Psilocybin as a novel drug in the treatment of major depressive disorder: a systematic review
Jakub Magdziak, Oliwia Borowska, Eliza Mędrek, Paulina Zegarska, Natalia Sałkowska, Natalia I Brzozowska, Karolina Zawadzka, Barbara Wardzyńska, Sara Awad, Hanna Markowska, Paulina Małyszczak, Katarzyna Zięba
Medical Science October 30, 2026 DOI: 10.54905/disssi.v30i176.e201ms3896 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Longitudinal Peer reviewed |
|---|---|
| Intervention | Psilocybin |
| Topics | Depression Psilocybin |
| Key findings | Argues that psilocybin-assisted treatment can produce rapid, meaningful improvements in depression, including for patients unresponsive to conventional treatments, and that some patients may show long-term benefits. The authors note that heterogeneity in samples, methods, and follow-up periods across the six reviewed studies limits direct comparison, and call for more research on optimal administration. |
Abstract
Major depressive disorder remains one of the most common and debilitating psychiatric disorders in the global population, with a significant number of patients not responding adequately to traditional antidepressant treatments.As such, the need for new methods has prompted studies exploring the use of psychedelic medicines, such as psilocybin, which is a serotonergic psychedelic drug produced by mushrooms from the Psilocybe genus.This literature review explores the use of psilocybin as a medicine in major depressive disorder, along with the sustainability of any improvements.A literature review was undertaken on six clinical studies on the use of psilocybin therapy for different kinds of depression.The literature review entailed both randomized clinical trials and longitudinal studies.There were several aspects of the research designs that we considered when reviewing the studies, including study design and methodology.Based on existing evidence, psilocybin-assisted treatments can lead to rapid and meaningful improvements in depression, even for patients who did not respond to conventional treatments.Large-scale randomized trials have been able to prove effectiveness on resistant patients, and further follow-up trials reveal that some patients may derive longterm benefits.But the variety in the sample group, methods used, and time periods observed makes a direct comparison hard.Psilocybin is one such promising pharmaceutical treatment for depression, especially for those who do not respond to existing treatments.Still, more studies are needed to gain a better understanding of how best to administer psilocybin.
Comparable studies
Other narrative reviews on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression | 2021 | Review | |
| Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... | 2021 | Review | n = 70 |
| Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review | 2020 | Review | |
| From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders | 2021 | Review |