Rationale Co-use of cannabis and nicotine is common among adolescents/young adults and is associated with poorer psychological and physical outcomes, compared with single substance use. Little is known about the impact of co-use on the developing brain. Objectives Preliminary investigation of the effects of nicotine on white matter (WM) cerebral blood flow (CBF) in adolescents/ young adults and its potential moderation by cannabis use. Methods Adolescent/young adult (16-22 years old) nicotine and tobacco product users (NTP; N = 37) and non-nicotine users (non-NTP; N = 26) underwent a neuroimaging session comprised of anatomical, optimized pseudo-continuous arterial spin labeling, and diffusion tensor imaging scans. Groups were compared on whole-brain WM CBF estimates and their relation to past-year cannabis use. Follow-up analyses assessed correlations between identified CBF clusters and corresponding fractional anisotropy (FA) values. Results Group by cannabis effects were observed in five clusters (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05; ≥ 11 contiguous voxels): non-NTP exhibited positive correlations between CBF and cannabis use in all clusters, whereas no significant relationships were observed for NTP. Greater CBF extracted from one cluster (including portions of right superior longitudinal fasciculus) was associated with reduced FA for non-NTP group only. Conclusions This is the first investigation of WM health as indexed by CBF, and its association with FA, in adolescents/young adults with nicotine and/or cannabis use. Results suggest that cannabis use by itself may be related to increased CBF in WM fiber tracts demonstrating poorer structural intergrity, yet the occurrence of even infrequent NTP use (greater than once per month) appears to diminish this relationship.

Cannabis use during adolescence has been linked to deleterious effects on brain integrity. This article summarizes findings from two prospective investigations (3 and 6 years, on average) on adolescent cannabis use from our laboratory that utilize structural neuroimaging and neurocognitive assessment approaches. Across most studies, findings suggest recency, frequency, and age of onset of cannabis use are likely key variables in predicting poorer neural health outcomes. There is some evidence that preexisting differences in brain architecture may also contribute to vulnerability and outcome differences. Ongoing large‐scale prospective studies of youth will be able to disentangle how both cannabis use as well as pre and postexposure differences play a role in divergent outcomes among youth who use cannabis.

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Nicotine and tobacco product (NTP) use has escalated, largely due to the advent of e-cigarettes. The NTP administration method (i.e., combustible cigarette, e-cigarette) may be an important differentiator. We assessed young adult substance use history, nicotine attitudes, mental health, and neurocognition by the NTP use method. Emerging adults (16–22 year olds) were divided into combustible NTP users (Combustible+ = 79, had used any combustible NTP in the last 6 months), non-combustible users (E-Cig = 43, had used non-combustible NTP, in the past 6 months), and NTP Naïve (n = 79; had not used NTP in the past 6 months) based on past 6-month NTP use patterns. Participants completed self-report and objective neurocognition measures. Analysis of covariance assessed mental health and neurocognition by group, controlling for confounds and correcting for multiple comparisons. Nicotine groups reported more favorable attitudes toward combustible cigarette and e-cigarette use, with taste as the primary reason for e-cigarette use. Combustible+ reported more nicotine dependence and craving. Substance use differed by group, with Combustible+ using the most NTP, alcohol, and cannabis. Nicotine groups reported higher depression and stress symptoms; male Combustible+ reported higher depression symptoms than other same-gender groups. Groups did not differ on neurocognition, though cannabis use was associated with inaccurate emotional Stroop responses. Overall, research suggests that young adult combustible users are likely qualitatively different from non-combustible users. Understanding the unique characteristics related to NTP product use will help guide intervention and prevention development.