etiology of this relationship. Neither genetic nor environmental correlations were significant and within-pair differences could be equated across all groups. Thus, causal and/or predispositional influences may link cannabis exposure and VS volume. Third, while the family structure in the HCP data is powerful, longitudinal data that are collected from prior to cannabis onset through later development is critical for substantiating causal claims (e.g. recent NIH efforts33). Fourth, the small sample size of discordant MZ twin pairs (Npairs=9) is a limitation. Fifth, the role of additional covariates cannot be excluded (e.g. childhood trauma is linked to both amygdala volumes34 and cannabis use35). Sixth, while we selected a priori regions of interest based on prior studies, other regions should be examined in future work (e.g. using whole brain voxel-wise analysis). Seventh, exploring other brain-related measures, like white matter integrity and task-related activity, might reveal different findings. Eighth, evidence for potential causal effects in opposite-sex sibling pairs was driven by a small number (N=14) of discordant pairs where the female sibling was the exposed member. A thorough examination of phenotypic data failed to distinguish these discordant exposed females from others in the sample. However, based on evidence for sex differences in the endocannabinoid
