Evaluating the risk of psilocybin for the treatment of bipolar depression: A review of the research literature and published case studies
David E. Gard, Mollie Pleet, Ellen Bradley, Andrew Penn, Matthew L. Gallenstein, Lauren S. Riley, Meghan DellaCrosse, Emily M. Garfinkle, Erin E. Michalak, Joshua Woolley
Journal of Affective Disorders Reports September 22, 2021 DOI: 10.1016/j.jadr.2021.100240 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 17 |
| Population | People with bipolar disorder |
| Topics | Psilocybin Depression |
| Keywords | Depression economics Bipolar disorder Psychotherapist Clinical psychology Hallucinogen Cognition |
| Citations | 33 |
| Key findings | A review of 17 cases suggests potential risk of activating a manic episode with psilocybin use in bipolar disorder, warranting caution, but a cautious trial is needed. |
Abstract
Growing evidence suggests that psilocybin, the active ingredient in hallucinogenic mushrooms, can rapidly and durably improve symptoms of depression, leading to recent breakthrough status designation by the FDA and legalization for mental health treatment in some jurisdictions. Depression in bipolar disorder is associated with significant morbidity and has few effective treatments. However, there is little available scientific data on the risk of psilocybin use in people with bipolar disorder. Individuals with bipolar disorder have been excluded from modern clinical trials, out of understandable concerns of activating mania or worsening the illness course. As psilocybin becomes more available, people with these disorders will likely seek psilocybin treatment for depression and have likely already been doing so in unregulated settings. Our goal here is to summarize the known risks of psilocybin use (and similar substances) in bipolar disorder and to systematically evaluate examples of published case history data, in order to critically evaluate the relative risk of psilocybin as a treatment for bipolar depression. We found 17 cases suggesting that there is potential risk for activating a manic episode, thereby warranting caution. Nonetheless, the relative lack of systematic data or common case examples indicating risk appears to show that a cautious trial, using modern trial methods focusing on appropriate ‘set’ and ‘setting’, targeted at those lowest at risk for mania in the bipolar spectrum (e.g., bipolar 2 disorder), is very much needed, especially given the degree to which depression impacts this population.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... | 2020 | Systematic review | n = 188 |
| The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression | 2020 | Meta-analysis | n = 117 |
| Psychedelics in the treatment of unipolar mood disorders: a systematic review Patients with broadly defined unipolar mood disorders | 2016 | Systematic review | n = 423 |
| Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... | 2023 | Systematic review with meta-analysis | n = 14 |
| Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Patients with life-threatening diseases and symptoms of anxiety or depression | 2018 | Systematic review | n = 445 |
Citations in the library
Cited by 31
- Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies European Neuropsychopharmacology August 7, 2023
- Risks and benefits of psilocybin use in people with bipolar disorder: An international web-based survey on experiences of ‘magic mushroom’ consumption Journal of Psychopharmacology December 14, 2022
- Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective Frontiers in Psychiatry December 17, 2021
- Dark loops: contagion effects, consistency and chemosocial matrices in psychedelic-assisted therapy trials Psychological Medicine July 19, 2023
- Adolescent Psychedelic Use and Psychotic or Manic Symptoms JAMA Psychiatry March 13, 2024
and 26 more in the library
Cites 38
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
and 33 more in the library