GNN graphic – credits, Psilocybe ovoideocystidiata CC 4.0. BY-SA Alan Rockefeller

Patients with clinical depression and treated with naturally-occurring psychedelic compounds are still free of symptoms five years later, according to new research.

It’s not a surprise considering the scientific literature on psychedelic therapy, with patients suffering from psychiatric distress ranking the therapy among the most profound and meaningful experiences they’ve ever had, alongside events such as religious conversions and the birth of children.

The study involved participants from a trial published in 2021 that found psilocybin—the primary psychedelic substance produced by mushrooms—was effective at treating major depressive disorder when combined with psychotherapy in adults.

Two-thirds of clinical trial participants treated with psilocybin-assisted therapy were in “complete remission” from their depression after five years, as well as a self-reported lasting improvement across a range of wellbeing measurements.

“We found that 67% were in remission at five years compared to 58% at one year,” said study lead author Professor Alan Davis, from Ohio State University, said:

“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.”

Davis co-led the 2021 study—when two participant groups, one receiving treatment right away and another on a wait-list treatment condition, received two doses of psilocybin combined with around 13 hours of psychotherapy.

“Five years later, most people continued to view this treatment as safe, meaningful, important, and something that catalyzed an ongoing betterment of their life. I think this is a sign that regardless of what the outcomes are, their lives were improved because they participated in something like this,” he said.

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.

When analyzing data at the five-year time point, the researchers assumed the very worst in order to avoid inflating their findings, and considered everyone who didn’t participate in the follow-up to have 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 Professor Davis. “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.”

Only three participants in the follow-up had reported receiving no depression-related treatment since the trial. Others reported taking antidepressant medications, trying psychedelics or ketamine treatment, or undergoing psychotherapy.

Before the psilocybin-assisted therapy, the patients lived with debilitating depression that interfered with their capacity to engage in life. But, after the trial, many described perceiving depression as “more situational and manageable.”

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

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.

The follow-up results, published in the Journal of Psychedelic Studies, showed that, at the five-year time point, 11 participants reported no adverse effects since the clinical trial, while 3 said they were unprepared for the heightened state of emotional sensitivity brought on by psilocybin.

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.

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

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