Depression remission endures 5 years after psilocybin trial

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Depression remission endures 5 years after psilocybin trial

Study suggests psychedelic-assisted therapy has long-term benefits

Two-thirds of clinical trial participants treated with psilocybin-assisted therapy for major depressive disorder were in complete remission from their depression five years later, a new study has found.

The study involved participants from a clinical trial published in 2021 that found psilocybin (the primary psychedelic substance in magic mushrooms) combined with psychotherapy in adults was effective at treating major depressive disorder.

An average of five years after the clinical trial, a majority of participants reported lasting depression remission as well as improvement in a range of well-being measures.

"We found that 67% were in remission at five years compared to 58% at one year. We also saw that across the board, anxiety, depression, global functioning, self-reported depression, all of these measures were showing the same signal of continued improvement up to five years later," said lead author Alan Davis, associate professor and director of the Center for Psychedelic Drug Research and Education (CPDRE) in The Ohio State University College of Social Work.

"Five years later, most people continued to view this treatment as safe, meaningful, important, and something that catalyzed an ongoing betterment of their life," said Davis, who co-led the 2021 trial at Johns Hopkins University. "It's important for us to understand the details of what comes after treatment. I think this is a sign that regardless of what the outcomes are, their lives were improved because they participated in something like this."

The follow-up results were published Sept. 4 in the Journal of Psychedelic Studies.

In the original trial, two participant groups - one receiving treatment right away and another on a wait-list treatment condition - received two doses of psilocybin combined with about 13 hours of psychotherapy. Overall, the participants experienced a significant and large reduction in depression symptoms, with half reporting remission from depression up to one year after the trial.

Of the 24 participants, 18 enrolled in the five-year follow-up, which consisted of a range of online questionnaires assessing depression, anxiety and functional impairment; a clinician-administered depression rating; and interviews to capture nuances of outcomes beyond the quantitative measures.

In analyzing data at the five-year time point, researchers conservatively estimated that those who didn't participate in the follow-up had experienced complete relapse and had returned to their pre-treatment levels of functioning.

"Even controlling for those baseline estimates from the people who didn't participate in the long-term follow-up, we still see a very large and significant reduction in depression symptoms," said Davis, who also holds faculty positions in internal medicine and psychology at Ohio State. "That was really exciting for us because this showed that the number of participants still in complete remission from their depression had gone up slightly."

The depression remission cannot be attributed solely to the 2021 trial treatment, the findings suggest. Only three participants in the follow-up had reported no depression-related treatment since the trial. Others reported taking antidepressant medications, trying psychedelics or ketamine treatment, or undergoing psychotherapy.

The follow-up interviews revealed context around those decisions to seek therapy, Davis said. Before the psilocybin-assisted therapy, these patients lived with debilitating depression that interfered with their capacity to engage in life. After the trial, many described perceiving depression as more situational and manageable.

"They believed that overall, they had greater capacity for positive emotions and enthusiasm, regardless of whether their depression came back or not. A lot of folks reported that these shifts led to important changes in how they related to their experiences of depression," Davis said.

A few of the people who had tried psychedelics on their own in the intervening years reported that the experiences were not as helpful because of the lack of a clinical support framework. This notion supports findings from another study Davis and colleagues conducted with the clinical trial group - that when it comes to reducing depression with psychedelic-assisted therapy, what matters even more than the drug is a strong relationship between the therapist and study participant.

At the five-year time point, 11 participants reported no adverse effects since the clinical trial. In looking back, three recalled they felt unprepared for the heightened emotional sensitivity that came with the psychedelic treatment, two said pre-trial weaning off medications and being on the waitlist was very difficult, and two believed integration therapy would have been helpful after the initial study.

Acknowledging the study sample is small, Davis said there is still a lot to learn - but that this first look at the durability of the effects of psilocybin-assisted therapy offers a glimpse at the potential lasting positive effects of the treatment.

"We believe that these data suggest that there is long-term efficacy with people who undergo these treatments," they said. "Some of the most debilitating aspects of depression are people isolating and withdrawing from things that are important to them. Despite some of those symptoms coming back, they found they weren't experiencing those same levels of impairment - that really speaks to the potential for some people that this treatment might catalyze future positive effects when they're going through depression."

This study was supported by the CPDRE at Ohio State, and the Center for Psychedelic and Consciousness Research at Johns Hopkins University, where Davis was an adjunct assistant professor at the time of the study.

Co-authors included Meghan DellaCrosse, Nathan Sepeda, Adam Levin, Hillary Shaub, Peter Gooch, Shoval Gilead, Skylar Gaughan and Stacey Armstrong of Ohio State, and Mary Cosimano, Taylor Washington and Frederick Barrett of Johns Hopkins.

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