Psychosis Vulnerability
What meta-analyses, a large Ontario cohort, NIDA and the esketamine label say about psychosis risk with psychedelics, who trials exclude, and what remains uncertain.
Content last updated . This page has not been medically reviewed.
Urgent help first
Seeing or hearing things that are not there, strong false beliefs, or being unable to tell what is real, especially with agitation or thoughts of self-harm, needs prompt medical help. In the US call 911 for danger or a medical emergency, or call or text 988 for the Suicide & Crisis Lifeline. For a possible poisoning, Poison Help is 1-800-222-1222. This page is education only. It does not tell anyone to start, stop or change a medicine.What "psychosis" means here
Psychosis is a state in which a person loses touch with reality, with hallucinations (perceiving things that are not there) or delusions (fixed false beliefs). Psychedelics change perception by design, so the question is different: do they trigger lasting psychosis, or worsen it in people who already have a psychotic illness, such as schizophrenia, or are at higher risk? Evidence labels used: established, mixed, insufficient evidence, evidence of harm.What the sources report
NIDA. There is some evidence that psychedelic drugs might bring about or trigger a schizophrenia-like illness in people with predisposing factors, but little evidence that they cause long-term psychiatric problems for most people. NIDA cites a 1966 study in which three of 65 people with pre-existing psychoses given LSD had persistent worsening lasting 3 to 8 months. In modern research, people with previously diagnosed psychosis or bipolar disorder, and sometimes other mental illnesses, are excluded as a precaution, and under these conditions the risk of psychosis or suicide is described as extremely low. NIDA adds that poor outcomes may be more likely outside clinical use. [1]Meta-analysis (2025). A review of human studies of LSD, psilocybin, mescaline, DMT and MDMA analyzed 131 publications, most of low quality. It estimated psychedelic-induced psychosis at 0.002% in population studies, 0.2% in uncontrolled trials and 0.6% in randomized trials. In uncontrolled trials that included people with schizophrenia, 3.8% developed long-lasting psychotic symptoms. Of people with psychedelic-induced psychosis, 13.1% later developed schizophrenia. The authors suggest schizophrenia might not be a definite exclusion for trials, but recommend a conservative approach because of the low quality and limited number of studies. [2] The rates differ because the groups differ: screened trial participants, volunteers in uncontrolled studies and whole populations are not comparable.
Ontario cohort (2025). Among 9,244,292 people without prior psychosis, 5,217 had an emergency department visit involving a hallucinogen. Within 3 years, 3.99% of them were diagnosed with a schizophrenia spectrum disorder, compared with 0.15% of the general population. After adjusting for other substance use and mental health conditions, the hazard ratio was 3.53 (95% confidence interval 3.05 to 4.09). [3] This shows an association, not that the substances caused the illness: people who reach an emergency department differ from other users, and early illness may itself lead to drug use or crises.
Salvia divinorum. A 2015 review and case series hypothesized that use might be associated with psychotic disorders, and said more research is needed. [4] Label: insufficient evidence.
Ketamine and esketamine. NIDA says ketamine and PCP can worsen symptoms in people with schizophrenia and can cause short-term episodes of psychosis. [1] The esketamine label says to carefully assess patients with psychosis before treatment, because of dissociation risk, and to start only if benefit outweighs risk. [5]
Family history
Evidence on how much a family history of psychosis changes risk with psychedelics: Proper evidence not found. A PubMed search for family history and psychosis in psilocybin research returned reviews on bipolar family history but no quantified psychosis estimate to cite. The question belongs with a clinician. For the bipolar side see mania and bipolar-related concerns.What the evidence cannot say
- It cannot say who will be affected. Studies show averages, not individual risk.
- Most data come from LSD and psilocybin; other substances have little. A result for one substance should not be applied to another.
- Cause is not settled. Most of the studies in the 2025 meta-analysis were of low quality. [2]
Next steps
Anyone with a personal or family history of psychosis, or who is worried about their own symptoms, should talk with a clinician: talking with a health professional. Related reading: psychedelic adverse effects and contraindications and screening and eligibility in clinical research.Frequently asked questions
Can psychedelics cause psychosis?
NIDA says they might trigger a schizophrenia-like illness in people with predisposing factors, with little evidence of long-term psychiatric problems for most people. [1]
How common is psychedelic-induced psychosis?
A 2025 meta-analysis estimated 0.002% in population studies and 0.6% in randomized trials, from mostly low-quality studies. [2]
Are people with schizophrenia allowed in psychedelic trials?
Modern trials generally exclude them, as a precaution. [1] The meta-analysis authors suggest this might be revisited but advise caution. [2]
Does an emergency visit for hallucinogens predict schizophrenia?
In Ontario, such visits were followed by a higher rate of diagnosis within 3 years, but this is an association in people who reached an emergency department. [3]
Are ketamine and esketamine different?
They are dissociatives. NIDA says ketamine can worsen schizophrenia symptoms, and the esketamine label calls for careful assessment of people with psychosis. [1][5]
References
- National Institute on Drug Abuse. Psychedelic and Dissociative Drugs. Read 2026-10-22.
- Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies. Mol Psychiatry 2025. Read 2026-10-22.
- Emergency department visits involving hallucinogen use and risk of schizophrenia spectrum disorder. JAMA Psychiatry 2025. Read 2026-10-22.
- The association of Salvia divinorum and psychotic disorders: a review of the literature and case series. J Psychoactive Drugs 2015. Read 2026-10-22.
- US National Library of Medicine, DailyMed. SPRAVATO (esketamine) nasal spray, FDA-approved prescribing information and Medication Guide. Read 2026-10-22.