CNN —
A single dose of a synthetic version of magic mushrooms’ mind-altering component, psilocybin, improved depression in people with a treatment-resistant form of the disease, a new study finds.
The randomized, double-blind clinical trial, which the authors called “the largest of its kind,” compared the results of a 25-milligram dose to 10-milligram and 1-milligram doses of a synthetic psilocybin, COMP360, administered in person by trained therapists.
The results of the study, published Wednesday in the New England Journal of Medicine, found “an immediate, rapid, fast-acting, sustained response to 25 milligrams (of COMP360),” said study co-author Dr. Guy Goodwin, Professor Emeritus of Psychiatry at the University of Oxford in the UK.
“This drug can be extracted from magic mushrooms, but that’s not how our compound is created. It is synthesized in a purely chemical process to produce a crystalline form,” said Goodwin, chief medical officer of COMPASS Pathways, the company that makes COMP360 and conducted the study.
Experts in the field found the study results promising.
“They clearly found a dose effect and a clinically meaningful improvement in just three weeks,” said Dr. Matthew Johnson, Professor of Psychedelics and Consciousness at Johns Hopkins Medicine in Baltimore. He was not involved in the new study.
“If you were in the 25 milligram group, you were almost three times as likely to react as you were in the 1 milligram group,” said Johnson, who co-authored the 2008 Safety Guidelines for Psychedelic Research.
Also of note was the rapid response to treatment.
“The maximum effect (was) observed the day after receiving the treatment. This is in contrast to standard antidepressants, which take several weeks to reach their maximum effect,” said Dr. Anthony Cleare, Professor of Psychopharmacology and Mood Disorders at King’s College London, in a statement. He was not involved in the study.
However, according to experts, there are a number of issues that need further investigation before this drug is available for clinical use.
“The effects wore off after three months and we need to know how best to prevent the depression from coming back,” Cleare said, adding that not enough is known about possible side effects.
“While the overall safety profile appears encouraging, great caution is obviously needed when using psychoactive substances such as psilocybin. Larger studies are on the way, which we hope will help answer these questions,” he said.
The clinical study took place at 22 sites in the United States, Canada, the United Kingdom and seven countries in Europe. The study was designed to test the safety of different dosages of the proprietary version of psilocybin.
The 233 study participants had treatment-resistant depression, which can only be diagnosed when a person fails to respond to two courses of antidepressants. Of the 9 million people in the US with medically treated depression, 3 million patients are treatment-resistant, studies have found. About 100 million people worldwide suffer from treatment-resistant depression, Goodwin said.
People with the condition are at high risk of physical illness, disability, hospitalization and suicide, the study said.
All study participants those on antidepressants had to wean off these drugs before the start of the study. Psychedelic treatment doesn’t work for people who are actively taking antidepressants—the receptors that psychedelics attach to in the brain are already flooded with serotonin from their current mood-altering drugs.
“Participants were asked not to take any antidepressant treatment during the first 3 weeks after study drug administration; However, these drugs could be started at any time during the study if deemed clinically necessary by an investigator.
Depression severity was rated for each subject the day before treatment using a psychological scale widely used by clinicians. Counselors trained to provide psychological support were present during the psychedelic trips, which lasted between six and eight hours. Participants also received two more therapy sessions in the first week, according to the study.
The level of depression was documented the day after the trip and five more times over a 12-week period. About 37% of the people taking the 25 milligram dose showed improvement. In fact, by week three, 29% were considered to be in remission, according to the study.
However, by week 12, the beneficial effect on depressive symptoms faded and no longer reached a statistically significant level, the study found.
“The frequency of sustained responses at week 12 was 20% in the 25 mg group, 5% in the 10 mg group, and 10% in the 1 mg group,” wrote psychobiologist Dr. Bertha Madras, director of the Addiction Neurobiology Laboratory at Harvard Medical School’s McLean Hospital in Belmont, Massachusetts, in an accompanying editorial. She did not take part in the study.
“This is not a spectacular response rate for psychiatric treatment … and we would only expect this to worsen over a longer period of follow-up,” he said dr Ravi Das, Associate Professor of Educational Psychology, Research Methods and Statistics at University College London by email. He, who was not involved in the study.
In addition, “there were an odd number of major depressive patients in each group; with significantly fewer severely depressed people in the apparently ‘effective’ (25 mg) dose group,” Das said in a statement. “This does not seem to be acknowledged in the newspaper.”
Headaches, nausea, fatigue, and dizziness plagued 77% of study participants and occurred at all dosage levels, which experts say is a typical reaction on the day of psilocybin administration.
A small number of people in all three dosing groups had suicidal thoughts or injured themselves during the 12-week follow-up period, the study found. In the first three weeks alone, two people in the 25-milligram group had suicidal thoughts and two intentionally injured themselves. Two people in the 10-milligram group were suicidal, one self-harmed and one was hospitalized for major depression, the study reported.
These behaviors are “common in treatment-resistant depression studies — most cases occurred more than a week after the COMP360 psilocybin session,” the company said.
“Keep in mind that this is the case for people who were not identified as having a significant risk of suicide when they entered the study. The numbers were quite small, but that needs careful consideration in later studies,” said Kevin McConway, professor emeritus of applied statistics at the Open University, a UK public research university.
The study results are promising, however Many questions remain, and it’s not known if this drug would be successful for different types of depression, said McConway, who was not involved with the study.
“You can’t tell us how effective this psilocybin plus therapy treatment is compared to other existing drug or non-drug treatments for depression,” McConway said, noting this as the next step for follow-up studies.