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Magic mushroom compound can ease depression, study involving Irish participants finds

A total of 233 people with in ten countries, including Ireland, took part in the trial

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Neil FetherstonhaughSunday World

The psychedelic compound found in magic mushrooms can help alleviate severe depression when combined with psychotherapy, the results of a new trial that included participants in Ireland has found.

The study has raised hopes that it could help people with treatment resistant depression (TRD).

A total of 233 people with TRD in ten countries, including Ireland, took part in the trial.

Researchers at Trinity College Dublin worked at the Irish study's site at Tallaght University Hospital.

The psilocybin in the study was not derived from magic mushrooms, but instead was created in a purely chemical process.

It examined the safety and potential antidepressant effects of a single dose of psilocybin (25mg, 10mg, or 1mg) with psychological support in people with TRD.

The study showed that psilocybin 25mg led to a statistically and clinically significant rapid reduction in symptoms of depression compared to 1mg.

Researchers have said that while more trials are needed, the results offer hope that psilocybin with psychological support will be an effective antidepressant treatment regime for some people with TRD.

Dr John R Kelly, Psychiatrist and Clinical Senior Lecturer at Trinity College, said the largest and most rigorous clinical trial of psilocybin to date, has paved the way for Phase III clinical trials.

These will determine whether it translates into a much-needed complementary treatment strategy in the psychiatry clinic.

The study that was launched in 2018 following promising preliminary findings is published in the latest edition of the New England Journal of Medicine.

The results from the largest clinical trial yet into psilocybin and depression were described as “exceptional” by Prof Guy Goodwin, the chief medical officer at Compass Pathways, the mental healthcare firm that led the trial conducted at 22 sites across the UK, Europe and North America.

An estimated 100 million people worldwide have treatment-resistant depression, 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 usually between 10 and 20pc,” Goodwin said. “We are seeing remission rates at three weeks of about 30pc… that is a very satisfactory outcome.”

Dr James Rucker, a consultant psychiatrist at South London and Maudsley NHS foundation trust, who worked on the trial at King’s College London, said treatment-resistant depression placed a “staggering” burden on patients and those around them, with a total cost to the UK of £3.9bn a year.

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 on the highest 25mg dose of psilocybin. Three weeks after having the drug, 29pc of this group were in remission, compared with nine pc and eight pc of the 10mg and 1mg groups respectively. At 12 weeks, benefits persisted in a fifth of those in the high-dose group, compared with one in 10 in the lowest-dose group.

Psilocybin is the main active ingredient in magic mushrooms. Inside the body, it is broken 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 regions of the brain talking to each other more than usual.

“That may seem like a bad thing but it isn’t,” said Rucker. “That happens every night: when you dream your brain becomes more plastic, slightly more chaotic, and it’s when new connections are formed.”

Patients on the trial spoke of being in a “waking dream” when they took psilocybin, a short-lived experience that wore off before they returned home.

“When the brain is in a more flexible state it opens what we consider to be a therapeutic window of opportunity,” Rucker said.

David Nutt, a professor of neuropsychopharmacology at Imperial College London, who was not involved in the trial, said the rapid effect of psilocybin suggested it was disrupting negative cycles of rumination in the patients, in effect acting as a “reset” on the brain.

Despite the apparent 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 their anxiety.

Suicidal behaviours were seen in three patients who did not respond to the 25mg 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 fully cleared from the patient’s bodies. A larger phase three trial that will explore the effects of two doses of psilocybin is due to start later this year.

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