Every culture has found chemical means of transcendence, and at some point the use of such intoxicants becomes inst.i.tutionalized at a magical or sacramental level; the sacramental use of psychoactive plant substances has a long history and continues to the present day in various shamanic and religious rites around the world.

At a humbler level, drugs are used not so much to illuminate or expand or concentrate the mind, to "cleanse the doors of perception," but for the sense of pleasure and euphoria they can provide.

All of these cravings, high or low, are nicely met by the plant kingdom, which has various psychoactive agents that seem almost tailored to the neurotransmitter systems and receptor sites in our brains. (They are not, of course; they have evolved to deter predators or sometimes to attract other animals to eat a plant's fruit and disseminate its seeds. Nevertheless, one cannot repress a feeling of wonder that there should be so many plants capable of inducing hallucinations or altered brain states of many kinds.)1

Richard Evans Schultes, an ethn.o.botanist, devoted much of his life to the discovery and description of these plants and their uses, and Albert Hofmann was the Swiss chemist who first synthesized LSD-25 in a Sandoz lab in 1938. Together Schultes and Hofmann described nearly a hundred plants containing psychoactive substances in their Plants of the G.o.ds, and new ones continue to be discovered (to say nothing of new compounds synthesized in the lab).2

Many people experiment with drugs, hallucinogenic and otherwise, in their teenage or college years. I did not try them myself until I was thirty and a neurology resident. This long virginity was not due to lack of interest.

I had read the great cla.s.sics-De Quincey's Confessions of an English Opium-Eater and Baudelaire's Artificial Paradises, among others-at school. I had read about the French novelist Theophile Gautier, who in 1844 paid a visit to the recently founded Club des Hashischins, in a quiet corner of the ile Saint-Louis. Hashish, in the form of a greenish paste, had recently been introduced from Algeria and was all the rage in Paris. At the salon, Gautier consumed a substantial piece of hash ("about as large as a thumb"). At first he felt nothing out of the ordinary, but soon, he wrote, "everything seemed larger, richer, more splendid," and then more specific changes occurred:

An enigmatic personage suddenly appeared before me ... his nose was bent like the beak of a bird, his green eyes, which he wiped frequently with a large handkerchief, were encircled with three brown rings, and caught in the knot of a high white starched collar was a visiting card which read: Daucus-Carota, du Pot d'or.... Little by little the salon was filled with extraordinary figures, such as are found only in the etchings of Callot or the aquatints of Goya; a pele-mele of rags and tatters, b.e.s.t.i.a.l and human shapes.... Singularly intrigued, I went straightaway to the mirror.... One would have taken me for a Javanese or Hindu idol: my forehead was high, my nose, lengthened into a trunk, curved onto my chest, my ears brushed my shoulders, and to make matters more discomforting still, I was the color of indigo, like Shiva, the blue deity.3

By the 1890s, Westerners were also beginning to sample mescal, or peyote, previously used only as a sacrament in certain Native American traditions.4

As a freshman at Oxford, free to roam the shelves and stacks of the Radcliffe Science Library, I read the first published accounts of mescal, including ones by Havelock Ellis and Silas Weir Mitch.e.l.l. They were primarily medical men, not just literary ones, and this seemed to lend an extra weight and credibility to their descriptions. I was captivated by Weir Mitch.e.l.l's dry tone and his nonchalance about taking what was then an unknown drug with unknown effects.

At one point, Mitch.e.l.l wrote in an 1896 article for the British Medical Journal, he took a fair portion of an extract made from mescal b.u.t.tons and followed this up with four further doses. Although he noted that his face was flushed, his pupils were dilated, and he had "a tendency to talk, and now and then ... misplaced a word," he nevertheless went out on house calls and saw several patients. Afterward, he sat down quietly in a dark room and closed his eyes, whereupon he experienced "an enchanted two hours," full of chromatic effects:

Delicate floating films of colour-usually delightful neutral purples and pinks. These came and went-now here, now there. Then an abrupt rush of countless points of white light swept across the field of view, as if the unseen millions of the Milky Way were to flow a sparkling river before the eye. In a minute this was over and the field was dark. Then I began to see zigzag lines of very bright colours, like those seen in some megrims [migraines].... It was in rapid, what I might call minute, motion.... A white spear of grey stone grew up to huge height, and became a tall, richly finished Gothic tower of very elaborate and definite design.... As I gazed every projecting angle, cornice, and even the face of the stones at their joinings were by degrees covered or hung with cl.u.s.ters of what seemed to be huge precious stones, but uncut, some being more like ma.s.ses of transparent fruit. These were green, purple, red, and orange.... All seemed to possess an interior light, and to give the faintest idea of the perfectly satisfying intensity and purity of these gorgeous colour-fruits is quite beyond my power. All the colours I have ever beheld are dull as compared to these.

He found he had no power to influence his visions voluntarily; they seemed to come at random or to follow some logic of their own.

Just as the introduction of hashish in the 1840s had led to a vogue for it, so these first descriptions of mescal's effects by Weir Mitch.e.l.l and others in the 1890s and the ready availability of mescaline led to another vogue-for mescal promised an experience not only richer, longer-lasting, and more coherent than that induced by hashish, but one with the added promise of transporting one to mystical realms of unearthly beauty and significance.

Unlike Mitch.e.l.l, who had focused on the colored, mostly geometric hallucinations that he compared in part to those of migraine, Aldous Huxley, writing of mescaline in the 1950s, focused on the transfiguration of the visual world, its investment with luminous, divine beauty and significance. He compared such drug experiences to those of great visionaries and artists, though also to the psychotic experiences of some schizophrenics. Both genius and madness, Huxley hinted, lay in these extreme states of mind-a thought not so different from those expressed by De Quincey, Coleridge, Baudelaire, and Poe in relation to their own ambiguous experiences with opium and hashish (and explored at length in Jacques Joseph Moreau's 1845 book Hashish and Mental Illness). I read Huxley's Doors of Perception and Heaven and h.e.l.l when they came out in the 1950s, and I was especially excited by his speaking of the "geography" of the imagination and its ultimate realm-the "Antipodes of the mind."5

Around the same time, I came across a pair of books by the physiologist and psychologist Heinrich Kluver. In the first one, Mescal, he reviewed the world literature on the effects of mescal and described his own experiences with it. Keeping his eyes closed, as Weir Mitch.e.l.l had done, he saw complex geometrical patterns:

Transparent oriental rugs, but infinitely small ... plastic filigreed spherical objets d'art [like] radiolaria ... wallpaper designs ... cobweb-like figures or concentric circles and squares ... architectural forms, b.u.t.tresses, rosettes, leafwork, fretwork.

For Kluver these hallucinations represented an abnormal activation in the visual system, and he observed that similar hallucinations could occur in a variety of other conditions-migraine, sensory deprivation, hypoglycemia, fever, delirium, or the hypnagogic and hypnopompic states that come immediately before and after sleep. In Mechanisms of Hallucination, published in 1942, Kluver spoke of the tendency to "geometrization" in the brain's visual system, and he regarded all such geometrical hallucinations as permutations of four fundamental "form constants" (he identified these as lattices, spirals, cobwebs, and tunnels). He implied that such constants must reflect something about the organization, the functional architecture, of the visual cortex-but there was little more to be said about this in the 1940s.

It might be said that both approaches-the "high," mystical approach of Huxley and the "low," neurophysiological approach of Kluver-were too narrowly focused and failed to do justice to the range and complexity of the phenomena that mescaline could induce. This became clearer in the late 1950s, when LSD, as well as psilocybin mushrooms and morning glory seeds (both of which contain LSD-like compounds), became widely available, ushering in a new hallucinogenic drug age and a new word to go with it: "psychedelic."

Daniel Breslaw, a young man just out of college in the 1960s, was one of the subjects in a study of LSD at Columbia University, and he gave a vivid description of the effects of psilocybin, which he took under supervision, so that his reactions could be observed.6 His first visions, like Weir Mitch.e.l.l's, were of stars and colors:

I closed my eyes. "I see stars!" I then burst out, finding the firmament spread out on the inside of my eyelids. The room about me receded into a tunnel of oblivion as I vanished into another world, fruitless to describe.... The heavens above me, a night sky spangled with eyes of flame, dissolve into the most overpowering array of colors I have ever seen or imagined; many of the colors are entirely new-areas of the spectrum which I seem to have hitherto overlooked. The colors do not stand still, but move and flow in every direction; my field of vision is a mosaic of unbelievable complexity. To reproduce an instant of it would involve years of labor, that is, if one were able to reproduce colors of equivalent brilliance and intensity.

Then Breslaw opened his eyes. "With the eyes closed," he noted, "one is not here, but inhabits a distant world of abstractions. But with eyes open, one glances around the physical universe with curiosity." Curiosity-and amazement, for the visual world he saw was bizarrely changed and continually changing, as Gautier had found with hashish. Breslaw wrote:

The room is fifty feet tall. Now it is two feet tall. A strange disparity here. Whatever comes into the focus of my eyes dissolves into whorls, patterns, arrangements. There is The Doctor. His face is crawling with lice. His gla.s.ses are the size of pressure cookers, and his eyes are those of some mammoth fish. He is beyond doubt the funniest sight I have ever seen, and I insist upon this point by laughing.... A footstool in the corner shrinks to a mushroom in jerky spasms, braces-and springs to the ceiling. Amazing!... In the elevator, the face of the operator grows hair, becomes an affably growing gorilla.

Time was immensely distended. The elevator descended, "pa.s.sing a floor every hundred years. Back in the room, I swim through the remaining centuries of the day. Every five eons or so a nurse arrives (in the aspect of a cougar, a differential equation, or a clock radio) and takes my blood pressure."

Animation and intentionality appeared everywhere, as did relationship and meaning:

Here is a fire extinguisher in a gla.s.s case, evidently an exhibit of some sort. A bit of staring reveals that the beast is alive: it coils its rubber hose around its prey and sucks flesh through the nozzle. The beast and I exchange glares, and then the nurse drags me away. I wave goodbye.

A smudge on the wall is an object of limitless fascination, multiplying in size, complexity, color. But more than that, one sees every relationship it has to the rest of the universe; it possesses, therefore, an endless variety of meanings, and one proceeds to entertain every possible thought there is to think about it.

And when the effects were most intense, there came a rich synesthesia-a mingling of all the senses, and of sensation and concepts. Breslaw noted, "Interchanges between the senses are frequent and astonishing: One knows the smell of a low B flat, the sound of green, the taste of the categorical imperative (which is something like veal)."

No two people ever have the same responses to such drugs; indeed, no two drug experiences are ever the same for the same person. Eric S. wrote to me to describe some of his experiences with LSD during the 1970s:

I was in my late twenties when a friend and I took some LSD. I had tripped many times before but this acid was different.... We noticed that we were talking to each other mentally through thoughts only, no verbal talk, tele-communicating. I thought in my head, "I want a beer," and he heard me and got me a beer; he thought, "Turn the music up" and I turned the music up.... It went on like this for some time.

Then I went to urinate, and in my urine stream was a video or movie of the past played back in reverse. Everything that had just happened in the room was coming out of me like watching a movie in my urine stream, playing in reverse. This totally blew my mind.

Then my eyes became a microscope, and I looked at my wrist and was able to see each individual cell breathing or respirating, like little factories with little puffs of gas shooting out of each cell, some blowing perfect smoke rings. My eyes were able to see inside each skin cell, and I saw that I was choking myself from the inside by smoking five packs of cigarettes a day and the debris was clogging my cells. At that second I quit smoking.

Then I left my body and hovered in the room above the whole scene, then found myself traveling through a tunnel of beautiful light into s.p.a.ce and was filled with a feeling of total love and acceptance. The light was the most beautiful, warm and inviting light I ever felt. I heard a voice ask me if I wanted to go back to Earth and finish my life or ... to go in to the beautiful love and light in the sky. In the love and light was every person that ever lived. Then my whole life flashed in my mind from birth to the present, with every detail that ever happened, every feeling and thought, visual and emotional was there in an instant. The voice told me that humans are "Love and Light." ...

That day will live with me forever; I feel I was shown a side of life that most people can't even imagine. I feel a special connection to every day, that even the simple and mundane have such power and meaning.

The effects of cannabis, mescaline, LSD, and other hallucinogenic drugs have an immense range and variety. Yet certain categories of perceptual distortion and hallucinatory experience may, to some extent, be regarded as typical of the brain's responses to such drugs.

The experience of color is often heightened, sometimes to an unearthly level, as Weir Mitch.e.l.l, Huxley, and Breslaw all observed. There may be sudden changes in orientation and striking alterations of apparent size. There may be micropsia or Lilliputian vision (little beings-elves, dwarfs, fairies, imps-are curiously common in these hallucinations), or there may be gigantism (macropsia).

There may be exaggerations or diminutions of depth and perspective or exaggerations of stereo vision-or even stereo hallucinations, seeing three-dimensional depth and solidity in a flat picture. Huxley described this:

I was handed a large colored reproduction of the well-known self-portrait by Cezanne-the head and shoulders of a man in a large straw hat, red-cheeked, red-lipped, with rich black whiskers and a dark unfriendly eye. It is a magnificent painting; but it was not as a painting that I now saw it. For the head promptly took on a third dimension and came to life as a small goblin-like man looking out through a window in the page before me.

The perceptual transformations and hallucinations induced by mescaline, LSD, and other hallucinogens are predominantly, but not exclusively, visual. There may be enhancements or distortions or hallucinations of taste and smell, touch and hearing, or there may be fusions of the senses-a sort of temporary synesthesia-"the smell of a low B flat, the sound of green," as Breslaw put it. Such coalescences or a.s.sociations (and their presumed neural basis) are creations of the moment. In this way they are quite different from true synesthesia, a congenital (and often familial) condition where there are fixed sensory equivalences that last a lifetime. With hallucinogens, time may appear to be distended or compressed. One may cease to perceive motion as continuous and see instead a series of static "snapshots," as with a film run too slowly. Such stroboscopic or cinematic vision is a not uncommon effect of mescaline. Sudden accelerations, slowings, or freezings of movement are also common with more elementary hallucinatory patterns.7

I had done a great deal of reading, but had no experiences of my own with such drugs until 1953, when my childhood friend Eric Korn came up to Oxford. We read excitedly about Albert Hofmann's discovery of LSD, and we ordered 50 micrograms of it from the manufacturer in Switzerland (it was still legal in the mid-1950s). Solemnly, even sacramentally, we divided it and took 25 micrograms each-not knowing what splendors or horrors awaited us-but, sadly, it had absolutely no effect on either of us. (We should have ordered 500 micrograms, not 50.)

By the time I qualified as a doctor, at the end of 1958, I knew I wanted to be a neurologist, to study how the brain embodies consciousness and self and to understand its amazing powers of perception, imagery, memory, and hallucination. A new orientation was entering neurology and psychiatry at that time; it was the opening of a neurochemical age, with a glimpse of the range of chemical agents, neurotransmitters, which allow nerve cells and different parts of the nervous system to communicate with one another. In the 1950s and 1960s, discoveries were coming from all directions, though it was far from clear how they fit together. It had been found, for instance, that the parkinsonian brain was low in dopamine, and that giving a dopamine precursor, L-dopa, could alleviate the symptoms of Parkinson's disease, while tranquilizers, introduced in the early 1950s, could depress dopamine and cause a sort of chemical parkinsonism. For about a century, the staple medication for parkinsonism had been anticholinergic drugs. How did the dopamine and acetylcholine systems interact? Why did opiates-or cannabis-have such strong effects? Did the brain have special opiate receptors and make opioids of its own? Was there a similar mechanism for cannabis receptors and cannabinoids? Why was LSD so enormously potent? Were all its effects explicable in terms of altering the serotonin in the brain? What transmitter systems governed wake-sleep cycles, and what might be the neurochemical background of dreams or hallucinations?

Starting a neurology residency in 1962, I found the atmosphere heady with such questions. Neurochemistry was plainly "in," and so-dangerously, seductively, especially in California, where I was studying-were the drugs themselves.

While Kluver had little idea of what the neural basis of his hallucinatory constants might be, rereading his book in the early 1960s was especially exciting to me in light of the groundbreaking experiments on visual perception that David Hubel and Torsten Wiesel were performing at the time, recording from neurons in the visual cortex in animals. They described neurons specialized for the detection of lines, orientations, edges, corners, etc., and these, it seemed to me, if stimulated by a drug or a migraine or a fever, might well produce just such geometrical hallucinations as Kluver had described.