Recent tobacco use has widespread associations with adolescent white matter microstructure

Importance: Given the prevalence of alcohol, cannabis, and tobacco use during adolescence, it is important to explore the relative relationship of these three substances with brain structure. Objective: To determine associations between recent alcohol, cannabis, and tobacco use and white and gray matter in a large sample of adolescents. Design, Setting, and Participants: MRI data were collected in N = 200 adolescents ages 14–18 (M = 15.82 years; 67% male; 61% Hispanic/Latino). On average, during the past month, participants reported consuming 2.05 drinks per 1.01 drinking day, 0.64 g per 6.98 cannabis use days, and 2.49 cigarettes per 12.32 smoking days. Main Outcomes and Measures: General linear models were utilized to examine past 30-day average quantities of alcohol, cannabis, and tobacco use, age, sex, and sex by substance interactions in skeletonized white matter (fractional anisotropy and axial, radial, and mean diffusivity) and voxel-based morphometry of gray matter (volume/density). Results: Tobacco use was negatively associated with white matter integrity (radial and mean diffusivity) with peak effects in inferior and superior longitudinal fasciculi. Cannabis use was negatively associated with white matter integrity (axial diffusivity) in a small cluster in the left superior longitudinal fasciculus. No associations were observed between recent alcohol use and white or gray matter overall, but interactions showed significant negative associations between alcohol use and white matter in females. Conclusions and Relevance: It is important to note that recent tobacco use, particularly given the popularity of e-tobacco/vaping in this age group, had widespread associations with brain structure in this sample of adolescents.