Chapter 14: Marijuana and the Cannabinoids

Question 1

What is cannabis?

Answer 1

Cannabis comes from the flowering hemp plant. It can be consumed as marijuana, hashish, or dab. Marijuana and hashish can be smoked or consumed orally. Dab is inhaled.

Question 2

What are the chemical constituents of cannabis?

Answer 2

1. THC

2. CBD

Question 3

What is THC?

Answer 3

THC is a psychoactive phytocannabinoid found in cannabis that accounts for its use as a drug.

Question 4

How is THC consumed?

Answer 4

When THC is inhaled, it is rapidly absorbed from the lungs into the circulation. It almost completely binds to plasma proteins and has a high plasma peak level. When THC is consumed orally, it is absorbed more slowly (compared to smoking) and has a lower peak plasma level.

Question 5

How is THC metabolized?

Answer 5

THC is metabolized by the liver and metabolites are excreted in the feces (primarily) and the urine. THC also accumulates in the body’s fat stores. The elimination half-life of THC is 20-30 hours.

Question 6

What is CBD?

Answer 6

CBD in a non-psychoactive phytocannabinoid found in cannabis that does not have the intoxicating and dependence-producing effects of THC.

Question 7

What are the cannabinoid receptors?

Answer 7

CB1

CB2

Question 8

Where is the CB1 receptor located?

Answer 8

The CB1 receptor is the main cannabinoid receptor in the brain where it is found in high density in the basal ganglia, cerebellum, hippocampus, and cerebral cortex. CB1 receptors are typically located on presynaptic axon terminals but some pyramidal neurons also have CB1 receptors.

Question 9

Where is the CB2 receptor located?

Answer 9

The CB2 receptor is found in the brain in microglia as well as in bone, adipose cells, the gastrointestinal tract, and the immune system.

Question 10

How do cannabinoid receptors work?

Answer 10

They are metabotropic G-protein coupled receptors. Receptor activation can inhibit cAMP formation, inhibit voltage-sensitive Ca2+ channels, and activate K+ channels. They inhibit the release of many different neurotransmitters.

Question 11

What are endocannabinoids?

Answer 11

Endocannabinoids are the endogenous neurotransmitter-like substance synthesized by the brain and they are agonists at cannabinoid receptors. Because they are lipid soluble and cannot be stored in vesicles they are synthesized and released as needed.

Question 12

What are the types of endocannabinoids?

Answer 12

1. Anandamide

2. 2-AG

Question 13

What is anandamide?

Answer 13

Anandamide is an endocannabinoid and partial agonist at CB1 receptors and has little efficacy at CB2 receptors. It is metabolized by the enzymes FAAH and COX-2.

Question 14

What is 2-AG?

Answer 14

2-AG is an endocannabinoid and full agonist at both the CB1 and CB2 receptors. It is metabolized by the enzymes MAGL and COX-2.

Question 15

How do endocannabinoids function?

Answer 15

1) act as retrograde messengers that activate CB1 receptors, inhibiting Ca2+ channel opening and neurotransmitter release
2) stays in the postsynaptic cell to activate either a cannabinoid receptor or TRPV1 cation channels
3) activates cannabinoid receptors on astrocytes which results in glutamate release from the astrocytes

Question 16

What do endocannabinoids have an effect on?

Answer 16

1. inhibit learning and memory processes
2. help regulate fear, anxiety, and reactions to stress
3. anti-depressant effect
4. energy metabolism
5. pain processing and perception

Question 17

What are the therapeutic uses of cannabinoids?

Answer 17

1. nausea and vomiting in cancer chemotherapy patients
2. wasting syndrome in people with AIDS
3. neuropathic pain and spasticity in patients with MS

Question 18

What are the subjective effects of cannabis consumption?

Answer 18

Subjective effects of intoxication are dose-dependent.

1. euphoria
2. disinhibition
3. relaxation
4. altered sensations
5. increased appetite

Question 19

What are the physiological effects of cannabis consumption?

Answer 19

1. increased blood flow to the skin causing warmth or flushing
2. increased HR
3. increased appetite

Question 20

What are the behavioural effects of cannabis consumption?

Answer 20

1. impairment in episodic verbal and working memory
2. impaired attention
3. impaired inhibitory control
4. impaired psychomotor performance

Question 21

Explain the rewarding and reinforcing effects of cannabinoids.

Answer 21

Cannabinoids indirectly effect the mesolimbic dopaminergic system through CB1 receptors on GABAergic interneurons in the VTA. Cannabis inhibits the release of GABA which has the effect of increasing the firing of dopaminergic neurons and increasing the release of dopamine in the nucleus accumbens.

Question 22

What effects does chronic cannabis use have?

Answer 22

1. impaired verbal learning
2. impaired memory
3. impaired attention and attentional bias
4. impaired psychomotor function
5. impaired executive function

Question 23

What are the neurochemical effects of chronic cannabis use?

Answer 23

1. desensitization of CB1 receptors
2. down-regulation of CB1 receptors
3. reduced dopamine synthesis in the striatum
4. reduced dopaminergic cell firing
5. increased CRF release
6. reduced volume of the hippocampus and parts of the PFC
7. deficits in white matter integrity