Researchers at Johns Hopkins Medicine have reported that, in a small study of adults with major depression, the administration of two doses of the hallucinogenic drug psilocybin, with supportive psychotherapy, produced large and rapid reductions in depressive symptoms. Most of the participants had improvement, and half of those who participated in the study had remission through the four weeks of follow-up.
Psilocybin, a substance found in so-called “hallucinogenic mushrooms,” produces visual and auditory hallucinations and profound alterations in consciousness within a few hours of ingestion. In 2016, Johns Hopkins Medicine researchers were the first to discover that psilocybin treatment in conjunction with psychological support reduced existential anxiety and depression in people with a life-threatening cancer diagnosis.
Currently, the results of the new study, published Nov. 4 in JAMA Psychiatry, hint that psilocybin might be effective in a much larger population of patients with major depression than previously appreciated.
A game changer
“The magnitude of the effect we observed was almost four times greater than what clinical studies have shown using conventional antidepressants on the market,” says Alan Davis, Ph.D., associate professor of Psychiatry and Behavioral Sciences in the School of Medicine. from Johns Hopkins University. “Since most other treatments for depression take weeks or months to work and can have undesirable effects, this could be a game changer, if these results are supported by future placebo-controlled clinical trials that are the method of reference”.
The published results cover only a four-week follow-up of 24 participants, all of whom received two psilocybin sessions, each lasting five hours, under the direction of the researchers.
Effective treatment
“Because there are different types of major depressive disorder that can cause variations in how people respond to treatment, I was surprised that nearly all of the participants in our study found psilocybin treatment effective,” says Roland Griffiths, Ph.D., professor of the Oliver Lee McCabe III Chair of Neuropsychopharmacology and Consciousness at Johns Hopkins University School of Medicine and Director of the Johns Hopkins Center for Psychedelic and Consciousness Research.
He notes that the major depression treated in the new study may have been different from the ‘reactive’ form of depression in the patients they enrolled in the cancer clinical study in 2016. Dr. Griffiths notes that public health officials urged his team to explore the effects of psilocybin in the broader population of those with major depressive disorder because of the much larger impact it could have on public health.
For the new study, the scientists recruited 24 people with a documented history of long-term depression, most of whom had suffered from persistent symptoms for about two years before enrolling in the study. The average age of the participants was 39 years; 16 were female and 22 identified as white, one person as Asian and one person as African American. Participants had to gradually stop taking their antidepressants before the study, with the support of their treating physician, in order to ensure safe exposure to this experimental treatment.
Thirteen participants received psilocybin treatment immediately after enrollment and preparatory sessions, and 11 participants received the same preparation and treatment after a delay of eight weeks.
Treatment consisted of two doses of psilocybin administered by two clinical supervisors who provided guidance and support. It took place at the Johns Hopkins Bayview Behavioral Biology Research Building, two weeks apart, between August 2017 and April 2019. Each treatment session lasted approximately five hours, and the participant lay on a couch, with a mask on and headphones playing music and supervisors present.
All participants were given the GRID-Hamilton Depression Rating Scale (a standard method for assessing depression) at enrollment, and also after one and four weeks after completing treatment. On this scale, a score of 24 or more indicates severe depression, 17 to 23 moderate depression, eight to 16 mild depression, and seven or less no depression.
At enrollment, participants had an average score of 23 on the depression assessment scale, but after one week and after four weeks of completing treatment, participants had an average score of eight on the scale for evaluation of depression. After treatment, most of the participants had a considerable reduction in their symptoms and almost half had remission of depression at the follow-up appointment. Participants in the delayed condition had no reductions in their symptoms before receiving psilocybin treatment.
Significant reduction
Of the group of 24 participants in total, 67% had a reduction of more than 50% in depression symptoms at the follow-up appointment one week later and 71% at the follow-up four weeks later. Overall, at four weeks after treatment, 54% of the participants were considered in remission — meaning that they no longer met the criteria to qualify as depressed.The researchers say they will follow the participants for a year afterward to determine how long the effects of psilocybin therapy last.
Dr. Griffiths, who began his research with psilocybin in the early 2000s and was initially viewed with skepticism and concern by some, states that he is pleased to have Johns Hopkins’ support and is encouraging to see the dozens of new businesses and research labs that have followed suit by doing their own research. He adds that a large number of companies are currently actively involved in developing marketable forms of psilocybin and related hallucinogens.
According to data provided by the National Institute of Mental Health, more than 17 million people in the United States and 300 million people in the world have had symptoms of major depression.
