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LCRS 1 - Pharmacology > Cannabis > Flashcards

Cannabis Flashcards

1
Q

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

A

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

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2
Q

What are the major routes of administration of cannabis?

A

Oral

Inhalation

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3
Q

What are the disadvantages of oral administration of cannabis?

A 
Very low bioavailability (5-15%)
Extensive first pass metabolism
Delayed onset (0.5-2h)
Slow absorption from gut prolongs duration
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4
Q

Why are the effects of cannabis very long lasting?

A

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

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5
Q

What is an alkaloid?

A 
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)
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6
Q

What is the most potent cannabinoid?

A

Delta-9 tetrahydrocannabinol (delta-9 THC)

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7
Q

What compound causes most of the negative effects of cannabis?

A

Delta-9 THC

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8
Q

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

A

Cannabidiol

Anti-psychotic to a certain degree

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9
Q

What is 11-hydroxy-THC?

A
  • Major metabolite of cannabis produced in liver

- More potent than delta 9-THC

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10
Q

Describe the excretion of 11-hydroxy-THC

A
  • Most excreted in bile into GIT
  • 65% GIT - enterohepatic circulation back into BS - exerts effects
  • 25% urine
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11
Q

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

A
  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

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12
Q

Explain the endogenous cannabinoid system

A

Body produces various cannabinoid-like substances with various effects

E.g. anandamide binds to cannabinoid receptors

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13
Q

Where are the different cannabinoid receptors found?

A

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

CB2 receptors on immune cells

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14
Q

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

A
  • G protein coupled
  • Negatively coupled with adenylate cyclase
  • Depressant as it slows down cell activity
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15
Q

What are the major effects of cannabis?

A
  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)
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16
Q

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

A
  • 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
17
Q

How does cannabis cause euphoria?

A
  • Cannabis binds to CB1Rs on GABA neurones
  • Switches off GABA function
  • Lose inhibitory influence over dopaminergic pathway
  • Dopaminergic neurones start firing –> EUPHORIA
18
Q

How does GABA affect the central reward pathway?

A
  • 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
19
Q

How does cannabis contribute to psychosis?

A
  • 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
20
Q

Compare the effects of THC alone and THC and cannabinoids together

A

THC alone - agitated and frightened

THC and cannabinoids - good

21
Q

How does cannabis affect food intake?

A

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

22
Q

How does cannabis affect the immune system?

A
  • 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
23
Q

What are dronabinol and nabilone and what do they do?

A
  • 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
24
Q

What is sativex? What does it treat?

A
  • CBR agonist
  • Delta 9-THC + cannabidiol
  • For symptom improvement in adult MS patients with moderate to severe spasticity
25
Q

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

A
  • CBR antagonist
  • Anti-obesity medication
  • Increased depression and suicidal thoughts
26
Q

Where are cannabinoids present?

A
  • 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)

LCRS 1 - Pharmacology (33 decks)

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