'Magic Mushrooms' Get a Win for Depression in Early Trial, Drugmaker Says

Psilocybin, the drug compound found in "magic mushrooms," reduced symptoms of treatment-resistant depression in a randomized phase IIB study, though was associated with some serious adverse events (AEs), drugmaker Compass Pathways announced by press release.

In the trial of more than 200 patients with treatment-resistant therapy who had stopped taking antidepressants before enrollment, a 25-mg dose of COMP360 psilocybin with ongoing psychological support led to a -6.6-point difference on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 3 versus a group who received a 1-mg dose of the product (P<0.001), and the difference remained significant through week 6.

A third arm of the study tested a 10-mg dose of psilocybin, but this showed no statistically significant difference over the 1-mg dose at week 3 (-2.5 points P=0.184). Results of the trial have not been peer-reviewed.

In the 25-mg group, 29.1% of patients achieved a remission (≥50% decrease in MADRS total score from baseline) at week 3, as compared to 7.6% in the 1-mg group. By week 12, these rates were 24.1% and 10.1%, respectively.

"Remission rates appear to be higher than seen in traditional medication studies," noted principal investigator David Hellerstein, MD, of Columbia University in New York City, in a statement. "These findings suggest that COMP360 psilocybin therapy could play a major role in psychiatric care, if approved."

During an investor call where Compass leadership presented the findings, Guy Goodwin, MD, the company's chief medical officer and a professor emeritus of psychiatry at Oxford University, said the results in the 25-mg group "show evidence for durability of response" for psilocybin therapy.

Of potential concern, however, were higher rates of treatment-emergent serious adverse events (AEs) with the higher psilocybin doses. These serious AEs -- which include suicidal behavior, suicidal ideation, and intentional self-injury -- occurred in five patients in the 25-mg group (6.3%), in six patients in the 10-mg group (8.0%), as compared to one patient in the 1-mg group (1.3%).

Matthew Johnson, PhD, a professor of psychiatry and psychedelics at Johns Hopkins Medicine in Baltimore, told MedPage Today that the early data look encouraging. Yet without more detailed information, questions remain about the nature of the trial's AEs, he said.

"Working with depressed people, these symptoms come with the territory. Suicidal behavior can encompass a broad range, from fleeting thoughts to more serious planning," Johnson said. "It is possible that an effective session might put people in a more difficult place psychologically as they're processing the experience, much like processing trauma. The treatment itself can bring up very difficult emotions and might potentially make things worse in the short-term."

Because details of the patients' reported suicidality weren't explored further, it's hard to assess in full, he explained.

Lars Christian Wilde, Compass' co-founder and president, said during the investor call that the differences in serious AE frequency were not statistically significant between dosing groups. Suicidal thoughts, self-injury, and even suicidal behaviors are also common among those suffering from treatment-resistant depression, he noted.

The study, the largest to test the compound to date according to the U.K.-based company, included 233 patients with treatment-resistant depression. Patients were randomized 1:1:1 to COMP360 psilocybin at the three doses along with ongoing psychological support from therapists. Participants were recruited from 10 countries across North America and Europe. Notably, 94% of patients had no prior experience with psilocybin.

Overall, 179 patients reported experiencing at least one treatment-emergent AE, with more than 90% falling in the mild-to-moderate category (83.5% in the 25-mg group, 74.7% in the 10-mg group, and 72.2% in the 1-mg group), the company noted.

Researchers from the company are planning to start a phase III trial next year, which will likely focus on the 25-mg dose. The leadership team also announced that the company will be embarking on a phase II trial of psilocybin therapy in the treatment of post-traumatic stress disorder.

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