Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies.
Michel Sabé, Adi Sulstarova, Alban Glangetas, Marco De Pieri, Luc Mallet, Logos Curtis, Hélène Richard-Lepouriel, Louise Penzenstadler, Federico Seragnoli, Gabriel Thorens, Daniele Zullino, Katrin Preller, Kerem Böge, Stefan Leucht, Christoph U Correll, Marco Solmi, Stefan Kaiser, Matthias Kirschner
Molecular psychiatry March 1, 2025 DOI: 10.1038/s41380-024-02800-5 via PubMed
Summary
AI-generated from the abstractA systematic review and meta-analysis assessed the risk of psychedelic-induced psychosis in people with schizophrenia. Among population studies, the incidence was 0.002%; in uncontrolled trials, 0.2%; and in randomized controlled trials, 0.6%. In uncontrolled trials that included individuals with schizophrenia, 3.8% developed long-lasting psychotic symptoms. Of those who experienced psychedelic-induced psychosis, 13.1% later developed schizophrenia. The evidence suggests schizophrenia might not be an absolute exclusion for clinical trials on psychedelics for treatment-resistant depression and negative symptoms, but low study quality and limited data warrant a conservative approach until more research is done.
Study at a glance
| Characteristics | Systematic review and meta-analysis Randomized Preregistered Peer reviewed |
|---|---|
| Population | Persons with schizophrenia or pre-existing psychotic disorders |
| Interventions | LSD psilocybin mescaline DMT MDMA |
| Keywords | Schizophrenia Psychedelics Mental health Drug safety Psychosis |
| Citations | 39 |
| Key finding | Incidence of psychedelic-induced psychosis was low overall (0.002% to 0.6%), but 3.8% of individuals with schizophrenia in uncontrolled trials developed long-lasting psychotic symptoms, and 13.1% of those with psychedelic-induced psychosis later developed schizophrenia. |
Abstract
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. 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. 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. 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.