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Randomized Controlled Trial
. 2024 Dec 2;7(12):e2449026.
doi: 10.1001/jamanetworkopen.2024.49026.

Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic: A Randomized Clinical Trial

Anthony L Back  1 , Timara K Freeman-Young  1 , Ladybird Morgan  2 , Tanmeet Sethi  1 , Kelsey K Baker  3 , Susanna Myers  3 , Bonnie A McGregor  4 , Kalin Harvey  5 , Marlene Tai  1 , Austin Kollefrath  1 , Brandon J Thomas  1 , Dennis Sorta  6 , Mendel Kaelen  7 , Benjamin Kelmendi  8 , Ted A Gooley  3
Affiliations
Randomized Controlled Trial

Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic: A Randomized Clinical Trial

Anthony L Back et al. JAMA Netw Open. .

Erratum in

  • Error in the Byline.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Jan 2;8(1):e2459278. doi: 10.1001/jamanetworkopen.2024.59278. JAMA Netw Open. 2025. PMID: 39804652 Free PMC article. No abstract available.
  • Errors in the Author Affiliations.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Jul 1;8(7):e2525303. doi: 10.1001/jamanetworkopen.2025.25303. JAMA Netw Open. 2025. PMID: 40638123 Free PMC article. No abstract available.

Abstract

Importance: The psychological morbidity experienced by physicians, advanced practice practitioners (APPs), and nurses from working during the COVID-19 pandemic includes burnout, depression, and posttraumatic stress disorder (PTSD).

Objective: To investigate whether psilocybin therapy could improve symptoms of depression, burnout, and PTSD in US clinicians who developed these symptoms from frontline clinical work during the pandemic.

Design, setting, and participants: This double-blind randomized clinical trial enrolled participants from February to December 2022. Participants included physicians, APPs, and nurses who provided frontline care for more than 1 month during the pandemic and had no prepandemic mental health diagnoses but had moderate or severe symptoms of depression at enrollment. Participants were randomly assigned to either the psilocybin or niacin arm. Data analysis was conducted between December 2023 and May 2024 and was based on the intention-to-treat principle.

Intervention: One intervention episode consisted of 2 preparation visits, 1 medication session, and 3 integration visits. At the medication session, participants received psilocybin, 25 mg, or niacin, 100 mg, orally.

Main outcome and measures: The primary outcome was a change from baseline (preparation 1 session) to day 28 (after medication administration) in symptoms of depression as measured by the clinician-administered Montgomery-Asberg Depression Rating Scale (MADRS) used by blinded raters. The secondary outcomes were a change in symptoms of burnout (measured with the Stanford Professional Fulfillment Index [SPFI]) and symptoms of PTSD (measured with the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]).

Results: A total of 30 clinicians (15 females [50%]; mean [range] age, 38 [29-60] years) participated, of whom 15 were randomly assigned to receive psilocybin and 15 to receive niacin. The mean change in symptoms of depression (MADRS scores) from preparation 1 session to day 28 was -21.33 (7.84) in the psilocybin arm compared with -9.33 (7.32) in the niacin arm, with a mean difference between arms of -12.00 (95% CI, -17.67 to -6.33; P < .001), a decrease in MADRS scores indicating improvement. The mean change in SPFI scores from preparation 1 session to day 28 showed a numerically larger improvement in symptoms of burnout in the psilocybin compared with the niacin arm (-6.40 [5.00] vs -2.33 [5.97]; P = .05) but was not statistically significant. Since the SPFI score change did not reach statistical significance, the PCL-5 score change was evaluated descriptively. The mean change in PCL-5 scores showed a numerically larger decrease in symptoms of PTSD from preparation 1 session to day 28 in the psilocybin vs the niacin arm (-16.67 [15.04] vs -6.73 [10.69]), but this difference was not statistically tested.

Conclusions and relevance: This randomized clinical trial found that psilocybin therapy resulted in a significant, sustained reduction in symptoms of depression experienced by clinicians after frontline work during the COVID-19 pandemic. The findings establish psilocybin therapy as a new paradigm of treatment for this postpandemic condition.

Trial registration: ClinicalTrials.gov Identifier: NCT05163496.

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Conflict of interest statement

Conflict of Interest Disclosures: Mr Harvey reported receiving other support from the University of Washington, which contracted Quantified Citizen Technologies Inc to provide implementation of the study protocol, data collection, and related services during the conduct of the study; receiving personal fees as chief technology officer and co-founder from Quantified Citizen Technologies Inc during the conduct of the study; being a minority investor in MycoMedica Life Sciences; being the co-founder and director of the Psychedelic Data Society; and being the co-founder and director of the Ketamine Assisted Therapy Association of Canada outside the submitted work. Mr Kaelen reported being the founder of and a shareholder in Wavepaths. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Diagram of Participant Flow Through the Trial
Figure 2.
Figure 2.. Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores for Individual Participants in Both Treatment Arms
MADRS scores ranged from 0 to 10, with the higher scores indicating worse symptoms. Boxes represent the interquartile range (between the 25th and 75th percentile, the horizontal line inside boxes represents the median, and the circle inside boxes represents the mean.
Figure 3.
Figure 3.. Longitudinal Symptoms of Depression From Baseline to 6 Months
Montgomery-Asberg Depression Rating Scale (MADRS) scores ranged from 0 to 60, with the higher scores indicating worse symptoms.
See this image and copyright information in PMC

References

    1. Ouyang H. I’m an E.R. doctor in New York. None of us will ever be the same. The New York Times. April 14, 2020. Accessed October 24, 2024. https://www.nytimes.com/2020/04/14/magazine/coronavirus-er-doctor-diary-...
    1. Ulfa M, Azuma M, Steiner A. Burnout status of healthcare workers in the world during the peak period of the COVID-19 pandemic. Front Psychol. 2022;13:952783. doi: 10.3389/fpsyg.2022.952783 - DOI - PMC - PubMed
    1. Lee BEC, Ling M, Boyd L, Olsson C, Sheen J. The prevalence of probable mental health disorders among hospital healthcare workers during COVID-19: a systematic review and meta-analysis. J Affect Disord. 2023;330:329-345. doi: 10.1016/j.jad.2023.03.012 - DOI - PMC - PubMed
    1. Leo CG, Sabina S, Tumolo MR, et al. Burnout among healthcare workers in the COVID 19 era: a review of the existing literature. Front Public Health. 2021;9:750529. doi: 10.3389/fpubh.2021.750529 - DOI - PMC - PubMed
    1. Shanafelt T, Ripp J, Trockel M. Understanding and addressing sources of anxiety among health care professionals during the COVID-19 pandemic. JAMA. 2020;323(21):2133-2134. doi: 10.1001/jama.2020.5893 - DOI - PubMed

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