The eCB system is comprised of lipid signaling molecules, anandamide (N-arachidonoylethanolamide; AEA (Devane et al., 1992)) and 2-arachidonoylglycerol (2-AG (Mechoulam et al., 1995)), the receptors for these lipids, CB1 and CB2 (Matsuda et al., 1990; Munro et al., 1993), and biosynthetic and catabolic enzymes that regulate eCB levels. AEA is hydrolyzed by the enzyme fatty acid amide hydrolase (FAAH (Cravatt et al., 1996; Deutsch and Chin, 1993)), and 2-AG is predominantly metabolized by monoacylglycerol lipase (MAGL (Blankman et al., 2007; Dinh et al., 2002)). While eCBs are rapidly metabolized in vivo, limiting the efficacy of exogenous administration, inhibition of their catabolic enzymes results in elevated eCB brain levels (Kathuria et al., 2003; Long et al., 2009). Thus, the availability of selective FAAH and MAGL inhibitors has made it possible to study the impact of elevating eCB levels in the whole animal.
