Cannabis use and psychotic-like experiences: A systematic review of biological vulnerability, potency effects, and clinical trajectories

Epidemiological data have provided evidence that psychotic-like experiences (PLEs) occur in the general population without clinical impairment. According to the psychosis continuum hypothesis, PLEs are subject to multiple risk factors. This review synthesizes current research on biological, substance use-related, and environmental risk factors for PLEs in non-clinical populations. PubMed/Medline and Scopus databases were searched for peer-reviewed studies published until January 2024 investigating risk factors for PLEs in non-clinical samples. Following PRISMA guidelines, 38 full-text articles were analyzed after title/abstract and full-text screening (PROSPERO registration ID: N 1001,807). Four main risk factor categories emerged. Biological vulnerabilities included specific metabolic profiles, genetic predisposition, and neurobiological alterations. Substance use patterns, particularly high-potency cannabis, showed significant associations with PLEs, with evidence for bidirectional relationships. Socio-demographic factors revealed influences of digital media use, ethnic density, and gender differences. Outcome studies demonstrated associations between PLEs and consequences including suicidal behavior and cognitive impairments. Findings suggest a complex interplay between multiple risk factors in PLE development. More attention should be paid to the interaction between biological vulnerabilities and environmental factors, as these experiences may represent important markers for mental health outcomes. A comprehensive assessment approach and proactive early intervention strategies are essential for the timely identification and management of at-risk individuals. Our findings support a multifactorial model where genetic vulnerabilities, cannabis use patterns, and socio-environmental factors influence PLE trajectories. The bidirectional cannabis-PLE relationship suggests self-regulatory mechanisms that could inform preventive interventions. Early identification of PLEs in young cannabis users represents a crucial opportunity for targeted clinical interventions.