Glossary
CB1 and CB2 receptors
Updated:
CB1 and CB2 are the two classic cannabinoid receptors. CB1 is the most abundant cannabinoid receptor in the central nervous system and mediates THC's intoxication. CB2 sits mainly on immune cells. THC is a partial agonist at both; CBD binds them weakly and acts through other routes.
CB1 and CB2 are G protein-coupled receptors. CB1 is the most abundant cannabinoid receptor in the brain and spinal cord, located mainly on axon terminals where it reduces neurotransmitter release. CB2 is expressed at much lower levels in the nervous system, mostly in microglia, and at higher levels in immune tissue (Lu and Mackie 2016).
THC is a partial agonist at both receptors, and its action at CB1 produces intoxication. That is why cannabinoids with stronger CB1 binding, such as THCP, raise more concern, and why THCV, which acts as a CB1 antagonist in vitro, behaves unlike THC at low doses (McPartland 2015).
CBD binds both receptors only weakly. Its effects are attributed to other mechanisms, including modulation of how CB1 responds to THC, enzyme inhibition and activity at non-cannabinoid receptors. Minor cannabinoids vary: a 2019 study reported CBC as a selective CB2 agonist with little CB1 activity (Udoh 2019).
Beyond CB1 and CB2, cannabinoids act on TRPV1 channels, GPR55 and serotonin receptors, which is why the endocannabinoid system is described as broader than its two named receptors.
Sources
- An Introduction to the Endogenous Cannabinoid System (Biol Psychiatry, 2016) PubMed (accessed 2026-10-13)
- Cannabichromene is a cannabinoid CB2 receptor agonist (Br J Pharmacol, 2019) PubMed (accessed 2026-10-13)
- Are cannabidiol and delta-9-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review (Br J Pharmacol, 2015) PubMed (accessed 2026-10-13)