Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression.
Carlton M Kelly, Mathieu Fradet, Catherine M Bostian, Anna Donnelly, Sara Ellis, Michael Ostacher, Scott Aaronson, Trisha Suppes
Journal of affective disorders November 1, 2026 Peer reviewed DOI: 10.1016/j.jad.2026.122063 via PubMed
Summary
Psilocybin, when administered with psychological support, was associated with improvements in anxiety, quality of life, functioning, and PTSD symptoms in Veterans with treatment-resistant depression. Participants showed a 59% reduction in anxiety severity at Week 3 and a 24% increase in quality of life scores. However, these effects were largely linked to concurrent improvements in depressive symptoms and were not statistically significant after adjustment. The study included 15 participants, with ten completing long-term follow-up.
Study at a glance
| Design | open-label trial |
|---|---|
| Sample size | 15 |
| Population | Veterans with treatment-resistant depression |
| Key finding | Psilocybin with psychological support led to improvements in anxiety, quality of life, functioning, and PTSD symptoms that correlated primarily with reductions in depressive symptoms. |
Abstract
Psilocybin has demonstrated promise for improving depressive symptoms in treatment-resistant depression, but its effects on anxiety, quality of life, functioning, and posttraumatic stress symptoms are less well studied. This study reports exploratory findings from an open-label trial in Veterans with TRD. Participants received a single 25-mg dose of psilocybin administered with psychological support. The primary endpoint was assessed 3 weeks post-dose, with follow-up extending to 12 months. Outcomes included anxiety severity (GAD-7), quality of life (Q-LES-Q-SF), functional impairment (WSAS), and posttraumatic stress disorder symptoms (PCL-5). Experiential outcomes were measured with the Mystical Experience Questionnaire (MEQ), Challenging Experiences Questionnaire (CEQ-30), and Emotional Breakthrough Inventory (EBI). Mixed-effects models were used to evaluate longitudinal changes, and correlation analyses examined associations between measures and changes in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale. Fifteen participants were included, with ten completing long-term follow-up. GAD-7 scores demonstrated sustained improvements through 12 months, with a 59% reduction from baseline at Week 3. Q-LES-Q-SF gains were significant through Week 12, with a 24% increase at Week 3, and WSAS improvements persisted through Month 6 before declining, with a 46% reduction at Week 3. These effects were no longer statistically significant after accounting for improvements in depression. Unadjusted PCL-5 reductions were observed at all timepoints. Exploratory analyses of acute subjective experiences did not correlate to treatment response. This study is limited by its small sample size and open-label design. Psilocybin with psychological support was associated with improvements in anxiety, quality of life, functioning, and PTSD symptoms which largely correlated to concurrent improvements in depressive symptoms. NCT04433858.