As we near the five-year mark since the start of the COVID-19 pandemic, the healthcare community is still wrestling with the psychological fallout of being on the frontlines of a global crisis. The relentless stress, grief, and exhaustion left many healthcare workers grappling with depression and burnout—scars that haven’t fully healed, even now. Long hours, scarce resources, and the emotional weight of treating critically ill patients left a mark that, let’s be honest, not even Gal Gadot’s all-star rendition of “Imagine” could fix. Now, five years later, researchers at Fred Hutch are exploring a far more unconventional (and, let’s face it, better) solution to help clinicians still struggling with post-COVID depression.
Psilocybin, a psychedelic compound found in ‘magic mushrooms’, has shown promise in treating depression, particularly in cases resistant to conventional therapies. Research has also explored its potential to alleviate psychological distress in cancer patients, helping to reduce anxiety, improve mood, and enhance their overall quality of life during treatment. Recently, Dr. Anthony Back at the University of Washington and Dr. Ted Gooley, a biostatistician in the Clinical Research Division published a clinical trial in JAMA Network Open investigating psilocybin as a treatment for persistent post-pandemic depression in clinicians without a pre-pandemic history of the condition.
The study brought together 30 brave clinicians willing to try something new. Participants were randomly split into two groups: one received a single 100 mg dose of niacin (vitamin B-3, the kind of thing you might find in a multivitamin), while the other group got 25 mg of psilocybin (aka, the “fun guy” in the room). To keep things fair, neither the participants nor the facilitators knew which treatment they were getting. The big question: would either group feel less depressed 28 days after their mystery dose?
All the clinicians took part in two preparation sessions, a medication session, and three follow-up integration sessions. During the initial preparatory meetings, a facilitator helped them reflect on their professional journey, process the lingering emotional baggage of the pandemic, and set intentions for their medication session. One participant summed it up bluntly during their session, saying the experience of being a doctor during the pandemic left them feeling “more disposable than a COVID-19 swab.”
For the medication session, participating clinicians donned an eye mask, kicked back in a study room with a curated playlist, and brought along a personal item symbolizing their commitment to healing. While the trial was technically blinded, it didn’t take a rocket scientist (or a psychedelic researcher) to figure out by the end of the session who had received niacin and who had taken psilocybin—a phenomenon commonly referred to as “functional unblinding” in the field.
The final stage involved three integration sessions, where clinicians unpacked their medication experience with a facilitator and shared any new insights or reflections that had emerged since. These sessions encouraged the use of the psychological flexibility model—the idea that learning to bend rather than break in the face of challenges can lead to better mental health, greater contentment, and maybe even a little more happiness along the way.
Throughout the study, depression was evaluated according to a scoring system called the Montgomery-Asberg Depression Rating Scale (MADRS), which ranges from 0-60 with higher scores indicating more severe symptoms. It consists of 10 clinician-rated items, including mood-related aspects such as sadness, tension, sleep disturbances, appetite changes, inability to feel, pessimistic thoughts, and suicidal ideation. And here’s the exciting part: clinicians in the psilocybin arm saw an impressive average drop of 21 points on their MADRS scores 28 days after the first preparation session, signaling a major improvement in symptoms. Meanwhile, the control group, who only received therapy and niacin, experienced a more modest 9-point drop. This suggests that while the support from preparation and integration sessions helped, it might have been the psilocybin that truly sparked the change. These results make a compelling case for psilocybin’s potential as a game-changer in treating post-pandemic depression in healthcare workers.
In addition to the MADRS score for depression, the study also used a tool called the Stanford Professional Fulfillment Index (SPFI) which assesses burnout in healthcare professionals by measuring factors such as emotional exhaustion, depersonalization, work-life imbalance, job satisfaction, cognitive dissonance, and perceived lack of support. While the study did report a greater decrease in SPFI with psilocybin (a 6-point drop compared to a 2-point drop), it did not quite meet the threshold for statistical significance (p = 0.052). The investigators note that the study was powered for the depression outcome and likely lacked power for the burnout outcome. When asked about the implications for their findings, Dr. Back stated that “psilocybin therapy showed impressive efficacy for depressive symptoms — for this condition, it is the most effective intervention ever tested in a rigorous clinical trial.”
All things considered, this study suggests that psilocybin could be a promising treatment for post-pandemic depression in frontline healthcare workers. So, while we can’t promise that psilocybin will turn all your bad days into good vibes, this study certainly suggests it’s a spore-tacular option to consider in the quest for better mental health—especially when the weight of the world feels a bit too heavy to carry alone.
This research was supported by the Steven and Alexandra Cohen Foundation, the Riverstyx Foundation, the Rita and Alex Hillman Foundation.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium member Dr. Ted Gooley contributed to this work.
Back AL, Freeman-Young TK, Morgan L, Sethi T, Baker KK, Myers S, McGregor BA, Harvey K, Tai M, Kollefrath A, Thomas BJ, Sorta D, Kaelen M, Kelmendi B, Gooley TA. Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic: A Randomized Clinical Trial. JAMA Network Open. 8(1):e2459278. DOI: 10.1001/jamanetworkopen.2024.49026.