In the DNS, 51% of the sample reported lifetime cannabis use, with 12% (n=52), 15% (n=66), 8.8% (n=38) and 15% (n=65) using cannabis 1–2, 3–10, 11–20 and >21 times during their lifetime respectively. Ever using cannabis and the frequency of use within lifetime users were not associated with rs1409568 genotype (C-allele carrier vs TT; only 2 individuals with CC genotype). However, the C allele, which was associated with increased likelihood of cannabis dependence in the meta-analysis, was associated with increased gray matter volume in the right hippocampus (2.13% greater than TT individuals; Cohen’s d = 0.62, maximal voxel p-fwe = 0.007; Bonferroni p-value for 6 a priori regions = .008; Supplemental Figure S7A). This association remained unchanged when cannabis use was included as a covariate in the analysis (Cohen’s d = 0.62, maximal voxel p-fwe = 0.008). Other regions previously associated with cannabis use (i.e., left hippocampus and bilateral amygdala and ventral striatum) showed no relationship with the SNP. Finally, ever having used cannabis was associated with increased volume in a cluster in the left hippocampus (3.18% greater in ever
