How to Change Your Mind: The New Science of Psychedelics

by Michael Pollan

LSD, was first synthesized by Albert Hofmann in 1938,

shortly before physicists split an atom of uranium for the first time. Hofmann, who worked for the Swiss pharmaceutical firm Sandoz, had been looking for a drug to stimulate circulation,

I didn’t know it at the time, but the difference between these two experiences of the same drug demonstrated something important, and special, about psychedelics: the critical influence of “set” and “setting.” Set is the mind-set or expectation one brings to the experience, and setting is the environment in which it takes place. Compared with other drugs, psychedelics seldom affect people the same way twice, because they tend to magnify whatever’s already going on both inside and outside one’s head.

Now that I had developed an intellectual appreciation for the potential value of these psychoactive substances, you might think I would have been more eager to try them. I’m not sure what I was waiting for: courage, maybe, or the right opportunity, which a busy life lived mainly on the right side of the law never quite seemed to afford. But when I began to weigh the potential benefits I was hearing about against the risks, I was surprised to learn that psychedelics are far more frightening to people than they are dangerous. Many of the most notorious perils are either exaggerated or mythical. It is virtually impossible to die from an overdose of LSD or psilocybin, for example, and neither drug is addictive.

The premise of psychedelic research is that this special group of molecules can give us access to other modes of consciousness that might offer us specific benefits, whether therapeutic, spiritual, or creative. Psychedelics are certainly not the only door to these other forms of consciousness—and I explore some non-pharmacological alternatives in these pages—but they do seem to be one of the easier knobs to take hold of and turn.

The whole idea of expanding our repertoire of conscious states is not an entirely new idea: Hinduism and Buddhism are steeped in it, and there are intriguing precedents even in Western science. William James, the pioneering American psychologist and author of The Varieties of Religious Experience, ventured into these realms more than a century ago. He returned with the conviction that our everyday waking consciousness “is but one special type of consciousness, whilst all about it, parted from it by the filmiest of screens, there lie potential forms of consciousness entirely different.”

James is speaking, I realized, of the unopened door in our minds. For him, the “touch” that could throw open the door and disclose these real...

(Mescaline, the psychedelic compound derived from the peyote cactus, was available to researchers at the time, but James was...

A final word on nomenclature. The class of molecules to which psilocybin and LSD (and mescaline, DMT, and a handful of others) belong has been called by many names in the decades since they have come to our attention. Initially, they were called hallucinogens.

many had come “to worship” Albert Hofmann, and indeed the event bore many of the hallmarks of a religious observance. Although virtually every person in that hall knew the story of LSD’s discovery by heart, Hofmann was asked to recite the creation myth one more time. (He tells the story, memorably, in his 1979 memoir, LSD, My Problem Child.)

until one April day in 1943, in the middle of the war, when Hofmann had “a peculiar presentiment” that LSD-25 deserved a second look. Here his account takes a slightly mystical turn. Normally, when a compound showing no promise was discarded, he explained, it was discarded for good. But Hofmann “liked the chemical structure of the LSD molecule,” and something about it told him that “this substance could possess properties other than those established in the first investigations.” Another mysterious anomaly occurred when he synthesized LSD-25 for the second time. Despite the meticulous precautions he always took when working with a substance as toxic as ergot, Hofmann must somehow have absorbed a bit of the chemical through his skin, because he “was interrupted in my work by unusual sensations.” Hofmann went home, lay down on a couch, and “in a dreamlike state, with eyes closed … I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors.” Thus unfolds the world’s first LSD trip, in neutral Switzerland during the darkest days of World War II. It is also the only LSD trip ever taken that was entirely innocent of expectation.

Intrigued, Hofmann decided a few days later to conduct an experiment on himself—not an uncommon practice at the time. Proceeding with what he thought was extreme caution, he ingested 0.25 milligrams—a milligram is one-thousandth of a gram—of LSD dissolved in a glass of water. This would represent a minuscule dose of any other drug, but LSD, it turns out, is one of the most potent psychoactive compounds ever discovered, active at doses measured in micrograms—that is, one thousandth of a milligram. This surprising fact would soon inspire scientists to look for, and eventually find, the brain receptors and the endogenous chemical—serotonin—that activates them like a key in a lock, as a way to explain how such a small number of molecules could have such a profound effect on the mind. In this and other ways, Hofmann’s discovery helped to launch modern brain science in the 1950s.

Now unfolds the world’s first bad acid trip as Hofmann is plunged into what he is certain is irretrievable madness. He tells his lab assistant he needs to get home, and with the use of automobiles restricted during wartime, he somehow manages to pedal home by bicycle and lie down while his assistant summons the doctor. (Today LSD devotees celebrate “Bicycle Day” each year on April 19.) Hofmann describes how “familiar objects and pieces of furniture assumed grotesque, threatening forms. They were in continuous motion, animated as if driven by an inner restlessness.” He experienced the disintegration of the outer world and the dissolution of his own ego. “A demon had invaded me, had taken possession of my body, mind, and soul. I jumped up and screamed, trying to free myself from him, but then sank down again and lay helpless on the sofa.” Hofmann became convinced he was going to be rendered permanently insane or might actually be dying. “My ego was suspended somewhere in space and I saw my body lying dead ...

The second watershed event of 2006 came only five weeks later when the U.S. Supreme Court, in a unanimous decision written by the new chief justice, John G. Roberts Jr., ruled that the UDV, a tiny religious sect that uses a hallucinogenic tea called ayahuasca as its sacrament, could import the drink to the United States, even though it contains the schedule I substance dimethyltryptamine, or DMT. The ruling was based on the Religious Freedom Restoration Act of 1993, which had sought to reinstitute the right (under the First Amendment’s religious freedom clause) of Native Americans to use peyote in their ceremonies, as they have done for generations.

The Court’s decision inspired something of a religious awakening around ayahuasca in America. Today there are close to 525 American members of the church, with communities in nine locations. To supply them, the UDV has begun growing the plants needed to make the tea in Hawaii and shipping it to groups on the mainland without federal interference. But the number of Americans participating in ayahuasca ceremonies outside the UDV has also mushroomed in the years since, and any given night there are probably dozens if not hundreds of ceremonies taking place somewhere in America (with concentrations in the San Francisco Bay Area and Brooklyn). Federal prosecutions for possession or importation of ayahuasca appear to have stopped, at least for the time being.

Of the three 2006 events that helped bring psychedelics out of their decades-long slumber, by far the most far-reaching in its impact was the publication that summer of the paper in Psychopharmacology described in the prologue—the one Bob Jesse e-mailed me at the time but that I didn’t bother to open. This event, too, had a distinctly spiritual cast, even though the experiment it reported was the work of a rigorous and highly regarded scientist: Roland Griffiths.

Somewhere along the way, Griffiths had what he modestly describes as “a funny kind of awakening”—a mystical experience. I was surprised when Griffiths mentioned this during our first meeting in his office, so I hadn’t followed up, but even after I had gotten to know him a little better, Griffiths was still reluctant to say much more about exactly what happened and, as someone who had never had such an experience, I had trouble gaining any traction with the idea whatsoever. All he would tell me is that the experience, which took place in his meditation practice, acquainted him with “something way, way beyond a material worldview that I can’t really talk to my colleagues about, because it involves metaphors or assumptions that I’m really uncomfortable with as a scientist.”

Griffiths had told Schuster a little about his spiritual practice and confided in him his growing discontent with conventional drug research. “You should talk to this guy,” Schuster told him. “They have some interesting ideas about working with entheogens,” he said. “You might have something in common.”

Doblin works out of a somewhat Dickensian office tucked into the attic of his rambling colonial in Belmont, Massachusetts, at a desk stacked to the ceiling with precarious piles of manuscripts, journal articles, photographs, and memorabilia reaching back more than forty years. Some of the memorabilia commemorates the time early in his career when Doblin decided the best way to end sectarian strife would be to mail a group of the world’s spiritual leaders tablets of MDMA, a drug famous for its ability to break down barriers between people and kindle empathy. Around the same time, he arranged to have a thousand doses of MDMA sent to people in the Soviet military who were working on arms control negotiations with President Reagan.

For Doblin, winning FDA approval for the medical use of psychedelics—which he believes is now in view, for both MDMA and psilocybin—is a means to a more ambitious and still more controversial end: the incorporation of psychedelics into American society and culture, not just medicine. This of course is the same winning strategy followed by the campaign to decriminalize marijuana, in which promoting the medical uses of cannabis changed the drug’s image, leading to a more general public acceptance.

“I was a diffusely located observer. I was coextensive with this emergence.” Here I let him know he was losing me. Long pause. “I’m hesitating because the words are an awkward fit; words seem too constraining.” Ineffability is of course a hallmark of the mystical experience. “The awareness transcends any particular sensory modality,” he explained, unhelpfully. Was it scary? “There was no terror, only fascination and awe.” Pause. “Um, maybe a little fear.” From here on, Jesse watched (or whatever you call it) the birth of … everything, in the unfolding of an epic sequence beginning with the appearance of cosmic dust leading to the creation of the stars and then the solar systems, followed by the emergence of life and from there the arrival of “what we call humans,” then the acquisition of language and the unfolding of awareness, “all the way up to one’s self, here in this room, surrounded by my friends. I had come all the way back to right where I was. How much clock time had elapsed? I had no idea.

I asked him if he agreed with something I’d read the Dalai Lama had said, that the idea that brains create consciousness—an idea accepted without question by most scientists—“is a metaphysical assumption, not a scientific fact.” “Bingo,” Jesse said. “And for someone with my orientation”—agnostic, enamored of science—“that changes everything.”

Here’s what I don’t get about an experience like Bob Jesse’s: Why in the world would you ever credit it at all? I didn’t understand why you wouldn’t simply file it under “interesting dream” or “drug-induced fantasy.” But along with the feeling of ineffability, the conviction that some profound objective truth has been disclosed to you is a hallmark of the mystical experience, regardless of whether it has been occasioned by a drug, meditation, fasting, flagellation, or sensory deprivation.

William James gave a name to this conviction: the noetic quality.

People feel they have been let in on a deep secret of the universe, and they cannot be shaken from that conviction. As James wrote, “Dreams cannot stand this test.” No doubt this is why some of the people who have such an experience go on to found religions, changing the course of history or, in ...

Myron Stolaroff, a prominent Silicon Valley electrical engineer who worked as a senior executive at Ampex, the magnetic recording equipment maker, until an LSD trip inspired him to give up engineering (much like Bob Jesse) for a career as a psychedelic researcher and therapist.

Beginning in the 1950s and continuing into the early 1970s, psychedelic compounds had been used to treat a variety of conditions—including alcoholism, depression, obsessive-compulsive disorder, and anxiety at the end of life—frequently with impressive results. But few of the studies were well controlled by modern standards, and some of them were compromised by the enthusiasm of the researchers involved.

Eight of the ten students receiving psilocybin reported a powerful mystical experience, while only one in the control group did. (Telling them 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 about the chapel, muttering things like “God is everywhere” and “Oh, the Glory!”)

Beginning in 1973, Stanislav Grof, the Czech émigré psychiatrist who is one of the pioneers of LSD-assisted psychotherapy, served as scholar in residence at Esalen, but he had conducted workshops there for years before. Grof, who has guided thousands of LSD sessions, once predicted that psychedelics “would be for psychiatry what the microscope is for biology or the telescope is for astronomy.

These tools make it possible to study important processes that under normal circumstances are not available for direct observation.” Hundreds came to Esalen to peer through that microscope, often in workshops Grof led for psychotherapists who wanted to incorporate psychedelics in their practices.

Many if not most of the therapists and guides now doing this work underground learned their craft at the feet of Stan Grof in the Big House at Esalen. Whether such work continued at Esalen after LSD was made illegal is uncertain, but it wouldn’t be surprising: the place is perched so far out over the edge of the continent as to feel beyond the reach of fe...

Grof began teaching instead something called Holotropic Breathwork, a technique for inducing a psychedelic state of consciousness without drugs, by means of deep, rapid, and rhythmi...

Around the same time, Rick Doblin and Charles Grob, a psychiatrist at UCLA, had succeeded in persuading the government to approve the first human trial of MDMA. (Grob is one of the first psychiatrists to advocate for the return of psychedelics to psychotherapy; he later conducted the first modern trial of psilocybin for cancer patients.) The year before the Esalen gathering (which Grob and Doblin both attended), David Nichols, a Purdue University chemist and pharmacologist, launched the Heffter Research Institute (named for the German chemist who first identified the mescaline compound in 1897) with the then improbable ambition of funding serious psychedelic science.

Shortly after the Esalen meeting, Schuster made what would turn out to be his most important contribution: telling Bob Jesse about his old friend Roland Griffiths, whom he described as exactly “the investigator beyond reproach” Jesse was looking for and “a scientist of the first order.” “Everything Roland’s done he’s devoted himself to completely,” Jesse recalls Schuster saying, “including his meditation practice. We think it’s changed him.” Griffiths had shared with Schuster his growing dissatisfaction with science and his deepening interest in the kind of “ultimate questions” coming up in his meditation practice. Schuster then made the call to Griffiths telling him about the interesting young man he’d just met at Esalen, explaining that they shared an interest in spirituality, and suggesting they should meet. After an exchange of e-mails, Jesse flew to Baltimore to have lunch with Griffiths in the cafeteria on the Bayview medical campus, inaugurating a series of conversations and meetings that would eventually lead to their collaboration on the 2006 study of psilocybin and mystical experience at Johns Hopkins.

But there was still one missing piece of the puzzle and the scientific team. Most of the drug trials Griffiths had run in the past involved baboons and other nonhuman primates; he had much less clinical experience working with humans and realized he needed a skilled therapist to join the project—a “master clinician,” as he put it. As it happened, Bob Jesse had met a psychologist at a psychedelic conference a few years before who not only filled the bill but lived in Baltimore. Still more fortuitous, this psychologist, whose name was Bill Richards, probably has more experience guiding psychedelic journeys in the 1960s and 1970s than anyone alive, with the possible exception of Stan Grof (with whom he had once worked). In fact, Bill Richards administered the very last legal dose of psilocybin to an American, at the Maryland Psychiatric Research Center at Spring Grove State Hospital in the spring of 1977. In the decades since, he had been practicing more conventional psychotherapy out of his home in a leafy Baltimore neighborhood called Windsor Hills, biding his time and waiting patiently for the world to come around so that he might work with psychedelics once again.

“In the big picture,” he told me the first time we met in his home office, “these drugs have been around at least five thousand years, and many times they have surfaced and have been repressed, so this was another cycle. But the mushroom still grows, and eventually this work would come around again. Or so I hoped.” When he got the call from Bob Jesse in 1998, and met Roland Griffiths shortly thereafter, he couldn’t quite believe his good fortune. “It was thrilling.”

Descriptions of such experiences always sound a little thin, at least when compared with the emotional impact people are trying to convey; for a life-transforming event, the words can seem paltry. When I mentioned this to Richards, he smiled. “You have to imagine a caveman transported into the middle of Manhattan. He sees buses, cell phones, skyscrapers, airplanes. Then zap him back to his cave. What does he say about the experience? ‘It was big, it was impressive, it was loud.’ He doesn’t have the vocabulary for ‘skyscraper,’ ‘elevator,’ ‘cell phone.’ Maybe he has an intuitive sense there was some sort of significance or order to the scene. But there are words we need that don’t yet exist. We’ve got five crayons when we need fifty thousand different shades.”

A few days after the experience, Richards returned to the lab and asked, “What was that drug you gave me? How is it spelled? “And the rest of my life is footnotes!”

Pahnke suggested Richards try one more time, but in a room with soft lighting, plants, and music and using a higher dose. Once again, Richards had “an incredibly profound experience. I realized I had not exaggerated the first trip but in fact had forgotten 80 percent of it.

“I have never doubted the validity of these experiences,” Richards told me. “This was the realm of mystical consciousness that Shankara was talking about, that Plotinus was writing about, that Saint John of the Cross and Meister Eckhart were writing about. It’s also what Abraham Maslow was talking about with his ‘peak experiences,’ though Abe could get there without the drugs.” Richards would go on to study psychology under Maslow at Brandeis University. “Abe was a natural Jewish mystic. He could just lie down in the backyard and have a mystical experience. Psychedelics are for those of us who aren’t so innately gifted.”

Richards emerged from those first psychedelic explorations in possession of three unshakable convictions. The first is that the experience of the sacred reported both by the great mystics and by people on high-dose psychedelic journeys is the same exper...

“You go deep enough or far out enough in consciousness and you will bump into the sacred. It’s not something we generate; it’s something out there waiting to be discovered. And this reliably happens to nonbelievers as well as believers.” Second, that, whether occasioned by drugs or other means, these experiences of mystical consciousness are in all likelihood the primal basis of religion. (Partly for this reason Richards believes that psychedelics should be part of a divinity student’s education.) And third, that consciousness is a property of the universe, not brains. On this question, he holds with Henri Bergson, the French philosopher, who conceived of the human mind as a kind of radio receiver, able to tune in to frequencies of energy and information that exist outside it. “If you wanted to fi...

In 1971, Richard Nixon declared Timothy Leary, a washed-up psychology professor, “the most dangerous man in America.” Psychedelics were nourishing the counterculture, and the counterculture was sapping the willingness of America’s young to fight. The Nixon administration sought to blunt the counterculture by attacking its neurochemical infrastructure.

Roland Griffiths points out that ours is not the first culture to feel threatened by psychedelics: the reason R. Gordon Wasson had to rediscover magic mushrooms in Mexico was that the Spanish had suppressed them so effectively, deeming them dangerous instruments of paganism. “That says something important about how reluctant cultures are to expose themselves to the changes these kinds of compounds can occasion,” he told me the first time we met. “There is so much authority that comes out of the primary mystical experience that it can be threatening to existing hierarchical structures.”

“This guy is lying on the couch right there where you are, with tears streaming down his face, and I’m thinking, how absolutely beautiful and meaningful this experience is. How sacred. How can this ever have been illegal? It’s as if we made entering Gothic cathedrals illegal, or museums, or sunsets! “I honestly never knew if this would happen again in my lifetime. And look at where we are now: the work at Hopkins has been going on now for fifteen years—five years longer than Spring Grove.”

All of the volunteers were “hallucinogen naive,” so had no idea what psilocybin felt like, and neither they nor their monitors knew in any given session whether they were getting psilocybin or a placebo, and whether that placebo was a sugar pill or any one of half a dozen different psychoactive drugs. In fact the placebo was Ritalin, and as it turned out, the monitors guessed wrong nearly a quarter of the time as to what was in the pill a volunteer had received.

Even years after their experiences in the trials, the volunteers I spoke to recalled them in vivid detail and at considerable length; the interviews lasted hours. These people had big stories to tell; in several cases, these were the most meaningful experiences of their lives, and they clearly relished the opportunity to relive them for me in great detail, whether in person, by Skype, or on the telephone. The volunteers were also required to write a report of their experiences soon after they occurred, and all of the ones I interviewed were happy to share these reports, which made for strange and fascinating reading. Many of the volunteers I spoke to reported initial episodes of intense fear and anxiety before surrendering themselves to the experience—as the sitters encourage them to do. The sitters work from a set of “flight instructions” prepared by Bill Richards, based on the hundreds of psychedelic journeys he has guided. The guides go over the instructions with the volunteers during the eight hours of preparation all of them receive before commencing their journeys.

The flight instructions advise guides to use mantras like “Trust the trajectory” and “TLO—Trust, Let Go, Be Open.” Some guides like to quote John Lennon: “Turn...

Volunteers are told they may experience the “death/transcendence of your ego or everyday self,” but this is “always followed by Rebirth/Return to the normative world of space & time. Safest way to return to normal is to entrust self unconditionally to the emerging experiences.” Guides are instructed to remind volunteers they’ll never be left alone and not to worry about the body while journeying because the guides are there to keep an eye on it. If you feel as if you are “dying, melting, dissolving, explodi...

“Open it” and “climb up it” are of course the...