Inactivation of ECs occurs predominantly through enzymatic hydrolysis of the transmitters. Fatty Acid Amide Hydrolase (FAAH) is the enzyme primarily responsible for the inactivation of AEA (Cravatt et al., 1996), and monoacylglycerol lipase (MAGL) is chiefly responsible for the breakdown of 2-AG (Dinh et al., 2002a; Dinh et al., 2002b; Karlsson et al., 1997; Karlsson et al., 2000). The existence of an EC membrane transport (EMT) mechanism is another possible means of inactivation that has been hotly debated (Lovinger, 2007). Proponents of the EMT’s existence cite data from pharmacological studies that show an increase in AEA without inhibiting FAAH activity (López-Rodríguez et al., 2003; Mahadevan and Razdan, 2005), but critics argue that to date no gene or specific molecular mechanism has been implicated in this process and passive diffusion mechanisms are sufficient for EC uptake (Deutsch et al., 2001; Glaser et al., 2003; Kaczocha et al., 2006). EC inactivation can also proceed through oxidation mediated by cyclooxygenase-2 (Fowler, 2007; Kozak et al., 2004), and recently, 2-AG was found to be degraded by α, β hydrolase domain 6 (ABHD6) in the cerebral cortex (Marrs et al., 2010).
