Association of Cannabis Use During Adolescence With Neurodevelopment

Key Points Question To what extent is cannabis use associated with magnetic resonance imaging–measured cerebral cortical thickness development during adolescence? Findings In this cohort study, linear mixed-effects model analysis using 1598 magnetic resonance images from 799 participants revealed that cannabis use was associated with accelerated age-related cortical thinning from 14 to 19 years of age in predominantly prefrontal regions. The spatial pattern of cannabis-related cortical thinning was significantly associated with a positron emission tomography–assessed map of cannabinoid 1 receptor availability. Meaning Results suggest that cannabis use during middle to late adolescence may be associated with altered cerebral cortical development, particularly in regions rich in cannabinoid 1 receptors.
Importance Animal studies have shown that the adolescent brain is sensitive to disruptions in endocannabinoid signaling, resulting in altered neurodevelopment and lasting behavioral effects. However, few studies have investigated ties between cannabis use and adolescent brain development in humans. Objective To examine the degree to which magnetic resonance (MR) imaging–assessed cerebral cortical thickness development is associated with cannabis use in a longitudinal sample of adolescents. Design, Setting, and Participants Data were obtained from the community-based IMAGEN cohort study, conducted across 8 European sites. Baseline data used in the present study were acquired from March 1, 2008, to December 31, 2011, and follow-up data were acquired from January 1, 2013, to December 31, 2016. A total of 799 IMAGEN participants were identified who reported being cannabis naive at study baseline and had behavioral and neuroimaging data available at baseline and 5-year follow-up. Statistical analysis was performed from October 1, 2019, to August 31, 2020. Main Outcomes and Measures Cannabis use was assessed at baseline and 5-year follow-up with the European School Survey Project on Alcohol and Other Drugs. Anatomical MR images were acquired with a 3-dimensional T1-weighted magnetization prepared gradient echo sequence. Quality-controlled native MR images were processed through the CIVET pipeline, version 2.1.0. Results The study evaluated 1598 MR images from 799 participants (450 female participants [56.3%]; mean [SD] age, 14.4 [0.4] years at baseline and 19.0 [0.7] years at follow-up). At 5-year follow-up, cannabis use (from 0 to >40 uses) was negatively associated with thickness in left prefrontal (peak: t785 = –4.87, cluster size = 1558 vertices; P = 1.10 × 10−6, random field theory cluster corrected) and right prefrontal (peak: t785 = –4.27, cluster size = 1551 vertices; P = 2.81 × 10−5, random field theory cluster corrected) cortices. There were no significant associations between lifetime cannabis use at 5-year follow-up and baseline cortical thickness, suggesting that the observed neuroanatomical differences did not precede initiation of cannabis use. Longitudinal analysis revealed that age-related cortical thinning was qualified by cannabis use in a dose-dependent fashion such that greater use, from baseline to follow-up, was associated with increased thinning in left prefrontal (peak: t815.27 = –4.24, cluster size = 3643 vertices; P = 2.28 × 10−8, random field theory cluster corrected) and right prefrontal (peak: t813.30 = –4.71, cluster size = 2675 vertices; P = 3.72 × 10−8, random field theory cluster corrected) cortices. The spatial pattern of cannabis-related thinning was associated with age-related thinning in this sample (r = 0.540; P
This cohort study examines the degree to which magnetic resonance imaging–assessed cerebral cortical thickness development is associated with cannabis use in a longitudinal sample of adolescents.