A Single Psilocybin Dose May Ease Treatment-Resistant Depression, UK Trial Finds

Thirty people with depression that had resisted other treatment swallowed a single 25 mg dose of psilocybin, the active ingredient in magic mushrooms. Twenty-nine others took a placebo. Six weeks later, researchers at King's College London compared how the two groups were doing, and the gap was wide.

The study, run through the UK's National Health Service, is described by its authors as the first to test psilocybin against a placebo inside that system. The authors did not respond to multiple requests for comment. Scott Aaronson, a psychedelic researcher at Sheppard Pratt, a psychiatric hospital in Baltimore, who was not involved, said that setting is the most important piece. In his view, it shows how psychedelics might move outside the ivory towers where they have existed, and he called a state-funded health system a key step toward legalizing them as medicine.

Only people with treatment-resistant depression could take part, meaning they had already tried at least two other ways of managing the diagnosis. Sally Meikle, a psychedelic researcher at the University of Melbourne who also was not involved, noted that these are typically people who have been unwell for decades. She called the findings quite encouraging.

The researchers measured results on a depression rating scale running from zero to 60. It asks about sleep, mood, concentration, cognitive symptoms, appetite and energy. At the outset, participants averaged 29.6, a level classed as moderate depression. After six weeks, the placebo group averaged 29.3, essentially unchanged. The psilocybin group averaged 16.3, which falls in the mild range, a difference of about 13 points. Participants also had weeks of talk therapy after dosing.

The stakes are large. Nearly 300 million people worldwide live with depression, and nearly 100 million of them have not responded to conventional treatments. A separate study estimated the condition will cost the global economy around $12 trillion between 2025 and 2050, about 0.46% of annual global gross domestic product.

Both outside experts urged caution. The trial had just 60 participants, one of whom dropped out after day one, and it looked only at depression. Meikle said larger studies are needed before the drug moves into public health systems, and pointed out that people with treatment-resistant depression often carry a great deal of comorbidity, or multiple overlapping conditions.

The treatment is also not simple to deliver. Patients have several preparation sessions with a team of two therapists, then a six-to-eight-hour dosing session usually attended by two therapists, followed by integration sessions, which are therapy-like check-ins requiring more hours with licensed professionals. In Australia, Meikle said, a round of psilocybin treatment can cost 20,000 to 30,000 Australian dollars, and because the national healthcare system does not yet cover any of this research, patients pay out of pocket. Aaronson expects a patchwork in the United States, with Medicare, Medicaid and private insurers each making their own decisions.

There are risks to the person, too. Some participants experience distress, anxiety and paranoia during the dosing session, and Meikle said those effects can continue after treatment. She put it plainly: not everyone improves. Some improve and keep the gain, some do not improve at all, and some get worse.

Aaronson still believes in the work. He said there are no terrific treatments for people who have failed multiple therapies for depression, and that researchers are now developing ways to help them. What to watch next is whether larger trials confirm the result, and how any approved treatment would be paid for.