A new cannabinoid receptor

The CB1 cannabinoid receptor mediates many of the psychoactive effects of {Delta}9THC, the principal active component of cannabis. However, ample evidence suggests that additional non-CB1/CB2 receptors may contribute to the behavioral, vascular, and immunological actions of {Delta}9THC and endogenous cannabinoids.

GPR55 is highly expressed in large dorsal root ganglion neurons and, upon activation by various cannabinoids ({Delta}9THC, the anandamide analog methanandamide, and JWH015) increases intracellular calcium in these neurons.

These results establish GPR55 as a cannabinoid receptor with signaling distinct from CB1 and CB2.

some potential pharmacology:

The development of potent, selective ligands will be important to define the role of GPR55. The aminoalkylindoles offer an intriguing lead because JWH015 is an agonist for GPR55, but the closely related compound WIN55,212–2 neither activates nor binds the receptor (Table 1) (6). The complex interaction of GPR55 with arylpyrazole CB1 antagonists such as SR1, AM251, and AM281 is noteworthy. We found SR1 to be a GPR55 antagonist, whereas Ryberg et al. (6) found the closely related compounds AM251 and AM281 to be an agonist and inactive, respectively. With the possible presence of GPR55 on adipocytes (5) and the clinical use of arylpyrazoles and related compounds, the interactions of these compounds with GPR55 and related receptors needs to be evaluated.