In this study, we investigated 12 tSNPs representing much of the genetic variability surrounding the genomic region encoding CB1, the principal receptor for endogenous and exogenous cannabinoids. Of these, three independent CNR1 tSNPs had significant effects on brain volumes in schizophrenia patients. CNR1 rs12720071-G-allele carriers, rs7766029-C homozygotes, and rs9450898-C homozygotes were associated with smaller WM brain volumes than their respective counterparts. CNR1 also interacts with heavy marijuana use to influence white matter volume deficits and cognitive dysfunction; these results are suggestive of combined gene×environment influences in mediating phenotypic features of schizophrenia. Specifically, rs12720071 SNP G-allele carriers may be especially vulnerable to the impact of marijuana misuse on influencing parietal lobe WM volumes and on impairing problem solving skills. Lastly, we found schizophrenia patients with marijuana abuse/dependence had smaller frontotemporal WM volumes than patients without heavy marijuana use.
