The current popularity of such writers as William Burroughs, Genet, and others, who specialize in the baroque recesses of human behavior, makes it seem as if, in this age of reason, we feel ourselves constrained within the confines of sanity and yearn for vicarious release.
The belief that in madness there may exist a core of numinous knowledge is a commonplace in all human societies. In the Western tradition, the doctrine that truth may be obtained through a state of mind in which reason is dislocated, a state of ecstatic revelation, is generally supposed to have originated with the Thracian worship of Dionysius, later becoming synthesized by Pythagorus, and to have received its most complete elaboration in the dialogues of Plato.
The class of drugs of which LSD-25 is the most potent member may prove for our time to be a very useful tool in exploring, via the scientific method, the roots of this age-old dilemma concerning the nature of perceived reality. That madmen may often be capable of incredible accomplishment should be obvious to everyone living in this century, whose history has been so monstrously deformed by the activities of an undeniable madman, Adolf Hitler. This one terrible example should quench all disputations concerning the correlations between mental aberration and accomplishment. These disputations most frequently arise in connection with accomplishment in the creative arts, where the biographies of many greatly talented people are replete with histories of bizarre behavior of one kind or another. It is impossible, however, to make such correlations on any kind of statistical basis, since for every "mad artist" on the model of Van Gogh, one can point to two equally creative, original, and productive artists on the sane and sober models of J. S. Bach or T. S. Eliot.
In addition to the artificially induced LSD state, there are other, naturally occurring temporary states in which there is a collapse of the normal routines by which the mind ordinarily processes the information it receives of the outside world. Not only Hitler but before him Alexander the Great, Julius Caesar, and Napoleon Bonaparte all reportedly suffered from mysterious seizures which overtook them at seemingly random times--often inconveniently. Dostoevsky also suffered from these states, and his reports of them are sufficiently detailed to permit a more certain medical diagnosis of his affliction--some kind of psycho-motor epilepsy. As he describes the "aura" which precedes his seizures, the language is remarkably similar to that used by LSD subjects. Dostoevsky wrote: "For a few moments I experience such happiness as is impossible under ordinary circumstances and of which other people can have no notion. I feel complete harmony in myself and in the world and this feeling is so strong and sweet that for several seconds of such bliss, one would give ten years of one's life; indeed, perhaps one's whole life." Others have reported on these aura states as well. Along with the feelings of peace and euphoria, there is a general impression of a clear and golden shimmering light. Quite often there is a sense of cerebral clarity as well, and solutions of a lovely simplicity appear for the most intractably knotted problems.
None of the names used to describe the class of drugs to which LSD belongs and which produce these peculiar states of altered consciousness is completely satisfactory. When they were first developed, they were called psychotomimetic (imitative of psychosis), but this term rang unhappily in the ears of many who felt that the word implied pathology and thus made a negative value judgment. Another name for them, hallucinogenic, was unfortunate in that it rendered an epistemological judgment--hallucinations being by definition unreal or untrue--and if one is to maintain a proper stance of scientific objectivity, one must suspend judgment regarding the reality of reality, for it is just possible that in some way these drugs augment our sense receptors or in some way so alter the mechanism of their functioning that another dimension of reality is made manifest. This last notion is the one implied in the term psychedelic (mind manifesting), which seems gradually to be coming into general use to describe both the class of drugs and those states of mind with which they are associated.
THERE is a vast literature running back for thousands of years which describes psychedelic experiences, long before 1938, when Albert Hofmann first synthesized d-lysergic acid dyethylamide. Some of the literature describes attacks, sudden, spontaneous, and totally unexpected, like that attack which overcame St. Paul on the road to Damascus. Other traditions in the literature describe states that were induced by fasting, by the sensory deprivation resulting from disciplined meditation (the willful exclusion of sensory input), by hysteria through frenzied dancing or orgiastic sexuality, by hypnosis, or by the use of various natural psychedelic intoxicants. Reports of these kinds of exalted states have come to us not only through the literature of religious fanaticism; such accomplished scientists as Pascal and Newton have written of being overcome by mystic trances to which they attribute many of their creative insights. William James well understood that the mystic was often able to effect an almost miraculous synthesis between this world of "imagined" reality and the world of phenomena. In recent years, psychology has tended, to its discredit, to ignore these elements of William James's thought. One of the happy by-products of LSD has been the revival of interest in William James on the part of academic psychologists who had previously thought that these concerns of his were a cranky eccentricity in the body of his worthwhile work. Two famous reports of modern times of this kind of correlation--between the hard factual world of science and the dreamworld of the psychedelic state--are those of Friedrich Kekule, the German chemist who has written that he was "presented with" the closed-chain theory of the structure of the benzene molecule during one such dream-trance state, and Otto Loewi, who wrote that in 1921 he awakened from a dream in which was described to him the means by which chemical transfer was accomplished between nerve and effecter cells. Loewi rushed down to his laboratory, where he proceeded to prove the reality of the dream--an accomplishment which led to the Nobel Prize.
From the time of Dionysius to the time of Plato, the cultures of the Mediterranean consented to this doctrine that claimed the existence of an order of ultimate reality which lies beyond apparent reality, and that this "paranormal" reality is accessible to the consciousness only when the "normal" routines of mental data processing are dislocated. It was Plato's pupil Aristotle who spoiled his master's game. Following upon Aristotle, Western philosophy became bifurcated. The philosophical temper of our civilization, being scientifically and technically oriented, is basically Aristotelian.
No such rational figure as Aristotle arose in the Orient to a position of equal eminence. Regardless of the reasons, Indian anatomists and zoologists, who were no doubt just as curious as the Greeks about the origins of life, and as skilled in dissection, did not feel compelled to set their disciplines up in opposition to metaphysics. Metaphysical philosophy and natural philosophy remained joined like Siamese twins. As a result, that discipline which became medicine in the West evolved into a system known as Kundilini Yoga in the Hindu culture. This was a system designed to produce in those who followed its teachings a condition of controlled "creative" madness.
In Western terms, Kundilini Yoga can be understood as a biological statement couched in the language of poetic metaphor. The system made a heroic attempt to join together the seeming disparate entities of body and mind. It is a very complicated doctrine; in oversimplified terms, the system encourages the practitioner to progress through the control of six stages, called chakras, of body-mind coordination. The sixth, the highest and most exalted state, is called the sahasrara.
The physiological site of this sixth chakra, the sahasrara, is located in the center of the forehead; it is symbolized by an eye--the so-called third eye, the inner eye, or the eye of the mind. When this eye is opened, a new and completely other dimension of reality is revealed to the practitioner of yoga. Western scholars when they first came upon this literature took the third eye to be an appropriately poetic metaphor and nothing else.
But in the middle of the nineteenth century, as the subcontinent of Australia and its surrounding territory came to be explored, a flurry of zoological interest centered upon a lizard native to the area, the tuatara (Sphenodon punctatum). This animal possessed, in addition to two perfectly ordinary eyes located on either side of its head, a third eye buried in the skull which was revealed through an aperture in the bone, covered by a transparent membrane, and surrounded by a rosette of scales. It was unmistakably a third eye, but upon dissection it proved to be nonfunctional. Though it still possessed the structure of a lens and retina, these were no longer in good working order; also lacking were appropriate neural connections to the brain. But the presence of this eye in the tuatara still poses a puzzle to present-day evolutionists, for almost all vertebrates possess a homologous structure in the center of their skulls. It is present in many fish, all reptiles, birds, and mammals (including humans). No functional role whatever could be imagined for this structure in humans, and it remained merely an anatomical curiosity until 1898, when Otto Heubner, a German physician, wrote a paper associating cancers of this organ with instances of precocious puberty in children. Heubner's observation was confirmed many times over in the intervening years and gave rise to a number of theories concerning the role of the pineal organ as a regulator of sexual maturity. Those who adhered to these theories considered the pineal to be a gland, but since no secretions could be isolated or identified as emanating from this organ, the theories remained unsubstantiated by clinical evidence.
IN 1948 no one was paying any attention to the pineal organ. A hematologist, Maurice Rapport, working in the Cleveland Clinic was engaged in the search for that substance in blood serum which could be related to the tendency of blood to clot, and which might also cause the constriction of blood vessels. He eventually found just such a substance; it tended to make blood form clots, and it tended to be a muscle- as well as a vaso-constrictor. Rapport named this substance serotonin; it is manufactured quite profusely by specialized cells lining the wall of the gut, and it is presumed to play a role of some kind in the peristaltic movements.
Directly as Rapport announced his discovery, the new chemical came under intensive scrutiny; biochemists were eager to find means of augmenting its role as a clotting agent and vasoconstrictor; they were also eager to find means of blocking these functions. It was E. J. Gaddum, a professor of pharmacology at the University of Edinburgh, who seems to have been one of the first to note a connection between serotonin and mental states of being. In a paper published in 1953, he pointed out the odd fact that LSD-25 was a potent antagonist to serotonin. Two biochemists working at the Rockefeller Institute, D. W. Woolley and E. Shaw, were similarly struck by this odd coincidence. They tested a number of other chemicals antagonistic to serotonin and wrote in a rather startled tone "Among each of these compounds are some that cause mental aberrations....If this be true, then the naturally occurring mental disorders--for example schizophrenia--which are mimicked by these drugs may be pictured as being the result of a cortical serotonin deficiency arising from metabolic failure rather than from drug action."
This announcement produced a thrill of excited hope, which was short-lived; there were other antagonists to serotonin just as potent as LSD which had no effect whatever on mental states. Serotonin also refused to pass through the so-called "blood-brain barrier." If it was injected into the bloodstream of an animal (or a human), it did not seem to pass into the brain. But the medical profession accommodated itself easily to this particular disappointment; for this discovery and a series of others which occurred during the same period gave rise to a whole new set of concepts concerning the roles of various chemical compounds manufactured within the brain. Many of them were molecules of a type known as amines. They were not, strictly speaking, hormones, since they were not produced and secreted by glandular tissue, but by scattered specialized cells, including nerve cells. They came to be called, in a quaint reversion to eighteenth-century diction, neurohumors. According to Webster, a humor is a fluid or juice of an animal or plant, specifically one of the four fluids--blood, phlegm, choler, and melancholy--conceived as entering into the constitution of the body and determining, by their relative proportions, a person's health and temperament; hence one's disposition, or state of mind, whether constitutional, habitual, or temporary. The discovery of the chemical nature of these humors led to the development of chemicals antagonistic to them and thus to entire families of humor-regulating drugs--the tranquilizers, anti-depressants, nervous-system stimulants, and so on.
But despite this new knowledge, the mystery of the LSD-serotonin antagonism persisted. Serotonin is not an unusual chemical in nature; it is found in many places--some of them odd, like the salivary glands of octopuses; others ordinary: it abounds in plants; bananas, figs, plums are especially rich in it. What was it doing in the brains of humans? What was its evolutionary history? In 1958 a Yale Medical School professor of dermatology named Aaron B. Lerner published a paper on the pineal gland which placed this elusive substance in some vague kind of historical perspective and provided for it a real functional role in the brains of mammals.
IT had been known since 1917 that if crushed pineal glands were introduced into water in which tadpoles were swimming, the skin color of the tadpoles would turn light. The chemical substance melanin is the pigment which darkens skin color. It is located in specialized cells scattered through the topmost layer of skin. Pineal extract caused these cells to contract in tadpole skin and in certain other reptiles which change their skin color in response either to mood or environmental setting. Lerner was interested in melanomas, cancers of the pigment cells of human skin; he was curious to find out if there was any possible connection between this skin-lightening substance found in pineals and cancer. After an incredible four-year project, during which time he dissected over 250,000 cattle pineal glands supplied to him by the Armour Company, he finally isolated the substance responsible, calling it melatonin, since it caused the contraction of melanin-producing cells.
He proved that melatonin was a hormone, that it was produced specifically by the pineal organ, and that therefore this organ was a true, functioning gland, not merely a vestigial sight organ, a relic from our reptilian past. He discovered, moreover, how melatonin was manufactured by the pineal--by the action of certain enzymes on a precursor chemical which must pre-exist in the pineal in order for it to be transformed into melatonin. This precursor chemical turned out to be serotonin.
But try as he would, Lerner could find no connection between melatonin and the pigment cells of mammalian skin. In fact, he could find no use whatever for melatonin in the body economy of mammals. The task of exploring the role played by melatonin in the bodies of mammals was undertaken by a brilliant biochemist, Julius Axelrod, working at the National Institutes of Health in Bethesda, Maryland, in the company of several young associates, notably Richard Wurtman and Solomon Snyder. They discovered the basic biochemical sequences performed by the pineal in the manufacture of melatonin; they found that it was produced from serotonin by the action of two enzymes, an acetylating enzyme and a methoxylating enzyme. By blocking or augmenting the action of these enzymes, Axelrod and his assistants were able, most ingeniously, to stimulate or suppress the organism's own manufacture of melatonin. In the course of this work, it became apparent that Otto Heubner's old contention that the pineal produced a substance which interfered with sexual development was very close to the truth. Melatonin did, in fact, suppress physiological sexuality in mammals. If test animals were stimulated to manufacture excessive amounts of melatonin, their gonads and ovaries tended to become reduced in size, to shrink, to atrophy. The estrous, or fertility, cycle in females could likewise be altered experimentally by doses of melatonin.
Now, two most curious functions had been attributed to the pineal gland, the third eye, the eye of the mind. It had now been established that this organ produced a chemical which had, indirectly at least, been associated with psychedelic states. It also produced a chemical which suppressed functional sexuality. The literature of religious mysticism in all ages and all societies has viewed the mystical passion of ecstasy as being somehow analogous to, or involved with, carnal passion. In the pineal gland, in the eye of the mind, were discovered a hormone and a neurohumor which were functionally associated with both kinds of passion.
Axelrod and his co-workers also discovered another incredible fact. The pineal gland produces its chemicals according to a regular oscillating beat, the basis of this beat being the so-called circadian rhythm. This pulse remains constant if darkness and light follow one another through the course of the day in a regular alternation. They found that the pineal responded somehow to light conditions, that by altering light conditions they could extend, contract, even stabilize the chemical production rhythms of the pineal.
How does the pineal perceive light, directly, by being a light sensor itself, still performing some of the functions of an eye; or indirectly, via the central nervous system? The evidence is still not conclusive. Light does penetrate bone and brain to reach the pineal in significant amounts. This was proved by a University of California zoologist, W. F. Ganong, who implanted photocells adjacent to the site of the pineal in sheep and got altered readings from his instruments depending on whether the animals were standing in direct sunlight or in shade. On the other hand, if animals are blinded, or have the nerves connecting the eye to the brain severed, some of the pineal rhythms are dampened, just as though the animals were being maintained in continual darkness. But there is still a sufficient number of discrepancies in the evidence to leave the question of direct light sensing by the pineal open for the moment. Axelrod and Wurtman believe that there are other, undiscovered chemicals being manufactured by the pineal, for they see signs of enzyme activity which cannot be accounted for by either serotonin or melatonin.
The fact that the pineal responds to light, even if this response is indirect via the central nervous system, has some fascinating and far-reaching conceptual applications. There are many behavioral changes which overtake animals as the seasons change, and which can be produced out of season in the laboratory by simulating the appropriate span of artificial daylight. Do such seasonal changes in mood and behavior persist in humans?
The great religious holy days of all faiths tend to cluster around the times of the solstices and equinoxes. Is it possible that the human pineal gland responds to these alterations in the length of daylight, and by changing the balance of neurohumors in the brain, perhaps effects a greater incidence of psychedelic states in certain susceptible individuals just at these crucial times? This possibility provides an entirely new potential dimension to our secular understanding of the religious experience.
Since Lerner had done his original pineal research at Yale, his colleagues belonging to various disciplines had become fascinated with his work even before it was published. As a result, Yale had a kind of head start in pineal research. Among the first to pursue the trail of pineal hormones and neurohumors was Nicholas Giarmin, a professor of pharmacology who had been a former student of Gaddum's at Edinburgh and remembered the connection Gaddum had made five years previous between LSD and serotonin. With him worked a professor of psychiatry, Daniel Freedman, who had become fascinated by the whole new field of pharmacology and states of mind. They began by measuring the serotonin contents of the various parts of the human brain at autopsy. In order to make these measurements, one must exploit the very limits of our technological capacities. Neurohumors exist in the brain in infinitesimally small amounts. They are measured by a unit known as the nanogram, which is one billionth of a gram. Not only are assay procedures highly critical, but since drastic chemical changes occur between that state which we call life and that which we define as death, it is difficult to prove that the amounts of any given entity found on autopsy are the same as those which might be found in the same tissue in the flush of life. Giarmin and Freedman confirmed that the human brain manufactures serotonin at various sites other than the pineal. It is produced in scattered isolated cells, but the density of these cells varies with their location in the brain. For example, in the thalamus, they discovered 61 nanograms of serotonin per gram of tissue; in the hippocampus, 56 ng.; in the central gray section of the midbrain, they found 482 ng. But in the pineal, they found 3140 ng. of serotonin per gram of tissue. The pineal was unmistakably the richest site of serotonin in the brain!
Since the pineal seems to produce serotonin in excess of its needs for melatonin production, what happens to this excess? Does the gland provide a kind of serotonin reservoir for the brain as a whole? Can one make a correlation between pineal serotonin and mental disorder? As its name would imply, the pineal looks like a miniature pine cone sitting in the middle of the brain atop a stalklike appendage. The vascular and neural connections between it and the rest of the body run down this 2 stalk into the spinal column and the central nervous a system, not into the brain proper. If serotonin from the pineal does get back into the brain proper, it a must do so through such a circuitous route that many workers discredit this possibility.
Though their work only accidentally impinged on making such correlations, Giarmin and Freedman did find that the pineals of certain deceased mental patients who had suffered from specified mental disorders showed a considerable excess of serotonin in their pineals. The average amount of serotonin found in the pineals of normal persons is about 3.52 micrograms per gland. One schizophrenic was found to have a pineal containing 10 micrograms of serotonin, while another patient, a sufferer from delirium tremens, had a pineal containing 22.82 micrograms of serotonin. Owing to the difficulties of obtaining the brains of the recently dead for autopsy, the Giarmin-Freedman sample is pathetically small, consisting only of thirteen cases. The same difficulties which confronted them also confront other workers who might be tempted to confirm these findings on a larger scale.
Strong suspicion has fallen now on serotonin as being one of the principal agents of the psychedelic experience, but whatever its role, it is certain that other neurohumors are additionally involved in the chemical transactions which produce the state. It is likely that LSD itself produces certain effects quite on its own. Studies made with tracer elements and the electron microscope now reveal that LSD strikes like a chemical guerrilla, entering into receptor granules in brain cells swiftly, and then leaving swiftly after a very short time, perhaps ten or twenty minutes (in animals). This initial period coincides with the onset of the most violent symptoms of the LSD state as it is observed in test animals. But when the twenty minutes are done, and the bulk of the LSD has left the receptor granules, it is replaced by what seems to be excessive, or supernormal, amounts of serotonin. Since the LSD state lasts for some ten hours, and during this time serotonin can be measured (again at autopsy) in supernormal amounts in receptor granules, it must be considered one of the important participants of that chemical transaction which produces the state. However, melatonin possesses the same basic indole molecular structure as the LSD molecule. It is not at all difficult to imagine how this substance could be metamorphosed into a psychedelic material. But so far, injections of melatonin have produced no altered mental states in humans.
The use of LSD in exploring these strange dislocated states of mind is most convenient because the effects are invariably reliable, and within certain limits quite predictable. All the neurohumors tend to alter, in one way or another, the data processing programming of the brain. LSD is one of the keys which open the compartment into which this drastic new programming can be introduced. Fasting as a means of altering body chemistry and so producing this kind of psychedelic state seems to be effective only among those who are marginally nourished in the first place. Sensory deprivation IS effective, and for those who can will themselves into a state of such intense meditation as will exclude incoming signals from the environment, the computer model provides a simple analogy. The brain is always working, but as these outside signals cease coming through, the brain begins processing peripheral data, memories from the past, sense impressions of such subtlety that they are normally bypassed in favor of more vivid input signals which affect survival and so on.
For most of us, most of the time, our world is a Darwinian environment. We must manipulate ourselves within it, or attempt to manipulate it in order to survive. These survival needs tend to color our appreciation of this world, and we are continually making judgments about it. Some, of these judgments are based on prior personal experience, others are provided by the culture. This "recognition system" is one of the elements disrupted by the psychedelic state. Normally we anticipate that water will feel wet. To the madman, or the person entranced by LSD, the wetness of water can come as an incredible surprise.
The principal question concerning psychedelic estates remains: How much disruption can the system tolerate? "Cowper came to me," writes William Blake, "and said: 'O that I were insane always.... Can you not make me truly insane? I will never rest till I am so. O that in the bosom of God I was hid. You retain health and yet are as mad as any of us--over us all.'"
The problem of how to maintain a certain madness while at the same time functioning at peak efficiency has now captured the attention of many psychiatrists. There seems to be a point at which "creative" madness becomes degenerative, impeding function rather than stimulating it. The mental hospitals are filled with patients who passed from transient, or occasional, psychedelic states into perpetual psychosis. Freedman, with the help of another Yale colleague, Malcolm Bowers, has collected a number of case histories of persons who were admitted into mental institutions for various acute psychotic seizures. But as they speak and write about the onset of their illness, they describe psychedelic experiences. Why did they not "pass through" the experience to be enriched by it, as did William Blake? Here, for example, is the report of a twenty-one-year-old student who was removed to a mental hospital in "a severely agitated delusional state":
"I [began to be] fascinated by the little insignificant things around me. There was an additional awareness of the world that would do artists, architects and painters good. I ended up by being too emotional, but I felt very much at home with myself, very much at ease....it was not a case of seeing more broadly, but deeper. I was losing touch with the outside world, and lost my sense of time....I could see more deeply into the problems other people had and would go directly into a deeper subject with a person. I had the feeling that I loved everybody in the world. Sharing emotions was like wiping the shadow away, wiping away a false face."
Bowers and Freedman do not tell us the final history of this patient. We do know, however, that Cowper asked for insanity and got it. He died a gibbering idiot, while Blake lived on into a ripe and irritable old age, still working, still writing, still slipping in and out of his mysterious states which allowed him a clear and brilliant vision of a world which, if the rest of us see at all, we see as through a glass darkly.
Man is unique by virtue of being possessed by intuitions concerning the scope of the mysterious universe he inhabits. He has devised for himself all manner of instruments to probe the nature of this universe. Now at last, with the molecule of this strange acid, he has found an instrument which opens the inner eye of the mind and which may hopefully allow him to explore the vast interior spaces where the history of millions of years of memories lie entangled among the roots of the primordial self. Through it we may find a means of understanding more clearly the roots of madness and of helping the insane to return to the world of commonplace reality.