The Best American Nonrequired Reading 2016

by Rachel Kushner

  This might help explain why so many cancer patients in the trials reported that their fear of death had lifted or at least abated: they had stared directly at death and come to know something about it, in a kind of dress rehearsal. “A high-dose psychedelic experience is death practice,” Katherine MacLean, the former Hopkins psychologist, said. “You’re losing everything you know to be real, letting go of your ego and your body, and that process can feel like dying.” And yet you don’t die; in fact, some volunteers become convinced by the experience that consciousness may somehow survive the death of their bodies.

  In follow-up discussions with Bossis, Patrick Mettes spoke of his body and his cancer as a “type of illusion” and how there might be “something beyond this physical body.” It also became clear that, psychologically, at least, Mettes was doing remarkably well: he was meditating regularly, felt he had become better able to live in the present, and described loving his wife “even more.” In a session in March, two months after his journey, Bossis noted that Mettes “reports feeling the happiest in his life.”

  How are we to judge the veracity of the insights gleaned during a psychedelic journey? It’s one thing to conclude that love is all that matters, but quite another to come away from a therapy convinced that “there is another reality” awaiting us after death, as one volunteer put it, or that there is more to the universe—and to consciousness—than a purely materialist world view would have us believe. Is psychedelic therapy simply foisting a comforting delusion on the sick and dying?

  “That's above my pay grade,” Bossis said, with a shrug, when I asked him. Bill Richards cited William James, who suggested that we judge the mystical experience not by its veracity, which is unknowable, but by its fruits: does it turn someone’s life in a positive direction?

  Many researchers acknowledge that the power of suggestion may play a role when a drug like psilocybin is administered by medical professionals with legal and institutional sanction: under such conditions, the expectations of the therapist are much more likely to be fulfilled by the patient. (And bad trips are much less likely to occur.) But who cares, some argue, as long as it helps? David Nichols, an emeritus professor of pharmacology at Purdue University—and a founder, in 1993, of the Heffter Research Institute, a key funder of psychedelic research—put the pragmatic case most baldly in a recent interview with Science: “If it gives them peace, if it helps people to die peacefully with their friends and their family at their side, I don’t care if it’s real or an illusion.”

  Roland Griffiths is willing to consider the challenge that the mystical experience poses to the prevailing scientific paradigm. He conceded that “authenticity is a scientific question not yet answered” and that all that scientists have to go by is what people tell them about their experiences. But he pointed out that the same is true for much more familiar mental phenomena.

  “What about the miracle that we are conscious? Just think about that for a second, that we are aware we’re aware!” Insofar as I was on board for one miracle well beyond the reach of materialist science, Griffiths was suggesting, I should remain open to the possibility of others.

  “I’m willing to hold that there’s a mystery here we don’t understand, that these experiences may or may not be ‘true,’” he said. “What’s exciting is to use the tools we have to explore and pick apart this mystery.”

  Perhaps the most ambitious attempt to pick apart the scientific mystery of the psychedelic experience has been taking place in a lab based at Imperial College, in London. There a thirty-four-year-old neuroscientist named Robin Carhart-Harris has been injecting healthy volunteers with psilocybin and LSD and then using a variety of scanning tools—including fMRI and magnetoencephalography (MEG)—to observe what happens in their brains.

  Carhart-Harris works in the laboratory of David Nutt, a prominent English psychopharmacologist. Nutt served as the drug-policy adviser to the Labour Government until 2011, when he was fired for arguing that psychedelic drugs should be rescheduled on the ground that they are safer than alcohol or tobacco and potentially invaluable to neuroscience. Carhart-Harris’s own path to neuroscience was an eccentric one. First, he took a graduate course in psychoanalysis—a field that few neuroscientists take seriously, regarding it less as a science than as a set of untestable beliefs. Carhart-Harris was fascinated by psychoanalytic theory but frustrated by the paucity of its tools for exploring what it deemed most important about the mind: the unconscious.

  “If the only way we can access the unconscious mind is via dreams and free association, we aren’t going to get anywhere,” he said. “Surely there must be something else.” One day, he asked his seminar leader if that might be a drug. She was intrigued. He set off to search the library catalogue for “LSD and the Unconscious” and found Realms of the Human Unconscious, by Stanislav Grof. “I read the book cover to cover. That set the course for the rest of my young life.”

  Carhart-Harris, who is slender and intense, with large pale-blue eyes that seldom blink, decided that he would use psychedelic drugs and modern brain-imaging techniques to put a foundation of hard science beneath psychoanalysis. “Freud said dreams were the royal road to the unconscious,” he said in our first interview. “LSD may turn out to be the superhighway.” Nutt agreed to let him follow this hunch in his lab. He ran bureaucratic interference and helped secure funding (from the Beckley Foundation, which supports psychedelic research).

  When, in 2010, Carhart-Harris first began studying the brains of volunteers on psychedelics, neuroscientists assumed that the drugs somehow excited brain activity—hence the vivid hallucinations and powerful emotions that people report. But when Carhart-Harris looked at the results of the first set of fMRI scans—which pinpoint areas of brain activity by mapping local blood flow and oxygen consumption—he discovered that the drug appeared to substantially reduce brain activity in one particular region: the “default-mode network.”

  The default-mode network was first described in 2001, in a landmark paper by Marcus Raichle, a neurologist at Washington University, in St. Louis, and it has since become the focus of much discussion in neuroscience. The network comprises a critical and centrally situated hub of brain activity that links parts of the cerebral cortex to deeper, older structures in the brain, such as the limbic system and the hippocampus.

  The network, which consumes a significant portion of the brain’s energy, appears to be most active when we are least engaged in attending to the world or to a task. It lights up when we are daydreaming, removed from sensory processing, and engaging in higher-level “meta-cognitive” processes such as self-reflection, mental time travel, rumination, and “theory of mind”—the ability to attribute mental states to others. Carhart-Harris describes the default-mode network variously as the brain’s “orchestra conductor” or “corporate executive” or “capital city,” charged with managing and “holding the entire system together.” It is thought to be the physical counterpart of the autobiographical self, or ego.

  “The brain is a hierarchical system,” Carhart-Harris said. “The highest-level parts”—such as the default-mode network—“have an inhibitory influence on the lower-level parts, like emotion and memory.” He discovered that blood flow and electrical activity in the default-mode network dropped off precipitously under the influence of psychedelics, a finding that may help to explain the loss of the sense of self that volunteers reported. (The biggest dropoffs in default-mode-network activity correlated with volunteers’ reports of ego dissolution.) Just before Carhart-Harris published his results, in a 2012 paper in Proceedings of the National Academy of Sciences, a researcher at Yale named Judson Brewer, who was using fMRI to study the brains of experienced meditators, noticed that their default-mode networks had also been quieted relative to those of novice meditators. It appears that, with the ego temporarily out of commission, the boundaries between self and world, subject and object, all dissolve. These are hallmarks of the mystical experience.

  If the default-mode ne
twork functions as the conductor of the symphony of brain activity, we might expect its temporary disappearance from the stage to lead to an increase in dissonance and mental disorder—as appears to happen during the psychedelic journey. Carhart-Harris has found evidence in scans of brain waves that, when the default-mode network shuts down, other brain regions “are let off the leash.” Mental contents hidden from view (or suppressed) during normal waking consciousness come to the fore: emotions, memories, wishes and fears. Regions that don’t ordinarily communicate directly with one another strike up conversations (neuroscientists sometimes call this “crosstalk"), often with bizarre results. Carhart-Harris thinks that hallucinations occur when the visual-processing centers of the brain, left to their own devices, become more susceptible to the influence of our beliefs and emotions.

  Carhart-Harris doesn’t romanticize psychedelics, and he has little patience for the sort of “magical thinking” and “metaphysics” they promote. In his view, the forms of consciousness that psychedelics unleash are regressions to a more “primitive style of cognition.” Following Freud, he says that the mystical experience—whatever its source—returns us to the psychological condition of the infant, who has yet to develop a sense of himself as a bounded individual. The pinnacle of human development is the achievement of the ego, which imposes order on the anarchy of a primitive mind buffeted by magical thinking. (The developmental psychologist Alison Gopnik has speculated that the way young children perceive the world has much in common with the psychedelic experience. As she puts it, “They’re basically tripping all the time.”) The psychoanalytic value of psychedelics, in his view, is that they allow us to bring the workings of the unconscious mind “into an observable space.”

  In The Doors of Perception, Aldous Huxley concluded from his psychedelic experience that the conscious mind is less a window on reality than a furious editor of it. The mind is a “reducing valve,” he wrote, eliminating far more reality than it admits to our conscious awareness, lest we be overwhelmed. “What comes out at the other end is a measly trickle of the kind of consciousness which will help us to stay alive.” Psychedelics open the valve wide, removing the filter that hides much of reality, as well as dimensions of our own minds, from ordinary consciousness. Carhart-Harris has cited Huxley’s metaphor in some of his papers, likening the default-mode network to the reducing valve, but he does not agree that everything that comes through the opened doors of perception is necessarily real. The psychedelic experience, he suggests, can yield a lot of “fool’s gold.”

  Nevertheless, Carhart-Harris believes that the psychedelic experience can help people by relaxing the grip of an overbearing ego and the rigid, habitual thinking it enforces. The human brain is perhaps the most complex system there is, and the emergence of a conscious self is its highest achievement. By adulthood, the mind has become very good at observing and testing reality and developing confident predictions about it that optimize our investments of energy (mental and otherwise) and therefore our survival. Much of what we think of as perceptions of the world are really educated guesses based on past experience (“That fractal pattern of little green bits in my visual field must be a tree”), and this kind of conventional thinking serves us well.

  But only up to a point. In Carhart-Harris’s view, a steep price is paid for the achievement of order and ego in the adult mind. “We give up our emotional lability,” he told me, “our ability to be open to surprises, our ability to think flexibly, and our ability to value nature.” The sovereign ego can become a despot. This is perhaps most evident in depression, when the self turns on itself and uncontrollable introspection gradually shades out reality. In “The Entropic Brain,” a paper published last year in Frontiers in Human Neuroscience, Carhart-Harris cites research indicating that this debilitating state, sometimes called “heavy self-consciousness,” may be the result of a “hyperactive” default-mode network. The lab recently received government funding to conduct a clinical study using psychedelics to treat depression.

  Carhart-Harris believes that people suffering from other mental disorders characterized by excessively rigid patterns of thinking, such as addiction and obsessive-compulsive disorder, could benefit from psychedelics, which “disrupt stereotyped patterns of thought and behavior.” In his view, all these disorders are, in a sense, ailments of the ego. He also thinks that this disruption could promote more creative thinking. It may be that some brains could benefit from a little less order.

  Existential distress at the end of life bears many of the psychological hallmarks of a hyperactive default-mode network, including excessive self-reflection and an inability to jump the deepening grooves of negative thought. The ego, faced with the prospect of its own dissolution, becomes hypervigilant, withdrawing its investment in the world and other people. It is striking that a single psychedelic experience—an intervention that Carhart-Harris calls “shaking the snow globe”—should have the power to alter these patterns in a lasting way.

  This appears to be the case for many of the patients in the clinical trial of psilocybin just concluded at Hopkins and N.Y.U. Patrick Mettes lived for seventeen months after his psilocybin journey, and, according to Lisa, he enjoyed many unexpected satisfactions in that time, along with a dawning acceptance of death.

  “We still had our arguments,” Lisa recalled. “And we had a very trying summer,” as they endured a calamitous apartment renovation. But Patrick “had a sense of patience he had never had before, and with me he had real joy about things,” she said. “It was as if he had been relieved of the duty of caring about the details of life. Now it was about being with people, enjoying his sandwich and the walk on the promenade. It was as if we lived a lifetime in a year.”

  After the psilocybin session, Mettes spent his good days walking around the city. “He would walk everywhere, try every restaurant for lunch, and tell me about all these great places he’d discovered. But his good days got fewer and fewer.” In March 2012, he stopped chemo. “He didn’t want to die,” she said. “But I think he just decided that this is not how he wanted to live.”

  In April, his lungs failing, Mettes wound up back in the hospital. “He gathered everyone together and said goodbye, and explained that this is how he wanted to die. He had a very conscious death.”

  Mettes’s equanimity exerted a powerful influence on everyone around him, Lisa said, and his room in the palliative-care unit at Mt. Sinai became a center of gravity. “Everyone, the nurses and the doctors, wanted to hang out in our room—they just didn’t want to leave. Patrick would talk and talk. He put out so much love.” When Tony Bossis visited Mettes the week before he died, he was struck by Mettes’s serenity. “He was consoling me. He said his biggest sadness was leaving his wife. But he was not afraid.”

  Lisa took a picture of Patrick a few days before he died, and when it popped open on my screen it momentarily took my breath away: a gaunt man in a hospital gown, an oxygen clip in his nose, but with shining blue eyes and a broad smile.

  Lisa stayed with him in his hospital room night after night, the two of them often talking into the morning hours. “I feel like I have one foot in this world and one in the next,” he told her at one point. Lisa told me, “One of the last nights we were together, he said, ‘Honey, don’t push me. I’m finding my way.’”

  Lisa hadn’t had a shower in days, and her brother encouraged her to go home for a few hours. Minutes before she returned, Patrick slipped away. “He wasn’t going to die as long as I was there,” she said. “My brother had told me, ‘You need to let him go.’”

  Lisa said she feels indebted to the people running the N.Y.U. trial and is convinced that the psilocybin experience “allowed him to tap into his own deep resources. That, I think, is what these mind-altering drugs do.”

  Despite the encouraging results from the N.Y.U. and Hopkins trials, much stands in the way of the routine use of psychedelic therapy. “We don’t die well in America,” Bossis recently said over lunch at a restaurant near the N.Y.U.
medical center. “Ask people where they want to die, and they will tell you at home, with their loved ones. But most of us die in an I.C.U. The biggest taboo in American medicine is the conversation about death. To a doctor, it’s a defeat to let a patient go.” Bossis and several of his colleagues described the considerable difficulty they had recruiting patients from N.Y.U.’s cancer center for the psilocybin trials. “I’m busy trying to keep my patients alive,” one oncologist told Gabrielle Agin-Liebes, the trial’s project manager. Only when reports of positive experiences began to filter back to the cancer center did nurses there—not doctors—begin to tell patients about the trial.

  Recruitment is only one of the many challenges facing a Phase III trial of psilocybin, which would involve hundreds of patients at multiple locations and cost millions of dollars. The University of Wisconsin and the University of California, Los Angeles, are making plans to participate in such a trial, but F.D.A. approval is not guaranteed. If the trial was successful, the government would be under pressure to reschedule psilocybin under the Controlled Substances Act, having recognized a medical use for the drug.

  Also, it seems unlikely that the government would ever fund such a study. “The N.I.M.H. is not opposed to work with psychedelics, but I doubt we would make a major investment,” Tom Insel, the institute’s director, told me. He said that the N.I.M.H. would need to see “a path to development” and suspects that “it would be very difficult to get a pharmaceutical company interested in developing this drug, since it cannot be patented.” It’s also unlikely that Big Pharma would have any interest in a drug that is administered only once or twice in the course of treatment. “There’s not a lot of money here when you can be cured with one session,” Bossis pointed out. Still, Bob Jesse and Rick Doblin are confident that they will find private money for a Phase III clinical trial, and several private funders I spoke to indicated that it would be forthcoming.