Journal Article

Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies

Thorens, Gabriel, Leucht, Stefan, Glangetas, Alban, Kaiser, Stefan, Sabé, Michel, Seragnoli, Federico, Correll, Christoph U., Richard-Lepouriel, Héléne, Sulstarova, Adi, De Pieri, Marco, Penzenstadler, Louise, Curtis, Logos, Zullino, Daniele, Kirschner, Matthias, Preller, Katrin, Mallet, Luc, Solmi, Marco, Böge, Kerem

2025

Overview

Background Persons with schizophrenia are excluded from psychedelic-assisted therapy due to concerns about the risk of triggering or worsening psychosis. However, there is limited meta-analytic data on the risk of psychedelic-induced psychosis in individuals with pre-existing psychotic disorders. Methods We conducted a systematic review, meta-analysis, and overview of reviews to assess the incidence of psychedelic-induced psychosis and symptom exacerbation in schizophrenia. Our pre-registered protocol (CRD42023399591) covered: LSD, psilocybin, mescaline, DMT, and MDMA, using data from Embase, PubMed, PsyARTICLES, PsyINFO, and trial registries up to November 2023. A random-effects model was used to calculate psychosis incidence, with standardized assessments of study quality. Results From 131 publications, we analyzed 14 systematic reviews, 20 reviews, 35 randomized-controlled trials (RCTs), 10 case-control studies, 30 uncontrolled trials (UCTs), and 22 cohort studies, most of which were low quality. Meta-analysis of nine studies showed an incidence of psychedelic-induced psychosis at 0.002% in population studies, 0.2% in UCTs, and 0.6% in RCTs. In UCTs including individuals with schizophrenia, 3.8% developed long-lasting psychotic symptoms. Of those with psychedelic-induced psychosis, 13.1% later developed schizophrenia. Sensitivity analyses confirmed the results. Conclusion In summary, the reviewed evidence suggests that schizophrenia might not be a definite exclusion criterion for clinical trials exploring safety and efficacy of psychedelics for treatment-resistant depression and negative symptoms. However, given the low quality and limited number of studies, more high-quality research is needed, and a conservative approach is recommended until further data is available.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 59/36 / 631/378 / 692/699/476/1414 / 692/699/476/1799 / Behavioral Sciences / Biological Psychology / Clinical trials / Emotional behavior / Hallucinogens - adverse effects / Humans / Lysergic Acid Diethylamide - adverse effects / Lysergide / MDMA / Medicine / Medicine & Public Health / Mental disorders / Mescaline / Meta-analysis / Neurosciences / Pharmacotherapy / Population studies / Psilocybin / Psilocybin - adverse effects / Psychedelic drugs / Psychiatry / Psychoses, Substance-Induced - epidemiology / Psychoses, Substance-Induced - etiology / Psychosis / Psychotic Disorders / Reviews / Schizophrenia / Schizophrenia - drug therapy / Sensitivity analysis / Systematic Review