Co-occurrence between adverse childhood experiences and cannabis use in psychosis risk and course: A stratified systematic review

Adverse childhood experiences and cannabis use are robustly associated with psychosis risk, with evidence suggesting their co-occurrence may synergistically amplify risk.

To synthesize evidence on the co-occurrence between adverse childhood experiences, cannabis use, and psychosis across different populations, examining effects across the psychosis spectrum and providing stage-specific intervention implications.

Systematic review of literature (January 2000–January 2024) across PubMed/MEDLINE, PsycINFO, Embase, and Web of Science. Studies were categorized into five groups: general population/community, high-risk, first-episode psychosis, established psychosis, and treatment-seeking clinical samples and intervention studies. Quality was assessed using appropriate tools.

Sixty-two studies were included (15 general population, 5 high-risk, 18 first-episode psychosis, 11 established psychosis, 13 treatment-seeking clinical and intervention studies). Epidemiological studies showed significant interactions, with odds ratios up to 20.9 in community samples and 31.0 in first-episode samples. Converging neurobiological mechanisms included HPA axis alterations, inflammatory processes, and endocannabinoid system dysfunction. Patients with combined exposure showed earlier onset (2.9–3.6 years), more severe positive symptoms, reduced treatment response, and poorer functional outcomes. Trauma-informed interventions integrated with substance use components showed promising results.

The co-occurrence between adverse childhood experiences and cannabis use represents a fundamental neurobiological phenomenon manifesting distinctively across the psychosis continuum. Evidence supports a developmental cascade model wherein trauma creates neurobiological vulnerability that subsequent cannabis exposure may exploit. Trauma-informed approaches simultaneously addressing trauma and cannabis use may significantly improve outcomes for this vulnerable population.