Cannabinoid receptor type 1 (CB1)
CB1The cannabinoid receptor type 1, or CB1, is the most abundant G protein-coupled receptor in the brain and the main site where THC produces intoxication.
CB1 sits on the ends of neurons that release neurotransmitters, where it responds to the body's endocannabinoids, anandamide and 2-AG. When activated it lowers the release of glutamate, GABA and other messengers, letting a receiving neuron fine-tune the signals it gets. The receptor is dense in the hippocampus, cerebellum, basal ganglia and cortex, which corresponds to THC's effects on memory, coordination and perception; it is sparse in the brainstem centers that control breathing. CB1 is also present in the liver, fat, gut and peripheral nerves.
CBD binds CB1 only weakly and does not activate it in the way THC does, which is why CBD is not intoxicating. Laboratory work suggests CBD may instead dampen CB1 signaling as a negative allosteric modulator, a mechanism still being studied and not yet tied to any confirmed effect in people. Dogs have a higher density of CB1 in the cerebellum and brainstem than people, one reason THC is more hazardous to them.