Cannabis and tobacco co-use and its association with striatal brain morphometry: Leveraging data from the ENIGMA addiction working group

BACKGROUND: The striatum plays a central role in the pathophysiology of addiction. Studies report that cannabis use is associated with greater striatal gray matter volume (GMV), while tobacco use is associated with both greater and lower striatal GMV. However, their combined effects on striatal GMV remain unclear.

METHODS: Using two MRI processing methods, we investigated associations between these substances and striatal GMV. Men and women from eight ENIGMA Addiction sites (N = 302) were parsed into 4 groups; individuals with: co-use (CT, n = 38); cannabis-only use (CO, n = 34); tobacco-only use (TO, n = 61), and controls (CTL, n = 169). Striatal GMV was assessed using (1) Freesurfer-extracted region-specific estimates and (2) voxel-based morphometry using FSL within a striatal mask. Analyses employed 2 × 2 ANCOVAs.

RESULTS: With Freesurfer, a main effect of cannabis use (CT and CO) emerged in the right nucleus accumbens, and was replicated using FSL (ps ≤ 0.05). With FSL, main effects of cannabis use were found in the putamen and caudate (ps ≤ 0.01), and were modulated by tobacco use (cannabis-tobacco interaction ps ≤ 0.02). Post-hoc comparisons revealed: CT =  CTL >  TO in the putamen and caudate (ps ≤ 0.04); and CTL >  CO (ps ≤ 0.06) and CT >  CO (p = 0.03) in the caudate.

CONCLUSIONS: Results demonstrate that in the putamen and caudate, individuals who co-use have greater GMV compared to those who use either substance alone, whereas individuals using either substance alone have lower GMV compared to controls. Future research should replicate our novel findings and investigate the clinical correlates of this unique pattern to clarify the functional significance of these findings.