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

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.