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    The Trip Treatment
    Research into psychedelics, shut down for decades, is now yielding exciting results.
    Michael Pollan
    February 9, 2015 Issue
    The New Yorker

    On an April Monday in 2010, Patrick Mettes, a fifty-four-year-old television news director being treated for a cancer of the bile ducts, read an article on the front page of the Times that would change his death. His diagnosis had come three years earlier, shortly after his wife, Lisa, noticed that the whites of his eyes had turned yellow. By 2010, the cancer had spread to Patrick’s lungs and he was buckling under the weight of a debilitating chemotherapy regimen and the growing fear that he might not survive. The article, headlined “HALLUCINOGENS HAVE DOCTORS TUNING IN AGAIN,” mentioned clinical trials at several universities, including N.Y.U., in which psilocybin—the active ingredient in so-called magic mushrooms—was being administered to cancer patients in an effort to relieve their anxiety and “existential distress.” One of the researchers was quoted as saying that, under the influence of the hallucinogen, “individuals transcend their primary identification with their bodies and experience ego-free states . . . and return with a new perspective and profound acceptance.” Patrick had never taken a psychedelic drug, but he immediately wanted to volunteer. Lisa was against the idea. “I didn’t want there to be an easy way out,” she recently told me. “I wanted him to fight.”

    Patrick made the call anyway and, after filling out some forms and answering a long list of questions, was accepted into the trial. Since hallucinogens can sometimes bring to the surface latent psychological problems, researchers try to weed out volunteers at high risk by asking questions about drug use and whether there is a family history of schizophrenia or bipolar disorder. After the screening, Mettes was assigned to a therapist named Anthony Bossis, a bearded, bearish psychologist in his mid-fifties, with a specialty in palliative care. Bossis is a co-principal investigator for the N.Y.U. trial.

    After four meetings with Bossis, Mettes was scheduled for two dosings—one of them an “active” placebo (in this case, a high dose of niacin, which can produce a tingling sensation), and the other a pill containing the psilocybin. Both sessions, Mettes was told, would take place in a room decorated to look more like a living room than like a medical office, with a comfortable couch, landscape paintings on the wall, and, on the shelves, books of art and mythology, along with various aboriginal and spiritual tchotchkes, including a Buddha and a glazed ceramic mushroom. During each session, which would last the better part of a day, Mettes would lie on the couch wearing an eye mask and listening through headphones to a carefully curated playlist—Brian Eno, Philip Glass, Pat Metheny, Ravi Shankar. Bossis and a second therapist would be there throughout, saying little but being available to help should he run into any trouble.

    I met Bossis last year in the N.Y.U. treatment room, along with his colleague Stephen Ross, an associate professor of psychiatry at N.Y.U.’s medical school, who directs the ongoing psilocybin trials. Ross, who is in his forties, was dressed in a suit and could pass for a banker. He is also the director of the substance-abuse division at Bellevue, and he told me that he had known little about psychedelics—drugs that produce radical changes in consciousness, including hallucinations—until a colleague happened to mention that, in the nineteen-sixties, LSD had been used successfully to treat alcoholics. Ross did some research and was astounded at what he found.

    “I felt a little like an archeologist unearthing a completely buried body of knowledge,” he said. Beginning in the nineteen-fifties, psychedelics had been used to treat a wide variety of conditions, including alcoholism and end-of-life anxiety. The American Psychiatric Association held meetings centered on LSD. “Some of the best minds in psychiatry had seriously studied these compounds in therapeutic models, with government funding,” Ross said.

    Between 1953 and 1973, the federal government spent four million dollars to fund a hundred and sixteen studies of LSD, involving more than seventeen hundred subjects. (These figures don’t include classified research.) Through the mid-nineteen-sixties, psilocybin and LSD were legal and remarkably easy to obtain. Sandoz, the Swiss chemical company where, in 1938, Albert Hofmann first synthesized LSD, gave away large quantities of Delysid—LSD—to any researcher who requested it, in the hope that someone would discover a marketable application. Psychedelics were tested on alcoholics, people struggling with obsessive-compulsive disorder, depressives, autistic children, schizophrenics, terminal cancer patients, and convicts, as well as on perfectly healthy artists and scientists (to study creativity) and divinity students (to study spirituality). The results reported were frequently positive. But many of the studies were, by modern standards, poorly designed and seldom well controlled, if at all. When there were controls, it was difficult to blind the researchers—that is, hide from them which volunteers had taken the actual drug. (This remains a problem.)

    By the mid-nineteen-sixties, LSD had escaped from the laboratory and swept through the counterculture. In 1970, Richard Nixon signed the Controlled Substances Act and put most psychedelics on Schedule 1, prohibiting their use for any purpose. Research soon came to a halt, and what had been learned was all but erased from the field of psychiatry. “By the time I got to medical school, no one even talked about it,” Ross said.

    The clinical trials at N.Y.U.—a second one, using psilocybin to treat alcohol addiction, is now getting under way—are part of a renaissance of psychedelic research taking place at several universities in the United States, including Johns Hopkins, the Harbor-U.C.L.A. Medical Center, and the University of New Mexico, as well as at Imperial College, in London, and the University of Zurich. As the drug war subsides, scientists are eager to reconsider the therapeutic potential of these drugs, beginning with psilocybin. (Last month The Lancet, the United Kingdom’s most prominent medical journal, published a guest editorial in support of such research.) The effects of psilocybin resemble those of LSD, but, as one researcher explained, “it carries none of the political and cultural baggage of those three letters.” LSD is also stronger and longer-lasting in its effects, and is considered more likely to produce adverse reactions. Researchers are using or planning to use psilocybin not only to treat anxiety, addiction (to smoking and alcohol), and depression but also to study the neurobiology of mystical experience, which the drug, at high doses, can reliably occasion. Forty years after the Nixon Administration effectively shut down most psychedelic research, the government is gingerly allowing a small number of scientists to resume working with these powerful and still somewhat mysterious molecules.

    As I chatted with Tony Bossis and Stephen Ross in the treatment room at N.Y.U., their excitement about the results was evident. According to Ross, cancer patients receiving just a single dose of psilocybin experienced immediate and dramatic reductions in anxiety and depression, improvements that were sustained for at least six months. The data are still being analyzed and have not yet been submitted to a journal for peer review, but the researchers expect to publish later this year.

    “I thought the first ten or twenty people were plants—that they must be faking it,” Ross told me. “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 who had been palpably scared of death—they lost their fear. The fact that a drug given once can have such an effect for so long is an unprecedented finding. We have never had anything like it in the psychiatric field.”

    I was surprised to hear such unguarded enthusiasm from a scientist, and a substance-abuse specialist, about a street drug that, since 1970, has been classified by the government as having no accepted medical use and a high potential for abuse. But the support for renewed research on psychedelics is widespread among medical experts. “I’m personally biased in favor of these type of studies,” Thomas R. Insel, the director of the National Institute of Mental Health (N.I.M.H.) and a neuroscientist, told me. “If it proves useful to people who are really suffering, we should look at it. Just because it is a psychedelic doesn’t disqualify it in our eyes.” Nora Volkow, the director of the National Institute on Drug Abuse (NIDA), emphasized that “it is important to remind people that experimenting with drugs of abuse outside a research setting can produce serious harms.”

    Many researchers I spoke with described their findings with excitement, some using words like “mind-blowing.” Bossis said, “People don’t realize how few tools we have in psychiatry to address existential distress. Xanax isn’t the answer. So how can we not explore this, if it can recalibrate how we die?”

    Herbert D. Kleber, a psychiatrist and the director of the substance-abuse division at the Columbia University–N.Y. State Psychiatric Institute, who is one of the nation’s leading experts on drug abuse, struck a cautionary note. “The whole area of research is fascinating,” he said. “But it’s important to remember that the sample sizes are small.” He also stressed the risk of adverse effects and the importance of “having guides in the room, since you can have a good experience or a frightful one.” But he added, referring to the N.Y.U. and Johns Hopkins research, “These studies are being carried out by very well trained and dedicated therapists who know what they’re doing. The question is, is it ready for prime time?”

    The idea of giving a psychedelic drug to the dying was conceived by a novelist: Aldous Huxley. In 1953, Humphry Osmond, an English psychiatrist, introduced Huxley to mescaline, an experience he chronicled in “The Doors of Perception,” in 1954. (Osmond coined the word “psychedelic,” which means “mind-manifesting,” in a 1957 letter to Huxley.) Huxley proposed 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 had his wife inject him with the drug on his deathbed; he died at sixty-nine, of laryngeal cancer, on November 22, 1963.

    Psilocybin mushrooms first came to the attention of Western medicine (and popular culture) in a fifteen-page 1957 Life article by an amateur mycologist—and a vice-president of J. P. Morgan in New York—named R. Gordon Wasson. In 1955, after years spent chasing down reports of the clandestine use of magic mushrooms among indigenous Mexicans, Wasson was introduced to them by María Sabina, a curandera—a healer, or shaman—in southern Mexico. Wasson’s awed first-person account of his psychedelic journey during a nocturnal mushroom ceremony inspired several scientists, including Timothy Leary, a well-regarded psychologist doing personality research at Harvard, to take up the study of psilocybin. After trying magic mushrooms in Cuernavaca, in 1960, Leary conceived the Harvard Psilocybin Project, to study the therapeutic potential of hallucinogens. His involvement with LSD came a few years later.

    In the wake of Wasson’s research, Albert Hofmann experimented with magic mushrooms in 1957. “Thirty minutes after my taking the mushrooms, the exterior world began to undergo a strange transformation,” he wrote. “Everything assumed a Mexican character.” Hofmann proceeded to identify, isolate, and then synthesize the active ingredient, psilocybin, the compound being used in the current research.

    Perhaps the most influential and rigorous of these early studies was the Good Friday experiment, conducted in 1962 by Walter Pahnke, a psychiatrist and minister working on a Ph.D. dissertation under Leary at Harvard. In a double-blind experiment, twenty divinity students received a capsule of white powder right before a Good Friday service at Marsh Chapel, on the Boston University campus; ten contained psilocybin, ten an active placebo (nicotinic acid). Eight of the ten students receiving psilocybin reported a mystical experience, while only one in the control group experienced a feeling of “sacredness” and a “sense of peace.” (Telling the subjects apart was not difficult, rendering the double-blind a somewhat hollow conceit: those on the placebo sat sedately in their pews while the others lay down or wandered around the chapel, muttering things like “God is everywhere” and “Oh, the glory!”) Pahnke concluded that the experiences of eight who received the psilocybin were “indistinguishable from, if not identical with,” the classic mystical experiences reported in the literature by William James, Walter Stace, and others.

    In 1991, Rick Doblin, the director of the Multidisciplinary Association for Psychedelic Studies (MAPS), published a follow-up study, in which he tracked down all but one of the divinity students who received psilocybin at Marsh Chapel and interviewed seven of them. They all reported that the experience had shaped their lives and work in profound and enduring ways. But Doblin found flaws in Pahnke’s published account: he had failed to mention that several subjects struggled with acute anxiety during their experience. One had to be restrained and given Thorazine, a powerful antipsychotic, after he ran from the chapel and headed down Commonwealth Avenue, convinced that he had been chosen to announce that the Messiah had arrived.

    The first wave of research into psychedelics was doomed by an excessive exuberance about their potential. For people working with these remarkable molecules, it was difficult not to conclude that they were suddenly in possession of news with the power to change the world—a psychedelic gospel. They found it hard to justify confining these drugs to the laboratory or using them only for the benefit of the sick. It didn’t take long for once respectable scientists such as Leary to grow impatient with the rigmarole of objective science. He came to see science as just another societal “game,” a conventional box it was time to blow up—along with all the others.

    Was the suppression of psychedelic research inevitable? Stanislav Grof, a Czech-born psychiatrist who used LSD extensively in his practice in the nineteen-sixties, believes that psychedelics “loosed the Dionysian element” on America, posing a threat to the country’s Puritan values that was bound to be repulsed. (He thinks the same thing could happen again.) Roland Griffiths, a psychopharmacologist at Johns Hopkins University School of Medicine, points out that ours is not the first culture to feel threatened by psychedelics: the reason Gordon Wasson had to rediscover magic mushrooms in Mexico was that the Spanish had suppressed them so thoroughly, deeming them dangerous instruments of paganism.

    “There is such a sense of authority that comes out of the primary mystical experience that it can be threatening to existing hierarchical structures,” Griffiths told me when we met in his office last spring. “We ended up demonizing these compounds. Can you think of another area of science regarded as so dangerous and taboo that all research gets shut down for decades? It’s unprecedented in modern science.”

    Early in 2006, Tony Bossis, Stephen Ross, and Jeffrey Guss, a psychiatrist and N.Y.U. colleague, began meeting after work on Friday afternoons to read up on and discuss the scientific literature on psychedelics. They called themselves the P.R.G., or Psychedelic Reading Group, but within a few months the “R” in P.R.G. had come to stand for “Research.” They had decided to try to start an experimental trial at N.Y.U., using psilocybin alongside therapy to treat anxiety in cancer patients. The obstacles to such a trial were formidable: Would the F.D.A. and the D.E.A. grant permission to use the drug? Would N.Y.U.’s Institutional Review Board, charged with protecting experimental subjects, allow them to administer a psychedelic to cancer patients? Then, in July of 2006, the journal Psychopharmacology published a landmark article by Roland Griffiths, et al., titled “Psilocybin Can Occasion Mystical-Type Experiences Having Substantial and Sustained Personal Meaning and Spiritual Significance.”

    “We all rushed in with Roland’s article,” Bossis recalls. “It solidified our confidence that we could do this work. Johns Hopkins had shown it could be done safely.” The article also gave Ross the ammunition he needed to persuade a skeptical I.R.B. “The fact that psychedelic research was being done at Hopkins—considered the premier medical center in the country—made it easier to get it approved here. It was an amazing study, with such an elegant design. And it opened up the field.” (Even so, psychedelic research remains tightly regulated and closely scrutinized. The N.Y.U. trial could not begin until Ross obtained approvals first from the F.D.A., then from N.Y.U.’s Oncology Review Board, and then from the I.R.B., the Bellevue Research Review Committee, the Bluestone Center for Clinical Research, the Clinical and Translational Science Institute, and, finally, the Drug Enforcement Administration, which must grant the license to use a Schedule 1 substance.)

    Griffiths’s double-blind study reprised the work done by Pahnke in the nineteen-sixties, but with considerably more scientific rigor. Thirty-six volunteers, none of whom had ever taken a hallucinogen, received a pill containing either psilocybin or an active placebo (methylphenidate, or Ritalin); in a subsequent session the pills were reversed. “When administered under supportive conditions,” the paper concluded, “psilocybin occasioned experiences similar to spontaneously occurring mystical experiences.” Participants ranked these experiences as among the most meaningful in their lives, comparable to the birth of a child or the death of a parent. Two-thirds of the participants rated the psilocybin session among the top five most spiritually significant experiences of their lives; a third ranked it at the top. Fourteen months later, these ratings had slipped only slightly.

    Furthermore, the “completeness” of the mystical experience closely tracked the improvements reported in personal well-being, life satisfaction, and “positive behavior change” measured two months and then fourteen months after the session. (The researchers relied on both self-assessments and the assessments of co-workers, friends, and family.) The authors determined the completeness of a mystical experience using two questionnaires, including the Pahnke-Richards Mystical Experience Questionnaire, which is based in part on William James’s writing in “The Varieties of Religious Experience.” The questionnaire measures feelings of unity, sacredness, ineffability, peace and joy, as well as the impression of having transcended space and time and the “noetic sense” that the experience has disclosed some objective truth about reality. A “complete” mystical experience is one that exhibits all six characteristics. Griffiths believes that the long-term effectiveness of the drug is due to its ability to occasion such a transformative experience, but not by changing the brain’s long-term chemistry, as a conventional psychiatric drug like Prozac does.

    A follow-up study by Katherine MacLean, a psychologist in Griffiths’s lab, found that the psilocybin experience also had a positive and lasting effect on the personality of most participants. This is a striking result, since the conventional wisdom in psychology holds that personality is usually fixed by age thirty and thereafter is unlikely to substantially change. But more than a year after their psilocybin sessions volunteers who had had the most complete mystical experiences showed significant increases in their “openness,” one of the five domains that psychologists look at in assessing personality traits. (The others are conscientiousness, extroversion, agreeableness, and neuroticism.) Openness, which encompasses aesthetic appreciation, imagination, and tolerance of others’ viewpoints, is a good predictor of creativity.

    “I don’t want to use the word ‘mind-blowing,’ ” Griffiths told me, “but, as a scientific phenomenon, if you can create conditions in which seventy per cent of people will say they have had one of the five most meaningful experiences of their lives? To a scientist, that’s just incredible.”

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    I read an op ed on this topic recently. I am wildly excited to see the doors into this research opening again. Granted, part of me is excited because I personally find psychedelics fun, fascinating, and I'm an organic chemist. Still the little research that was done on them years ago showed some very interesting, and in some cases promising leads. Now we're beginning to see them even more so. For a while research was being mostly limited to non-psychedelic use, such as cluster headache medication. One of the best ways to understand the brain, is to study an abnormal brain. We know so little about psychology and how it physiologically manifests. Psychedelics produce altered states in a somewhat predictable manner. We stand to learn so much from this alone. I'm hoping this gets rolled into the BRAIN initiative in some manner.

    I'm hoping to get my hands on some shrooms this summer. Last time I did them was 2011 and it wasn't a good experience. I need to pick up where I left off.
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