Lecture 17: Cannabis

Question 1

What is Cannabis?

Answer 1

A genus of flowering plant that contains many bioactive compounds

Question 2

What are the most studied bioactive compounds from Cannabis?

Answer 2

THC and CBD

Question 3

What are Cannabinoids?

Answer 3

A class of chemical compounds that act at the cannabinoid receptors

Question 4

What are some common non-cannabinoid chemicals?

Answer 4

Terpenoids

Question 5

What gives cannabis plants their characteristic smell?

Answer 5

Terpenoids

Question 6

What effects can terpenoids have?

Answer 6

Terpenoids can be anti-inflammatory, anti-bacterial, and anti anxiety

Question 7

What is absorption or bioavailability?

Answer 7

The fraction of an administered drug that reaches effectors

Question 8

What is the bioavailability of smoked THC?

Answer 8

25%

Question 9

What is the bioavailability of ingested THC?

Answer 9

6%

Question 10

Why is THC rapidly taken up by tissues with high blood flow?

Answer 10

Because it is very lipophilic

Question 11

Which tissues accumulate THC more slowly and release it over a longer period of time?

Answer 11

Tissues with less blood flow

Question 12

Where does THC metabolism occur?

Answer 12

In the liver

Question 13

Which liver enzyme works on THC?

Answer 13

Cytochrome P450 2C9

Question 14

What kind of receptors ar Cannabinoid receptors?

Answer 14

Inhibitory G-protein coupled receptors

Question 15

What are the two types of Cannabinoid receptors?

Answer 15

CB1 and CB2

Question 16

What does activation of CB receptors do?

Answer 16

Because they are inhibitory G protein coupled receptors they decrease cAMP and inhibits the influx of calcium and decreases synaptic transmission and neurotransmitter release

Question 17

What kind of agonist is THC and the CB1 receptors?

Answer 17

A partial agonists

Question 18

What is a partial agonist at CB1 receptors?

Answer 18

THC

Question 19

What is the mechanism of action of CBD?

Answer 19

The mechanism of action of CBD is poorly understood but it is though that is is a negative allosteric modulator at CB1

Question 20

How does CBD affect THC?

Answer 20

It can blunt the psychotropic effects of THC

Question 21

What are the most abundant GPCRs in the body?

Answer 21

CB1 receptors

Question 22

Where are CB1 receptors found?

Answer 22

• Brain
• Peripheral organs
• Peripheral nerves

Question 23

Where are CB2 receptors mostly found?

Answer 23

On immune cells, glial cells

Question 24

What are the acute adverse effects of THC?

Answer 24

• Panic attacks
• Severe anxiety
• psychosis
• paranoia
• hyperemesis

Question 25

How can cannabis affect a fetus?

Answer 25

Cannabis use may lead to neuroanatomical and behavior changes in offspring

Question 26

How is Cannabis and Schizophrenia related?

Answer 26

Cannabis use can be linked to the development of psychosis. And can worsen psychosis

Question 27

What is Psychological Dependance?

Answer 27

Compulsive drug seeking behavior in which the individual uses the drug repetitively for personal satisfaction, often in the face of known risks to health

Question 28

What is COMT?

Answer 28

An enzymes that is important in breaking down the monoamine neurotransmitters

Question 29

What do people with the valine copies in the gene have?

Answer 29

A much higher risk of developing schizophrenia if they use cannabis during adolescence

Question 30

What is Physiological dependance revealed?

Answer 30

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

Question 31

What is Cannabis Withdrawal?

Answer 31

It is mild and short lived. With symptoms of restlessness, irritability, mild agitation, insomnia, nausea and cramping

Question 32

What is addiction?

Answer 32

The inability to control the use of legal or illegal substances despite negative consequences

Question 33

What are synthetic cannabinoids?

Answer 33

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

Question 34

Why are synthetic cannabinoids developed?

Answer 34

Because it's easier to determine the dose when there is only one compound present and their are decreased off target effects

Question 35

What are the some of the types of Synthetic Cannabinoids?

Answer 35

Nabilone Dronabinol Nabiximols Rimonabant

Question 36

What receptors do synthetic Nabilone and Dronabinol target?

Answer 36

CB1 receptors

Question 37

What kind of agonists are Nabilone and Dronabinol?

Answer 37

Partial agonists at the CB1 receptor

Question 38

How is Nabilone and Dronabinol taken?

Answer 38

Orally

Question 39

What are Nabiximols?

Answer 39

A synthetic cannabinoid that has a 1:1 mixture of THC and CBD

Question 40

What is Nabiximol used for?

Answer 40

It is used for relief of pain in adult patients suffering from MS or cancer

Question 41

What is Dronabinol used for?

Answer 41

Nausea and vomiting in patients who undergo chemotherapy and anorexia in AIDS

Question 42

What does Rimonabant do at the receptor?

Answer 42

It is an inverse agonist at the CB1 receptor

Question 43

What was Rimonabant used for?

Answer 43

It was approved for obesity but later withdrawn for serious adverse effects by suppressing appetite

Question 44

What are Endogenous Cannabinoids?

Answer 44

The molecules that the body makes themselves to bind to cannabinoid receptors

Question 45

What are the two types of Endogenous Cannabinoids?

Answer 45

Anandamide (AEA) and 2-arachidonoylglycerol (2-AG)

Question 46

What are Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) made from?

Answer 46

The phospholipid bilayer of the membrane

Question 47

How is Anandamide made from the Phospholipid Bilayer?

Answer 47

N-acetyltransferase converts it into NAPE and Phospholipase D converts Anandamide

Question 48

How is 2-AG made from the Phospholipid Bilayer?

Answer 48

Phospholipase C converts it to DAG and DAG lipase converts it into 2-AG

Question 49

What kind of neurotransmitters are AEA and 2-AG?

Answer 49

They are retrograde neurotransmitters

Question 50

How are AEA and 2-AG synthesized

Answer 50

Neurotransmitters that are not stored in vesicles but are synthesized on demand when needed

Question 51

Why are AEA and 2-AG retrograde neurotransmitters?

Answer 51

Because they act on the cannabinoid receptors on the presynaptic membrane and inhibit the neuron because they target Gi

Question 52

How do endocannabinoids affect other neurotransmitters?

Answer 52

They decrease neuronal release of other transmitters

Question 53

What is synthesis of 2AG and AEA stimulated by?

Answer 53

An increase concentration of intracellular calcium when the postsynaptic neuron becomes depolarized by the action of a neurotransmitters

Question 54

What are AEA and 2AG cleared from the synapse and inactivated by?

Answer 54

Fatty-acid amide hydrolase (FAAH) or monoacylglycerol (MAGL)

Question 55

What effects do FAAH/MAGL inhibitors have?

Answer 55

They are analgesic but do not produce typical psychoactive effects of THC, sedation, catalepsy or hypothermia