Psilocybin, an Effective Treatment for Major Depressive Disorder in Adults - A Systematic Review
Open accessAbstract
Psilocybin is a classical psychedelic which has been utilised for healing purposes for millenia. However, with its classification as a Schedule I substance, research into this compound is scarce with few FDA-approved clinical studies. Despite this, profound findings into its antidepressant effects (largely through its action on 5-HT1a receptors) in mental illnesses such as major depressive disorder have rapidly increased interest back into their potential therapeutic benefits. This systematic review provides an analysis of the studies examining the clinical use of psilocybin for major depressive disorder. In total 6 studies were selected, including 319 participants, with half being randomised controlled trials and half open label trials. In every study psychological support was included as an integral part of the treatment. It was found that every study significantly favoured the use of psilocybin in reducing depressive symptoms, with few side effects. This gives psilocybin an advantage over commonly prescribed selective serotonin reuptake inhibitors (SSRIs), which carry more risk and cause more adverse effects. This drug therefore shows promise for being used as a clinical treatment for major depressive disorder, however future research should develop a paradigm for its use, with the timing of sessions and type of psychological support specified to allow for more precise analysis of the clinical effects of the drug. Additionally, more studies into its clinical efficacy are needed for appropriate detection of any publication bias. With this, psilocybin could prove to be revolutionary in treating depression and become an alternative medication to SSRIs.
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According to a recent meta-analysis, use of psilocybin (at doses ranging from 1 mg to 25 mg) in patients not currently taking any other psychotropic medications resulted in significant reductions in depressive symptoms.
“According to a recent meta-analysis, which included three RCTs and three open-label studies, the use of psilocybin (at doses ranging from 1 mg to 25 mg) to patients not currently taking any other psychotropic medications resulted in significant reductions in depressive symptoms. 38”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [38]
The Methods exclude participants currently taking other psychotropic medications, and the Results report significant reductions in depressive symptoms. Although the Included Studies and Trials Characteristics section gives a study-dose range of 1–25 mg, the main analysis used medium-to-high doses; the Primary Outcomes section says the 1 mg and 10 mg doses produced non-significant clinical responses. The claim therefore overstates the finding if it implies significant benefit across the stated dose range. (LLM, conf=0.88)
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Serotonergic neuromodulation of synaptic plasticity
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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
- Watford, T., & Masood, N.
- Affiliations
- Keele University (GB)
- Corresponding author
- Watford, Tessa
- Venue
- Clinical Psychopharmacology and Neuroscience
- Published
- 2023-10-16
- Volume
- 22
- Issue
- 1
- Pages
- 2-12
- ISSN
- 1738-1088 (ISSN-L)
- 2093-4327
- PMC
- PMC10811389
- OpenAlex
- W4387651512
- Cited by
- 23
- References
- 41
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 6
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Clinical Psychopharmacology and Neuroscience (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Keele University
- 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, major depressive disorder, antidepressant effects, 5-HT1A receptor, classical psychedelics, Schedule I drug classification, psychological support, selective serotonin reuptake inhibitors, adverse effects, treatment efficacy
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