Safety of psilocybin lays groundwork for research in treatment-resistant depression

A psilocybin formulation was well tolerated among healthy patients, which supports research into its use for treatment-resistant depression, according to data presented at the American Society of Clinical Psychopharmacology Annual Meeting.

“During the past decade, there has been a renewed interest in psilocybin as a potential treatment for depressive symptoms, and a number of studies have been presented,” Hans Eriksson, MD, chief medical officer of COMPASS Pathways, said during a virtual presentation. “All of these studies have contained instruments to assess severity of depression. There has been a fairly consistent signal of a rapid and substantial improvement that is maintained over time, but so far, there is no large, randomized controlled study that has reported out.”

Eriksson and colleagues sought to explore the safety and feasibility of simultaneous psilocybin administration with 1:1 psychological support. They conducted the current study after COMPASS Pathways received FDA breakthrough therapy designation for its formulation of psilocybin therapy, called COMP360.

The researchers conducted the exploratory, phase 1, randomized, double-blind, placebo-controlled study to evaluate the effects of 10 mg and 25 mg COMP360 compared with placebo among 89 healthy participants. They stratified participants by age and sex and randomly assigned them 1:1:1 to placebo, 10 mg of psilocybin or 25 mg of psilocybin administered orally. Participants received 1:1 support from a trained assisting therapist, as well as supervision from a lead therapist, during administration sessions. During the approximately 6-hour sessions, session leaders encouraged participants to relax and engage in introspection. Key inclusion criteria included men or women aged 18 to 65 years at screening. Key exclusion criteria included current or past history of numerous psychiatric disorders, including schizophrenia and bipolar disorder, as well as history of these disorders among a first-degree relative, current or previous substance dependency or abuse, current or recent psychiatric medications and prior psilocybin exposure within 1 year of informed consent signing. Safety endpoints included vital signs, suicidality, adverse events and serious adverse events, and clinical laboratory tests.

The researchers completed 25 dosing sessions, with up to six participants per session.

Throughout the study’s 12-week duration, Eriksson and colleagues observed 511 adverse events, of which 217 (96.7%) occurred in the 25 mg arm, 203 (96.7%) in the 10 mg arm and 91 (89.7%) in the placebo arm. The investigators determined that 473 (92.6%) of these were potentially related to study treatment, including 208 (95.9%) in the 25 mg arm, 188 (92.6%) in the 10 mg arm and 77 (84.6%) in the placebo arm. They reported no serious adverse events, and no adverse events led to withdrawal. The most frequently reported adverse events included hallucination, illusion, altered mood, headache, euphoric mood and fatigue. Among all treatment arms across the 12-week trial, the median duration of adverse events was 1 day. Further, 68% of all adverse events resolved on the day of dosing, and 92% of those likely to be psychedelic in nature resolved by day 1.

“Psilocybin has been used for many years and is considered one of the safest psychoactive substances,” Eriksson said. “It may also be efficacious for several disorder of the central nervous system and in other related therapeutic areas.”