How to Change Your Mind

by Michael Pollan

  As for the unwell, the patients who stand to gain the most are probably those suffering from the kinds of mental disorders characterized by mental rigidity: addiction, depression, obsession.

  “There are a range of difficulties and pathologies in adults, like depression, that are connected with the phenomenology of rumination and an excessively narrow, ego-based focus,” Gopnik says. “You get stuck on the same thing, you can’t escape, you become obsessive, perhaps addicted. It seems plausible to me that the psychedelic experience could help us get out of those states, create an opportunity in which the old stories of who we are might be rewritten.” The experience could work as a kind of reset—as when you “introduce a burst of noise into a system” that has gotten locked into a rigid pattern. Quieting the default mode network and loosening the grip of the ego—which she suggests may be illusory anyway—might also be helpful to such people. Gopnik’s idea of a brain reboot sounded very much like Carhart-Harris’s notion of shaking the snow globe: a way to boost entropy, or heat, in a system that has gotten frozen stuck.

  Soon after publishing his entropy paper, Carhart-Harris resolved to put some of his theories into practice by testing them on patients. For the first time, the lab expanded its focus from pure research to a clinical application of that work. David Nutt secured a grant from the U.K. government for the lab to conduct a small pilot study looking at the potential of psilocybin to relieve the symptoms of “treatment-resistant depression”—patients who hadn’t responded to the usual therapeutic protocols and drugs.

  Doing clinical work was definitely outside Carhart-Harris’s experience and comfort zone, as well as the lab’s. One unfortunate early episode pointed up the inherent tensions between the roles of the clinician, devoted solely to the patient’s welfare, and the scientist, intent on gathering data as well. After being injected with LSD in a trial Carhart-Harris was running (not a clinical trial, it should be pointed out), a volunteer in his late thirties named Toby Slater began feeling anxious in the fMRI scanner and asked to get out. After taking a break, Slater, perhaps hoping to please the researchers, volunteered to get back in the machine so they could complete the experiment. (“I’m afraid he could see my disappointment,” Carhart-Harris recalls, ruefully.) But Slater’s anxiety returned: “I felt like a lab rat,” he told me. He asked to get out again and tried to leave the lab. The researchers had to persuade him to stay and let them administer a sedative.

  Carhart-Harris describes the episode—one of the very few adverse events seen in the Imperial research—as “a learning experience” and, by all accounts, he has since shown himself to be a compassionate and effective clinician as well as an original scientist—surely a rare combination. The response of most patients in the depression trial, as we will see in the following chapter, has been remarkably positive, at least in the short term. Over dinner at a restaurant in West London, Robin told me about one severely depressed woman in the trial whom over the course of several meetings he had never once seen smile. As he sat with her during her psilocybin journey, “she smiled for the very first time.

  “‘It’s nice to smile,’ she said.

  “After it was over, she told me she had been visited by a guardian angel. She described a presence of some kind, a voice that was entirely supportive and wanted her to be well. It would say things like ‘Darling, you need to smile more, hold your head up high, stop looking down at the ground. Then it reached over and pushed up my cheeks,’ she said, ‘lifting the corners of my mouth.’

  “That must have been what was happening in her mind when I observed her smiling,” Robin said, now smiling himself, broadly if a bit sheepishly. In the aftermath of her experience, the woman’s depression score dropped from thirty-six to four.

  “I have to say, that was a very nice feeling.”

  CHAPTER SIX

  THE TRIP TREATMENT

  Psychedelics in Psychotherapy

  One: Dying

  AT NEW YORK UNIVERSITY, psilocybin trips take place in a treatment room carefully decorated to look more like a cozy den than a hospital suite. The effect almost works, but not entirely, for the stainless steel and plastic fittings of modern medicine peek through the domestic scrim here and there, chilly reminders that the room you are tripping in is still in the belly of a big city hospital complex.

  Against one wall is a comfortable couch long enough for a patient to stretch out on during a session. An abstract painting—or is it a cubist landscape?—hangs on the opposite wall, and on the bookshelves large-format books about art and mythology share space with native craft items and spiritual knickknacks—a large glazed ceramic mushroom, a Buddha, a crystal. This could be the apartment of a well-traveled shrink of a certain age, one with an interest in Eastern religions and the art of what used to be called primitive cultures. Yet the illusion crumbles as soon as you lift your gaze to the ceiling, where the tracks that would ordinarily support the curtains dividing one hospital bed from another traverse the white acoustic tiles. And then there is the supersized bathroom, ablaze with fluorescent light and outfitted with the requisite grab bars and pedals.

  It was here in this room that I first heard the story of Patrick Mettes, a volunteer in NYU’s psilocybin cancer trial who, in the course of a turbulent six-hour psilocybin journey on the couch where I now sat, had a life-changing—or perhaps I should say death-changing—experience. I had come to interview Tony Bossis, the palliative care psychologist who guided Mettes that day, and his colleague Stephen Ross, the Bellevue psychiatrist who directed the trial, which sought to determine whether a single high dose of psilocybin could alleviate the anxiety and depression that often follow a life-threatening cancer diagnosis.

  While Bossis, hirsute and bearish, looks the part of a fifty-something Manhattan shrink with an interest in alternative therapies, Ross, who is in his forties, comes across as more of a straight arrow; neatly trimmed in a suit and tie, he could pass for a Wall Street banker. A bookish teenager growing up in L.A., Ross says he had no personal experience of psychedelics and knew next to nothing about them before a colleague happened to mention that LSD had been used successfully to treat alcoholics in the 1950s and 1960s. This being his psychiatric specialty, Ross did some research and was astonished to discover a “completely buried body of knowledge.” By the 1990s, when he began his residency in psychiatry at Columbia and the New York State Psychiatric Institute, the history of psychedelic therapy had been erased from the field, never to be mentioned.

  The trial at NYU, along with a sister study conducted in Roland Griffiths’s lab at Johns Hopkins, represents one of a handful of efforts to pick up the thread of inquiry that got dropped in the 1970s when sanctioned psychedelic therapy ended. While the NYU and Hopkins trials are assessing the potential of psychedelics to help the dying, other trials now under way are exploring the possibility that psychedelics (usually psilocybin rather than LSD, because, as Ross explained, it “carries none of the political baggage of those three letters”) could be used to lift depression and break addictions—to alcohol, cocaine, and tobacco.

  None of this work is exactly new: to delve into the history of clinical research with psychedelics is to realize that most of this ground has already been tilled. Charles Grob, the UCLA psychiatrist whose 2011 pilot study of psilocybin for cancer anxiety cleared the path for the NYU and Hopkins trials, acknowledges that “in a lot of ways we are simply picking up the torch from earlier generations of researchers who had to put it down because of cultural pressures.” But if psychedelics are ever to find acceptance in modern medicine, all this buried knowledge will need to be excavated and the experiments that produced it reprised according to the prevailing scientific standards.

  Yet even as psychedelic therapies are being tested by modern science, the very strangeness of these molecules and their actions upon the mind is at the same time testing whether Western medicine can deal with the implicit challenges they pose. To cite one obvious example, co
nventional drug trials of psychedelics are difficult if not impossible to blind: most participants can tell whether they’ve received psilocybin or a placebo, and so can their guides. Also, in testing these drugs, how can researchers hope to tease out the chemical’s effect from the critical influence of set and setting? Western science and modern drug testing depend on the ability to isolate a single variable, but it isn’t clear that the effects of a psychedelic drug can ever be isolated, whether from the context in which it is administered, the presence of the therapists involved, or the volunteer’s expectations. Any of these factors can muddy the waters of causality. And how is Western medicine to evaluate a psychiatric drug that appears to work not by means of any strictly pharmacological effect but by administering a certain kind of experience in the minds of the people who take it?

  Add to this the fact that the kind of experience these drugs sponsor often goes under the heading of “spiritual,” and you have, with psychedelic therapy, a very large pill for modern medicine to swallow. Charles Grob well appreciates the challenge but is also refreshingly unapologetic about it: he describes psychedelic therapy as a form of “applied mysticism.” This is surely an odd phrase to hear on the lips of a scientist, and to many ears it sounds dangerously unscientific.

  “For me that is not a medical concept,” Franz Vollenweider, the pioneering psychedelic researcher, told Science magazine, when asked to comment on the role of mysticism in psychedelic therapy. “It’s more like an interesting shamanic concept.” But other researchers working on psychedelics don’t run from the idea that elements of shamanism might have a role to play in psychedelic therapy—as indeed it has probably done for several thousand years before there was such a thing as science. “If we are to develop optimal research designs for evaluating the therapeutic utility of hallucinogens,” Grob has written, “it will not be sufficient to adhere to strict standards of scientific methodology alone. We must also pay heed to the examples provided us by such successful applications of the shamanic paradigm.” Under that paradigm, the shaman/therapist carefully orchestrates “extrapharmacological variables” such as set and setting in order to put the “hyper-suggestible properties” of these medicines to best use. This is precisely where psychedelic therapy seems to be operating: on a frontier between spirituality and science that is as provocative as it is uncomfortable.

  Yet the new research into psychedelics comes along at a time when mental health treatment in this country is so “broken”—to use the word of Tom Insel, who until 2015 was director of the National Institute of Mental Health—that the field’s willingness to entertain radical new approaches is perhaps greater than it has been in a generation. The pharmacological toolbox for treating depression—which afflicts nearly a tenth of all Americans and, worldwide, is the leading cause of disability—has little in it today, with antidepressants losing their effectiveness* and the pipeline for new psychiatric drugs drying up. Pharmaceutical companies are no longer investing in the development of so-called CNS drugs—medicines targeted at the central nervous system. The mental health system reaches only a fraction of the people suffering from mental disorders, most of whom are discouraged from seeking treatment by its cost, social stigma, or ineffectiveness. There are almost forty-three thousand suicides every year in America (more than the number of deaths from either breast cancer or auto accidents), yet only about half of the people who take their lives have ever received mental health treatment. “Broken” does not seem too harsh a characterization of such a system.

  Jeffrey Guss, a Manhattan psychiatrist and a coinvestigator on the NYU trial, thinks the moment could be ripe for psychotherapy to entertain a completely new paradigm. Guss points out that for many years now “we’ve had this conflict between the biologically based treatments and psychodynamic treatments. They’ve been fighting one another for legitimacy and resources. Is mental illness a disorder of chemistry, or is it a loss of meaning in one’s life? Psychedelic therapy is the wedding of those two approaches.”

  In recent years, “psychiatry has gone from being brainless to being mindless,” as one psychoanalyst has put it. If psychedelic therapy proves successful, it will be because it succeeds in rejoining the brain and the mind in the practice of psychotherapy. At least that’s the promise.

  For the therapists working with people approaching the end of life, these questions are of more than academic interest. As I chatted with Stephen Ross and Tony Bossis in the NYU treatment room, I was struck by their excitement, verging on giddiness, at the results they were observing in their cancer patients—after a single guided psilocybin session. At first, Ross couldn’t believe what he was seeing: “I thought the first ten or twenty people were plants—that they must be faking it. They were saying things like ‘I understand love is the most powerful force on the planet’ or ‘I had an encounter with my cancer, this black cloud of smoke.’ People were journeying to early parts of their lives and coming back with a profound new sense of things, new priorities. People who had been palpably scared of death—they lost their fear. The fact that a drug given once could have such an effect for so long is an unprecedented finding. We have never had anything like that in the psychiatric field.”

  This is when Tony Bossis first told me about his experience sitting with Patrick Mettes as he journeyed to a place in his mind that, somehow, lifted the siege of his terror.

  “You’re in this room, but you’re in the presence of something large. I remember how, after two hours of silence, Patrick began to cry softly and say, twice, ‘Birth and death is a lot of work.’ It’s humbling to sit there. It’s the most rewarding day of your career.”

  As a palliative care specialist, Bossis spends a lot of his time with the dying. “People don’t realize how few tools we have in psychiatry to address existential distress.” Existential distress is what psychologists call the complex of depression, anxiety, and fear common in people confronting a terminal diagnosis. “Xanax isn’t the answer.” If there is an answer, Bossis believes, it is going to be more spiritual in nature than pharmacological.

  “So how do we not explore this,” he asks, “if it can recalibrate how we die?”

  * * *

  • • •

  IT WAS ON AN APRIL MONDAY in 2010 that Patrick Mettes, a fifty-three-year-old television news director being treated for a cancer of his bile ducts, read the article on the front page of the New York Times that would change his death. His diagnosis had come three years earlier, shortly after his wife, Lisa Callaghan, noticed that the whites of his eyes had suddenly turned yellow. By 2010, the cancer had spread to Patrick’s lungs, and he was buckling under the weight of an especially debilitating chemotherapy regime and the dawning realization that he might not survive. The article, headlined “Hallucinogens Have Doctors Tuning In Again,” briefly mentioned research at NYU, where psilocybin was being tested to relieve existential distress in cancer patients. According to Lisa, Patrick had no experience with psychedelics, but he immediately determined to call NYU and volunteer.

  Lisa was against the idea. “I didn’t want there to be an easy way out,” she told me. “I wanted him to fight.”

  Patrick placed the call anyway and, after filling out some forms and answering a long list of questions, was accepted into the trial. He was assigned to Tony Bossis. Tony was roughly the same age as Patrick; he is also a soulful man of uncommon warmth and compassion, and the two immediately hit it off.

  At their first meeting, Bossis told Patrick what to expect. After three or four preparatory sessions of talking therapy, Patrick would be scheduled for two dosings—one of them an “active placebo” (in this case a high dose of niacin, which produces a tingling sensation), and the other a capsule containing twenty-five milligrams of psilocybin. Both sessions would take place in the treatment room where I met Bossis and Ross. During each session, which would last the better part of a day, Patrick would lie on the couch wearing eyeshades and listening through headphones to a playlist o
f carefully curated music—Brian Eno, Philip Glass, Pat Metheny, and Ravi Shankar, as well as some classical and New Age compositions. Two sitters—one of them male (Bossis) and the other female (Krystallia Kalliontzi)—would be in attendance for the duration, saying very little but available to help should he run into any trouble. In preparation, the two shared with Patrick the set of “flight instructions” written by the Hopkins researcher Bill Richards.

  Bossis suggested that Patrick use the phrase “Trust and let go” as a kind of mantra for his journey. Go wherever it takes you, he advised: “Climb staircases, open doors, explore paths, fly over landscapes.” But the most important advice for the journey he offered is always to move toward, rather than try to flee, anything truly threatening or monstrous you encounter—look it straight in the eyes. “Dig in your heels and ask, ‘What are you doing in my mind?’ Or, ‘What can I learn from you?’”

  * * *

  • • •

  THE IDEA OF GIVING a psychedelic drug to the dying was first broached not by a therapist or scientist but by Aldous Huxley in a letter to Humphry Osmond, proposing a research project involving “the administration of LSD to terminal cancer cases, in the hope that it would make dying a more spiritual, less strictly physiological process.” Huxley himself had his wife, Laura, give him an injection of LSD when he was on his own deathbed, on November 22, 1963.

  By then, Huxley’s idea had been tested on a number of cancer patients in North America. In 1965, Sidney Cohen wrote an essay for Harper’s (“LSD and the Anguish of Dying”) exploring the potential of psychedelics to “alter[] the experience of dying.” He described treatment with LSD as “therapy by self-transcendence.” The premise behind the approach was that our fear of death is a function of our egos, which burden us with a sense of separateness that can become unbearable as we approach death. “We are born into an egoless world,” Cohen wrote, “but we live and die imprisoned within ourselves.”