Alcohol and cannabis co-use and longitudinal gray matter volumetric changes in early and late adolescence

Abstract

Background: Previous studies have characterized the impact of substance use on cerebral structure and function in adolescents. Yet, the great majority of prior studies employed a small sample, presented cross-sectional findings, and omitted potential sex differences.

Methods: Using data based on 724 adolescents (370 females) curated from the NCANDA study, we investigated how gray matter volumes (GMVs) decline longitudinally as a result of alcohol and cannabis use. The impacts of alcohol and cannabis co-use and how these vary across assigned sex at birth and age were examined. Brain imaging data comprised the GMVs of 34 regions of interest and the results were evaluated with a Bonferroni correction.

Results: Mixed-effects modeling showed faster volumetric declines in the caudal middle frontal cortex, fusiform, inferior frontal, superior temporal (STG), and supramarginal (SMG) gyri, at -0.046 to -0.138 cm³ /year in individuals with prior-year alcohol and cannabis co-use, but not those engaged in alcohol or cannabis use only. These findings cannot be explained by more severe alcohol use among co-users. Further, alcohol and cannabis co-use in early versus late adolescence predicted faster volumetric decline in the STG and SMG across assigned sex at birth.

Conclusions: Findings highlight the longitudinal impact of alcohol and cannabis co-use on brain development, especially among youth reporting early adolescent onset of use. The volumetric decline was noted in cortical regions in support of attention, memory, executive control, and social cognition, suggesting the pervasive effect of alcohol and cannabis co-use on brain development.

Keywords: National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA); adolescence; alcohol and cannabis co-use; brain development; gray matter volume (GMV); longitudinal.

Figure 1.

Brain regions that showed statistically significant associations, after Bonferroni corrections, between annual brain volume changes and alcohol and/or cannabis use 1-year prior, as demonstrated by the main mixed model (see also Table 2). Colors correspond to uncorrected p-values. CMF: caudal middle frontal cortex; Fusiform: Fusiform gyrus; PO: inferior frontal gyrus, pars opercularis.

Figure 2.

Annual volume changes (cm³) vs. age among female (F) and male (M) controls (no alcohol or cannabis use ever) of the five statistically significant regions as shown in Table 2: caudal middle frontal cortex, fusiform gyrus, inferior frontal gyrus (IFG), pars opercularis, superior temporal gyrus, and supramarginal gyrus. Solid and dashed lines show linear regressions and their 95% confidence intervals. The fitted lines are negative showing decreasing volumes year after year. Only the slope for supramarginal gyrus among females was marginally significant (Bonferroni corrected p-value = 0.044; Bonferroni p-values > 0.313 for all other slopes).

Figure 3.

Annual volumetric changes (higher bars: faster declines) in (A) females and (B) males by substance use group and developmental stage, as shown by the modulation model (Table 4) after covariate adjustment. Annual rates were shown separately by the prior year substance use and developmental stage (Early: early adolescents, Late: late adolescents). Statistically significant differences after Bonferroni correction were marked by horizontal bars. P values, uncorrected: *** <0.001.