The stratification of the two groups according to the age of first cannabis use in the same clusters shows that a decrease in gray matter volume can occur with a heavy amount of cannabis consumption, independent of the years of usage (Figure 2, panel b). The comparison between the ‘Occasional late' subgroup and both the ‘Regular' subgroups shows a significant difference at P<0.05 in each cluster of interest. Recreational consumption begun early in adolescence (ie, ‘Occasional early' subgroup) significantly affects the GM volume in two regions out of three. These are located in left parahippocampal gyrus (P=0.04) and right temporal pole (P=0.04); the left insula shows only a trend at P=0.09. The effect size measured by Cohen's d was large (d>1) in each significant comparison. The results for the other four regions are presented in the Supplementary File S1.
