Cannabis

Question 1

What reward pathways in the brain are activated by drugs of abuse?

Answer 1

Drugs of abuse hijack body’s natural reward pathway - dopamine release

Reward pathway consists of a collection of dopaminergic neurones that originate in ventral tegmental area (VTA) and project to nucleus accumbens (NAcc)

Dopamine release at nucleus accumbens stimulates feelings of reward and euphoria

Question 2

What are the major routes of administration of cannabis?

Answer 2

Oral

Inhalation

Question 3

What are the disadvantages of oral administration of cannabis?

Answer 3

Very low bioavailability (5-15%)
Extensive first pass metabolism
Delayed onset (0.5-2h)
Slow absorption from gut prolongs duration

Question 4

Why are the effects of cannabis very long lasting?

Answer 4

Cannabis is very lipid soluble
Adipose tissue is a massive store of cannabinoids
They slowly leak back into bloodstream and exert effects

Question 5

What is an alkaloid?

Answer 5

Any of a class of nitrogenous organic compounds of plant origin which have pronounced physiological actions on humans
Include many drugs (morphine, quinine) and poisons (atropine, strychnine)

Question 6

What is the most potent cannabinoid?

Answer 6

Delta-9 tetrahydrocannabinol (delta-9 THC)

Question 7

What compound causes most of the negative effects of cannabis?

Answer 7

Delta-9 THC

Question 8

Which cannabinoid seems to protect against some of the negative effects of delta-9 THC?

Answer 8

Cannabidiol

Anti-psychotic to a certain degree

Question 9

What is 11-hydroxy-THC?

Answer 9

• Major metabolite of cannabis produced in liver

- More potent than delta 9-THC

Question 10

Describe the excretion of 11-hydroxy-THC

Answer 10

• Most excreted in bile into GIT
• 65% GIT - enterohepatic circulation back into BS - exerts effects
• 25% urine

Question 11

Why does blood [delta 9-THC] give a poor measure of cannabis intoxication?

Answer 11

1. Other toxic metabolites contributing, e.g. 11-hydroxy-THC

2. Build-up of cannabinoids in fat can’t be measure in blood - slowly leaks out into BS to exert effects

Question 12

Explain the endogenous cannabinoid system

Answer 12

Body produces various cannabinoid-like substances with various effects

E.g. anandamide binds to cannabinoid receptors

Question 13

Where are the different cannabinoid receptors found?

Answer 13

CB1 receptors in brain - hippocampus, cerebellum, cerebral cortex, basal ganglia

CB2 receptors on immune cells

Question 14

What type of receptors are cannabinoid receptors? What does this mean about the drug classification of cannabis?

Answer 14

• G protein coupled
• Negatively coupled with adenylate cyclase
• Depressant as it slows down cell activity

Question 15

What are the major effects of cannabis?

Answer 15

1. Memory loss - limbic regions (amnestic effects/decreased BDNF)
2. Impaired psychomotor performance - cerebral cortex
3. Tachycardia - activates TRPV1R to stimulate Ca influx
4. Vasodilation (conjunctivae)

Question 16

Why is the low expression of the CB1 receptor in the medulla important?

Answer 16

• Medulla is responsible for controlling cardio-resp function
• Low expression of CB1R means cannabis cannot really influence cardio-resp control
• Tf can’t overdose on cannabis to the point of killing yourself

Question 17

How does cannabis cause euphoria?

Answer 17

• Cannabis binds to CB1Rs on GABA neurones
• Switches off GABA function
• Lose inhibitory influence over dopaminergic pathway
• Dopaminergic neurones start firing –> EUPHORIA

Question 18

How does GABA affect the central reward pathway?

Answer 18

• GABA exerts a negative influence on dopaminergic neurones of the central reward pathway
• Prevents reward system from permanently firing
• Keeps system suppressed until you need reward system to be activated

Question 19

How does cannabis contribute to psychosis?

Answer 19

• Anterior cingulate cortex is involved in performance monitoring and behavioural adjustment
• At most basic level, ACC deals with error detection
• Cannabis –> hypoactivity in ACC –> impaired behavioural performance adjustment

Question 20

Compare the effects of THC alone and THC and cannabinoids together

Answer 20

THC alone - agitated and frightened

THC and cannabinoids - good

Question 21

How does cannabis affect food intake?

Answer 21

Stimulates food intake

Positive effect on neurones in lateral hypothalamus:

1. Presynaptic inhibition of GABA increases melanin-concentrating hormone neuronal activity
2. Increased orexin production

Orexinergic and MCH neurones both stimulate appetite

GABA inhibits MCH neurones –> cannabis inhibits GABA –> removes inhibition of MCH neurones

Question 22

How does cannabis affect the immune system?

Answer 22

• Very powerful immunosuppressant in chronic users
• Negative effects on no. of immune cells
• Decreases B and T cell number
• Decreases cytolytic activity of NK cells

Question 23

What are dronabinol and nabilone and what do they do?

Answer 23

• Type of delta-9 THC
• CBR agonists
• Bind to CBRs and activate them
• Anti-emetics in chemo
• Dronabinol also for loss of appetite and weight loss in AIDS

Question 24

What is sativex? What does it treat?

Answer 24

• CBR agonist
• Delta 9-THC + cannabidiol
• For symptom improvement in adult MS patients with moderate to severe spasticity

Question 25

What is rimonabant? Why was it pulled from the market?

Answer 25

• CBR antagonist
• Anti-obesity medication
• Increased depression and suicidal thoughts

Question 26

Where are cannabinoids present?

Answer 26

• Marijuana/cannabis – leaves and flowering tops of Cannabis sativa plant
• Hashish – resinous material of cannabis plant, leaves, flowers and seeds of plant, and also in resin secreted by female plant
• Hash oil – plant extract (with organic solvents)