Cannabis and suicide risk in first-episode psychosis: Mechanisms, interactions, and intervention strategies

Cannabis use represents a significant risk factor for both psychotic disorders and suicidal behaviors, with growing evidence suggesting complex interactions between these variables. This systematic review examines the relationship between cannabis use and suicide risk in first-episode psychosis (FEP) patients, and explores underlying mechanisms, moderating factors, and intervention strategies. Following PRISMA guidelines, we analyzed 50 studies involving 12,764 FEP patients. Results demonstrate that cannabis use, especially high-potency cannabis used regularly, is associated with significantly increased suicide risk with studies consistently reporting elevated odds ratios (ranging from 1.43 to 1.84), and dose-dependent effects-daily use showing higher risk (studies reporting OR: 2.73, 95 % CI: 1.89-3.94) and high-THC cannabis carrying greatest risk (OR: 3.12, 95 % CI: 2.11-4.62). Multiple mechanisms mediate this relationship: neurobiological alterations in the endocannabinoid system, exacerbation of depressive symptoms, impaired cognitive functions, increased duration of untreated psychosis, and reduced treatment adherence. Key vulnerability factors include early-onset cannabis use (before age 15-16), female gender, history of childhood trauma, and comorbid psychiatric disorders. Critical high-risk periods were identified, particularly the first month after treatment initiation and following hospital discharge. Effective intervention strategies include integrated early intervention programs combining pharmacological treatment with psychosocial approaches, specifically cognitive-behavioral therapy, motivational interviewing, and family interventions. Emerging evidence suggests potential therapeutic benefits of CBD and specific risk management protocols. This review highlights the clinical importance of assessing cannabis use patterns in FEP patients and implementing targeted interventions during critical periods, particularly given the increasing availability of high-potency cannabis products globally.