Lecture 7

Question 1

Cannabinoids

Answer 1

Compounds made by the cannabis plant

Question 2

Things that act on the human cannabinoid receptors (6)

Answer 2

○ Phyto cannabinoids
○ Delta9 tetrahydrocannabinol (THC)
○ CBD
○ Endo cannabinoids
○ Anandamide
○ 2AG

Question 3

CBD has been investigated because

Answer 3

it does not cause an euphoric high, but may have health benefits

Question 4

___ is the most abundant in the brain

Answer 4

2AG
- More than anandamide but they both perform the same function
- Agonists of the CB1 receptor

Question 5

What activates CB1 receptors

Answer 5

Endocannabinoids, and THC

Question 6

What is the most abundant G protein coupled receptor in the brain

Answer 6

CB1 receptors

Question 7

CB1 receptors are also widely expressed in

Answer 7

the body
- lungs, liver, kidney, pancreas, and bone

Question 8

CB2 receptors are expressed

Answer 8

in the brain at lower levels. They are often thought of as “peripheral cannabinoid receptors” because they are more highly expressed in the body than the brain.

Question 9

CB2 receptors are activated by

Answer 9

THC and endocannabinoids

Question 10

cannabinoid system is like

Answer 10

the brain’s equalizer, modulating the intensity of every neuronal signal

Question 11

where else are CB2 receptors found

Answer 11

immune cells

Question 12

what makes endocannabinoids

Answer 12

postsynaptic neurons
- eCBs are made by enzymes that convert membrane lipids into eCBs.
- The eCBs diffuse out and bind to the nearby CB1 receptors on presynaptic neurons (at axon terminal).

Question 13

The eCBs are quickly degraded by

Answer 13

other enzymes so they act for a very short time.

Question 14

When eCBs bind to the CB1 receptor,

Answer 14

they activate the receptor

Question 15

The CB1 receptor activation causes the presynaptic neuron to

Answer 15

release LESS neurotransmitter

Question 16

Endocannabinoids characteristics

Answer 16

○ Quickly degraded –fast acting
○ modulators to correct level of neurotransmission
○ Appetite stimulant
○ Reduces pain (part of descending pathway)
○ Promotes learning & memory
○ Promotes bone formation

Question 17

characteristics of THC

Answer 17

○ Long-lasting – acute effects last for hours, accumulates in fat tissues and remains in body for weeks
○ Appetite stimulant & anti-emetic
○ Reduces pain (analgesic) and muscle spasticity
○ Impairs learning & memory
○ Hallucinations (sensory & time distortion)
○ Psychosis

Question 18

acute effects of cannabis

Answer 18

• Euphoria – high
• Analgesia
• Sleepiness
• Reduces anxiety (but causes anxiety in some people)
• Hallucinations & time distortion
• Reduces nausea (but can cause excessive vomiting in some people)
• Increased appetite
• Fatal overdose rare (accidents can occur while intoxicated)

Question 19

Effects of chronic cannabis consumption

Answer 19

• Tolerance to effects – dose escalation
• Physical dependence and withdrawal
• Cannabis use disorder - addiction
• Withdrawal symptoms: agitation, anger, depression, insomnia, loss of appetite, weight loss, headache, nausea, vomiting, sweating, strange/upsetting dreams

Question 20

THC is prescribed with the drug name

Answer 20

dronabinol (marinol)

Question 21

THC is approved to treat

Answer 21

anorexia in HIV/AIDS, treat nausea and vomiting induced by chemotherapy

Question 22

nabilone is a synthetic analog of

Answer 22

THC

Question 23

Nabilone is approved to treat

Answer 23

anorexia with AIDS, nausea and vomiting from chemo

Question 24

THC and CBD mixed medication is called

Answer 24

Nabiximol (Sativex) - mouth spray

Question 25

what is Nabiximol used for

Answer 25

• Used for MS, white matter tracks are losing their myelination and there is no balanced contraction of muscles
• Reduces muscle spasticity and pain that accompanies multiple sclerosis.
• Reduces pain in cancer patients.

Question 26

Medical uses of CBD

Answer 26

for Dravet Syndrome (childhood onset epilepsy) (not for other forms)

Question 27

what is the medical drug name for the CBD medication for Dravet

Answer 27

epidiolex

Question 28

what else is epidiolex being tested for treatment for

Answer 28

chronic pain and inflammatory disorders

Question 29

cannabis and psychosis

Answer 29

• cannabis is associated with increased risk of experiencing schizophrenia
• early cannabis use (15 yo) confers greater risk for schizophrenia
• risk was specific to cannabis use, and early cannabis use did not predict later depression

Question 30

is Cannabis addictive

Answer 30

• Cannabis use disorder (cannabis addiction) and cannabis withdrawal are now part of the DSM-V.
• Daily cannabis use leads to tolerance (downregulation of CB1 receptors), dependence & withdrawal.
• People who seek treatment for cannabis use disorder have usually been smoking for several years (10+) and have tried unsuccessfully to quit multiple times.

Question 31

Withdrawal symptoms of Cannabis

Answer 31

Withdrawal symptoms (may take weeks to subside): depression & anxiety, insomnia, GI disturbances, reduced appetite.

Question 32

CB1 receptor antagonist

Answer 32

rimonabant

Question 33

what was rimonabant

Answer 33

tldr: proposed treatment for drugs treating schizophrenia and bipolar but it didnt work
- THC in cannabis increases appetite. Would CB1 receptor antagonist reduce appetite? This could be a good treatment to aid weight loss with obesity.
- Since CB1 agonists like THC can cause psychosis, would a CB1 antagonist be an antipsychotic?
- Current treatments for schizophrenia and bipolar disorder cause weight gain, so a treatment that reduces psychosis and weight gain could be a substantial improvement for therapy.
- Several CB1 antagonists were developed by different pharmaceutical companies and were in clinical trials for weight loss.
- Rimonabant was approved in EU in 2005. It reduced food intake and promoted weight loss.
- Unfortunately, it also caused suicidal ideation and Sanofi-Aventis discontinued the production of the medicine in 2008. Merck and Pfizer also halted their programs.