific conclusions about effects on performance
Cannabis and Driving
Cannabis typically reported to impair driving
Does not impair judgement or slow reaction time
Decreases drivers ability to attend to peripheral stimuli
You can stop just as quickly, but you don’t notice things you should stop for
-Effects on behaviour of nonhumans
Unconditioned behaviour
Biphasic effect on SMA (spontaneous motor activity) – increases activity, then a depression; depressive effect is more powerful, lasts longer, and is more resistant to tolerance
Reduction in aggression
Decreased food intake and weight loss
As potent as morphine as an analgesic
Cannabis and Conditioned Behaviour
THC interferes with tasks that require short-term memory (maze and matching to sample tasks)
Correlated with suppression of cell firing in hippocampus
Also affects tasks that require timing
Cannabis and Dissociation
Produces dissociation in rats – unable to transfer to a nondrug state what had been learned in a drug state
Also produces dissociation in humans
Drug state discrimination
Rats easily discriminate THC from placebo
Partial generalization to sedatives, no generalization to any other drug class
Experienced human users can distinguish marijuana cigarettes containing 0% THC from ones containing 2.7%, or 1.7% THC
0.09% THC was identified as placebo
Cannabis and Tolerance
In lab animals tolerance develops quickly – within 5 to 6 days of repeated dosing
-Most rapid for increases in activity
-Slowest for depression of activity
-No tolerance to anorexic or discriminative effects
Tolerance is associated with decreases in cannabinoid receptors and downregulation/desensitization
Human tolerance is more difficult to pin down
–Reports of sensitization or reverse tolerance
—-Never seen in the laboratory
—-Likely has to do with users being more efficient in their delivery – require less to get high
–Tolerance occurs to effects of low and high doses after 4 days of consecutive administration
—-No tolerance to increased food consumption
Cannabis Withdrawal
Occurs in animals after prolonged administration of high doses
–Usually an increase in activity
In humans, withdrawal occurs within 1 to 3 days of abstinence, peaks between days 2 and 6, and lasted up to 14 days
–Appetite change, restlessness, craving
Self-administration in humans and nonhumans
Readily self-administered by humans
Doesn’t appear to depend on THC content
Titration
–People are not able to titrate their dosage very effectively
–Don’t really adjust well based on variations in potency
–Factors other than dose must control marijuana intake
(people tend not to smoke differently depending on the potency
Epidemiology of Cannabis
In North America, cannabis is a social drug
–Most users begin smoking in groups, and solitary smoking isn’t as common, although it is increasing
–Users tend to be casual, and consume low amounts of THC
–Tend to decrease and stop using after a period of time
In other countries, where cannabis has a long history of use, use is chronic and sustained
—India, Egypt, Greece, Morocco, Jamaica
—-Use everyday and consume high amount of THC
—-Use may persist for 20-40 years
Prevalence stats and cannabis use
NZ and Aus have the highest cannabis use globally - which makes sense given how easy it is to grow here and the fact it is more accessible than importing foreign drugs
Harmful effects
Cannabis use is a highly controversial topic
Proponents cite the many medical uses
Opponents cite the potential for harm and association with criminal behavior
But is cannabis really harmful?
– Wathed the ‘reefer madness’ video which was from the 1930s in America suggesting weed caused people to go insane, murder people, commit suicide, be violent etc
Violence and aggression - and cannabis
- One of the oldest beliefs is that cannabis directly causes violence and aggression
- In the vast majority of studies, no relation between cannabis use and violence has been found
- If there is a correlation, it is a decrease in violence with cannabis use
- Most documented incidents of violence after cannabis use occur in people with a history of psychiatric illness or when taken in combination with other drugs
Mental disturbance and cannabis
Larger than usual doses can cause “freak-outs”
Overwhelming anxiety and paranoia
Acute psychosis: positive, negative, and cognitive symptoms
Generally occurs with a mix of drugs, usually hallucinogens
Cannabis and schizophrenia
A number of studies have reported associations between cannabis use and later development of schizophrenia. Suggests high cannabis use and schizo are correlated
Little evidence to suggest that cannabis use by itself causes schizophrenia (causality)
Probably speeds up the emergence of SCZ symptoms in people who would develop the disease anyway (directionality)
Power et al., 2014
Did a twin study assessing people’s polygenetic risk (by scoring it) and then comparing propensity to using cannabis.
Found that when neither twin used cannabis they also had lower polygenic risk scores and when both twins used they had higher scores
This supports the idea that people genetically inclined to develop schizophrenia for whatever reason are more likely to use cannabis (not the other way around)
Pasman et al., GWAS of lifetime cannabis use and psychiatric traits
Looked at directionality and causality between cannabis and schizo onset
Found that there was no evidence for cannabis causing schizo when using a conservative p value.
With a more liberal p value, 1/3 stat tests gave a significant result for canabis causing schizo
But schizo causing cannabis use produce 3/5 stat significant results
Permanent intellectual impairment and brain damage with cannabis use
In nonhumans, some evidence that high doses of THC damage cells
In humans, no evidence that cannabis use produces any lasting brain damage or cognitive impairment
Not in adults (Pope et al., 2001)
Not in youth (Fried et al., 2002)
Can cause acute deficits in cognition but not long term damage
Amotivational syndrome
Change in lifestyle, ambitions, apathy, loss of effectiveness, diminished capacity or willingness to carry out complex long-term plans, endure frustration, concentrate for long periods, follow routines, or successfully master new material
Evidence is equivocal; not known whether cannabis directly impacts motivation
–Issue is not settled
Is cannabis a gateway drug?
- a video to watch if ya wana
but ultimately, weed isn’t a gateway drug. Prohibition is the gateway drug as it means that weed smokers are having to go through drug dealers to get pot and it’s not regulated etc
Reproduction and Testosterone and cannabis
Marijuana has been shown to decrease testosterone levels in males
–Unclear whether this is problematic
–Levels of testosterone vary considerably between individuals
Dose dependent effects on sexual behaviour and arousability
Males
–Increased sexual desire
–Decreased erectile functioning
Females
–Increases sexual desire, satisfaction, pleasure, and orgasm quality
Does not appear to have negative effects on fetal development
–Some evidence that later developmental problems are associated, but no causal link
Immunity and Cannabis
Previously thought that cannabis antagonizes the immune system
Now recognized that its effects on immune system functioning are much more complex
–No conclusive evidence that cannabis users are more prone to disease or infection than nonusers
Cancer
Marijuana smoke contains 50 to 70% more carcinogens than tobacco smoke
Users inhale more deeply and hold smoke in their lungs longer
Still no conclusive link between cannabis and cancer
– Confounded by the fact that cannabis users often smoke tobacco
– Might accelerate the cancer causing effects of tobacco
Some studies have found that THC is a potential antioxidant
More recent studies have failed to show a link between cannabis and cancer
More careful research is needed
Cannabis in New Zealand
Most widely used illegal drug in New Zealand
Illegal to possess any amount – punishable by a 3 month jail term or $500 fine
–Subject to the Misuse of Drugs Act 1975
Approved cannabis based pharmaceuticals can be prescribed by a doctor, but are not subsidized
–Patients must meet strict criteria to qualify
–Unapproved products can be approved on a case-by-case basis by the Minister of Health
Medicinal use of cannabis is legal
Synthetic cannabis
Symptoms
- aggression/agitation
- paranoid delusions
- depression
- hallucinations
- suicidal thoughts
- impending doom thoughts
- panic and heart attacks
-inability to speak
- psychosis
- body temp fluctuations
SUPER BAD STUFF DONT DO ITT
