Importantly, by leveraging the familial design of the HCP, we demonstrated that amygdala volumetric reductions among cannabis users are primarily attributed to familial factors shared by twins/siblings. Overlapping genetic factors (ρg) were the only significant source of covariance; a significant correlation between individual-specific environmental factors (ρe) would be expected if the causal hypothesis were supported29. The discordant sibling analyses further confirmed this; even in the absence of cannabis exposure, smaller amygdala volumes were observed among individuals with heightened familial liability, given their sibling’s cannabis use. However, interpretations from our sibling analyses should be tempered by our limited sample size to examine discordant MZ pairs only. This predisposition to smaller brain volumes, even in the absence of manifest cannabis use, casts considerable doubt on hypotheses that cannabis use, at least at the levels noted in this sample, causes reductions in amygdala volumes. Instead, both the exposed and unexposed siblings in discordant pairs and concordant exposed pairs tended to have smaller amygdala volumes than concordant unexposed individuals.
