Endocannabinoids such as 2-arachidonoyl glycerol (2-AG; ) and arachidonoyl ethanolamide (AEA; ) are biologically active lipids that are involved in a number of synaptic processes including activation of cannabinoid (CB) receptors. Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) mediate the hydrolysis of AEA and 2-AG, respectively. MAGL inhibitor 21 selectively binds to MAGL (K = 0.4 µM) and reversibly blocks the enzyme’s activity in mouse brain with an IC value of 0.18 µM. Comparatively, MAGL inhibitor 21 is reported to inhibit FAAH activity in mouse brain with an IC value of 59 µM. This compound does not bind CB or CB receptors and does not inhibit the related serine hydrolases ABHD6 and ABHD12 (Ks > 10 µM). In a mouse model of multiple sclerosis, 5 mg/kg of MAGL inhibitor 21 has been used to ameliorate progression of the disease without producing detrimental CB-mediated effects.