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Updated: Jan 31, 2026

Administration of Δ9-Tetrahydrocannabinol (THC) in Adolescent and Adult Mice
Published on: August 1, 2025
Adolescent Brain Surface Area Pre- and Post-Cannabis and Alcohol Initiation
M Alejandra Infante1, Kelly E Courtney1, Norma Castro1
1Department of Psychiatry, University of California San Diego, La Jolla, California.
Objective:
Changes in gray matter volume and thickness are associated with adolescent alcohol and cannabis use, but the impact of these substances on surface area remains unclear. The present study expands on previous findings to examine the impact of alcohol and cannabis on surface area before and after use initiation.
Method:
Scans for 69 demographically similar youth were obtained at baseline (ages 12-14 years; before substance use) and at 6-year follow-up (ages 17-21 years). Participants were classified into three groups based on substance use: alcohol use initiators (ALC, n = 23), alcohol and cannabis use initiators (ALC+CU, n = 23), and individuals with minimal substance use (<3 lifetime alcohol and 0 marijuana use episodes; CON, n = 23). For each hemisphere, group differences in surface area across time (pre- and post-substance use initiation) and significant group-by-time interactions were examined individually for 34 cortical regions using repeated measures analysis of covariance. A vertex-wise analysis assessed group differences in surface area percent change.
Results:
A significant group-by-time interaction was found in three regions, bilateral medial orbitofrontal cortices and right insula. Although all regions showed decreases in surface area over time (ps < .05), a more substantial decrease was identified in the ALC group. Of note, the right medial orbitofrontal cortex survived the conservative vertex-wise analyses (p < .001), as a more substantial decrease was found in the ALC compared to the ALC+CU group in this region.
Conclusions:
Surface area in the medial orbitofrontal cortex may be a useful intermediate phenotype for exploring the mechanisms underlying the effects of substance use on brain development.
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