THE ENZYMATIC REGULATION OF ENDOCANNABINOID SIGNALING

 THE ENZYMATIC REGULATION OF ENDOCANNABINOID SIGNALING – OUR STATE OF UNDERSTANDING AND THE FUTURE CHALLENGES THAT REMAIN 

Benjamin F. Cravatt 

The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA Endogenous cannabinoids (endocannabinoids) constitute an emerging class of signaling lipids that act on both central and peripheral cannabinoid receptors, which also mediate the effects of delta9-tetrahydrocannabinol, the active component of marijuana. The magnitude and duration of endocannabinoid signaling are tightly controlled in vivo by the action of multiple biosynthetic and degradative enzymes. Much progress has been made in understanding the identity and function of these endocannabinoid-related enzymes. Nonetheless, many challenges remain, including confirming the contribution made by specific enzymes to endocannabinoid metabolism in vivo, developing selective pharmacological tools to perturb the function of these enzymes in living systems, and ascertaining the behavioral consequences of short- and long-term alterations in endocannabinoid tone. The vigorous pursuit of these objectives promises to not only enrich our understanding of the role that the endocannabinoid system plays in mammalian physiology and pathology, but also offers exciting possibilities for the development of next-generation therapeutics for a range of human disorders.