Cannabinoid receptor

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates– a class of cell membrane receptors in the G protein-coupled receptor superfamily.^[1][2][3][4] As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains.^[5] Cannabinoid receptors are activated by three major groups of ligands:

• Endocannabinoids;
• Phytocannabinoids (plant-derived such as tetrahydrocannabinol (THC) produced by cannabis);
• Synthetic cannabinoids (such as HU-210).

All endocannabinoids and phytocannabinoids are lipophilic.

There are two known subtypes of cannabinoid receptors, termed CB₁ and CB₂.^[6][7] The CB₁ receptor is expressed mainly in the brain (central nervous system or "CNS"), but also in the lungs, liver and kidneys. The CB₂ receptor is expressed mainly in the immune system, in hematopoietic cells,^[8] and in parts of the brain.^[9]

The protein sequences of CB₁ and CB₂ receptors are about 44% similar.^[10][11] When only the transmembrane regions of the receptors are considered, amino acid similarity between the two receptor subtypes is approximately 68%.^[5] In addition, minor variations in each receptor have been identified. Cannabinoids bind reversibly and stereo-selectively to the cannabinoid receptors. Subtype selective cannabinoids have been developed which theoretically may have advantages for treatment of certain diseases such as obesity.^[12]

Enzymes involved in biosynthesis/inactivation of endocannabinoids and endocannabinoid signaling in general (involving targets other than CB1/2-type receptors) occur throughout the animal kingdom.^[13]