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.

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.