G protein-coupled receptor 55 (GPR55)

G protein-coupled receptor 55, or GPR55, is a cell-surface receptor in bone, gut, nerves and immune cells that responds to certain lipids and, in the laboratory, to some cannabinoids.

GPR55 shares little sequence with CB1 or CB2, yet it was proposed as a cannabinoid receptor after cell studies showed it responds to THC, anandamide and several synthetic ligands. Its most accepted natural signal is lysophosphatidylinositol, a membrane-derived lipid. Unlike CB1, which lowers neuronal activity, GPR55 activation raises calcium inside cells and can promote excitation, cell growth and bone-remodeling activity, so its effects often run opposite to those of the classical cannabinoid receptors.

The term appears in discussions of CBD's mechanism because CBD has been reported to block GPR55 in cell-based experiments, and this antagonism has been proposed as one reason CBD behaves differently from THC. That work remains preclinical, the receptor's classification as cannabinoid is still contested, and no effect in people has been tied to it.