Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials
This systematic review and meta-analysis found that psilocybin markedly reduces depressive symptom severity in patients with primary MDD or TRD, with both single‑dose and two‑dose regimens producing significant improvements. Two‑dose administration sometimes yielded more pronounced and longer‑lasting effects, but it remains unclear whether this reflects dosing or other confounding factors, so standardised head‑to‑head trials are needed.
Authors
- Salvetti, G.
- Saccenti, D.
- Moro, A. S.
Published
Abstract
Current pharmacological treatments for major depressive disorder (MDD) are often only partially effective, with many patients experiencing no significant benefit, leading to treatment-resistant depression (TRD). Psilocybin, a classical serotonergic psychedelic, has emerged as a notable emerging treatment for such disorders. The aim of this systematic review and meta-analysis is to summarize and discuss the most recent evidence about the therapeutic effects of single-dose and two-dose psilocybin administration on the severity of depressive symptoms, as well as compare the efficacy of these interventions among patients with a primary diagnosis of MDD or TRD. Articles were collected from EBSCOhost and PubMed following the PRISMA guidelines, yielding 425 articles with 138 duplicates. After screening 287 records, 12 studies met the eligibility criteria and were included in the review. A quantitative analysis of the studies indicates that psilocybin is highly effective in reducing depressive symptoms severity among patients with primary MDD or TRD. Both single-dose and two-dose psilocybin treatments significantly reduced depressive symptoms severity, with two-dose administration sometimes yielding more pronounced and lasting effects. However, it is unclear if this was solely due to dosage or other factors. Future research should include standardized trials comparing these dosing strategies to better inform clinical practice.
Research Summary of 'Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials'
Introduction
Major depressive disorder (MDD) is a highly prevalent, disabling condition associated with substantial personal and economic burden and incomplete response to existing treatments. Luciano and colleagues note that about 30% of patients do not respond to two or more standard psychotherapeutic or pharmacological approaches and are commonly labelled as having treatment-resistant depression (TRD). Conventional antidepressants have delayed onset, side effects (for example sexual dysfunction, weight gain, sleep disruption) and withdrawal phenomena, which together motivate the search for novel treatments. Psilocybin, a serotonergic psychedelic found in Psilocybe fungi, has re-emerged as a candidate because it can induce rapid antidepressant effects and may engage processes such as synaptic plasticity via TrkB–BDNF signalling in addition to activity at serotonin receptors. This systematic review and meta-analysis was undertaken to synthesise the recent clinical-trial evidence comparing single-dose and two-dose psilocybin administration for patients with a primary diagnosis of MDD or TRD. The study set out to (1) summarise therapeutic effects of single- and two-dose regimens on depressive symptom severity, and (2) compare the efficacy of those two dosing strategies, noting that trials vary in dose, psychological support, and design and that no recent meta-analysis had directly compared one- versus two-dose approaches in an MDD/TRD sample.
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Study Details
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- APA Citation
Salvetti, G., Saccenti, D., Moro, A. S., Lamanna, J., & Ferro, M. (2024). Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials. Brain Sciences, 14(8), 829. https://doi.org/10.3390/brainsci14080829
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