EThe highly anticipated results of the largest study ever on psilocybin were announced on Tuesday, with Compass Pathways revealing that the psychedelic drug was highly effective as a therapy for treatment-resistant depression. Still, the company’s stock price had fallen more than 20% by noon, possibly due to security concerns among investors.
The Phase 2b study is the largest randomized, controlled, double-blind trial of psilocybin, the psychedelic compound in magic mushrooms. The company said it found that patients given the highest dose, 25 milligrams, had a significant decrease in depressive symptoms compared to those given 1 milligram, a dose so low that it works like a placebo.
Overall, 29.1% of patients in the highest dose group were in remission three weeks after treatment, compared with 7.6% of those in the control group, and more than a quarter of patients in the 25 arm. milligrams were still in remission for three weeks. months after treatment.
Those who received the highest dose also experienced a mean reduction on a measure of clinical depression (the Montgomery-Asberg Depression Rating Scale) that was 6.6 points higher than those who took 1 milligram. Other patients received a 10 milligram dose, but there was no statistically significant impact for these patients compared to the 1 milligram arm.
“Everyone agrees that such a result has never been seen before in depression research, so we are incredibly pleased with this result,” said Lars Christian Wilde, co-founder and president of Compass.
Boris Heifets, a neuroscience researcher at Stanford who studies psychedelics and was not part of the study, agreed the results are “super promising.” The effectiveness of psilocybin at three weeks, according to the Compass study, is roughly comparable to the effects of ketamine at one day, according to a smaller study from 2013, he added, suggesting that the benefits of psilocybin hold up well over time. “We still lack a lot of detailed data,” he added, but the summarized results are “pretty good news”.
The study, which enrolled 233 patients at multiple sites in Europe and North America, is the most rigorous psilocybin trial for treatment-resistant depression and adds considerable weight to earlier and smaller studies of the drug that were also promising. The U.S. Food and Drug Administration has granted Compass Pathways the Breakthrough Therapy designation, which means the drug approval process will be speeded up if studies continue to show positive results. Compass is working to start a phase 3 trial next year; current results suggest he will likely use a 25 milligram dose, but Wilde said that decision will be made following conversations with regulators.
The company’s published results, which were not published in a medical journal or peer reviewed, included side effect data showing a small number of serious adverse events. Overall, 12 patients reported serious adverse events occurring during treatment, including five in the 25 milligram group and six in the 10 milligram group; these included suicidal behavior and self-harm. Only one patient in the 1 milligram group experienced a serious adverse event.
“Suicidal behavior has been reported at least a month after treatment was given and it has occurred in patients who were essentially unresponsive,” Guy Goodwin, Compass chief medical officer, said on an appeal to investors Tuesday morning. In at least one case, however, suicidal ideation was reported at the start of treatment, he added.
The numbers are small enough that the difference between the treatment arms is not statistically significant, said Wilde, noting that suicidal behaviors and thoughts are common in depressed patients. “We are dealing with a severe patient population, both in terms of the severity of the patients and the duration of their depressive episode,” he said. “Unfortunately, these events are to be expected.” There have been three suicides in studies of esketamine, the only psychedelic currently approved for treatment-resistant depression, he said.
Researchers in previous studies have reported a “disappointment reaction,” where patients’ symptoms worsen because the new treatment does not immediately cure their depression. The difference between the treatment arms is unexpected, Heifets said, because patients tend to be more depressed if they are assigned to a placebo and not receiving effective treatment: “If anything, I would expect that it happens the other way around. But, he added, suicidal behavior is common in research on depressed patients. “This means it’s not attributable to the fact that psilocybin has a suicidal side effect,” he said.
Goodwin said the researchers plan to study the data in more detail, including analyzing responses to a questionnaire that all patients took for a suicidal assessment, to better understand the link.
If you or someone you know is considering suicide, contact the National Suicide Prevention Lifeline at 1-800-273-8255 (Español: 1-888-628-9454; deaf and hard of hearing: 1-800-799-4889) or the crisis text line by texting HOME at 741741.