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.