Abstract
Despite the significant societal and personal burden of cannabis use, the impact of long-term use and Cannabis Use Disorder (CUD) on white matter microstructure is still unclear. Previous studies show inconsistent findings, in part due to heterogeneity in methodology, variable severity of cannabis use, and potential confounding effects of other mental health issues and substance use. The goal of this diffusion tensor imaging (DTI) study was to compare whole-brain white matter microstructure between 39 near daily cannabis users and 28 controls closely matched on age, sex, alcohol use, cigarette use and mental health. Within the group of cannabis users, associations between white matter microstructure and recent cannabis use, dependence severity, and age of onset and duration of weekly use were investigated. White matter microstructure did not differ between cannabis users and controls and did not covary with recent cannabis use, dependence severity, or duration of use. Earlier onset of weekly cannabis use was related to lower fractional anisotropy (FA) in various sections of the right inferior longitudinal fasciculus and uncinate fasciculus. These findings suggest that long-term near-daily cannabis use does not necessarily affect white matter microstructure, but vulnerability may be higher during adolescence. These findings underscore the importance of sample composition and warrant further studies that investigate the moderating role of age of onset in the impact of cannabis on the brain.