TY - JOUR T1 - Endocannabinoid Overload JF - Molecular Pharmacology JO - Mol Pharmacol SP - 993 LP - 995 DO - 10.1124/mol.110.069427 VL - 78 IS - 6 AU - Aron H. Lichtman AU - Jacqueline L. Blankman AU - Benjamin F. Cravatt Y1 - 2010/12/01 UR - http://molpharm.aspetjournals.org/content/78/6/993.abstract N2 - The signaling capacity of endogenous cannabinoids (“endocannabinoids”) is tightly regulated by degradative enzymes. This Perspective highlights a research article in this issue (p. 996) in which the authors show that genetic disruption of monoacylglycerol lipase (MAGL), the principal degradative enzyme for the endocannabinoid 2-arachidonoylglycerol (2-AG), causes marked elevations in 2-AG levels that lead to desensitization of brain cannabinoid receptors. These findings highlight the central role that MAGL plays in endocannabinoid metabolism in vivo and reveal that excessive 2-AG signaling can lead to functional antagonism of the brain cannabinoid system. ER -