This preprint, randomized controlled trial (n=25) evaluates the safety and efficacy of psilocybin-assisted psychotherapy (PAP/PAT) combined with mindfulness-based stress reduction (MBSR) for frontline healthcare providers with depression and burnout during the COVID-19 pandemic. Results show greater improvements in depression (QIDS-SR-16), burnout (MBI-HSS-MP), demoralization (DS-II), and connectedness (WCS) in the MBSR+PAP group compared to MBSR alone, with no serious adverse events reported.

Abstract of Psilocybin-Assisted Group Psychotherapy + MBSR for Frontline Healthcare Providers

“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.”

Authors: Benjamin R. Lewis, John Hendrick, Kevin Byrne, Madeleine Odette, Chaorong Wu & Eric L. Garland

Summary of Psilocybin-Assisted Group Psychotherapy + MBSR for Frontline Healthcare Providers

The study by Lewis and colleagues addresses the increasing prevalence of depression and burnout among frontline healthcare providers, particularly during the COVID-19 pandemic. These mental health issues, characterised by emotional exhaustion, depersonalisation, and reduced personal accomplishment, have been exacerbated by heightened clinical demand, limited resources, and increased personal risk. Burnout also undermines clinician-patient relationships by reducing empathy and compassion.

Mindfulness-Based Stress Reduction (MBSR), a structured mindfulness training programme, has shown effectiveness in alleviating depression and burnout in various populations, including healthcare providers. Psilocybin, a psychedelic compound, has similarly demonstrated significant antidepressant effects in previous studies. Emerging evidence suggests a potential synergy between mindfulness training and psilocybin-assisted therapy (PAP). The combination might activate overlapping brain circuits, potentially enhancing the durability of therapeutic outcomes. However, existing studies often rely on individual therapy formats, limiting scalability and neglecting potential benefits of group interventions.

This trial is the first to evaluate the combined efficacy of MBSR and group-format psilocybin-assisted psychotherapy in addressing depression and burnout among frontline healthcare providers.

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Find this paper

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

Open Access | Google Scholar | Backup | 🕊

Cite this paper (APA)

Lewis, B., Hendrick, J., Byrne, K., Odette, M., Wu, C., & Garland, E. (2025). Psilocybin-Assisted Group Psychotherapy+ Mindfulness Based Stress Reduction (MBSR) for Frontline Healthcare Provider COVID-19 Related Depression and Burnout: A Randomized Clinical Trial. medRxiv, 2024-12.

Study details

Compounds studied
Psilocybin

Topics studied
Depression

Study characteristics
Original Open-Label Randomized

Participants
25 Humans

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 25 mg | 1x

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