A patient presents with euphoria, conjunctival injection, increased appetite, impaired short-term memory, and slowed reaction time 2 hours after cannabis use. Urine drug screen is positive for cannabinoids. Which receptor mechanism mediates the psychoactive effects?
- A Partial agonism at CB1 receptors in the prefrontal cortex, hippocampus and basal ganglia ✓
- B Full agonism at CB2 receptors mediating immune modulation
- C Inverse agonism at CB1 receptors reducing adenylyl cyclase activity
- D Blockade of TRPV1 channels in the limbic system
Explanation
Delta-9-THC acts as a partial agonist at CB1 receptors (G-protein coupled, Gi-linked) concentrated in the prefrontal cortex (cognition), hippocampus (memory), cerebellum (coordination), and basal ganglia (motor control). Activation inhibits adenylyl cyclase and modulates presynaptic neurotransmitter release. Euphoria, impaired working memory, and increased appetite (via hypothalamic CB1 activation) are CB1-mediated effects. CB2 receptors are primarily peripheral and immunological. Cannabidiol (CBD) has partial agonist/negative allosteric modulator properties and lacks significant psychoactivity.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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