Psilocybin-assisted therapy for depression: A systematic review and meta-analysis
Abstract
The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. Systematic searches were conducted to search for randomized clinical trials and open-label trials that evaluated depression symptoms after psilocybin therapy. Data was pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in depression severity, determined by calculating the change in depression ratings from baseline to the primary endpoint in the psilocybin arm versus the control arm. The literature search yielded 1734 studies, and 13 studies (n = 686) were included in either qualitative and/or quantitative analyses. The meta-analysis included 9 studies (pooled n = 596) and yielded a large effect size in favour of psilocybin (SMD = -0.78; p<0.001). Risk ratios for response and remission were large and significant in favour of psilocybin. A review of open-label trials showed robust decreases in depressive symptoms following psilocybin administration. These findings provide preliminary evidence for antidepressant efficacy with psilocybin-assisted psychotherapy, however, further studies are needed to evaluate safety and efficacy and to optimize treatment protocols.
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“This critical review does not intend to systematically summarize the extent of the effect of psilocybin, given the number of reviews already available in the literature, 29,38 but rather to offer an expert clinical opinion on the available evidence and possible future perspectives.”
- Authors
- Haikazian, S., Chen-Li, D. C. J., Johnson, D. E., Fancy, F., Levinta, A., Husain, M. I., Mansur, R. B., McIntyre, R. S., & Rosenblat, J. D.
- Affiliations
- University Health Network (CA)
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Rosenblat, Joshua D.
- ORCID
- Venue
- Psychiatry Research
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 329
- Pages
- 115531
- ISSN
- 0165-1781 (ISSN-L)
- OpenAlex
- W4387521434
- Cited by
- 134
- References
- 19
- Citations by year
- 2026: 48 · 2025: 53 · 2024: 33
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Psychiatry Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Health › Religion, Spirituality, and Psychology
- Keywords
- psilocybin, psilocybin-assisted therapy, depression, major depressive disorder, life-threatening illness, antidepressant efficacy, depression severity, remission, psychedelic therapy
- MeSH terms
- Antidepressive Agents, Depression, Major Depressive Disorder, Depressive Disorder, Major, Hallucinogens, Humans, Psilocybin, Psychotherapy
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