A single dose of magic mushrooms’ psilocybin treats severe depression

The highest dosage of the drug had the greatest impact on people’s depression.
Deena Theresa
Psilocybin mushrooms.
Psilocybin mushrooms.


A new clinical study known to be the "largest of its kind" has found that a drug based on psilocybin, the active hallucinogen found in psychedelic, or magic mushrooms, effectively improved depression in people when administered in a single dose.

The trial was led by COMPASS Pathways across 22 international sites, including the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London and South London and Maudsley NHS Foundation Trust.

According to the study, the randomized, double-blind trial comprised 233 patients who took the doses in various degrees: a 0.00088 ounce (25-milligram), 0.00035 ounces (10mg), and 3.5274e-5 ounce (1mg) dose of synthetic psilocybin, COMP360, administered along with psychological support. Researchers found that participants who took the highest dosage reported a greater reduction in levels of depression three weeks after taking the dose compared to those who took the lowest 1mg dose.

However, the groups reported side effects such as headaches, nausea, and thoughts around suicide, and support must always be on hand.

The trial gives hope to around 100 million people suffering from "treatment-resistant" depression

The study reports that approximately 100 million people in the world suffer from 'treatment-resistant' depression, meaning they are immune to at least two antidepressant treatments for their major depressive disorder.

"This can lead to a variety of other problems that seriously impact patients and the people around them. Treatment options are often limited and come with troublesome side effects or stigma. Therefore, new paradigms of treatment are needed, and clinical research of new treatments is important," Dr. James Rucker, co-lead Psychoactive Trials Group at King's IoPPN and consultant psychiatrist at South London and Maudsley NHS Foundation Trust, said in a statement published by the institution.

"Psilocybin therapy may be a new paradigm of treatment, but this needs to be tested in clinical trials."

Three weeks after having the drug, along with a couple of therapy sessions, one-third of the group went into rapid remission, i.e., 29 percent of the group who were administered the 25mg dose of psilocybin. One in three was found to be no longer depressed at the end of the trial, and one in five felt a significant improvement at 12 weeks.

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"We saw positive results in a particularly difficult-to-treat a group of patients, and the highest dose of COMP360 psilocybin had the greatest impact on people's depression. This suggests that COMP360 psilocybin has a true pharmacological effect, a finding that is critical for it to be recognized as a new treatment option in the future," said Dr. Guy Goodwin, chief medical officer, COMPASS Pathways.

Psilocybin has been the focus of research for some time

The group suffered adverse effects during the 12-week study. Eighty-four percent of participants in the 25mg group, 75 percent in the 10mg group, and 72 percent in the 1mg group experienced headache, nausea, and dizziness. All dose groups also saw suicidal ideation and intentional self-injury, "as is common in treatment-resistant depression studies," according to the release.

For some years now, scientists have been investigating how psilocybin, the psychedelic compound in magic mushrooms, relieved severe depression symptoms and treated alcohol addiction.

"These findings are a positive step in the right direction. Our task now is to investigate psilocybin for treatment-resistant depression in larger trials with more participants, comparing it both to placebo and established treatments," said Rucker.

The study was published in the New England Journal of Medicine.


Background: Psilocybin is being studied for use in treatment-resistant depression.

Methods: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery–Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).

Results: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were −12.0 for 25 mg, −7.9 for 10 mg, and −5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P<0.001) and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P=0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups.

Conclusions: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder.

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