The study investigates the role of monoglyceride lipase (MGL) in the inactivation of the endocannabinoid 2-arachidonoylglycerol (2-AG). MGL is a serine hydrolase that converts monoglycerides to fatty acid and glycerol. The authors cloned MGL from rat brain cDNA and found that its mRNA is heterogeneously expressed in the brain, with higher levels in regions containing CB1 cannabinoid receptors. Immunohistochemical studies showed that MGL is localized presynaptically in the hippocampus. Overexpression of MGL in cortical neurons using adenovirus-mediated gene transfer reduced NMDA/carbachol-induced 2-AG accumulation without affecting anandamide levels. These results suggest that MGL is a primary enzyme responsible for 2-AG inactivation in intact neurons, highlighting its potential as a target for pharmacological intervention in diseases where endocannabinoids play a role.The study investigates the role of monoglyceride lipase (MGL) in the inactivation of the endocannabinoid 2-arachidonoylglycerol (2-AG). MGL is a serine hydrolase that converts monoglycerides to fatty acid and glycerol. The authors cloned MGL from rat brain cDNA and found that its mRNA is heterogeneously expressed in the brain, with higher levels in regions containing CB1 cannabinoid receptors. Immunohistochemical studies showed that MGL is localized presynaptically in the hippocampus. Overexpression of MGL in cortical neurons using adenovirus-mediated gene transfer reduced NMDA/carbachol-induced 2-AG accumulation without affecting anandamide levels. These results suggest that MGL is a primary enzyme responsible for 2-AG inactivation in intact neurons, highlighting its potential as a target for pharmacological intervention in diseases where endocannabinoids play a role.