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Hallucinogen in 'magic mushrooms' relieves depression in largest clinical trial to date
This is the largest-ever clinical trial of psilocybin as a depression treatment.
Psilocybin, the hallucinogen found in "magic mushrooms," helped to relieve symptoms in people with hard-to-treat depression in the largest clinical trial of its kind to date, the trial's organizers announced Tuesday (Nov. 9).
Earlier this year, a small study suggested that psilocybin might work as well as the common antidepressant escitalopram (Lexapro) at relieving moderate to severe depression, and other past research has hinted at the drug's promise, Live Science previously reported. But this new trial, conducted by the pharmaceutical company Compass Pathways, is the largest gold-standard trial of psilocybin to date, so its results could carry more weight than previous research, STAT reported.
That said, the trial's results have not yet been peer-reviewed or published in a journal, so further review of the data is warranted.
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The trial included 233 participants from 10 countries in North America and Europe. The participants were split into three groups, each of which received a different dose of psilocybin "in conjunction with psychological support," according to a statement from Compass Pathways. All of the participants had stopped taking antidepressants prior to the trial's start.
Seventy-nine patients received a one-time 25-milligram dose of the drug, 75 received a 10-milligram dose and 79 received a 1-milligram dose. The lowest dose effectively functioned as a placebo, meaning it served as a point of comparison for the higher-dose treatments, according to STAT. The trial was double-blinded, meaning neither the trial organizers or the participants knew which treatment dose was given to each patient.
The trial organizers used the Montgomery-Asberg Depression Rating Scale (MADRS), a common measure of clinical depression, to evaluate the participants' symptoms before treatment and then three weeks afterward. By the third week, the ratings of the people in the 25-milligram-dose group had fallen 6.6 more points, on average, than the ratings of the people in the low-dose group, the researchers found. But the ratings in the 10-milligram group were not significantly different from those in the low-dose group.
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Related: 11 odd facts about 'magic' mushrooms
Overall, 29.1% of the patients in the 25-milligram-dose group had entered remission by the third week, compared with only 7.6% of the placebo group. And three months after the treatment, 24.1% of the 25-milligram group still showed a "sustained response," meaning their MADRS scores had fallen by at least half and remained that low over time. By comparison, 10.1% of the placebo group showed a sustained response, according to the company statement.
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During the trial, 12 participants experienced a "serious adverse event," such as suicidal behavior, intentional self-injury or suicidal ideation. Five of these participants were in the 25-milligram group, six were in the 10-milligram group and one was in the 1-milligram group. These kinds of symptoms commonly occur in those with treatment-resistant depression, the company statement noted, and some of the incidents of suicidal behavior occurred in patients who were "essentially non-responding" to the treatment, said Guy Goodwin, Compass Pathways' chief medical officer, according to STAT.
Because the number of people who experienced serious adverse events was small, there's not a statistically significant difference in incidence of these adverse events among the three groups, STAT reported. But Compass Pathways plans to assess the data in more detail, to see if there's a possible link between psilocybin dosage and the chance of suicidal ideation.
Overall, the trial's results are "super promising," although "we're still missing a lot of the detailed data," Boris Heifets, a neuroscientist at Stanford University who studies psychedelics but was not part of the study, told STAT.
Given the strong results, Compass Pathways plans to move ahead with a late-stage clinical trial of psilocybin, likely using the 25-milligram dose, but that detail still needs to be discussed with regulators, Lars Christian Wilde, co-founder and president of Compass Pathways, told STAT. The recent trial was a so-called Phase 2B trial, which was intended to figure out the appropriate dose; the next trial, a Phase 3, will test that chosen dose in a larger group.
If you or someone you know needs help, contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255).
Read more about the recent trial in STAT.
Originally published on Live Science.
Nicoletta Lanese is the health channel editor at Live Science and was previously a news editor and staff writer at the site. She is a recipient of the 2026 AHCJ International Health Study Fellowship, with a project focused on antibiotic stewardship practices in Japan and the U.S. They hold a graduate certificate in science communication from UC Santa Cruz and degrees in neuroscience and dance from the University of Florida. Beyond Live Science, Lanese's work has appeared in The Scientist, Science News, the Mercury News, Mongabay and Stanford Medicine Magazine, among other outlets. Based in NYC, she also remains involved in dance and performs in local choreographers' work.