Treating depression is a major challenge, since among the millions of people affected worldwide, only one in five tends to respond well to antidepressants. And for many people who are eventually helped by drugs, it can take months, even years of cycling through the various medications to find the one that works best. In the meantime, their depression persists, and sometimes worsens.

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Now, there’s a new, albeit controversial, approach being considered by scientists. A team led by Robin Carhart-Harris, a research fellow at the center for neuropsychopharmacology at Imperial College of London, report on the encouraging results of a small group of people treated with psilocybin. Also known as magic mushrooms, psilocybin is a psychedelic drug that promotes hallucinations and reduces inhibitions.

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That’s the aspect of the drug’s effects on the brain on which Carhart-Harris and his team focused. Previous studies showed that in people with depression, parts of the brain associated with self-reflection tend to be overactive, and experts believe that may contribute to some of the rumination and negative thinking that’s the hallmark of the disease.

Because psilocybin can have almost the opposite effect on the brain, Carhart-Harris and his team wanted to investigate how psilocybin might affect depression. In their small study published in the journal Lancet Psychiatry, they studied only a dozen people who had failed to respond to at least two previous treatments for their depression. They gave them two doses of psilocybin and scanned their brains using fMRI. The participants also answered questions about their depression symptoms at the start of the study and periodically for three months.

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After one week, all reported improvement in their depression and two-thirds of the people were depression-free. By three months, about 58% showed improvement, five were in remission while five relapsed. “What these data show is that this is doable, and seems to be well tolerated,” says Carhard-Harris. “The efficacy of the treatment is impressive.”

But he’s also the first to note that the study involved only a small number of people, and these people may not be representative of the broader population of people with depression. For one, only one had not used psilocybin for depression before, and most referred themselves to the study, likely because of their interest of belief in the idea of using the drug for their depression. There was also no control group, so it’s possible there was a bias toward seeing improvements among both the participants and the researchers.

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In an accompanying commentary about the study, Philip Cowen, professor of psychopharmacology at the University of Oxford, agrees that the results are encouraging but cautions that more work is needed to fully understand how psilocybin might play a role in treating depression. Researchers first need to document whether psilocybin, for example, does something that current treatments cannot, or works in a way that is unique enough to warrant pursuing it further.

Based on his brain scan studies, and on other studies that hint at the more fundamental change that the drug can produce, Carhart-Harris is convinced that psilocybin works in a unique way to treat depression. “Psychedelic by definition means mind revealing, so what psychedelics like psilocybin offer are a way to reveal things that may be difficult to see that might be contributing to depression — things that have happened in the past, relationships and other issues we tend to put in the back of our minds and avoid but can compound depression.” It’s the same way that psychotherapy works, but perhaps more quickly.

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If that’s true, says Cowen, “having a profound psychological experience that changes the way you feel and think so you feel differently about yourself would be something rather novel,” he says.

The findings are part of growing research into more effective ways to treat depression. Work on compounds like ketamine, also a popular club drug for its dissociative effects, also looks encouraging. “On the one hand, people with depression suffer,” says Dr. Philip Muskin, professor of psychiatry at Columbia University and chair of the scientific program committee at the American Psychiatric Association. “Thinking outside the box is crucial and we need to be thinking about novel compounds to treat depression. But we should be careful. It’s not that everyone who is depressed should go out and dig up mushrooms.”

In the study, the participants were given the drug in a very controlled environment, in a darkened room with a therapist present who could help them through the peak hallucinatory periods and then work with them to understand what they experienced. More research on how psychedelic drugs should be given to treat mental illness are worth studying, he says. “I do think it’s very exciting and we should be looking scientifically at how this can help patients. If we get one more patient better, then that’s fantastic.”

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