First, while the normative sampling of the HCP is a strength, we were limited by sample size from examining heavy/problematic cannabis use, which has been inconsistently associated with volumetric alterations27,30. Furthermore, as heavy/problem cannabis use is often associated with psychiatric problems31, severity and chronicity of use may have been limited by the HCP’s exclusion of individuals receiving extended psychiatric treatment or hospitalization. Also, data was not available on recent duration/frequency of use, which has been linked to structural changes32. Thus, even though we noted similar evidence of association with lighter (<100 times) and heavier (≥100 times) lifetime cannabis exposure, we were underpowered to test this in our sibling analyses and cannot exclude the role of causal factors at higher levels of cannabis exposure. Second, though right VS volume and cannabis use were significantly related, we were unable to disentangle the 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
