Psychedelic therapy, there is still too little talk about side effects

In November 2021, when the British company that produces substances for therapy psychedelic Compass Pathways made known the results of its trial of psilocybin in patients suffering from forms of depression resistant to other treatments, the company’s shares are dropped by nearly 30 percent. The breakdown would be been provoked by the modest results of research, but also by a number of serious side effects occurred during the experiment.

In a time of great enthusiasm for psychedelics, the debate around the potential harm caused by them has remained somewhat taboo. After all, the field, vilified for decades, has only recently become popular again. As clinical trials increase – and as these types of drugs become more commercialized – more negative episodes are likely to occur. It’s probably time for one more candid debate about the potential side effects of psychedelicseven if it means dampening the excitement in the industry.

The results of the experiment, now published fully on New England Journal of Medicine, represent the largest randomized, controlled, double-blind study of psilocybin therapy ever conducted. The participants – 233, spread over twenty-two locations and ten countries – were divided into three more or less equal groups. One group received one milligram of COMP360, the synthetic psilocybin by Compass, a dose so low that it served as a placebo. The next group received 10mg and the last 25mg. Psychological support was also offered along with the treatment.

Side effects

Although the results have been promising, the picture that emerges is not that of a miracle cure. In the 25 mg group, 29 percent of patients were in remission after three weeks, compared with 8 percent in the placebo group. Over time, however, the positive effects diminished: after twelve weeks, only 20 percent of patients who had taken high doses were still responsive, a non-statistically significant improvement over the placebo group. At the same time, 179 of the 233 patients who participated in the study reported at least one side effect, such as headaches, nausea, fatigue or insomnia: an inconvenience, sure, but not an overly serious one. Twelve patients instead experienced serious side effects as manifestations suicidal tendencies, such as self-harm. Five of the patients in the higher dose group also exhibited suicidal attitudes, as did six in the 10 mg group. The same happened to only one patient in the group who took a placebo.

“Is that to be expected in a study like this? To some extent yes”, says Natalie Gukasyan, professor and medical director of the Johns Hopkins Center for Psychedelic & Consciousness Research. When working with such a vulnerable patient group as those with treatment-resistant depression, one can expect higher rates of suicidal tendencies. However, it is worth noting, according to the researcher, that the amount of these events was greater in the group receiving higher doses, which leads to the question of whether the drug actually played a role. According to the researcher, it would have been useful to include in the study the participants’ previous suicide attempts, an important predictor of future similar behaviors.

Transparency and expectations

Given the general reluctance to dwell on the negative aspects of psychedelics, it is good that Compass has been transparent about adverse events, says Joost Breeksema, a doctoral candidate who studies patients’ experiences with psychedelics at the University Medical Center in Groningen, USA. Netherlands. In August 2022, Breeksema released a item which examined the way adverse events were reported in psychedelic research, finding that this was done inconsistently and probably insufficiently. Many of the studies reviewed by Breeksema reported no adverse effects, an unlikely reality. Finding Compass Pathways”reported adverse effects more rigorously than many other studies in our systematic review”, explains Breeksema.