Cannabis Flashcards
What is an alkaloid?
Nitrogenous compound
Plant origin
Pronounced physiological effects
What is the most potent cannabinoid in cannabis?
Delta-9-tetrahydrocannabinol (Δ9-THC)
What can protect against the psychotic effects of Δ9-THC somewhat?
Cannabidiol, another cannabinoid
Why are current brands of cannabis more pro-psychotic than they previously were?
The Δ9-THC:cannabidiol ratio has been increased
What proportion of cannabis reaches the bloodstream when inhaled?
1/3
Explain the pharmacokinetics of cannabis and the brain
Enters and leaves brain quickly and so the peak effects last for max 2 hours
Recall the pharmacokinetics of cannabis when administered intravenously
Very lipid soluble so accumulates in poorly-perfused fatty tissue
Fatty acid conjugates of cannabinoids accumulate in fat and can leak into the bloodstream for up to 30 days
Where is cannabis metabolised?
Liver
What is the major metabolite of cannabis?
11-hydroxy-THC
Why is serum Δ9-THC a poor measure of intoxication?
The 11-hydroxy-THC metabolite is more potent than Δ9-THC itself, and since it is excreted via the bile is often caught in enterohepatic cycling
Recall the elements of the body’s endogenous cannabinoid system
Body produces cannabinoid-like substances and receptors:
CB1 = brain
CB2 = immune cells
Receptors are Gi-linked GPCRS
Why is cannabis classed as a depressant?
Activates GPCRs that are negatively linked to adenylate cyclase
Why does cannabis produce feelings of euphoria?
Agonises CB1 receptor in brain
CB1 INHIBITS GABA
GABA has a negative influence on DA release in the nucleus accumbens - so cannabis –> more DA release
What interaction of cannabis has linked it to schizophrenia and psychosis?
Interactions in anterior cingulate cortex = area of brain involved in error detection
Why does cannabis produce “the munchies”?
Cannabis and cannabinoids inhibits GABA in the lateral hypothalamus - which has positive effects on orexigenic and melanin-concentrating hormone neurons
Recall the effects of cannabis on the immune system
Reduces B and T cell number and the cytolytic activity of NK cells
Recall 3 additional negative effects of annabis, other than psychosis, immunosuppression and appetite stimulation
Memory loss
Depressed psychomotor performance
CVS effects
Why can cannabis cause memory loss?
Depressive effects on hippocampus as it decreases effects of brain-derived neurotropic factor (BDNF)
Recall and explain the 2 main CVS effects of cannabis
Tachycardia - due to increased Ca++ release because of TRV1 stimulation
Bloodshot eyes - due to conjunctival vasodilation
How come an overdose on cannabis cannot kill you?
CB1 presence in the medulla (cardiorespiratory centre) is very low
How might a CB receptor agonist be used therapeutically? Give 4 examples
- Prevention of nausea in chemotherapy patients
- Stimulate appetite in AIDS patients
- Analgesic
- Pain-relief in MS
Give 2 examples of THC analogues
Dronabinol
Nabilone
How might a CB receptor antagonist be used clinically?
Anti-obesity
What is rimonabant, and what is the main issue with its clinical use?
CB-antagonist used to treat obesity - was linked to deppression
Name the reward system in the brain
Mesolimbic system
Describe the structure of the mesolimbic system
Dopaminergic neurons
Originate in VTA and project onto nucleus accumbens
DA release –> euphoria
What is the fastest method of administration of a drug of abuse?
Smoking
