Limitations notwithstanding, this study finds evidence across two samples that the minor A allele of rs604300 within MGLL exerts protective effects against childhood abuse-related increases in cannabis dependence. We further extend these findings to show that rs604300 genotype interacts with early life stress to predict amygdala habituation, providing a neural mechanism for future study in the context of cannabis dependence symptoms. Consistent with the proposed hypothesis that cannabis dependence symptoms may arise from using cannabis to cope with stress, a post-hoc structural equation model showed that reporting that one uses cannabis to alter one's mood indirectly linked the interaction between rs604300 and childhood sexual abuse to cannabis dependence symptoms only among G allele homozygotes. These findings await further replication and validation from independent studies.
