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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)

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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.

Comparable studies

Other non-randomized and open-label trials on psilocybin for depression, most cited first.

Study Year Design Participants
Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Patients with moderate-to-severe, unipolar, treatment-resistant major depression 2016 Open-label feasibility trial n = 12
Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression 2017 Open-label trial n = 20
Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression 2018 Clinical trial n = 20
Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Patients with major depressive disorder 2021 Open-label study n = 24
Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Individuals diagnosed with moderate to severe, treatment-resistant depression 2017 Open-label study n = 20

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Depression Psilocybin Altered states of consciousness PTSD Philosophy of mind

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Psilocybin for depression