A newly published report in the Journal of the American Medical Association (JAMA) finds that psilocybin-assisted therapy in a group of frontline clinicians during the COVID-19 pandemic “resulted in a significant, sustained reduction of symptoms of depression.”
“In this randomized clinical trial, we aimed to investigate whether psilocybin therapy could improve symptoms of depression, burnout, and PTSD in clinicians who developed these symptoms from frontline clinical work during the pandemic,” authors wrote in the new report, adding that their findings “establish psilocybin therapy as a new paradigm of treatment for this postpandemic condition.”
The study, published on Thursday in the journal JAMA Network Open, consisted of 30 clinicians who were divided into two groups of 15. One group received a 25 milligram dose of psilocybin, while the other took a 100-mg dose of niacin. Regardless of group, participants completed multiple visits with facilitators: two preparation visits, one medication session—at which they took either the psilocybin or niacin—and three integration visits.
Researchers evaluated the clinicians on measures of both depression and occupational burnout. They observed decreases among the psilocybin group in both categories, though they said only the decreases in depressive symptoms were statistically significant.
Measures of depressive symptoms fell over the course of a month in the psilocybin group, dropping 21.33 points on the Montgomery–Asberg Depression Rating Scale (MADRS). The niacin group, by contrast, saw a reduction of 12 points.
“The results for the primary outcome showed a statistically significant improvement in symptoms of depression (as measured by the MADRS) for participants in the psilocybin arm, which was sustained for most of the participants for 6 months,” the report says. “This 21-point decrease in MADRS score is striking when a 6- to 9-point change in the MADRS score is considered clinically meaningful.”
“Psilocybin therapy was associated with a significant and sustained reduction in symptoms of depression experienced by physicians, [advanced practice practitioners], and nurses after their frontline work during the COVID-19 pandemic.”
As for burnout, results “showed a numerically larger decrease (indicating improvement) in burnout symptoms in the psilocybin arm compared with the niacin arm.”
“The change in symptoms of burnout did not reach statistical significance, but this small trial may have been inadequately powered for this outcome,” they added. “Furthermore, while the significance of the change in PTSD symptoms was not analyzed due to the hierarchical analytic plan, the 16 point decrease in PCL-5 scores [which measure PTSD symptoms] for the psilocybin arm was well above the 10-point decrease considered clinically meaningful.”
Anthony Back, the lead investigator of the study, said in a press release that “for doctors and nurses who feel burned out or disillusioned or disconnected from the patient care they want to provide, this study shows that psilocybin therapy is safe and can help these clinicians work through those feelings and get better.”
“I think psilocybin gave them the opportunity to really see their own feelings and see their own situation in a way that they could have more compassion for themselves and more understanding about what had really happened,” he said. “It was effective because it gave them a new perspective on what they were facing, in a way that they could take action.”
Among the limitations of the new study, researchers acknowledge, are its relatively small size and possibility for “unknown biases” in the recruitment process. Notably, they said that 2,247 clinicians indicated interest in participating, though only 30 could be enrolled.
Also, while the study was blinded, 100 percent of participants were able to distinguish after 2 hours whether they’d received psilocybin or niacin.
“Functional unblinding is an issue for all studies involving psychedelic therapies;” the report says, “in this study, it was mitigated with a primary outcome assessed by blinded raters who had no contact with the therapist team. This, however, may not address other effects that unblinding could have.”
Another potentially noteworthy finding is the proportion of participants who reported changes to their employment in the healthcare field following the use of psilocybin, though those results are statistically noisier because participants who initially received niacin were given the option to later receive open-label psilocybin.
“Employment changes over the course of the trial follow-up were notable,” authors wrote. “Because most participants assigned to the niacin group [12 of 15 clinicians] went on to receive open-label psilocybin, these results are reported for the entire group. During their follow-up, 21 participants (70%) reported a change in their work role or full-time equivalent status that substantially changed their responsibility or institution; 8 (27%) remained in the same position; and 1 (3%) remained unemployed. No one left the health care field.”
The new study was authored by a 15-person research team led by Anthony Back, a physician and researcher at the University of Washington. Other members of the team are affiliated with the Fred Hutchinson Cancer Research Center, the Yale School of Medicine and other research and treatment organizations in Seattle, British Columbia, San Francisco and London.
Back previously testified to a Washington state Senate panel in February 2023, when lawmakers were considering psychedelics research and access legislation. He said at the time that while not all the concerns around psilocybin have been exhaustively studied, denying legal access to the substance carries its own set of health and safety risks.
“My trial is only about 75 percent done so I can’t give you final results,” Back told the committee at the time. “But what I can share is that what I have seen so far are some remarkable responses for clinicians who were suffering in a way that completely blocked their ability to do the work they love.”
One lawmaker asked Back whether he felt the state was ready to legalize psilocybin services or whether “we should wait until we have some results from your clinical trial and any other clinical trials that might be underway.”
“Obviously it would be lovely if we could wait until incredibly definitive results were in from everything,” Back replied. But waiting years to offer safe access to psilocybin, he added, “is not doing justice to the mental health crisis that I am seeing now.”
While the authors described the new study as “the first to demonstrate the utility of psilocybin therapy in the treatment of physicians, APPs [advanced practice practitioners], and nurses who developed moderate to severe symptoms of depression in the course of frontline work during the COVID-19 pandemic,” it’s not the first to look at psilocybin and depression more generally, nor is it the first to examine psychedelics and occupational burnout.
Results of a separate clinical trial published by JAMA last December “suggest efficacy and safety” of psilocybin-assisted psychotherapy for treatment of bipolar II disorder, a mental health condition often associated with debilitating and difficult-to-treat depressive episodes.
JAMA also published research last year finding that people with major depression experienced “clinically significant sustained reduction” in their symptoms after just one dose of psilocybin.
Earlier this year, the federal government itself published a web page acknowledging the potential benefits the psychedelic substance might provide—including for treatment of alcohol use disorder, anxiety and depression. The page also highlights psilocybin research being funded by the federal government into the drug’s effects on pain, migraines, psychiatric disorders and various other conditions.
Posted on the website of the National Center for Complementary and Integrative Health (NCCIH), which is part of the National Institutes of Health, the page includes basic information about what psilocybin is, where it comes from, the legal status of the drug and preliminary findings around safety and efficacy. The NCCIH page highlights three possible areas of application: alcohol use disorder, anxiety and existential distress and depression.
As for burnout among high-stress workers, another recent study of emergency first responders suggests that a single self-administered dose of psilocybin can help “to address psychological and stress related symptoms stemming from a challenging work environment, known to contribute to occupational burnout.”
Yet another promising application for psychedelics could be pain management. NCCIH notes on its psilocybin page that the agency is currently funding research to study the safety and efficacy of psychedelic-assisted therapy for chronic pain, while other federally funded research is looking into “the effect of psilocybin on people with chronic low-back pain and depression in regard to their emotions and perceptions of pain.”
Findings of another study suggest that the use of full-spectrum psychedelic mushroom extract has a more powerful effect than chemically synthesized psilocybin alone, which could have implications for psychedelic-assisted therapy. The findings imply that the experience of entheogenic mushrooms may involve a so-called “entourage effect” similar to what’s observed with cannabis and its many components.
More than a year ago, the Biden administration said it was “actively exploring” the possibility of creating a federal task force to investigate the therapeutic potential of psilocybin, MDMA and others ahead of the anticipated approval of the substances for prescription use. Bipartisan congressional lawmakers, state legislators and military veterans had previously sent letters to the head of the U.S. Department of Health and Human Services (HHS) urging regulators to consider establishing an “interagency taskforce on the proper use and deployment of psychedelic medicine and therapy.”
Lawmakers at the time noted that even National Institute on Drug Abuse (NIDA) Director Nora Volkow had said that the “train has left the station” on psychedelics and had written that “people are going to use them regardless of whether regulators act.”
Ahead of the incoming Trump administration, some believe Robert F. Kennedy Jr. the pick to lead the U.S. Department of Health and Human Services (HHS) could advance reforms around both psychedelics and marijuana. If his appointment goes through, Kennedy will be in a unique position of influence to follow up on those goals, commanding control of the nation’s health apparatus that oversees the Food and Drug Administration (FDA) and other critical agencies.
On the other hand, author Michael Pollan, who wrote a book on psychedelics, recently said RFK could be “very dangerous” to the psychedelics movement despite being a supporter of reform.
“The fact that someone this high up in this administration is supportive of psychedelic-assisted therapy is encouraging in one way,” Pollan said. “But in another, I think it could be very dangerous to the movement, because if the science of psychedelics gets tangled up with the anti-science agenda around vaccines or fluoride, that could do long-term damage to psychedelics.”
Photo courtesy of Wikimedia/Mushroom Observer.