Cannabis Use and Brain Volume in Adolescent and Young Adult Cannabis Users: Effects Moderated by Sex and Aerobic Fitness.

OBJECTIVES:Studies examining the impact of adolescent and young adult cannabis use on structural outcomes have been heterogeneous. One already-identified moderator is sex, while a novel potential moderator is extent of aerobic fitness. Here, we sought to investigate the associations of cannabis use, sex, and aerobic fitness levels on brain volume. Second, we explored brain-behavior relationships to interpret these findings. METHODS:Seventy-four adolescents and young adults (36 cannabis users and 38 controls) underwent 3 weeks of monitored cannabis abstinence, aerobic fitness testing, structural neuroimaging, and neuropsychological testing. Linear regressions examined cannabis use and its interaction with sex and aerobic fitness on whole-brain cortical volume and subcortical regions of interests. RESULTS:No main-effect differences between cannabis users and nonusers were observed; however, cannabis-by-sex interactions identified differences in frontal, temporal, and paracentral volumes. Female cannabis users generally exhibited greater volume while male users exhibited less volume compared to same-sex controls. Positive associations between aerobic fitness and frontal, parietal, cerebellum, and caudate volumes were observed. Cannabis-by-fitness interaction was linked with left superior temporal volume. Preliminary brain-behavior correlations revealed that abnormal volumes were not advantageous in either male or female cannabis users. CONCLUSIONS:Aerobic fitness was linked with greater brain volume and sex moderated the effect of cannabis use on volume; preliminary brain-behavior correlations revealed that differences in cannabis users were not linked with advantageous cognitive performance. Implications of sex-specific subtleties and mechanisms of aerobic fitness require large-scale investigation. Furthermore, present findings and prior literature on aerobic exercise warrant examinations of aerobic fitness interventions that aimed at improving neurocognitive health in substance-using youth.