Psilocybin Therapy Reduces Depression in Frontline Clinicians Affected by the COVID-19 Pandemic

A new randomized clinical trial found that psilocybin therapy significantly reduces symptoms of depression in clinicians who developed psychological distress after frontline work during the COVID-19 pandemic. The study, published in JAMA Psychiatry, suggests that the psychedelic compound may offer a novel treatment for healthcare workers experiencing postpandemic depression, burnout, and posttraumatic stress disorder (PTSD).

The double-blind trial enrolled 30 clinicians, including physicians, advanced practice practitioners, and nurses, all of whom had provided at least 1 month of direct frontline care during the pandemic. None had preexisting mental health conditions, but all presented with moderate or severe depression at the time of enrollment.

Participants were randomly assigned to receive either a single 25 mg dose of psilocybin or an active placebo of 100 mg niacin. The intervention included two preparatory therapy sessions, a supervised medication session, and three follow-up integration visits. The primary outcome was a change in depression severity, measured using the Montgomery-Asberg Depression Rating Scale (MADRS), while secondary outcomes assessed burnout and PTSD symptoms.

By day 28, clinicians in the psilocybin group showed a significant reduction in MADRS scores, with an average decrease of 21.33 points compared with 9.33 points in the niacin group. The difference between groups was statistically significant (mean difference of -12.00, P < .001), indicating a strong antidepressant effect. While the psilocybin group also exhibited greater improvements in burnout and PTSD symptoms, these secondary outcomes did not reach statistical significance.

The observed antidepressant effect was greater than that typically seen with conventional medications, and benefits were sustained for 6 months following treatment. However, researchers caution that the study’s small sample size limits generalizability, and functional unblinding—where participants correctly identified their treatment group—may have influenced results. Additionally, psilocybin was administered within a structured therapeutic setting, raising questions about whether the benefits were due to the medication itself or the surrounding psychological support.

“The results establish psilocybin therapy as a new paradigm of treatment for this postpandemic condition and add to the evidence of psilocybin therapy for depression,” the study authors concluded. “Further research is warranted to assess the role of psilocybin therapy in meeting the well-being challenges faced by clinicians in the workplace.”

Reference:
Back AL, Freeman-Young TK, Morgan L, et al. Psilocybin therapy for clinicians with symptoms of depression from frontline care during the COVID-19 pandemic: a randomized clinical trial. JAMA Netw Open. 2024;7(12):e2449026. Published 2024 Dec 2. doi:10.1001/jamanetworkopen.2024.49026