NEJM's largest trial to date has shown that COMP360 psilocybin can reduce depressive symptoms

A multicentre clinical trial led by COMPASS Pathways across 22 international locations, including King's College London, South London and the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) of the Maudsley NHS Foundation Trust, found that a single 25mg dose of COMP360 psilocybin, plus psychological support, had a significant effect
in reducing depressive symptoms in participants with treatment-resistant depression.

About 100 million people worldwide suffer from treatment-resistant depression, meaning they do not respond to at least two antidepressant medications used to
treat major depressive disorder.

The study, published in the New England Journal of Medicine, investigated baseline changes in depression severity using the Montgomery-Sberg Depression Rating Scale to evaluate participants with treatment-resistant depression for 12 weeks, taking a single dose of COMP360 psilocybine
while providing psychological support.
The researchers found that participants reported a greater reduction
in depression scores after three weeks of taking a single dose of 25 mg of COMP360 psilocybin, compared to participants who took the lowest dose of 1 mg of COMP360 psilocybin.

Some adverse effects such as headache, nausea, dizziness, fatigue and suicidal
thoughts were reported in all dose groups.

The Phase 2b clinical trial was conducted
at 22 sites in 10 countries in Europe (Czech Republic, Denmark, Germany, Ireland, Netherlands, Portugal, Spain and the United Kingdom) and North America (Canada and the United States) between March 1, 2019 and September 27, 2021.
233 patients with treatment-resistant depression were randomly assigned to receive a single dose of 25 mg, 10 mg, or 1 mg of COMP360 psilocybin and received psychological support; People who received a dose of 1 mg served as a control group
.
Neither the participants nor the researchers knew which dose
the participants received.

Dr James Lack, a consultant psychiatrist and group leader of the IoPPN Psychoactive Trials Group at King's College London, South London and the Maudsley NHS Foundation Foundation, who was involved in the study, said:

"While many patients with mental health issues get better with existing treatments, there is still a small percentage of patients who don't get
better even after trying a number of different treatments.
" This is sometimes referred to as "treatment resistance"
.
This can lead to a wide variety of other problems that seriously affect the patient and those around
them.
Treatment options are often limited, with bothersome side effects and/or stigma
.
Therefore, new treatment models are needed, and clinical research of new therapies is important
.
Psilocybin therapy may be a new therapeutic paradigm, but this needs to be tested
in clinical trials.
We are doing this in the psychoactive trial group, where we are working with colleagues at Maudsley Center for Advanced Therapy to deliver new, groundbreaking treatments
.
”

"This study is the largest clinical trial to date using psilocybin for treatment-resistant depression and showed that a single dose of 25 mg psilocybin improved depressive symptoms
in participants compared to a 1 mg dose (control).
" These findings are a positive step in the right direction
.
Our task now is to study the efficacy of psilocybin for treatment-resistant depression in large clinical trials with more participants and compare
it with placebo and existing treatments.
”

Professor Guy Goodwin, Chief Medical Officer of COMPASS Pathways, said: "Our COMP360 psilocybin treatment study, published in the world's most prestigious peer-reviewed medical journal, is a proud moment
for all participants.
"We saw positive results in a particularly difficult-to-treat group of patients, with the highest dose of COMP360 psilocybin having the greatest impact
on depression in people.
" This suggests that COMP360 psilocybin has a real pharmacological effect, a finding that is crucial
for it to be recognized as a new treatment option in the future.
We look forward to launching our Phase III project later this year to bring us closer to providing psychosocial support
to patients in urgent need of COMP360 psilocybin.
" ”

The severity of depressive symptoms was assessed for all participants the day before taking COMP360 psilocybin, and follow-up was assessed
at days 2, 1, 3, 6, 9, and 12.

Participants were given COMP360 psilocybin in a dedicated room to provide a non-clinical and sedating atmosphere
.
This psychedelic effect lasted from 6 to 8 hours, during which an experienced therapist provided psychological support
in the room.
All therapists received a detailed training program
designed for the trial.
After the psychedelic effect completely dissipated, the participants were able to
go home.

The researchers found that participants who received a 25 mg dose of COMP360 psilocybin experienced a faster and greater decline in depression scores (p<0.
001)
than those who received a 1 mg control dose with psychological support.

During the 12-week study period, adverse effects including headache, nausea, dizziness, and fatigue occurred in 84% of the 25 mg dose group, 75% in the 10 mg dose group, and 72%
in the 1 mg dose group.
Suicidal ideation and intentional self-injury were seen in all dose groups, which are common
in treatment-resistant depression studies.
Most cases occurred after
taking COMP360 psilocybin for more than a week.
There was no significant deterioration
in suicidal ideation scores on the MADRS scale in any dose group.
Three non-responders in the 25 mg group reported suicidal behavior for at least one month after taking COMP360
.