CB1 receptor

The cannabinoid receptor type 1 (CB1) is a G-protein-coupled receptor concentrated in the central nervous system — densely in the cortex, hippocampus, basal ganglia, cerebellum, and limbic regions. It is the primary target through which THC produces both its therapeutic effects (analgesia, antiemesis, appetite stimulation, muscle-relaxation) and its psychoactive and unwanted effects (cognitive impairment, anxiety at higher doses, ataxia, tachycardia).

CB1 density in cortical and limbic regions explains the cognitive and affective effects; density in basal ganglia and cerebellum explains motor effects. CB1 is sparse in brainstem cardiorespiratory centres, which is the structural reason cannabinoids — unlike opioids — are not associated with fatal respiratory depression at typical therapeutic doses.

CBD has minimal direct CB1 agonist activity, which is why it is non-intoxicating despite acting on the same broader endocannabinoid system. Selective CB1 antagonists were trialled clinically (e.g. rimonabant for obesity) but withdrawn due to psychiatric adverse effects, illustrating how disrupting CB1 signalling has wide consequences.