Patients report no signs of depression five years after psilocybin treatment

The benefits of psilocybin-assisted therapy for major depression reportedly endures for years, if not forever.

In a new analysis of people who took part in a 2020 psilocybin clinical trial, 67 percent were still in full remission from depression an average of five years later – up from 58 percent at the one-year mark.

Study lead author Alan Davis is an associate professor and director of the Center for Psychedelic Drug Research and Education at The Ohio State University.

“Across the board – anxiety, depression, global functioning, self-reported depression – we kept seeing the same signal of continued improvement,” said Davis.

The follow-up results offer a rare long view of outcomes after psychedelic-assisted therapy, an area where long-term data are still sparse.

Understanding psilocybin – the basics

Psilocybin is a natural compound found in certain mushrooms, often called “magic mushrooms.” When you ingest psilocybin, your body quickly converts it into psilocin, the active form that interacts with your brain.

Psilocin closely resembles serotonin, a key neurotransmitter, so it binds to serotonin receptors – especially the 5-HT2A receptor.

This binding alters the way nerve cells communicate, which leads to changes in perception, mood, and thought patterns.

From a scientific standpoint, psilocybin disrupts the brain’s usual patterns of activity and connectivity.

Brain imaging studies show that it quiets the “default mode network,” a system linked to self-reflection and the inner voice we all carry.

At the same time, it boosts communication between brain regions that don’t normally interact.

Curing depression with psilocybin

The peer-reviewed study, published in 2021, enrolled adults with major depressive disorder and compared two groups: one received psilocybin treatment immediately, and the other started after a wait-list period.

All the participants ultimately completed a standardized protocol: two dosing sessions with psilocybin paired with about 13 hours of psychotherapy (including preparation, support during sessions, and integration).

The initial results showed large reductions in depression severity, with half of participants in remission up to one year.

Tracking patients over time

Of the 24 people in the original trial, 18 took part in the five-year check-in. Online questionnaires were used to assess depression, anxiety, and functional impairment.

The researchers also applied a clinician-rated depression scale and conducted qualitative interviews to capture changes the numbers might miss.

The team made a conservative assumption to avoid overstating success. They counted the six who did not return as having fully relapsed to pre-treatment levels.

Even under that assumption, depression scores remained “very large and significantly” reduced at five years, Davis noted, and the share of participants in complete remission nudged upward.

More than psilocybin

The lasting gains cannot be chalked up solely to the two psilocybin sessions. Only three people reported no additional depression-related treatment in the years since.

Others used antidepressant medications, tried ketamine or other psychedelics, or engaged in psychotherapy.

Interviews helped explain that context. Many participants described life with depression as profoundly constricted before the trial – too little energy, too little hope to engage.

Afterward, several said their depression felt more situational and manageable. They reported a greater capacity for positive emotion and motivation, and a different relationship to low moods when they returned.

A few who experimented with psychedelics on their own found the experiences less helpful without a clinical framework. This underscores a theme from other work by Davis and colleagues: the therapeutic container matters.

A strong alliance with trained therapists, structured preparation, and integration support may play as big a role as the drug itself.

Psilocybin safety over time

At the five-year mark, 11 of 18 participants reported no adverse effects since the trial. Looking back, three remembered feeling unprepared for the heightened emotional sensitivity that followed their dosing sessions.

Two said tapering off medications and waiting during the original trial was especially difficult, and two wished they’d had more formal integration therapy afterward.

The study is small, non-randomized at follow-up, and based on a motivated sample – limitations the authors emphasize.

With just 18 people contributing long-term data, it’s impossible to generalize broadly or disentangle psilocybin’s contribution from other treatments and life changes.

Larger, placebo-controlled trials with systematic follow-up will be needed to test durability, dosing strategies, and who benefits most.

Psilocybin, depression, and healthcare

Even with the study’s limitations, the pattern is encouraging. Many participants maintained remission or continued to function better.

Several described a shift that outlasted symptom scores – more engagement with family, work, and meaningful activities, and fewer episodes of withdrawal and isolation, which are among depression’s most disabling features.

“Five years later, most people continued to view this treatment as safe, meaningful, and important – something that catalyzed an ongoing betterment of their life,” Davis said.

“Despite some symptoms coming back, they weren’t experiencing the same levels of impairment – suggesting this approach might, for some, kick-start lasting positive change.”

The bottom line: psilocybin-assisted therapy remains experimental, and it’s not a depression cure-all. But in this small cohort, the combination of guided psychedelic sessions and psychotherapy was associated with durable relief – and in many cases, a different relationship to depression – years down the road.

The study is published in the Journal of Psychedelic Studies.

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