G protein coupled receptor 55 (GPR55) is a cannabinoid receptor activated by a number of endo‐, phyto‐ and synthetic cannabinoid ligands such as THC, JWH015 and anandamide^1-3.

GPR55 is only 13.5% identical to the canonic cannabinoid receptor CB₁ and 14.4% identical to CB₂. Upon ligand binding, it initiates a signaling cascade quite distinct from those used by CB₁ and CB₂ that eventually leads to an increase in intracellular calcium levels. 

GPR55 belongs to the Class A GPCRs. It shares many similarities with rhodopsin and as all other G-protein coupled receptors in its basic structure of seven transmembrane domains, intracellular C- terminus and extracellular N-terminal extensions⁴. The protein is highly expressed in large dorsal root ganglion neurons and its mRNA is present in the brain and periphery¹.

GPR55 has a role in self‐renewing adult neural stem cell development and in hippocampal neurogenesis³. Experiments with mice in which GPR55 has been inactivated reveal a role for this receptor in neuropathic and inflammatory pain as well as in bone physiology. Thus deciphering the pharmacology of this receptor could lead to new therapeutics in these fields⁵.