Psilocybin-assisted group therapy may help reduce depression and burnout among healthcare workers

A new clinical trial suggests that a single dose of psilocybin, combined with mindfulness training, may offer short-term relief from depression and burnout for frontline healthcare workers. Published in PLOS Medicine, the study found that participants who received both psilocybin and mindfulness-based stress reduction reported greater and faster improvements in depressive symptoms than those who received mindfulness training alone. The effects on depression were most notable two weeks after the intervention but became less pronounced by six months. The study also found preliminary evidence that the combination may improve emotional exhaustion, demoralization, and feelings of connectedness.

Depression and burnout among doctors and nurses have become more common in recent years, especially during and after the COVID-19 pandemic. Medical professionals have faced long hours, high patient loads, and personal health risks. These pressures have strained emotional well-being and placed many at risk of depression, anxiety, and emotional exhaustion.

Burnout is typically described as a state of physical and emotional depletion, often involving feelings of detachment, lowered sense of accomplishment, and disconnection from others. Both burnout and depression are linked with poorer job performance and worse patient care.

Mindfulness-based stress reduction, a standardized program involving meditation and awareness practices, has shown some benefit in reducing emotional distress. Psilocybin, a psychedelic compound found in certain mushrooms, has also gained attention for its potential to reduce symptoms of depression.

“The COVID-19 pandemic amplified and exacerbated existing distress and burnout among healthcare workers. This is a significant problem with very limited existing interventions,” said study author Benjamin R. Lewis, an associate professor of psychiatry at the Huntsman Mental Health Institute at the University of Utah and the principal investigator of the University of Utah Psychedelic Science Initiative.

“I, as well as my co-author John Hendrick, not only saw this first hand but experienced this personally. This project felt like something we could do that would advance the field, work to address this issue, and also make a direct impact within our own healthcare community. We were also very interested in this overlap of mindfulness practice and psychedelic interventions, and investigating the ways these practices might mutually inform each other.”

The trial enrolled 25 participants, all of whom were either physicians or registered nurses with firsthand experience providing care to patients during the COVID-19 pandemic. To be eligible, individuals had to report at least one month of frontline clinical work during the pandemic and meet clinical thresholds for both depression and burnout. Specifically, participants had to meet diagnostic criteria for a depressive disorder, as measured by a score of 10 or higher on a standard screening tool (the Patient Health Questionnaire-9), and show elevated levels of emotional exhaustion and either depersonalization or low personal accomplishment on the Maslach Burnout Inventory, which is designed to assess burnout in medical professionals.

“I’ve been a clinician for my entire career, and I was very well acquainted with healthcare provider burnout,” Lewis said. “However I was nonetheless astonished by how severe the suffering was. Within days of putting up posters for our trial we had 700+ clinicians interested in participating. No doubt this is in part due to the effect of hanging posters with the word ‘psilocybin’ on it, but this clearly did not account for what we found when we began screening individuals for participation. This really impressed upon me how much suffering goes on right in our midst and how much of this is under the surface.”

Participants were randomly assigned to one of two groups. One group received an eight-week mindfulness-based stress reduction (MBSR) course by itself. The other group received the same mindfulness training but also participated in a structured group psilocybin intervention. This included a single psilocybin dosing session (25 milligrams), along with preparatory and integration meetings with therapists.

The main goal was to see whether adding psilocybin led to greater reductions in depression symptoms two weeks after the intervention. Depression was measured using a widely used questionnaire known as the Quick Inventory of Depressive Symptoms.

At the two-week mark, the group that received psilocybin in addition to mindfulness training showed a larger reduction in depression scores. On average, their depression scores dropped by 7.2 points, compared to a 2.8-point reduction in the mindfulness-only group. Nearly half of the participants in the psilocybin group showed remission of depression symptoms at two weeks, compared to just one in the mindfulness-only group. By six months, however, the difference between groups had narrowed, and both groups showed similar improvements.

“We compared MBSR alone to MBSR + group psilocybin and both groups demonstrated significant improvement,” Lewis told PsyPost. “By the 6 month endpoint the MBSR alone group had ‘caught up’ as it were, suggesting that the addition of psilocybin accelerated or catalyzed the benefits of mindfulness training,”

Secondary outcomes suggested potential benefits in other areas as well. At two weeks, the psilocybin group had larger reductions in depersonalization and demoralization, and reported stronger feelings of social and emotional connectedness. These effects, however, did not remain statistically significant after adjusting for multiple comparisons. Still, the trends tended to favor the group that received psilocybin.

Importantly, the study also tracked safety. No serious adverse events were reported. Some participants experienced temporary side effects such as nausea or anxiety during the psilocybin session, but none required medication or medical intervention. No participants showed signs of worsening mental health or suicidality during the study.

“This study involved very busy physicians and nurses who were nonetheless able to make the commitment to an 8 week mindfulness curriculum and, for those randomized to the psilocybin arm, additional group sessions for preparation and integration,” Lewis said. “This combination was feasible as well as safe as evidenced by our rates of adverse events and the absence of any serious adverse events.”

The study used a group format for the psilocybin sessions, which may have contributed to improvements in connectedness and reduced feelings of isolation. Participants were supported by therapists and peers, which the authors suggest might enhance the social benefits of the experience.

The researchers also examined whether the intensity of participants’ altered states of consciousness related to treatment outcomes. Many in the psilocybin group reported what was described as a “complete mystical experience,” involving feelings of unity, transcendence, and profound meaning.

Interestingly, these experiences were strongly linked to improvements in depression, emotional exhaustion, and connectedness, and the association appeared independent of whether psilocybin was administered, suggesting that self-transcendent states induced by either psychedelics or intensive mindfulness practice may play a role in recovery.

“I think a common misunderstanding of a process involving psilocybin is that it is some kind of magic pill, or fix — i.e. some kind of cure for depression, or suffering,” Lewis said. “In the process of working with participants with this intervention, you really see what comes up for them, how they work with this, and how you as a team can create the conditions that might support that kind of work. I think it is also a misconception to over-emphasize the ‘special’ or ‘mystical’ aspects of a psychedelic experience. In this sense grounding this within a mindfulness training program may help to better integrate these experiences within day to day ordinary life.”

While the study points to promising early findings, it had several limitations that affect how the results should be interpreted. First, the sample size was small, and most participants were white women. This limits how broadly the results can be applied. A larger and more diverse sample would be needed to confirm the findings.

Second, the study was not blinded, meaning participants knew which treatment they were receiving. This can influence expectations and possibly affect outcomes. However, the researchers found that expectations were more strongly linked to outcomes in the mindfulness-only group, suggesting the improvements seen in the psilocybin group may not have been driven by expectancy alone.

There was also no placebo condition, which limits the ability to isolate the effects of psilocybin itself. The psilocybin group received an emotionally intense experience, while the mindfulness-only group participated in a day-long silent retreat. Though both are immersive, they differ in emotional intensity and novelty.

Finally, the improvement in depression was most notable at the two-week follow-up and became less pronounced over time. By six months, the mindfulness-only group had largely “caught up” in terms of depression scores. This suggests that psilocybin may act more as a catalyst that accelerates benefits rather than producing sustained effects on its own.

The study offers preliminary evidence that adding a single dose of psilocybin to a mindfulness program can lead to more rapid reductions in depression among healthcare workers facing burnout. The findings point to the potential value of combining psychedelic therapy with established mental health interventions in a group setting.

Still, the results should be viewed as a starting point. The authors emphasize the need for larger trials that can test the effects across more diverse populations and over longer periods of time. They also recommend study designs that can better separate the effects of psilocybin from other components of the intervention.

“I’d love to run a factorial design study along these lines where you can include a group with mindfulness training alone, psilocybin alone, mindfulness + psilocybin, and mindfulness + placebo condition,” Lewis said. “This would require a larger study but would be a necessary next step to really understanding the relative contributions of these different elements.”

“This was a deeply meaningful process for me and has been the highlight of my professional career,” he added.

The study, “Psilocybin-assisted group psychotherapy and mindfulness-based stress reduction for frontline healthcare provider COVID-19-related depression and burnout: A randomized controlled trial,” was authored by Benjamin R. Lewis, John Hendrick, Kevin Byrne, Madeleine Odette, Chaorong Wu, and Eric L. Garland.