How to Change Your Mind: The New Science of Psychedelics

by Michael Pollan

The soul should always stand ajar. —EMILY DICKINSON

One good way to understand a complex system is to disturb it and then see what happens. By smashing atoms, a particle accelerator forces them to yield their secrets. By administering psychedelics in carefully calibrated doses, neuroscientists can profoundly disturb the normal waking consciousness of volunteers, dissolving the structures of the self and occasioning what can be described as a mystical experience. While this is happening, imaging tools can observe the changes in the brain’s activity and patterns of connection. Already this work is yielding surprising insights into the “neural correlates” of the sense of self and spiritual experience. The hoary 1960s platitude that psychedelics offered a key to understanding—and “expanding”—consciousness no longer looks quite so preposterous.

Psychedelic aficionados would probably categorize what we had as a low-dose “aesthetic experience,” rather than a full-blown ego-disintegrating trip.

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.

Carl Jung once wrote that it is not the young but people in middle age who need to have an “experience of the numinous” to help them negotiate the second half of their lives.

Specifically, the psychologist felt that LSD gave her insight into how young children perceive the world. Kids’ perceptions are not mediated by expectations and conventions in the been-there, done-that way that adult perception is; as adults, she explained, our minds don’t simply take in the world as it is so much as they make educated guesses about it. Relying on these guesses, which are based on past experience, saves the mind time and energy, as when, say, it’s trying to figure out what that fractal pattern of green dots in its visual field might be. (The leaves on a tree, probably.) LSD appears to disable such conventionalized, shorthand modes of perception and, by doing so, restores a childlike immediacy, and sense of wonder, to our experience of reality, as if we were seeing everything for the first time. (Leaves!)

What is striking about this whole line of clinical research is the premise that it is not the pharmacological effect of the drug itself but the kind of mental experience it occasions—involving the temporary dissolution of one’s ego—that may be the key to changing one’s mind.

After trying them once, animals will not seek a second dose, and repeated use by people robs the drugs of their effect.

If you need to be reminded how completely mental habit blinds us to experience, just take a trip to an unfamiliar country. Suddenly you wake up! And the algorithms of everyday life all but start over, as if from scratch. This is why the various travel metaphors for the psychedelic experience are so apt.

The efficiencies of the adult mind, useful as they are, blind us to the present moment. We’re constantly jumping ahead to the next thing. We approach experience much as an artificial intelligence (AI) program does, with our brains continually translating the data of the present into the terms of the past, reaching back in time for the relevant experience, and then using that to make its best guess as to how to predict and navigate the future.

MDMA operates through a different set of pathways in the brain and has a substantially different social history from that of the so-called classic psychedelics. Of these, I focus primarily on the ones that are receiving the most attention from scientists—psilocybin and LSD—which means that other psychedelics that are equally interesting and powerful but more difficult to bring into the laboratory—such as ayahuasca—receive less attention.

Hoping to escape those associations and underscore the spiritual dimensions of these drugs, some researchers have proposed they instead be called “entheogens”—from the Greek for “the divine within.” This strikes me as too emphatic. Despite the 1960s trappings, the term “psychedelic,” coined in 1956, is etymologically accurate. Drawn from the Greek, it means simply “mind manifesting,” which is precisely what these extraordinary molecules hold the power to do.

“The true method of knowledge is experiment.”

Why did they evolve the ability to produce a chemical compound so closely related to serotonin, the neurotransmitter, that it can slip across the blood-brain barrier and temporarily take charge of the mammalian brain? Was it a defense chemical, intended to poison mushroom eaters? That would seem to be the most straightforward explanation, yet it is undermined by the fact the fungus produces the hallucinogen almost exclusively in its “fruiting body”—that part of the organism it is happiest to have eaten. Was there perhaps some benefit to the mushroom in being able to change the minds of the animals that eat it?

On the first interpretation, the mind-altering power of psilocybin argues for a firmly materialist understanding of consciousness and spirituality, because the changes observed in the mind can be traced directly to the presence of a chemical—psilocybin. What is more material than a chemical? One could reasonably conclude from the action of psychedelics that the gods are nothing more than chemically induced figments of the hominid imagination.

psychoactive LBMs (mycologist shorthand for “little brown mushrooms”)

There was never any doubt who could best help me on this quest, assuming he was willing. Paul Stamets, a mycologist from Washington State who literally wrote the book on the genus Psilocybe,fn2 in the form of the authoritative 1996 field guide Psilocybin Mushrooms of the World.

Stamets has made it his life’s work to right this wrong, by speaking out on their behalf and by demonstrating the potential of mushrooms to solve a great many of the world’s problems. Indeed, the title of his most popular lecture, and the subtitle of his 2005 book, Mycelium Running, is “How Mushrooms Can Help Save the World.”

But Stamets’s aspirations for the fungal kingdom go well beyond turning petrochemical sludge into arable soil. Indeed, in his view there is scarcely an ecological or medical problem that mushrooms can’t help solve. Cancer? Stamets’s extract of turkey tail mushrooms (Trametes versicolor) has been shown to help cancer patients by stimulating their immune systems. (Stamets claims to have used it to help cure his mother’s stage 4 breast cancer.)

Colony collapse disorder (CCD)? After watching honeybees visiting a woodpile to nibble on mycelium, Stamets identified several species of fungus that bolster the bees’ resistance to infection and CCD.

don’t think I’m saying anything about Paul Stamets to which he would object. He writes in his book that mycelia—the vast, cobwebby whitish net of single-celled filaments, called hyphae, with which fungi weave their way through the soil—are intelligent, forming “a sentient membrane” and “the neurological network of nature.” The title of his book Mycelium Running can be read in two ways. The mycelium is indeed always running through the ground, where it plays a critical role in forming soils, keeping plants and animals in good health, and knitting together the forest. But the mycelium are also, in Stamets’s view, running the show—that of nature in general and, like a neural software program, the minds of certain creatures, including, he would be the first to tell you, Paul Stamets himself. “Mushrooms are bringing us a message from nature,” he likes to say. “This is a call I’m hearing.”

Psilocybes are saprophytes, living off dead plant matter and dung. They are denizens of disturbed land, popping up most often in the habitats created by ecological catastrophe, such as landslides, floods, storms, and volcanoes. They also prosper in the ecological catastrophes caused by our species: clear-cut forests, road cuts, the wakes of bulldozers, and agriculture. (Several species live in and fruit from the manure of ruminants.) Curiously, or perhaps not so curiously, the most potent species occur less often in the wild than in cities and towns; their predilection for habitats disturbed by us has allowed them to travel widely, “following streams of debris,” including our own. In recent years, the practice of mulching with wood chips has vastly expanded the range of a handful of potent Psilocybes once confined to the Pacific Northwest.

“How do I know if a mushroom is a psilocybin producing species or not?” “If a gilled mushroom has purplish brown to black spores, and the flesh bruises bluish, the mushroom in question is very likely a psilocybin-producing species.” This is definitely a big help, though I wouldn’t mind something more categorical than “very likely.” He then offers a sobering caveat. “I know of no exceptions to this rule,” he adds, “but that does not mean there are none!”

The blue pigment is in fact evidence of oxidized psilocin, one of the two main psychoactive compounds in a Psilocybe. (The other is psilocybin, which breaks down into psilocin in the body.) To determine if the mushroom in question had purplish-brown or black spores, I began making spore prints. This involves cutting the cap off a mushroom and placing it, gill side down, on a piece of white paper. (Or black paper if you have reason to believe the mushroom has white spores.) Within hours, the mushroom cap releases its microscopic spores, which will form a pretty, shadowy pattern on the paper (reminiscent of a lipstick kiss) that you can then try to decide is purplish brown or black—or rust colored, in which case you might have a deadly Galerina on your hands.

psychotomimetic, which is to say, a mind drug that mimicked psychoses.

Yes, “the toad,” or to be more precise, the smoked venom of the Sonoran Desert toad (Incilius alvarius), also called the Colorado River toad, which contains a molecule called 5-MeO-DMT that is one of the most potent and fast-acting psychotropic drugs there is. No, I had never heard of it either. It is so obscure, in fact, that the federal government did not list 5-MeO-DMT as a controlled substance until 2011.

Actually, there were three different molecules in question—psilocin, LSD, and 5-MeO-DMT—but even a casual glance at their structures (and I say this as someone who earned a D in high school chemistry) indicates a resemblance. All three molecules are tryptamines. A tryptamine is a type of organic compound (an indole, to be exact) distinguished by the presence of two linked rings, one of them with six atoms and the other with five. Living nature is awash in tryptamines, which show up in plants, fungi, and animals, where they typically act as signaling molecules between cells. The most famous tryptamine in the human body is the neurotransmitter serotonin, the chemical name of which is 5-hydroxytryptamine. It is no coincidence that this molecule has a strong family resemblance with the psychedelic molecules.

The group of tryptamines we call “the classic psychedelics” have a strong affinity with one particular type of serotonin receptor, called the 5-HT2A. These receptors are found in large numbers in the human cortex, the outermost, and evolutionarily most recent, layer of the brain. Basically, the psychedelics resemble serotonin closely enough that they can attach themselves to this receptor site in such a way as to activate it to do various things. Curiously, LSD has an even stronger affinity with the 5-HT2A receptor—is “stickier”—than serotonin itself, making this an instance where the simulacrum is more convincing, chemically, than the original. This has led some scientists to speculate that the human body must produce some other, more bespoke chemical for the express purpose of activating the 5-HT2A receptor—perhaps an endogenous psychedelic that is released under certain circumstances, perhaps when dreaming. One candidate for that chemical is the psychedelic molecule DMT, which has been found in trace amounts in the pineal gland of rats.

Many researchers acknowledge that a strong placebo effect may be at work when a drug as suggestible as 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.) Here we bump into one of the richer paradoxes of the psilocybin trials: while it succeeds in no small part because it has the sanction and authority of science, its effectiveness seems to depend on a mystical experience that leaves people convinced there is more to this world than science can explain. Science is being used to validate an experience that would appear to undermine the scientific perspective in what might be called White-Coat Shamanism.