Long-term outcomes of single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - 12-month data from an open-label pilot study.
Sara Ellis, Catherine Bostian, Anna Donnelly, Wendy Feng, Katherine Eisen, Melanie Lean, Elizabeth Conlan, Michael Ostacher, Scott T Aaronson, Trisha Suppes
Journal of Affective Disorders June 9, 2025 DOI: 10.1016/j.jad.2025.119655 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label pilot study Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Veterans with severe treatment-resistant depression |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | 12-month follow-up |
| Topics | Depression Psilocybin |
| Keywords | Long-term outcomes Psychedelics Veterans mental health Psychedelic medicine Psilocybin therapy Clinical research |
| Citations | 3 |
| Post-publication review | 1 comment on PubPeer (opens in new tab) · last active September 2025 |
| Registration | NCT04433858 |
| Key points | A single 25 mg dose of psilocybin produced significant reductions in depression severity that persisted for 12 months, although the antidepressant effect began to wane after 6 months and more substantially after 9 months. |
Abstract
One-third of Veterans with major depressive disorder suffer from treatment-resistant depression (TRD). This is the first study to evaluate the long-term outcomes of psilocybin in Veterans with severe TRD. This paper presents 12-month results from an open-label pilot study assessing the effects of 25 mg psilocybin in Veterans with severe TRD, defined as a major depressive episode failing to respond to ≥5 treatments, or lasting >2 years. 10 out of 15 participants completed the 12-month follow-up. Depression severity was measured by Montgomery-Åsberg Depression Rating scale (MADRS) at 6, 9, and 12 months posttreatment. Response was defined as ≥50 % reduction in MADRS, and remission as ≤10 MADRS score. Depression scores show significant reductions from baseline across all timepoints. However, there was an increase in MADRS scores from short-term timepoints (Weeks 3 and 12) to Month 12. Of 10 participants, at Month 6, 80 % met response and 50 % met remission criteria for the MADRS. At Month 9, acute responses began to wane. At Month 12, 40 % maintained response and 30 % maintained remission. Limitations include the small sample size and its uncontrolled, unblinded design. In this first-of-kind study on long-term effects of psilocybin for Veterans with severe TRD, depression scores showed significant sustained reductions up to 12-months. However, the antidepressant effects began to wane at 6 months, and then more substantially after 9 months, although these increases in MADRS did not reach statistical significance. Further research is needed. ClinicalTrials.gov Identifier: NCT04433858.
Comparable studies
Other non-randomized and open-label trials on psilocybin for depression, most cited first.
Citations in the library
Cited by 4
- Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review International Journal of Molecular Sciences September 10, 2026
- Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression. Journal of Affective Disorders June 4, 2026
- Predictors of the Effectiveness of Psychedelics in Treating Depression—A Scoping Review International Journal of Molecular Sciences February 26, 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 22
- 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 17 more in the library