Psilocybin Shows Lasting Impact on Major Depression
Psilocybin — the psychoactive compound that gives “magic mushrooms” their punch — may ease major depressive disorder (MDD) for as long as five years after a single guided session, according to data unveiled June 18 at the Psychedelic Science 2025 conference in Denver.
Researchers revisited 21 volunteers who took part in a 2020 randomized study published in JAMA Psychiatry. Each participant had received one high-dose psilocybin experience paired with 11 hours of psychotherapy.
Original outcomes: One month post-treatment, 17 of 24 patients reported improvement; 14 met criteria for full remission.
Five-year check-in: 67 % of the re-contacted group still qualified as depression-free, and most reported lower anxiety plus smoother day-to-day functioning.
“Many told us their symptoms were either weaker or far less disruptive, even half a decade later,” said co-author Alan Davis, who leads Ohio State University’s Center for Psychedelic Drug Research and Education.
Doug Drysdale, CEO of Toronto-based biotech firm Cybin (not involved in the study), called the numbers “very encouraging,” noting that a therapy effective after just one or two doses “would be a major leap beyond antidepressants that demand daily use.”
Researchers point to several potential advantages:
Durability – Sustained symptom relief cuts down on years of medication adherence.
Speed – Classic antidepressants can take weeks to work; psilocybin benefits often surface within days.
Psychological Shift – Participants say the session changed perspectives, helping them pursue meaningful goals even if symptoms later returned.
Natural changes: Life events in the five-year gap weren’t controlled.
Small sample: Twenty-one people can’t stand in for millions with MDD.
Extra support: Psychotherapy and any interim medications may have shaped outcomes.
“Rigorous, larger trials are still essential,” Davis stressed.
Early papers suggest psilocybin may help mothers with post-partum depression feel “reconnected” to themselves and their infants. A phase-2 Cleveland Clinic trial is now testing a psilocybin-analog drug, RE104, in that population.
Ryan Moss, chief science officer at Filament Health, reminds clinicians that psychedelic sessions can trigger anxiety, paranoia, or cardiovascular spikes. Controlled settings with trained guides and medical oversight remain the gold standard.
NYU’s Dr. Rachel Yehuda and Dr. Charles Marmar echo that stance. “There’s real promise if we move slowly and carefully,” Fox News medical analyst Dr. Marc Siegel summarized after interviewing the pair. “Outside a regulated framework, the risks rise sharply.”
Early evidence hints that a single, professionally supervised psilocybin journey could deliver multi-year relief for some people with major depression. The scientific community is intrigued — and moving methodically — to confirm just how durable and scalable that hope might be.
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