Cannabis CB1 receptor effects — MRCPsych Paper A MCQ

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ModerateNeurophysiology and neurochemistryCannabis CB1 receptor effectsMRCPsych Paper A

A 22-year-old man develops transient paranoia and perceptual disturbance shortly after using high-potency cannabis. Delta-9-tetrahydrocannabinol produces its acute psychoactive effects mainly through partial agonism at a widely expressed presynaptic Gi/o-coupled receptor in the central nervous system. Which receptor is this?

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Correct answer: E — CB1 cannabinoid receptors

Delta-9-tetrahydrocannabinol, the principal intoxicating constituent of cannabis, acts mainly as a partial agonist at central CB1 cannabinoid receptors. CB1 receptors are presynaptic Gi/o-coupled receptors whose activation inhibits neurotransmitter release; downstream modulation of glutamate, GABA and dopamine contributes to perceptual changes and transient psychosis-like symptoms. CB2 receptors are more strongly associated with immune and peripheral tissues and are not the principal mediator of cannabis intoxication. GABA-B receptors are also inhibitory Gi/o-coupled receptors but are not THC's primary target. Serotonin 5-HT2A receptors principally mediate classic psychedelic effects, while dopamine D2 signalling may contribute downstream to psychotic symptoms but is not the receptor directly targeted by THC.

Reference: Bloomfield MA et al. The neuropsychopharmacology of cannabis: A review of human imaging studies. Pharmacology & Therapeutics. 2019;195:132-161. https://pubmed.ncbi.nlm.nih.gov/30347211/