Cannabinoid Receptor-Related Orphan G Protein-Coupled Receptors

Of the druggable group of G protein-coupled receptors in the human genome, a number remain which have yet to be paired with an endogenous ligand – orphan GPCR. Amongst these100 or so entities, three have been linked to the cannabinoid system. GPR18, GPR55 and GPR119 exhibit limited sequence homology with the established CB1 and CB2 cannabinoid receptors. However, the pharmacology of these orphan receptors display overlap with CB1 and CB2 receptors, particularly for GPR18 and GPR55. The linking of GPR119 to the cannabinoid receptors is less convincing and emanates from structural similarities of endogenous ligands active at these GPCR, but which do not cross-react. This review describes the evidence for describing these orphan GPCR as cannabinoid receptor-like receptors.