The present study is remarkably consistent with these preclinical observations. We show, for the first time in humans, that CNR1 genotype plays a stress adaptive role in the etiology of anhedonia and depression. When coupled with the rodent literature, our study suggests the possibility of a significant therapeutic role of the endocannabinoid system in depression57;58. However, which elements of the endocannabinoid system will need to be targeted remains to be examined. For instance, our work, consistent with animal experiments, focuses attention on the gene encoding the CB1 receptor and a number of clinical studies of CB1 inverse agonist, Rimonabant (for weight loss), have shown serious side-effects of depression59–63 and suicidality62;64 and thus, more research is required to understand the precise role of CNR1 and specifically rs1049353 in this domain. Whether the adverse effects of Rimonabant are moderated by rs1049353 or other CNR1 genotypes may also be of particular interest, particular in future drug development.
