Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression.
Carlton M Kelly, Mathieu Fradet, Catherine Bostian, Anna Donnelly, Sara Ellis, Michael Ostacher, Scott T Aaronson, Trisha Suppes
Journal of Affective Disorders June 4, 2026 DOI: 10.1016/j.jad.2026.122063 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label trial Longitudinal Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Veterans with treatment-resistant depression |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | Single dose, 3-week primary endpoint, follow-up to 12 months |
| Topics | Anxiety Depression Psilocybin |
| Keywords | Posttraumatic stress disorder Veteran |
| Registration | NCT04433858 |
| Key findings | Psilocybin with psychological support was associated with improvements in anxiety, quality of life, functioning, and PTSD symptoms that largely correlated with concurrent improvements 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.