MOLECULAR CHARACTERIZATION OF A PERIPHERAL RECEPTOR FOR CANNABINOIDS

THE major active ingredient of marijuana, DELTA9-tetrahydrocannabinol (DELTA9-THC), has been used as a psychoactive agent for thousands of y ears. Marijuana, and DELTA9-THC, also exert a wide range of other effe cts including analgesia, anti-inflammation, immunosuppression, anticon vulsion, alleviation of intraocular pressure in glaucoma, and attenuat ion of vomiting1. The clinical application of cannabinoids has, howeve r, been limited by their psychoactive effects, and this has led to int erest in the biochemical bases of their action. Progress stemmed initi ally from the synthesis of potent derivatives of DELTA9-THC4,5, and mo re recently from the cloning of a gene encoding a G-protein-coupled re ceptor for cannabinoids6. This receptor is expressed in the brain but not in the periphery, except for a low level in testes. It has been pr oposed that the non-psychoactive effects of cannabinoids are either me diated centrally or through direct interaction with other, non-recepto r proteins1,7,8. Here we report the cloning of a receptor for cannabin oids that is not expressed in the brain but rather in macrophages in t he marginal zone of spleen.