TY - JOUR T1 - Endocannabinoid overload JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.110.069427 SP - mol.110.069427 AU - Aron Lichtman AU - Jacqueline Blankman AU - Benjamin Cravatt Y1 - 2010/01/01 UR - http://molpharm.aspetjournals.org/content/early/2010/10/15/mol.110.069427.abstract N2 - The signaling capacity of endogenous cannabinoids ("endocannabinoids") is tightly regulated by degradative enzymes. This Perspective highlights a research article in this issue, where 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 -