Can psychedelics trigger mania? What a new meta-analysis reveals

A new systematic review and meta-analysis, published in Molecular Psychiatry Conducted by an international team led by researchers from Geneva University Hospital, the study examines how often serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) and MDMA can trigger hypomania or a manic episode, and who is most at risk.
The researchers searched databases and trial registers up to and including 26 January 2026 and included 23 studies that met the inclusion criteria, four of which were suitable for the meta-analysis itself.

Why this research is relevant

Psychedelics are increasingly being studied as a treatment for mood disorders such as depression.
At the same time, there have long been concerns that these drugs may actually cause the opposite effect in people with a predisposition to bipolar disorder: a (hypo)manic episode.
The key question the authors sought to answer was whether such mood swings are temporary, or whether the use of psychedelics can contribute to persistent bipolar symptoms or a diagnostic transition to bipolar disorder.

How common is it?

The reported rates of dysphoria/euphoria, hypomania or mania following psychedelic use varied widely, depending on the population studied.
In controlled clinical trials of psilocybin-assisted therapy for severe depression, this percentage was only 5,8%, whilst in naturalistic studies among people who already had bipolar disorder, it rose to 30%.
When manic symptoms did occur, they were generally acute in nature and self-limiting: in other words, they resolved of their own accord, without leading to a persistent manic episode.

Who is most at risk?

The observational studies included in this review point to a number of clear risk factors for the onset of manic or hypomanic symptoms following the use of psychedelics.
An increased risk was observed in particular among people with bipolar I disorder, people with a familial susceptibility for mood disorders, people who using several substances at the same time (polydrug use), and use that unaccompanied or illegal takes place, i.e. outside a clinical or therapeutic setting.
This is in line with what is often seen in the literature on psychedelics: the setting, supervision and careful screening for underlying vulnerabilities make a substantial difference to the risk profile.

Does it lead to a permanent bipolar diagnosis?

A key part of this review concerned registry studies that examined diagnostic transition: Does an episode following the use of psychedelics actually develop into a persistent bipolar disorder?
These register-based studies revealed a prevalence of 4% (95% confidence interval 2–8%, based on N = 7,478 individuals) for subsequent transition to bipolar disorder.
An important detail: the authors found little evidence that this signal can be attributed specifically to hallucinogens, which suggests that other factors (such as underlying vulnerability) play at least as significant a role.

The authors’ conclusion

The researchers conclude that serotonergic psychedelics are a low but clinically relevant risk have an effect on temporary mood-related symptoms in vulnerable individuals, whilst they relatively safe remain within controlled clinical settings.
At the same time, they emphasise that the long-term effects and the consequences of repeated exposure have not yet been sufficiently investigated, and they strongly advocate for thorough longitudinal follow-up studies.

Addition

For anyone who is considering experimenting with psychedelics themselves, or who is already doing so, this research provides a good opportunity to take another critical look at their own (family) history.
The combination of factors identified in this review as increasing the risk – bipolar I disorder, a family history of mood disorders, poly-drug use and unsupervised use – is precisely why a thorough initial assessment and screening are so important.
At Triptherapie, we therefore ask about psychiatric history and family vulnerability before a session is scheduled, precisely because acute mood swings such as hypomania can, in most cases, be anticipated and mitigated with the right preparation and support.
This study once again highlights that the setting and the support provided not only contribute to a more pleasant experience, but also play a direct role in reducing psychiatric risks.

Source: Eskinazi M, Nasserdine R, Cusin RM, et al. "Psychedelic-induced hypomania and mania: a systematic review and meta-analysis." Mol Psychiatry. 29 May 2026. doi: 10.1038/s41380-026-03657-6.