PT  - JOURNAL ARTICLE
AU  - Aron Lichtman
AU  - Jacqueline Blankman
AU  - Benjamin Cravatt
TI  - Endocannabinoid overload
AID  - 10.1124/mol.110.069427
DP  - 2010 Jan 01
TA  - Molecular Pharmacology
PG  - mol.110.069427
4099  - http://molpharm.aspetjournals.org/content/early/2010/10/15/mol.110.069427.short
4100  - http://molpharm.aspetjournals.org/content/early/2010/10/15/mol.110.069427.full
AB  - 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.