Psilocybin as an alternative to conventional treatments: A systematic review
Deivid Antonio Cahuasqui-Mendoza
Gaceta Médica de Caracas April 22, 2026 DOI: 10.47307/gmc.2026.134.s2.32 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Qualitative Peer reviewed |
|---|---|
| Population | Adults aged 18-65 with DSM-5 diagnoses of depression and/or anxiety |
| Intervention | Psilocybin-assisted therapy with psychotherapeutic support |
| Topics | Psilocybin |
| Key findings | Psilocybin-assisted therapy is a promising alternative for treatment-resistant depression and anxiety, but methodological heterogeneity across studies precludes quantitative synthesis. |
Abstract
Introduction. Limitations of conventional treatments for depression and anxiety, particularly in treatment-resistant cases, have driven interest in alternative therapeutic approaches. Psilocybin, a serotonergic agonist with demonstrated effects on neuroplasticity and large-scale brain networks, has emerged as a promising therapeutic option. Materials and methods: A systematic review of controlled clinical trials published between 2020 and 2025 was conducted in accordance with PRISMA guidelines. Searches were performed in PubMed/MEDLINE, Scopus, PsycINFO, Web of Science, and the Cochrane Library. Eligible studies included adults aged 18-65 years with DSM-5 diagnoses of depression and/or anxiety who received psilocybin-assisted therapy with psychotherapeutic support. Risk of bias was assessed using RoB 2, the Jadad scale, and the Newcastle–Ottawa Scale. Due to methodological heterogeneity, a qualitative narrative synthesis was performed.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin, 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 |
| Blinding and expectancy confounds in psychedelic randomized controlled trials | 2021 | Systematic review | |
| Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Patients from included clinical trials | 2016 | Systematic review | |
| 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 |
| Default Mode Network Modulation by Psychedelics: A Systematic Review Participants from included studies | 2022 | Systematic review |