CONTRIBUTORS KEM was involved in data collection, developing the study concept, data processing, performing data analyses, interpreting the results, and writing the manuscript under KML's supervision. KML designed the study's methods and worked closely with KEM to develop the study concept, perform data analyses, interpret the results, and draft the manuscript. AMT was involved in data collection and data processing. MMK assisted in data collection, data processing, and preparation of the final manuscript.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms.Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18–30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis.Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02).Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions.

Objective Nicotine use is widely prevalent among youth, and is associated with white matter microstructural changes as measured by diffusion tensor imaging (DTI). In adults, nicotine use is generally associated with lower fractional anisotropy (FA), but in adolescents/young adults (≤30 years), microstructure appears healthier, indicated by higher FA. This cross-sectional study examined associations between nicotine use and white matter microstructure using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in young adults. Methods Fifty-three participants (18 nicotine users [10 female]/35 controls [17 female]) ages 18–25 underwent MRI scan, neuropsychological battery, toxicology screening, and drug use interview. Nicotine group associations with FA and MD were examined in various white matter tracts. In significant tracts, AD and RD were measured. Exploratory correlations were conducted between significant tracts and verbal memory and sustained attention/working memory performance. Results Nicotine users exhibited significantly lower FA than controls in the left anterior thalamic radiation, left inferior longitudinal fasciculus, left superior longitudinal fasciculus—temporal, and left uncinate fasciculus. In these tracts, AD and RD did not differ, nor did MD differ in any tract. White matter quality was positively correlated with sustained attention/working memory performance. Conclusions Cigarette smoking may disrupt white matter microstructure. These results are consistent with adult studies, but inconsistent with adolescent/young adult studies, likely due to methodological and sample age differences. Further studies should examine longitudinal effects of nicotine use on white matter microstructure in a larger sample.

Background: Growing evidence suggests that cannabis and alcohol (and especially binge alcohol drinking) use independently alters neural structure and functioning, particularly during sensitive developmental time periods (e.g., emerging adulthood). However, few studies have investigated the effects of same-day use of these two substances. Here, white matter (WM) integrity was investigated in relation to binge alcohol drinking, cannabis, and same-day binge and cannabis co-use in adolescents and emerging adults. Methods: FreeSurfer's TRACULA was used to assess WM in emerging adults (n = 75; 16-26 years old). Timeline Followback calculated past month cannabis use, binge episodes, and same-day cannabis and binge drinking couse. Multiple regressions investigated WM by past month cannabis, binge, and co-use. Results: Results revealed co-use episodes were related to lower fractional anisotropy (FA), an overall measure of neuronal integrity, in three tracts (left inferior longitudinal fasciculus [ILF], p = 0.02; right anterior thalamic radiation [ATR], p = 0.01; and left cingulum cingulate gyrus [CCG], p = 0.01); and lower axial diffusivity in left ILF (p = 0.03). Cannabis use was significantly related to greater FA in left ILF (p = 0.005), left ATR (p = 0.02), right ATR (p = 0.05), left CCG (p = 0.006), right CCG (p = 0.03), and right superior longitudinal fasciculus parietal (p = 0.03). Binge episodes related to greater FA in right ATR (p = 0.03). Conclusions: These findings suggest that co-use was associated with lower WM integrity across frontolimbic tracts. In addition, greater FA was related to greater cannabis use across several tracts and binge alcohol use in one tract. Co-users also appeared to be more severe substance users. Future research should investigate the potential independent and interactive effects of these substances on pre-clinical and clinical levels.

No abstract