Something unexpected happened when, early in 2017, Roland Griffiths and Stephen Ross brought the results of their clinical trials to the FDA, hoping to win approval for a larger, phase 3 trial of psilocybin for cancer patients. Impressed by their data—and seemingly undeterred by the unique challenges posed by psychedelic research, such as the problem of blinding, the combining of therapy and medicine, and the fact that the drug in question is still illegal—the FDA staff surprised the researchers by asking them to expand their focus and ambition: to test whether psilocybin could be used to treat the much larger and more pressing problem of depression in the general population.
As the regulators saw it, the data contained a strong enough “signal” that psilocybin could relieve depression; it would be a shame not to test the proposition, given the enormity of the need and the limitations of the therapies now available. Ross and Griffiths had focused on cancer patients because they thought it would be easier to win approval to study a controlled substance in people who were already seriously ill or dying. Now the government was telling them to raise their sights. “It was surreal,” Ross told me, twice, as he recounted the meeting, still somewhat stunned at the response and outcome. (The FDA declined to confirm or deny this account of the meeting, explaining that it doesn’t comment on drugs in development or under regulatory review.)
Much the same thing happened in Europe, when, in 2016, researchers approached the European Medicines Agency (EMA)—the European Union’s drug-regulating body—seeking approval to use psilocybin in the treatment of anxiety and depression in patients with life-changing diagnoses. “Existential distress” is not an official DSM diagnosis, the regulators pointed out, so the national health services won’t cover it. But there’s a signal here that psilocybin could be useful in treating depression, so why don’t you do a big, multisite trial for that?
The EMA was responding not only to the Hopkins and NYU data but also to the small “feasibility study” of the potential of using psilocybin to treat depression that Robin Carhart-Harris had directed in David Nutt’s lab at Imperial College. In the study, the initial results of which appeared in Lancet Psychiatry in 2016, researchers gave psilocybin to six men and six women suffering from “treatment-resistant depression”—meaning they had already tried at least two treatments without success. There was no control group, so everyone knew he or she was getting psilocybin.
After a week, all of the volunteers showed improvement in their symptoms, and two-thirds of them were depression-free, in some cases for the first time in years. Seven of the twelve volunteers still showed substantial benefit after three months. The study was expanded to include a total of twenty volunteers; after six months, six remained in remission, while the others had relapsed to one degree or another, suggesting the treatment might need to be repeated. The study was modest in scale and not randomized, but it demonstrated that psilocybin was well tolerated in this population, with no adverse events, and most of the subjects had seen benefits that were marked and rapid.*
The EMA was sufficiently impressed with the data to suggest a much larger trial for treatment-resistant depression, which afflicts more than 800,000 people in Europe. (This is out of a total of some 40 million Europeans with depressive disorders, according to the World Health Organization.) Rosalind Watts was a young clinical psychologist working for the National Health Service when she read an article about psychedelic therapy in the New Yorker.
The idea that you might actually be able to cure mental illness rather than just manage its symptoms inspired her to write to Robin Carhart-Harris, who hired her to help out with the depression study, the lab’s first foray into clinical research. Watts guided several sessions and then conducted qualitative interviews with all of the volunteers six months after their treatments, hoping to understand exactly how the psychedelic session had affected them.
Watts’s interviews uncovered two “master” themes. The first was that the volunteers depicted their depression foremost as a state of “disconnection,” whether from other people, their earlier selves, their senses and feelings, their core beliefs and spiritual values, or nature. Several referred to living in “a mental prison,” others to being “stuck” in endless circles of rumination they likened to mental “grid-lock.” I was reminded of Carhart-Harris’s hypothesis that depression might be the result of an overactive default mode network—the site in the brain where rumination appears to take place. The Imperial depressives also felt disconnected from their senses. “I would look at orchids,” one told Watts, “and intellectually understand that there was beauty, but not experience it.”
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For most of the volunteers, the psilocybin experience had sprung them from their mental jails, if only temporarily. One woman in the study told me that the month following her session was the first time she had been free from depression since 1991. Others described similar experiences:
“It was like a holiday away from the prison of my brain. I felt free, carefree, reenergized.”
“It was like the light switch being turned on in a dark house.”
“You’re not immersed in thought patterns; the concrete coat has come off.”
“It was like when you defrag the hard drive on your computer . . . I thought, ‘My brain is being defragged, how brilliant is that!’”
For many of the volunteers, these changes in the experience of their own minds persisted:
“My mind works differently. I ruminate much less, and my thoughts feel ordered, contextualized.”
Several reported reconnecting to their senses:
“A veil dropped from my eyes, things were suddenly clear, glowing, bright. I looked at plants and felt their beauty. I can still look at my orchids and feel that: that is one thing that has really lasted.”
Some reconnected to themselves: “I had an experience of tenderness toward myself.” “At its most basic, I feel like I used to before the depression.” Others reconnected to other people:
“I was talking to strangers. I had these full long conversations with everybody I came into contact with.”
“I would look at people on the street and think, ‘How interesting we are’—I felt connected to them all.”
And to nature:
“Before, I enjoyed nature; now I feel part of it. Before I was looking at it as a thing, like TV or painting. You’re part of it, there’s no separation or distinction, you are it.”
“I was everybody, unity, one life with 6 billion faces. I was the one asking for love and giving love, I was swimming in the sea, and the sea was me.”
The second master theme was a new access to difficult emotions, emotions that depression often blunts or closes down completely. Watts hypothesizes that the depressed patient’s incessant rumination constricts his or her emotional repertoire. In other cases, the depressive keeps emotions at bay because it is too painful to experience them.
This is especially true in cases of childhood trauma. Watts put me in touch with a thirty-nine-year-old man in the study, a music journalist named Ian Rouiller, who, along with his older sister, had been abused by his father as a child. As adults, the siblings brought charges against their father that put him in jail for several years, but this hadn’t relieved the depression that has trailed Ian for most of his life.
“I can remember the moment when the horrible cloud first came over me. It was in the family room of a pub called the Fighting Cocks in St. Albans. I was ten.” Antidepressants helped for a while, but “putting the plaster over the wound doesn’t heal anything.” On psilocybin, he was able for the first time to confront his lifelong pain— and his father.
“Normally, when Dad comes up in my head, I just push the thought away. But this time I went the other way.” His guide had told him he should “go in and through” any frightening material that arose during his journey.
“So this time I looked him in the eye. That was a really big thing for me, to literally face the demon. And there he was. But he was a horse! A military horse standing on its hind legs, dressed in a military outfit with a helmet, and holding a gun. It was terrifying, and I wanted to push the image aside, but I didn’t. In and through: Instead, I looked the horse in the eyes—and promptly started to laugh, it was so ridiculous.
“That’s when what had been a bad trip really turned. Now I had every sort of emotion, positive, negative, it didn’t matter. I thought about the [Syrian] refugees in Calais and started crying for them, and I saw that every emotion is as valid as any other. You don’t cherry-pick happiness and enjoyment, the so-called good emotions; it was okay to have negative thoughts. That’s life. For me, trying to resist emotions just amplified them. Once I was in this state, it was beautiful—a feeling of deep contentment. I had this overwhelming feeling—it wasn’t even a thought—that everything and everyone needs to be approached with love, including myself.”
Ian enjoyed several months of relief from his depression as well as a new perspective on his life—something no antidepressant had ever given him. “Like Google Earth, I had zoomed out,” he told Watts in his six-month interview. For several weeks after his session, “I was absolutely connected to myself, to every living thing, to the universe.” Eventually, Ian’s overview effect faded, however, and he ended up back on Zoloft.
“The sheen and shine that life and existence had regained immediately after the trial and for several weeks after gradually faded,” he wrote one year later. “The insights I gained during the trial have never left and will never leave me. But they now feel more like ideas,” he says.
He says he’s doing better than before and has been able to hold down a job, but his depression has returned. He told me he wishes he could have another psilocybin session at Imperial. Because that’s currently not an option, he’ll sometimes meditate and listen to the playlist from his session. “That really does help put me back in that place.”
More than half of the Imperial volunteers saw the clouds of their depression eventually return, so it seems likely that psychedelic therapy for depression, should it prove useful and be approved, will not be a onetime intervention. But even the temporary respite the voluneers regarded as precious, because it reminded them there was another way to be that was worth working to recapture. Like electroconvulsive therapy for depression, which it in some ways resembles, psychedelic therapy is a shock to the system—a “reboot” or “defragging”—that may need to be repeated every so often. (Assuming the treatment works as well when repeated.) But the potential of the therapy has regulators and researchers and much of the mental health community feeling hopeful.
“I believe this could revolutionize mental health care,” Watts told me. Her conviction is shared by every other psychedelic researcher I interviewed.
This article is excerpted from How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence by Michael Pollan, published by Penguin Press, an imprint of Penguin Publishing Group, a division of Penguin Random House, LLC, out now. Copyright © 2018 by Michael Pollan.
Correction 5/25/18: This story was originally published with the headline The Two Things Psychedelics Do to Most People With Depression. It has since been corrected for accuracy.
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