What are the cannabinoid receptor types?
Two cannabinoid receptors are confirmed and named by the International Union of Basic and Clinical Pharmacology: CB1 and CB2. Both belong to the G-protein coupled receptor family. CB1 was cloned in 1990. CB2 was cloned in 1993. THC, the main psychoactive compound in cannabis, binds both as a partial agonist. CBD binds neither with high affinity.
Role of CB1 and CB2 Receptors in Cannabis
CB1 receptor
CB1 is coded by the CNR1 gene. It ranks among the most abundant G-protein coupled receptors in the human brain. Density is highest in the cerebellum, hippocampus, basal ganglia and cortex. Density is low in the brainstem, which controls breathing and heart rate.
cb2 receptors and immune system
- Location: neurons, on presynaptic terminals
- Signaling: Gi/o coupled, lowers cyclic AMP
- Function: controls release of glutamate, GABA, dopamine and acetylcholine
- Outside the brain: liver, fat tissue, pancreas, gut, heart, immune cells
Endogenous agonists are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). 2-AG is present at higher levels in tissue.
CB2 receptor
CB2 is coded by the CNR2 gene. It sits in large numbers on immune cells: macrophages, B cells, T cells and microglia. Spleen and tonsil tissue show high CB2 levels. In a healthy brain, CB2 expression is low. Inflammation and nerve injury raise it.
cannabinoid receptor agonists list
CB2 activation does not produce the cannabis-like effects seen with CB1 activation in animal models. No CB2-selective drug had FDA approval as of 2025. Research targets include pain, inflammation and fibrosis.
Other targets called cannabinoid receptors
Several receptors respond to endocannabinoids but do not meet the IUPHAR criteria for CB1 or CB2.
- GPR55: responds to anandamide and some plant cannabinoids; often called the third receptor
- GPR18: linked to N-arachidonoyl glycine
- TRPV1: capsaicin receptor; anandamide and CBD activate it
- PPAR alpha and PPAR gamma: nuclear receptors tied to metabolism
- 5-HT1A: serotonin receptor; CBD acts as an agonist
Why the split matters
CB1 and CB2 differ in tissue distribution, which shapes effects. CB1 in the cortex and hippocampus ties to memory and perception. CB1 in the cerebellum ties to balance and movement. Low CB1 density in the brainstem is one reason cannabis does not stop breathing the way opioids do. CB2 acts on immune signaling without a strong central effect.
Quick reference
- CB1 gene: CNR1
- CB2 gene: CNR2
- Endogenous ligands: anandamide, 2-AG
- Plant ligands: THC (partial agonist at both), CBD (negative allosteric modulator at CB1)