How adolescent cannabis use reshapes the developing brain — a systematic review

Background and hypothesis Cannabis use initiation during adolescence has increased globally, raising concerns about neurodevelopmental consequences during this critical period when the brain undergoes extensive remodeling in cannabinoid receptor-rich regions. Study design This systematic review examines neurodevelopmental consequences of adolescent cannabis use, focusing on structural brain changes, cognitive impacts, addiction vulnerability, and long-term outcomes. We searched PubMed, EMBASE, PsycINFO, and Web of Science (2000-2025) for studies examining cannabis effects in adolescent populations. Following PRISMA guidelines, two reviewers screened 3,421 records and assessed 156 full-text articles, including studies with neuroimaging, cognitive assessments, or longitudinal follow-up. Study results Thirty-six studies involving 8,432 participants met criteria: 23 longitudinal cohorts (62.2%), 8 cross-sectional (22.2%), 4 RCTs (11.1%), and 1 case-control study (2.8%). Neuroimaging revealed dose-dependent alterations including reduced prefrontal cortical and hippocampal/amygdala volumes, accelerated cortical thinning in longitudinal studies, and impaired white matter connectivity correlating with initiation age. Cognitive findings were mixed — some showed persistent deficits after prolonged abstinence in adolescent-onset users, others found no effects after controlling for confounders. Epidemiological studies consistently showed elevated addiction risk (ORs 3.9–7.2) in adolescents versus adults. Long-term associations included educational difficulties, mental health problems, and functional impairment, though causal relationships remained unclear. Conclusions Adolescent cannabis use associates with structural brain changes, elevated addiction risk, and variable cognitive effects, suggesting greater vulnerability versus adult-onset use. However, methodological limitations including confounders, heterogeneous definitions, and observational designs limit causal inference. Findings support age-specific prevention and specialized interventions while highlighting needs for rigorous longitudinal research establishing causality. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifierCRD420251165329.