Psychedelics and psychosis: A systematic review of recent-era studies (1984-2025)

This systematic review evaluates the relationship between classical psychedelic drugs (D-Lysergic acid N,N-diethylamide, psilocybin, ayahuasca/N-N-dimethyl-tryptamine, and mescaline) and the emergence of psychotic symptoms, aiming to synthesize evidence from contemporary studies (1984-2025) regarding the risk factors, prevalence, and clinical characteristics of psychosis related to psychedelic use, to provide clinicians, therapists, and policymakers with a framework for identifying and mitigating risks related to these substances.

Fifty-two papers were included, comprising 1 larger-scale studies involving over 100,000 individuals and 34 case reports. Population-based data showed no consistent correlation between lifetime psychedelic use and psychosis. Controlled clinical settings showed minimal risk, with one documented case of transient delusions across all trials. Emergency and toxicological data reported higher rates of psychotic symptoms, likely reflecting the severity of cases prompting medical attention. Among case reports, 58% of individuals had a personal or family psychiatric history. First-episode psychosis, although rare, was documented in otherwise healthy individuals.

The risk of prolonged psychosis remains remarkably low in controlled clinical settings where rigorous screening and supervision are employed. Personal/family history of psychosis and unsupervised, naturalistic use appear to be risk factors for psychosis. Although causality remains difficult to establish, these findings support the need for careful risk stratification, the adoption of clear diagnostic parameters, and trained clinical oversight as psychedelic-assisted therapies advance toward broader clinical populations.