Interestingly, MAGL inhibition also mimics THC, particularly its anxiolytic and antidepressant-like properties (Wiley et al., 2014), and attenuates cannabis withdrawal in rodents (Schlosburg et al., 2009). Moreover, much like stress, chronic exposure to THC in rodents is associated with desensitization of CB1 receptors and reduction in AEA and 2-AG. Consistent with the potential importance of MAGL in problematic cannabis use, two independent prior cannabis dependence linkage studies have identified the chromosomal region on 3p where MGLL resides (Agrawal et al., 2008; Hopfer et al., 2007). Thus, there is considerable evidence that MAGL, in concert with FAAH and CB1, plays a critical role in the behavioral experiences associated with THC, particularly its effects on mood.
