Psychedelic-induced hypomania and mania: a systematic review and meta-analysis.

Mickael Eskinazi; Rayan Nasserdine; Romane M Cusin; Pantelis Baniotoupoulos; Luigi F Saccaro; Marco De Pieri; Tamara Corino; Federico Seragnoli; Jean-Francois Briefer; Tatiana Aboulafia Brakha; H&#xe9;l&#xe8;ne Richard-Lepouriel; Louise Penzenstadler; Kerem B&#xf6;ge; Matthias Kirchner; Daniele Zullino; Mikkel H&#xf8;jlund; Jacopo Sapienza; Marta Bosia; Ana Catalan; Eduard Vieta; Marco Solmi; Michel Sab&#xe9;

doi:10.1038/s41380-026-03657-6

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Psychedelic-induced hypomania and mania: a systematic review and meta-analysis.

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Abstract

Serotonergic psychedelics are increasingly investigated as treatments for affective disorders. Concerns persist regarding their potential to induce hypomania or mania, particularly in individuals with bipolar spectrum vulnerability. Whether these substances precipitate transient mood switches or contribute to persistent bipolar illness or diagnostic transition remains unclear. We conducted a systematic review of human studies examining manic or hypomanic symptoms following exposure to serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA (CRD420251160656). Databases and trial registries were searched through January 26, 2026. Eligible designs included randomized and non-randomized clinical studies, registry-based cohorts, cross-sectional surveys, and longitudinal observational studies. Outcomes included dysphoria/euphoria, manic or hypomanic symptoms and transition to bipolar disorder. Risk of bias was assessed using ROBINS-I, ROB2 or NIH tools. Twenty-three studies met inclusion criteria, four contributing to meta-analysis. Rates of psychedelic-associated dysphoria/euphoria, hypomania or mania ranged from 5.8% in controlled trials of psilocybin-assisted psychotherapy for major depressive disorders to 30% in naturalistic studies of individuals with bipolar disorder. When present, manic symptoms were typically acute and self-limited. Observational studies identified higher risks among individuals with bipolar I disorder, familial vulnerability, polysubstance use, and unsupervised or illegal use. Registry-based cohorts examining diagnostic transitions showed a prevalence of subsequent transition to bipolar disorder of 4% (95% CI 2-8%; N = 7478; I² = 32.1%), with little evidence for a hallucinogen-specific signal. Overall, serotonergic psychedelics appear to pose a low but clinically meaningful relative risk of transient mood-related symptoms in susceptible individuals while remaining relatively safe in controlled clinical settings. Long-term outcomes and repeated exposure remain insufficiently studied, underscoring the need for rigorous longitudinal research.

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Humans Hallucinogens Mania Bipolar Disorder Psilocybin Lysergic Acid Diethylamide N-Methyl-3,4-methylenedioxyamphetamine Systematic Review Journal Article Meta-Analysis Review

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Mickael Eskinazi, Rayan Nasserdine, Romane M Cusin, Pantelis Baniotoupoulos, Luigi F Saccaro, Marco De Pieri, Tamara Corino, Federico Seragnoli, Jean-Francois Briefer, Tatiana Aboulafia Brakha, Hélène Richard-Lepouriel, Louise Penzenstadler, Kerem Böge, Matthias Kirchner, Daniele Zullino, Mikkel Højlund, Jacopo Sapienza, Marta Bosia, Ana Catalan, Eduard Vieta, Marco Solmi, Michel Sabé. 2026-05-29. Psychedelic-induced hypomania and mania: a systematic review and meta-analysis.. https://doi.org/10.1038/s41380-026-03657-6

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Bipolar Disorder subject Hallucinogens subject Humans subject Journal Article subject Mania subject Meta-Analysis subject Systematic Review; Journal Article; Meta-Analysis; Review resource Systematic reviews study

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