The Evaluation of the Efficacy and Safety of the Use of Psilocybin in the Treatment of Adults with Treatment-Resistant Depression
Rishika Scott, James Smith
Emerging Minds Journal for Student Research January 25, 2026 DOI: 10.59973/emjsr.317 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Open-label Peer reviewed |
|---|---|
| Sample size | 7 |
| Population | Patients with treatment-resistant depression |
| Interventions | Psilocybin Selective serotonin reuptake inhibitors (SSRIs) Psychotherapy |
| Dose | 25 mg |
| Topics | Psilocybin Depression |
| Keywords | Dosing Depression economics Clinical trial Hallucinogen Randomized controlled trial Pharmacology Medline |
| Key findings | Psilocybin at 25 mg per dosing session is effective for reducing depressive severity in treatment-resistant depression. |
Abstract
Treatment-resistant depression (TRD) has been well-researched within scientific literature, although the therapeutic value of psilocybin is not fully understood. The aim of this systematic review is to determine a stable and effective dosage unit to inform health professionals of the benefits of psilocybin, using peer-reviewed literature and meta-analysis. The review will also compare selective serotonin reuptake inhibitors (SSRIs) with psychotherapy to draw conclusions and recommendations of psilocybin therapy to improve day-to-day living for affected patients. PubMed and the University of Portsmouth Discovery online database (EBSCOhost) were individually utilised from December 2024 to March 2025. Five open-label studies and 2 randomised controlled trials (RCTs) were selected to assess psilocybin efficacy and safety. Appraisal checklists along with search criteria were used to determine eligibility and reliability of these data. The random-effects meta-analyses demonstrated that psilocybin at 25 mg within specific integrated sessions was effective at treating TRD compared to 10 mg and 1 mg by comparing clinical trials between two doses and single doses. Psilocybin at 25 mg was found to significantly reduce patients’ depressive severity compared to the baseline, which was prevalent in the two-dose studies (n = 5) compared to the single-dose studies (n = 2), due to the number of studies produced. The overall evidence suggests that psilocybin is an effective therapeutic for treatment-resistant depression, with a dosage unit of 25 mg administered as a single capsule per dosing session, with one dose per clinical session. Limitations to the evidence and this review have affected the overall results; therefore, more relevant studies are needed.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin for depression, 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 |
| 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 |
| Psychedelics in the treatment of unipolar mood disorders: a systematic review Patients with broadly defined unipolar mood disorders | 2016 | Systematic review | n = 423 |
| Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... | 2023 | Systematic review with meta-analysis | n = 14 |
| Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Patients with life-threatening diseases and symptoms of anxiety or depression | 2018 | Systematic review | n = 445 |