Week 7: Cannabis (only in exam)

Question 1

Cannabis Sativa History

Answer 1

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

Question 2

The Cannabinoids

Answer 2

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

Question 3

Neuropharmacology of Cannabis and cannabinoid receptors

Answer 3

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

Question 4

Action of cannabinoids in the synapse

Answer 4

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

Question 5

CB1 Receptor and Dopamine

Answer 5

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

Question 6

Effects of cannabis on the body

Answer 6

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

Question 7

Effects on sleep from cannabis

Answer 7

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)

Question 8

Medically useful effects of cannabis

Answer 8

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

Question 9

Effects on behaviour and performance of humans

Answer 9

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

Question 10

Mood changes and getting high

Answer 10

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

Question 11

Perception and Cannabis

Answer 11

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

Question 12

Memory and Cannabis

Answer 12

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

Question 13

Cannabis and Creativity

Answer 13

Widely reported subjective effect is enhanced creativity
Objective research does not support this assertion

Question 14

Cannabis and Performance

Answer 14

High doses of cannabis impair certain tasks
Incredible variability in effects on performance
Very difficult to reach specific conclusions about effects on performance

Question 15

Cannabis and Driving

Answer 15

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

Question 16

-Effects on behaviour of nonhumans

Answer 16

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

Question 17

Cannabis and Conditioned Behaviour

Answer 17

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

Question 18

Cannabis and Dissociation

Answer 18

Produces dissociation in rats – unable to transfer to a nondrug state what had been learned in a drug state
Also produces dissociation in humans

Question 19

Drug state discrimination

Answer 19

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

Question 20

Cannabis and Tolerance

Answer 20

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

Question 21

Cannabis Withdrawal

Answer 21

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

Question 22

Self-administration in humans and nonhumans

Answer 22

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

Question 23

Epidemiology of Cannabis

Answer 23

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

Question 24

Prevalence stats and cannabis use

Answer 24

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

Question 25

Harmful effects

Answer 25

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

Question 26

Violence and aggression - and cannabis

Answer 26

• 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

Question 27

Mental disturbance and cannabis

Answer 27

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

Question 28

Cannabis and schizophrenia

Answer 28

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)

Question 29

Power et al., 2014

Answer 29

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)

Question 30

Pasman et al., GWAS of lifetime cannabis use and psychiatric traits

Answer 30

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

Question 31

Permanent intellectual impairment and brain damage with cannabis use

Answer 31

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

Question 32

Amotivational syndrome

Answer 32

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

Question 33

Is cannabis a gateway drug?

Answer 33

• 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

Question 34

Reproduction and Testosterone and cannabis

Answer 34

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

Question 35

Immunity and Cannabis

Answer 35

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

Question 36

Cancer

Answer 36

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

Question 37

Cannabis in New Zealand

Answer 37

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

Question 38

Synthetic cannabis

Answer 38

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