The Effects of Nicotine and Cannabis Co-Use During Late Adolescence on White Matter Fiber Tract Microstructure

Co-use of cannabis and nicotine and tobacco products (NTPs) in adolescence/young adulthood is common and associated with worse outcomes than the use of either substance in isolation. Despite this, little is known about the unique contributions of co-use to neurostructural microstructure during this neurodevelopmentally important period. This study sought to investigate the interactive effects of nicotine and cannabis co-use on white matter fiber tract microstructure in emerging adulthood.

A total of 111 late adolescent (16-22 years old) nicotine (NTP; n = 55, all past-year cannabis users) and non-nicotine users (non-NTP; n = 56, 61% reporting cannabis use in the past year) completed demographic and clinical interviews and a neuroimaging session comprising anatomical and diffusion-weighted imaging scans. Group connectometry analysis identified white matter tracts significantly associated with the interaction between nicotine group and past-year cannabis use according to generalized fractional anisotropy (GFA).

Nicotine Group × Cannabis Use interactions were observed in the right and left cingulum and left fornix tracts (false discovery rate = 0.053), where greater cannabis use was associated with increased GFA in the cingulum and left fornix, but only when co-used with nicotine.

This report represents the first group connectometry analysis in late adolescent/young adult cannabis and/or NTP users. Results suggest that co-use of cannabis and NTPs results in a structurally distinct white matter phenotype as compared with cannabis use only, although to what extent this may change over time with more chronic nicotine and cannabis use remains to be examined in future work.