Lecture 15 - Cannabis

Question 1

What is cannabis?

Answer 1

genus of flowering plant. contains many bioactive compounds, but most studied are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the primary psychoactive compound in cannabis

Question 2

What are cannabinoids

Answer 2

class of chemical compounds that act at the cannabinoid receptors

Question 3

What is bioavailability?

Answer 3

fraction of an administered drug that reaches effectors

Question 4

What is the absorption of smoking cannabis?

Answer 4

-rapid and efficient delivery from lungs to brain
- bioavailability of smoked THC is 25%, reaching peak plasma concentration in 6-10 minutes

Question 5

What is the absorption of ingesting cannabis?

Answer 5

bioavailability around 6%, time to peak plasma concentration is 2-6 hours

Question 6

What is the distribution of THC

Answer 6

• highly lipophilic so rapidly taken up by tissues with high blood flow including heart, lungs, brain and liver
• tissues with less blood flow accumulate THC more slowly and release it over a longer period of time
• THC stored in fat in chronic, frequent cannabis smokers can be released into the blood for days

Question 7

What is the metabolism and elimination of THC

Answer 7

• THC metabolism occurs mostly in the liver by cytochrome P450 2C9 enzyme producing the metabolites 11-OH- THC and THC-COOH
• within 5 days, 80-90% is excreted, primarily as metabolites, 65% in feces and 25% in urine
• can detect THC in urine 2-5 days for low dose THC, but can extend to weeks in chronic daily cannabis smokers

Question 8

What are cannabinoid receptors

Answer 8

inhibitory G-protein coupled receptors (Gi coupled)

Question 9

What are the two flavours of cannabinoid receptors

Answer 9

CB1 and CB2

Question 10

How do CB receptors affect cAMP

Answer 10

decrease cAMP which inhibits influx of calcium in the firing neuron and inhibits neurotransmitter release

Question 11

What is THC at CB1

Answer 11

partial agonist

Question 12

What are CB1 receptors?

Answer 12

• are among the most abundant GPCRs
• found in brain, peripheral organs and peripheral nerves

Question 13

What are CB2 receptors

Answer 13

mostly distributed on immune cells

Question 14

What are acute effects of THC?

Answer 14

panic attacks, severe anxiety, psychosis, paranoia, convulsions, hyperemesis. These are rare and usually associated with high doses of THC

Question 15

What are prenatal effects of THC?

Answer 15

cannabis use may lead to neuroanatomical and behavioural changes in offspring. fetal growth affected (particularly neurodevelopment), but dose-response relationship not identified

Question 16

What causes lung cancer

Answer 16

smoked cannabis

Question 17

What is effect of THC on driving

Answer 17

• increase the risk for being in a motor vehicle accident. THC impairs perception, psychomotor performance, cognitive functions and affective functions. Decreased reaction time

Question 18

What is psychological dependence

Answer 18

compulsive drug-seeking behaviour in which the individual uses the drug receptively for personal satisfaction, often in the face of known risks to health

Question 19

What is physiological dependence

Answer 19

revealed when withdrawal of the drug produces symptoms and signs that are frequently opposite of those sought by the user

Question 20

What is cannabis withdrawal

Answer 20

-relatively mild and short-lived
- symptoms of restlessness, irritability, mild agitation, insomnia, nausea, and cramping.
- may be worse in chronic, long-term users, and may contribute to continued drug use

Question 21

What is addiction

Answer 21

defined as the inability to control the use of legal or illegal substances despite negative consequences
- diagnosed by 11 diagnostic criteria

Question 22

What are synthetic cannabinoids

Answer 22

a manufactured compound whose properties imitate those of the active constituents of cannabis

Question 23

Why are synthetic cannabinoids better

Answer 23

• increased specificity
• decreased off target effects
• easier dosing
• better controlled studies

Question 24

What is nabilone?

Answer 24

synthetic analog of THC

Question 25

What is dronabinol

Answer 25

trans isomer of delta9-THC, approved for nausea and vomiting in patients who undergo chemotherapy and anorexia in AIDS wasting syndrome

Question 26

What is common of nabilone and dronabinol?

Answer 26

• both are partial agonist at CB1 receptor
• both nabilone and dronabinol are taken orally. Oral THC analogs have less psychotropic effects than cannabis

Question 27

What are nabiximols?

Answer 27

• botanical drug (cannabis extract)
• 1:1 mixture of THC and cannabinol, sublingual spray
• first licensed in Canada for relief of pain in adult patients suffering from multiple sclerosis or cancer
• less psychotropic effects than smoked cannabinoids

Question 28

What is rimonabant

Answer 28

• inverse agonist at the CB1 receptor
• approved for the treatment for obseity, but then withdrawn after linked to suicide ideation

Question 29

What are endocannabinoids?

Answer 29

mediate mood, feeding, motor function
- come in two flavours: anadamide (AEA), and 2-arachinoyl glycerol (2-AG)

Question 30

What are AEA and 2-AG

Answer 30

retrograde neurotransmitter
- not stored in vesicles, but rather synthesized on demand when and where they are needed

Question 31

What is endocannabinoid signalling

Answer 31

• endocannabinoids decrease neuronal release of other transmitters
• synthesis of 2AG or AEA is stimulated by increase in concentration of intracellular calcium when the postsynaptic neuron becomes depolarized by the action of a neurotransmitter
• produced only in regions of brain that are activated

Question 32

What is endocannabinoid metabolism

Answer 32

AEA and 2AG are rapidly cleared from the synapse and inactivated by fatty-acid amide hydrolase (FAAH) or monoacylclycerol ligase (MAGL). suppression of these enzymes prolongs the activity of endocannabinoids