The New England Journal of Medicine published on Wednesday the largest clinical trial ever conducted to assess the effect of psilocybin, a psychoactive substance found naturally in hallucinogenic mushrooms.
A single 25-milligram dose reduced symptoms of depression in people who had failed several conventional treatments, the new study found.
It is estimated that 100 million people worldwide suffer from treatment-resistant depression. Some experts see psychedelics as a possible way to help them.
The researchers tested a synthetic version of psilocybin developed by the UK startup Compass Pathway, which also funded the trials.
A total of 233 people in 10 countries participated in the study, during which they discontinued ongoing treatment but received psychological support.
They were divided into three groups, randomly receiving 1 milligram, 10 milligrams, or 25 milligrams of the treatment.
The participants were never alone in the sessions, which lasted between six and eight hours in a special room.
Some described being immersed in “a dreamlike state” that could be remembered, James Rucker, a co-author of the study, said at a news conference.
One participant required a sedative during the session due to anxiety. But the side effects seen (headaches, nausea, anxiety) were generally mild and resolved quickly.
– More studies are needed –
Three weeks later, those who received 25 mg showed significant improvement compared to those who received lower doses, in a baseline measure of depression. Just under 30% were in remission.
“It is the strongest evidence yet and suggests that further, larger and longer randomized trials of psychedelics are warranted,” said Andrew McIntosh, a professor of psychiatry at the University of Edinburgh.
One day “psilocybin could provide a potential alternative to antidepressants that have been prescribed for decades,” added McIntosh, who was not involved in the study.
Another expert was more cautious.
“We still don’t know enough about potential side effects, particularly whether some people may experience worsening of some symptoms,” said Anthony Cleare, a professor of psychopharmacology in London, who was not involved in the study.
Phase 2 trials were designed to determine the dose and confirm the existence of an appropriate effect.
Phase 3 events, involving more participants, are scheduled to start this year and end in 2025.
Compass Pathway is already in contact with the US Food and Drug Administration (FDA) and European regulators.
In the trials, three participants showed suicidal behavior among those given 25 mg, compared to none of the other groups.
However, this was more than 28 days after treatment, noted Guy Goodwin, a professor of psychiatry at Oxford and medical director of Compass Pathways.
“Our hypothesis is that the differences happened by chance… but we can only figure this out by doing more experiments,” he said.
The question of long-term impact also remains open, as when the participants were followed up at three months, it had vanished. Repeat doses may be necessary, and future trials will test two doses, Goodwin said.
– “Greater flexibility” –
Psilocybin produces an increase in dopamine (which regulates mood) and another neurotransmitter that can promote brain plasticity, Rucker said.
“When the brain is more flexible, it opens up what we think of as a therapeutic window of opportunity, where, in the context … of psychotherapy, you may be able to bring about positive changes in people’s minds,” Rucker said. .
Psilocybin, which is not addictive, promotes “increased communication between brain regions,” added Nadav Liam Modlin, also a co-author of the study.
This substance is also studied for other pathologies, such as post-traumatic stress, anorexia, anxiety and addictions.
In 2020, the state of Oregon voted in favor of the therapeutic use of psilocybin. Exemptions have also been granted in Canada.
But at the federal level it is treated as a dangerous drug, in the same category as heroin.
