Nearly a third of patients with severe depression experienced rapid remission after a single 25mg dose of psilocybin followed by therapy sessions aimed at helping patients identify the causes and possible solutions to their depression, the researchers said. The results from the largest clinical trial to date of psilocybin and depression were described as “outstanding” by Professor Guy Goodwin, the chief medical officer at Compass Pathways, the mental health company which led the trial which was carried out at 22 sites in the UK. Europe and the North. America. An estimated 100 million people worldwide have treatment-resistant depression, which is defined as a major depressive disorder that has not responded to at least two antidepressant treatments. About half of those affected are unable to perform routine daily tasks. “Response rates in this group with treatment-resistant depression are typically between 10 and 20 percent,” Goodwin said. “We’re seeing three-week remission rates of around 30% … that’s a very satisfying result.” Dr James Rucker, consultant psychiatrist at South London and the Maudsley NHS Foundation Trust, who worked on the trial at King’s College London, said treatment-resistant depression took its toll on patients and those around them, at a total cost to the UK of 3 £.9 billion per year. The phase 2b clinical trial enrolled 233 patients with resistant depression and randomly assigned them to receive a single capsule of either 1 mg, 10 mg or 25 mg of a synthetic psilocybin called Comp360. Patients listened to a relaxing playlist and wore eye shadow to turn their attention inward for at least six hours while the psychedelic took hold. A therapist was present to ensure patients were safe and well. The volunteers continued to have therapy sessions the day after taking the drug and one week later. Results published in the New England Journal of Medicine show that depression scores, measured on the standard Montgomery-Åsberg Depression Scale, improved immediately after treatment in all three arms of the trial. The most significant impact was in those with the highest dose of 25 mg psilocybin. Three weeks after taking the drug, 29% of this group was in remission, compared with 9% and 8% of the 10mg and 1mg groups, respectively. At 12 weeks, the benefits remained at one-fifth of those in the high-dose group, compared to one in 10 in the lowest-dose group. Psilocybin is the main active ingredient in magic mushrooms. Inside the body, it breaks down into a substance called psilocin, which releases waves of neurotransmitters in the brain. MRI scans show that brain activity becomes more chaotic on psilocin, with different areas of the brain talking to each other more than usual. “That might seem bad, but it’s not,” Rucker said. “This happens every night: when you dream your brain becomes more plastic, slightly more chaotic, and that’s when new connections are made.” Patients in the trial said they were in a “waking dream” when they took psilocybin, a short-lived experience that ended before they went home. The increased connectivity in the brain appears to be a more lasting effect, however, lasting a few weeks and potentially making the brain more receptive to treatment. Archie Bland and Nimo Omer take you to the top stories and what they mean, free every weekday morning Privacy Notice: Newsletters may contain information about charities, online advertising and content sponsored by external parties. For more information, see our Privacy Policy. We use Google reCaptcha to protect our website and Google’s Privacy Policy and Terms of Service apply. “When the brain is in a more flexible state, it opens up what we think is a therapeutic window of opportunity,” Rucker said. David Nutt, professor of neuropsychopharmacology at Imperial College London, who was not involved in the trial, said psilocybin’s rapid effect suggested it interrupted negative cycles of rumination in patients, effectively acting as a “reset” in the brain. Despite the obvious benefits, many patients reported side effects in the trial, the most common being headaches, nausea, dizziness and fatigue. One person had a bad trip and was given a sedative to help with his anxiety. As is common with treatment-resistant depression, a number of patients in different arms of the trial reported self-harm and suicidal thoughts. Suicidal behaviors were observed in three patients who did not respond to the 25 mg dose of psilocybin at least one month after taking the drug. According to Nutt, these cases were probably random events and unrelated to the dose of psilocybin, which would have been completely cleared from the patient’s body. A larger phase 3 trial investigating the effects of two doses of psilocybin is due to start later this year.
