In November 2021, when the psychedelic company Compass Pathways release the top result of the trial that looked at psilocybin in patients with treatment-resistant depression, the company’s stock nearly plummeted. 30 percent. The dive is reported was driven by the slightly average study results – but also by the dispersion of serious adverse events that occurred during the trial.
In the midst of a renaissance of hallucinations, it was taboo to expose their potential harms. The field, vilified for decades, has finally returned to the mainstream only recently. But as clinical trials get larger – and drugs become increasingly commercialized – more negative outcomes are likely. With the Compass test results suggesting this, perhaps now is the time to open up the conversation about the potential side effects of hallucinations – even if it means making hype built.
Those results, now published full in New England Journal of Medicine, represents the largest, randomized, controlled, double-blind psilocybin therapy study ever conducted. The participants — 233 of them, across 22 locations in 10 countries — were divided into three roughly equal groups. One group received 1 milligram of COMP360, Compass’ synthetic psilocybin, at a dose so low that it was given as a placebo. The next group received 10 mg and the last group 25 mg. Psychological support is also provided along with treatment.
The results are promising, if not paint the picture of a miracle cure. In the 25 mg group, 29% of patients were in remission after three weeks compared with just 8% in the placebo group. Over time, the positive effects diminished: After 12 weeks, only 20% of patients on the high dose were still responding — an improvement over the placebo group that was not statistically significant.
At the same time, 179 of the 233 patients in the trial reported at least one side effect, such as headache, nausea, fatigue, or insomnia – irritability, sure, but not a significant cause for concern. fear. But 12 patients experienced serious adverse events. They are defined as manifestations of suicidal ideation, including self-harm. Five patients in the highest dose group reported suicidal behavior, as did six patients in the 10 mg group. This was compared with just one in the placebo group.
“Is this to be expected in a trial like this? To some extent, yes,” said Natalie Gukasyan, assistant professor and medical director of the Johns Hopkins Center for Psychedelic & Consciousness Research. When you work with a vulnerable group of patients like those with treatment-resistant depression, the rate of suicidal thoughts is higher. But what’s remarkable, she said, was that there was a higher rate of these events in the higher-dose group, which raises the question of whether drugs played a role. One thing she thought it would be helpful to include in the study was the lifetime history of previous suicide attempts in the participants, which is an important predictor of future suicidal behavior. future.
Joost Breeksema, a doctoral candidate who studies patient experiences of hallucinations at the University Medical Center Groningen in the Netherlands, said, given the general caution of noticing the downsides of hallucinations, It is a good thing that the Compass foretells adverse events. In August 2022, Breeksema published a review reviewed how adverse events in psychedelic research were flagged, and found that they were inconsistent and possibly underreported. Many of the trials Breeksema has reviewed have reported no side effects – an unlikely fact. The Compass Path study “reported more rigorous adverse events than many other trials during our systematic review,” he said.
