The endocannabinoid system has two receptors with known sequences: CB1 and CB2. CB1 was cloned in 1990. CB2 was cloned in 1993. THC binds CB1. CBD binds CB1 at a site separate from the THC site. Other receptors, such as TRPV1 and GPR55, also respond to endocannabinoids and to plant compounds.
CB1 receptors
CB1 comes from the gene CNR1 on chromosome 6. The human protein holds 472 amino acids. It sits in the brain, spinal cord, and peripheral nerves. Counts are high in the cortex, hippocampus, basal ganglia, and cerebellum. Counts are low in the brainstem, which controls breathing.
what makes cb2 receptors an anti inflammatory target
- THC acts as a partial agonist at CB1. Reported Ki values fall between about 5 nM and 80 nM across lab assays.
- 2-AG acts as a full agonist at CB1.
- Anandamide acts as a partial agonist at CB1, with lower affinity than 2-AG.
- CBD acts as a negative allosteric modulator at CB1. It changes the receptor shape and weakens THC binding.
CB1 also appears in the liver, fat tissue, muscle, and gut. That spread explains effects on appetite, motility, and energy use.
Cannabinoid Receptor Agonists and Antagonists
CB2 receptors
CB2 comes from the gene CNR2 on chromosome 1. The protein holds 360 amino acids. It sits on immune cells: B cells, T cells, macrophages, and microglia. Tissue counts are high in the spleen, tonsils, and thymus. Counts in a healthy brain are low. Counts rise when microglia activate after injury or disease.
THC binds CB2 with lower affinity than CB1. No CB2-selective drug has approval in the United States as of 2024.
Endocannabinoids
Anandamide was identified in 1992. 2-AG was identified in 1995. Cells build both on demand from lipid precursors. They are not stored in vesicles. FAAH breaks down anandamide. MAGL breaks down 2-AG. The enzymes set how long each signal lasts.
Other receptors in the network
- TRPV1: the capsaicin receptor. CBD binds it as an agonist.
- GPR55: some researchers call it CB3. CBD acts as an antagonist.
- PPAR-gamma: CBD binds it. The receptor sits in the nucleus and controls gene activity.
- 5-HT1A: a serotonin receptor. CBD binds it as an agonist.
Receptors and route of use
Receptor binding does not set onset time. Route does. Inhaled THC reaches peak blood levels in 2 to 10 minutes. Oral THC reaches peak levels in 30 to 120 minutes. Oral doses also pass through the liver, where THC converts to 11-hydroxy-THC, a compound with higher CB1 affinity. That step makes edible effects stronger and longer for many users.
Products sold as CB1-targeted or CB2-targeted often carry no receptor assay data. Labels list THC and CBD content. They rarely list Ki values or binding data.