G protein-coupled receptor 18 (GPR18)

G protein-coupled receptor 18, or GPR18, is a cell-surface receptor found on immune cells and in parts of the nervous system whose natural signal is still debated.

GPR18 belongs to the same large family as CB1 and CB2 but is classed as an orphan receptor because researchers have not agreed on its native ligand. The leading candidate is N-arachidonoylglycine, a molecule related to anandamide, and some studies report that THC and certain synthetic cannabinoids also activate it. The receptor is expressed by microglia, macrophages and cells of the spleen and testes, and it appears to influence immune-cell migration and, in the eye, fluid pressure.

Readers meet GPR18 in discussions of whether the endocannabinoid system has more than two receptors; it is often listed alongside GPR55 as a possible third cannabinoid receptor, a designation the International Union of Basic and Clinical Pharmacology has not adopted. CBD has been described as a GPR18 antagonist in a small number of cell studies, but the evidence is early and no conclusion about its effects in people or animals can be drawn.