L4 - CANNABIS

Question 1

Regarding the history of cannabis policy in Canada, what significant events are the dates below corresponding to?

1923
1971
2001
2018

Answer 1

1923: Cannabis is added to the Schedule of the Opium and Narcotic control Act to prohibit use

1971: Commission recommends decriminalizing possession and personal cultivation – ignored

2001: Canada introduced the Marihuana Medical Access Regulations Act. This made Canada the first country to legalize cannabis for medical use

2018: National legalization of recreational cannabis in Canada

Question 2

True or false: since the legalization of cannabis in Canada, most population age groups show a trend of increasing cannabis use.

Answer 2

True.

Question 3

What is the fastest growing population group of cannabis users in Canada?

Answer 3

Aging adults (55 yrs +).

Question 4

Approximately how many cannabinoids does herbal cannabis contain?

Answer 4

More than 80.

Question 5

What are the two most studied cannabinoids?

Answer 5

Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

Question 6

How many cannabinoid(s) is/are psychoactive? Which one(s)?

Answer 6

Only THC.

Question 7

Is cannabis addictive?

Answer 7

Yes, cannabis indirectly stimulates dopamine in the rewarding regions of the brain.

Question 8

Cannabis sativa contains a higher ratio ____ and produce more ____ effects. Cannabis indica contains a higher ratio ____ and produce more ____ effects.

CBD:THC
stimulating
sedating
THC:CBD

Answer 8

Cannabis sativa contains a higher ratio THC:CBD and produce more stimulating effects. Cannabis indica contains a higher ratio CBD:THC and produce more sedating effects.

CBD:THC
stimulating
sedating
THC:CBD

Question 9

What can account for the increasing potency of cannabis?

Answer 9

Selective breeding and more advanced cultivation methods.

Question 10

What trend is the population’s perception of cannabis following? What event in the past 5 years could contribute to sustain this trend?

Answer 10

Less and less perception of risk of harm from cannabis.
Legalization of recreational cannabis use in Canada.

Question 11

What components make up the endocannabinoid system?

Answer 11

Endogenous cannabinoids + cannabinoid receptors + related enzymes (synthesis and degradation).

Question 12

What are the two endocannabinoids?

Answer 12

Anandamide and arachidonylglycerol (2-AG).

Question 13

Endocannabinoids are retrograde messengers. What does that mean?

Answer 13

They travel “backward” in the synapse, from the postsynaptic neuron to the presynaptic neuron. Therefore, the endocannabinoid receptors are located on the presynaptic neurons.

Question 14

What are the two enzymes responsible for the degradation of anandamide and 2-AG?

Answer 14

FAAH
MAGL

Question 15

True or false: cannabinoid receptors are found all over the body and are numerous.

Answer 15

True.

Question 16

True or false: cannabinoid receptors are equally spread all over the body.

Answer 16

False: both endocannabinoid types form clusters in specific parts of the body.

Question 17

Name the two types of cannabinoid receptors and indicate where they are most likely to be found in the body.

Answer 17

CB1R: brain.
CB2R: periphery and immune cells.

Question 18

____ is a partial agonist for CB1R and full agonist for CB2R. ____ is a full agonist for CB1R and CB2R

Anandamide
2-AG

Answer 18

Anandamide is a partial agonist for CB1R and CB2R. 2-AG is a full agonist for CB1R and CB2R

Anandamide
2-AG

Question 19

List two general roles of the endocannabinoid system.

Answer 19

Neuromodulatory maintenance of homeostasis.
Modulate effects of cannabinoids and other addictive drugs.

Question 20

True or false: dysregulation of endocannabioids has been associated with psychiatric disorders.

Answer 20

True.

Question 21

What is accounting for the very long half life of THC? Up to how many days after cannabis consumption can metabolites of THC be found in the body?

Answer 21

THC deposits in adipose tissue and is later released back into bloodstream. Metabolites can be detected up to 28 days after use.

Question 22

THC is a partial agonist of what receptor?

Answer 22

CB1R

Question 23

Describe the affinity of CBD and its relationship to CB1R and CB2R.

Answer 23

Little affinity for both receptors.
Antagonist for both receptors.
Non-competitive negative allosteric modulator of CB1R.

Question 24

In light of the pharmacodynamic effects of CBD on CB1R, why is it revealing to look at the THC:CBD ratio when studying the potency of cannabis?

Answer 24

CBD is a non-competitive antagonist of CB1R, on which acts THC. Therefore, the more cannabis contains CBD, the less THC will produce effects.

Question 25

List regions of the brain that are concentrated in CB1R.

Answer 25

Basal ganglia Cerebellum NAcc Hippocampus

Question 26

What is the most fatal short-term physiological effect of cannabis?

Answer 26

Impaired motor coordination (car accidents).

Question 27

What portion of cannabis users will meet for a CUD in their lifetime?

Answer 27

30%

Question 28

Briefly describe the cannabis withdrawal trajectory.

Answer 28

Symptoms beginning after 24h. Peak at 7 days. Dissipate after 28 days.

Question 29

True or false: CUD can lead to respiratory and cardiovascular problems.

Answer 29

True.

Question 30

List some cognitive chronic effects from CUD.

Answer 30

Poorer executive functions, verbal ability, attention and memory.

Question 31

Under what circumstances can chronic use of cannabis lead to permanent cognitive impairments?

Answer 31

When used during development of endocannabinoid system (during adolescence in humans).

Question 32

Why is a FAAH inhibitor proposed as a pharmacotherapy for CUD?

Answer 32

Decreases degradation of anandamide -> more anandamide available -> more competition with THC for CB1R -> less THC effects.

Question 33

Which cannabis treatment has the best efficiency?

Answer 33

Mix of 3 behavioural therapies: cognitive-behavioural therapy, motivational enhancement therapy and contingency management.

Question 34

Neuromodulation treatments for cannabis target what area of the brain?

Answer 34

DLPFC.

Question 35

Regarding mental health, what is frequent cannabis use amongst teenagers predicting?

Answer 35

Twofold increase in risk for later depression and anxiety.

Question 36

What is WIN 55-212?

Answer 36

Synthetic agonist receptor CB1

Question 37

THC or CBD is a partial agonist of 5-HT1A?

Answer 37

CBD

Question 38

In regard of the localization of CB1 neurons, why could we expect their agonists to have an effect on mood and emotion?

Answer 38

CB1R and 5-HT neurons are co-localized in the limbic system.

Question 39

What is the effect of WIN on the activity of serotoninergic neurons at low doses? In high dose? What are the corresponding behaviours?

Answer 39

Increase in firing -> antidepressant. Decrease in firing -> antidepressant property lost.

Question 40

Immobility of the animal in the force swimming test is an indicator of what?

Answer 40

Depression.

Question 41

What is rimonabant?

Answer 41

CB1R antagonist.

Question 42

What principally determines whether THC has antidepressants effects or not?

Answer 42

Whether THC administration is repeated or not. Single dose -> mixed effects Repeated -> antidepressant

Question 43

Describe the effect of CBD on 5-HT neurotransmission after the administration of cumulative acute doses and daily repeated doses?

Answer 43

Acute single dose: decreases the firing rate of 5-HT DRN neurons via 5HT1A. Repeated doses (7 days): increases the firing rate of 5-HT DRN neurons via 5-HT1A desensitization.

Question 44

Does one acute dose of THC increase 5-HT activity?

Answer 44

Unclear.

Question 45

What region of the brain is the last to develop?

Answer 45

PFC

Question 46

True or false: long-term marijuana use in people using cannabis at young age can impact the neurodevelopment of the brain.

Answer 46

True.

Question 47

True or false: chronic use of TCT in rats affected 5-HT firing activity, but did not impact the endocannabinoid system (endocannabinoid levels and receptor density).

Answer 47

False: endocannabinoid system is changed.

Question 48

What are animal studies revealing about the effects of long-term THC administration in adult and adolescent cohorts?

Answer 48

-Decreased 5-HT firing activity in adults and adolescents. -Anhedonia behaviour is mostly observed amongst -adolescents. -Less neurobiological changes in adulthood. -Cognitive and social behaviour impairments in adolescents. -Females are most sensitive to THC-induced depression.

Question 49

How does cannabis consumption affect dopamine levels?

Answer 49

Increase in DA release in NAcc (addictive).

Question 50

How does cannabis withdrawal affect dopamine levels?

Answer 50

Decrease in VTA DA firing.

Question 51

True or false: cannabis increases risk for psychosis even in the absence of predisposition.

Answer 51

True.

Question 52

What are clinical studies revealing about cannabis consumption and the frisk for depression?

Answer 52

Cannabis increases the risk of depression in a dose-response manner.

Question 53

Regarding depression, anxiety and suicidal ideations, what would a meta-analysis predict for cannabis consumption in young people?

Answer 53

Important increase in risk of depression. No anticipated change in anxiety. Important increase of suicidal ideations.

Question 54

Why are withdrawal symptoms from cannabis hard to identify?

Answer 54

Because they can appear very late (THC takes about 28 days to leave the system).