Psychedelic treatment with psilocybin may help treat major depression

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In a study of adults with major depression, Johns Hopkins Medicine researchers reported that two doses of the psychedelic substance psilocybin, given with supportive psychotherapy, produced rapid and large reductions in depressive symptoms. Most participants showed improvement and half of the study participants obtained remission by four weeks of follow-up.

A compound found in so-called magic mushrooms, psilocybin produces visual and auditory hallucinations and profound changes in consciousness within hours of ingestion.

In 2016, researchers Johns Hopkins Medicine first reported that treatment with psychologically sustained psilocybin significantly improved life-threatening anxiety and depression in people diagnosed with life-threatening cancer.

Now the findings of the new study, recently published in JAMA Psychiatry, suggests that psilocybin may be effective in a much larger population of patients with major depression than previously assessed.

“The magnitude of the effect we saw was about four times greater than what clinical trials have shown for traditional antidepressants on the market,” says Alan Davis, Ph.D., assistant professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine.

Because most other treatments for depression take weeks or months to work and can have side effects, this could be a game changer if these findings are maintained in future placebo-controlled clinical trials.

What the findings on psilocybin indicate


The published findings cover only a four-week follow-up of 24 participants, all undergoing two five-hour psilocybin sessions under the guidance of researchers.

“Because there are several types of major depressive disorder that can lead to variations in how people respond to treatment, I was surprised that most study participants found psilocybin treatment to be effective,” says Roland Griffiths, Ph.D. Oliver Lee McCabe III Professor of Neuropsychopharmacology of Consciousness at Johns Hopkins University School of Medicine and Director of the Johns Hopkins Center for Psychedelic Research and Consciousness.

He says the major depression treated in the new study could have been different from the “reactive” form of depression in patients he studied in the 2016 cancer study. Griffiths says his team was encouraged by public health officials to explore the effects of psilocybin on the wider population of those with major depressive disorder, due to the potentially much greater impact on health.

For the new study, researchers recruited 24 people with a documented long-term history of depression, most of whom had persistent symptoms for about two years before enrolling in the study.

The average age of the participants was 39 – 16 were women, and 22 were identified as white, one person identified as Asian and one person identified as African American. Participants had to reduce any antidepressants before the study with the help of their personal physician to ensure safe exposure to this experimental treatment.

How the study went

Thus, 13 participants received psilocybin treatment immediately after recruitment and after the training sessions, and 11 participants received the same preparation and treatment after an eight-week delay.

Treatment consisted of two doses of psilocybin administered by two clinical monitors who provided guidance. Doses were administered two weeks apart between August 2017 and April 2019 at the Johns Hopkins Bayview Medical Center Behavioral Biology Research Building. Each treatment session lasted about five hours, with the participant lying on a couch wearing a scarf over his eyes and headphones playing music in the presence of monitors.

All participants received the GRID-Hamilton Depression Rating Scale – a standard tool for assessing depression – upon enrollment and one to four weeks after completion of treatment.

A score of 24 or higher indicates severe depression, 17-23 moderate depression, 8-16 mild depression, and 7 or less lack of depression. At enrollment, participants had an average score on the depression scale of 23, but one week and four weeks after treatment, they had an average score on the depression scale of 8.

After treatment, most participants experienced a substantial decrease in symptoms, and almost half were in remission of depression.

For the entire group of 24 participants, 67% showed a reduction of over 50% in the symptoms of depression at one-week follow-up and 71% at four-week follow-up. In general, four weeks after treatment, 54% of participants were considered in remission – which means that they are no longer qualified as depressed.

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