Psilocybin-Assisted Group Psychotherapy + Mindfulness Based Stress Reduction (MBSR) for Frontline Healthcare Provider COVID-19 Related Depression and Burnout: A Randomized Clinical Trial
This randomised controlled trial in 25 frontline physicians and nurses found that adding group psilocybin‑assisted psychotherapy (25 mg) to an 8‑week MBSR curriculum produced larger reductions in depressive symptoms at two weeks and greater improvements on burnout subscales, demoralisation and connectedness than MBSR alone. The intervention was well tolerated (only grade 1–2 adverse events, no serious AEs), suggesting that combining psilocybin with mindfulness training may be a promising treatment for COVID‑19‑related depression and burnout in healthcare providers.
Authors
- Lewis, B. R.
- Hendrick, J.
- Byrne, K.
Published
Abstract
Objective
This clinical trial sought to evaluate the safety and preliminary efficacy of psilocybin and MBSR for frontline healthcare providers with symptoms of depression and burnout related to the COVID-19 pandemic.
Methods
This was a randomized controlled trial that enrolled physicians and nurses with frontline clinical work during the COVID-19 pandemic and symptoms of depression and burnout. Participants were randomized in a 1:1 ratio to either an 8-week MBSR curriculum alone or an 8-week MBSR curriculum plus group psilocybin-assisted psychotherapy (PAP) with 25mg psilocybin. Symptoms of depression and burnout were assessed at baseline, and 2-weeks and 6-months post intervention utilizing the Quick Inventory of Depressive Symptoms (QIDS-SR-16) and Maslach Burnout Inventory Human Services Survey for Medical Professionals (MBI-HSS-MP), respectively. Secondary outcome measures included the Demoralization Scale (DS-II) and the Watt’s Connectedness Scale (WCS). Adverse events and suicidality were assessed through 6-month follow-up. Results 25 participants were enrolled and randomized. There were 12 study-related AEs recorded that were Grade 1-2 and no serious AEs. There was larger decrease in QIDS score for the MBSR+PAP arm compared to MBSR-only from baseline to 2-weeks post-intervention and significant between-group differences favoring MBSR+PAP on subscales of the MBI-HSS-MP as well as the DS-II and WCS.
Conclusions
Group psilocybin-assisted therapy plus MBSR was associated with clinically significant improvement in depressive symptoms without serious adverse events and with greater reduction in symptoms than MBSR alone. Study findings suggest that integrating psilocybin with mindfulness training may represent a promising treatment for depression and burnout among physicians and nurses.
Research Summary of 'Psilocybin-Assisted Group Psychotherapy + Mindfulness Based Stress Reduction (MBSR) for Frontline Healthcare Provider COVID-19 Related Depression and Burnout: A Randomized Clinical Trial'
Introduction
Depression and burnout among physicians and nurses are described as worsening crises within the US healthcare system that were amplified by the COVID-19 pandemic through elevated clinical demand, resource constraints and increased personal risk. Burnout is framed as a syndrome of emotional exhaustion, depersonalisation and reduced personal accomplishment that can impair clinician–patient relationships. Mindfulness training, particularly the established Mindfulness-Based Stress Reduction (MBSR) programme, is presented as an evidence-based behavioural intervention that can reduce symptoms of depression, anxiety and burnout in patients and healthcare providers. Separately, psychedelics such as psilocybin have shown efficacy for depressive symptoms, and there is growing interest in potential synergy between mindfulness training and psychedelic-assisted psychotherapy (PAP), based on overlapping neural mechanisms and the idea that psychedelic experiences may deepen mindfulness skills and produce more durable change when combined with formal training. Lewis and colleagues set out to evaluate whether adding group-format psilocybin-assisted psychotherapy to an 8-week MBSR curriculum is safe, feasible, and more effective than MBSR alone for frontline physicians and nurses with COVID-19–related depressive symptoms and burnout. The trial aimed to examine feasibility and safety outcomes, with the primary clinical endpoint defined as change in depressive symptoms at two weeks post-intervention using the QIDS-SR-16, and multiple secondary outcomes including burnout subscales, demoralization and measures of connectedness. The study also explored expectancy and experiential measures as potential moderators or correlates of outcomes.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Lewis, B. R., Hendrick, J., Byrne, K., Odette, M., Wu, C., & Garland, E. L. (2025). Psilocybin-Assisted Group Psychotherapy + Mindfulness Based Stress Reduction (MBSR) for Frontline Healthcare Provider COVID-19 Related Depression and Burnout: A Randomized Clinical Trial. https://doi.org/10.1101/2024.12.31.24319806
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