The Therapeutic Potential of Psychedelics for Treatment-resistant Depression: Reality or Hallucination? A Systematic Review.
Natia Horato, Felipe Dalvi-Garcia, Pablo E P Dutra, Antonio E Nardi
Journal of Clinical Psychopharmacology January 12, 2026 DOI: 10.1097/JCP.0000000000002122 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Double-blind Open-label Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Participants diagnosed with treatment-resistant depression (TRD) |
| Topics | Depression Psychedelic-assisted therapy |
| Keywords | Psychedelics |
| Citations | 1 |
| Key findings | The use of psychedelics in the treatment of treatment-resistant depression suggests efficacy across different classes of these substances. |
Abstract
Treatment-resistant depression (TRD), a clinical subtype of major depressive disorder (MDD), is associated with greater severity and functional impairment, representing a significant challenge in psychiatric care. Recent studies suggest that the use of psychedelics can provide rapid and substantial improvement in the severity of depressive symptoms. Therefore, the aim of this systematic review is to evaluate and synthesize the evidence on the efficacy of psychedelics in the treatment of TRD. Studies were included if they enrolled participants diagnosed with TRD, used scales to assess depression severity, reported effect sizes or provided metrics for calculating effect sizes of the intervention, and involved single-blind, double-blind, or open-label trials, including single-arm studies. Fifteen articles were included in this systematic review, 10 of which were randomized double-blind controlled trials (RCTs) and 5 open-label clinical trials. All studies were summarized and analyzed, providing a current overview of the scientific literature on the therapeutic potential of typical and atypical psychedelics in TRD. The use of psychedelics in the treatment of treatment-resistant depression represents an alternative and complementary therapeutic approach to traditional treatments, suggesting efficacy across different classes of these substances.
Comparable studies
Other systematic reviews and meta-analyses on depression, most cited first.
Citations in the library
Cited by 2
- Psychedelics and longevity: implications for lifespan, healthspan and functional aging Longevity July 5, 2026
- Psilocybin and ayahuasca in treatment-resistant depression: clinical evidence, methodological constraints and ethical challenges: a narrative review Frontiers in Psychiatry September 15, 2026
Cites 21
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
and 16 more in the library