Childhood stress, particularly sexual abuse, is amongst the most prominent risk factors for problems related to mood and anxiety as well as cannabis dependence (Duncan et al., 2008; Lindert et al., 2014). The persistent use and misuse of drugs in individuals exposed to CSA, as well as to childhood physical abuse, may reflect coping behavior (Bujarski et al., 2012; Potter, Vujanovic, Marshall-Berenz, Bernstein, & Bonn-Miller, 2011; Vilhena-Churchill & Goldstein, 2014; Walsh et al., 2014), and this relationship may be susceptible to eCB-regulated modulation in the BLA. Speculatively, individuals with increased MAGL function, corresponding to reduced availability of 2-AG, may be more prone to poorer stress recovery, which could lead to stress-induced elevations in anxiety and resulting emotion regulation with cannabis. Conversely, if the minor A allele of rs604300 is associated with MAGL reductions, then this stress-adaptive state, as reflected by enhanced amygdala habituation in the context of prior stress exposure, might result in stress adaptation, and downstream, with less problematic cannabis use. This also fits well with our pathway analysis, as well as with rodent studies showing the involvement of the eCB in extinction of aversive memories (de Bitencourt, Pamplona, & Takahashi, 2013).
