Off-target cannabinoid effects mediated by GPR55

Given the vast therapeutic potential of the endocannabinoid system, the revelation of a novel cannabinoid-sensitive target was treated with great excitement. The orphan G-protein coupled receptor 55 (GPR55) was initially touted as a novel cannabinoid target in early industrial patent literature. Consequently, numerous studies have revealed GPR55 expression in a diverse array of cells and tissues, regulating various physiological and pathological processes. Although a confusing cannabinoid profile has prevented its classification as a cannabinoid receptor, the therapeutic potential of the receptor cannot be denied, with roles in cancer progression, bone resorption and analgesia. This commentary aims to summarize GPR55 expression data and speculate on potential therapeutic exploitation of this enigmatic orphan receptor.