Psilocybin-assisted psychotherapy produces large, rapid, and sustained antidepressant effects

Combining the psychedelic drug psilocybin with supportive psychotherapy results in substantial rapid and enduring antidepressant effects among patients with major depressive disorder, according to a new randomized clinical trial. The findings have been published in JAMA Psychiatry.

The new study provides more evidence that psilocybin, a compound found in so-called magic mushrooms, can be a helpful tool in the treatment of psychiatric conditions.

“Prior studies in cancer patients and in an uncontrolled clinical trial in depressed patients using psilocybin-assisted therapy showed promising results. Because there had not been a control group those prior studies were limited,” said study author Alan K Davis, an assistant professor at Ohio State University and adjunct assistant professor at Johns Hopkins University.

“We were interested in testing whether psilocybin-assisted therapy would be helpful for people with depression because depression is one of the most prevalent and debilitating conditions in the world.”

In the study, which was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, 27 people with a long-term documented history of depression were randomly assigned to either begin treatment immediately or after an 8-week delay.

The treatment consisted of 18 sessions. During two of these sessions, psilocybin doses were administered by two clinical monitors who provided guidance and reassurance. The doses were given two weeks apart and each psilocybin session lasted approximately five hours, with the participant lying on a couch wearing eyeshades and headphones that played music, in the presence of the monitors.

The participants completed a measure of depression and other psychological assessments upon enrollment, and at one and four weeks following completion of their treatment. Most participants showed a substantial decrease in their depression symptoms following the treatment, and almost half were in remission from depression at the follow-up. Those in the delayed group didn’t show decreases in their symptoms before receiving the psilocybin treatment.

“Depressed participants completed therapy and 2 psilocybin sessions. Participants in the immediate treatment group had a large decrease in depression following treatment compared to those in the waitlist control group,” Davis told PsyPost.

“After both groups had received treatment, 71% of participants had a clinically significant response to the treatment (greater than 50% decrease in depression scores) at 4-weeks post-intervention and 54% were in remission from depression at 4-weeks post-intervention. This represents a large effect of this treatment among people with major depressive disorder, approximately 4 times larger effect compared to studies of antidepressant drugs.”

However, the participants reported some challenging experiences during the psilocybin sessions, the most common being “I felt like crying”, “Sadness”, “Emotional and/or physical suffering”, “Feeling my heart beating”, and “Feeling my body shake/tremble.” Many also experienced mild-to-moderate headache.

One participant dropped out of the study because of anxiety about their first psilocybin session. Another participant dropped out of the study after their first psilocybin session because of sleeping issues — but “it was not clear whether sleep difficulties were exacerbated by the intervention,” the researchers said. A third participant chose not to undergo a second psilocybin session after showing a reduction in depression symptoms immediately following their first session.

“Although this study is an important step in this line of research, the lack of placebo control and a short term follow-up (1 month) limits our understanding of how well this treatment works. We are currently working on analyzing long-term follow-up data from this study where we followed participants up to 1 year after their treatment. Current studies are testing psilocybin therapy against placebo in a large multi-site trial in the U.S. and Europe,” Davis said.

He also noted that the drug is not a miracle cure.

“Psychotherapy is substantial. We provide approximately 11 hours of therapy to each person in addition to the two full-day psilocybin therapy sessions. It is likely the combination of psychotherapy and psilocybin that makes this treatment efficacious. This treatment will always have a psychotherapy component and will not be approved by the FDA as a stand-alone medication,” Davis explained.

The study, “Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial“, was authored by Alan K. Davis, Frederick S. Barrett, Darrick G. May, Mary P. Cosimano, Nathan D. Sepeda, Matthew W. Johnson, Patrick H. Finan, and Roland R. Griffiths.