Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - A first-in-kind open-label pilot study.
Sara Ellis, Catherine Bostian, Wendy Feng, Eileen Fischer, Garrett Schwartz, Katherine Eisen, Melanie Lean, Elizabeth Conlan, Michael Ostacher, Scott T Aaronson, Trisha Suppes
Journal of Affective Disorders January 15, 2025 DOI: 10.1016/j.jad.2024.09.133 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label trial Pilot study Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Veterans with severe treatment-resistant depression |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | 12 weeks |
| Topics | Depression Psilocybin |
| Keywords | #depression mental health Mood disorder Clinical depression #veterans military veterans Service members Ex-military #psilocybin magic mushrooms Hallucinogens Psychedelics |
| Citations | 23 |
| Registration | NCT04433858 |
| Key findings | A single 25 mg dose of psilocybin produced response in 60% and remission in 53% of veterans with severe treatment-resistant depression at three weeks, with 47% maintaining response at twelve weeks. |
Abstract
The enduring and severe depression often suffered by Veterans causes immense suffering and is associated with high rates of suicide and disability. This is the first study to evaluate the efficacy and safety of psilocybin in Veterans with severe treatment-resistant depression (TRD). 15 Veterans with severe TRD (major depressive episode failing to respond to ≥5 treatments, or lasting >2 years) received 25 mg of psilocybin. Primary outcome was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Response was defined s ≥ 50 % reduction in MADRS, and remission as ≤10 MADRS score. Psychedelic experience was assessed using the Five-Dimensional Altered States of Consciousness scale (5D-ASC). Safety measures included assessment of suicidality and adverse events. Participants on antidepressants were tapered to avoid drug interactions. Of 15 participants, 60 % met response and 53 % met remission criteria at Week 3. At 12 weeks, 47 % maintained response, and 40 % remission. Co-morbid PTSD did not significantly influence study outcomes. The psychedelic experience reported in 5D-ASC did not correlate with response. Participants judged to need antidepressants were restarted and considered non-responders from that timepoint (n = 4). No unexpected adverse events occurred. Limitations include the small sample size, and the uncontrolled and unblinded nature of the study. In this first study on psilocybin for Veterans with severe TRD, a surprising response and remission was seen. Many Veterans had PTSD though no moderating impact of response was observed. The degree of psychedelic experience did not correlate with depression changes. Further study is warranted. ClinicalTrials.gov Identifier: NCT04433858.