Everything about the psychedelic drugs has been a subject of angry controversy; the argument begins with the question of what they should be called and what substances are properly classified as belonging to the group once it is named. Their psychological effects are diverse and variable and a wide variety of other substances, human activities, and physiological conditions occasionally produce similar effects; so any specific list of drugs or any name that implies a defining characteristic seems too restrictive. Besides, all the available names and definitions were unfortunately molded into ideological weapons during the political-cultural warfare of the 1960s, so that choosing, say, whether to call the drugs "psychotomimetic"or "psychedelic" is now often imagined to imply a decision about social philosophy and even metaphysical world view. And the inclusion of a given drug in this category that lacks a principled definition or an agreed-upon name may profoundly affect public attitudes toward it and the legal penalties faced by its users. It is an unsatisfactory situation caused partly by our limited scientific understanding and partly by the angry passions that tend to fill an intellectual void when the issue is drugs.

Like the mystical experience they are said to induce, these drugs may be best defined by negatives. They are not sedatives, hypnotics, narcotics, stimulants, depressants, deliriants, anesthetics, analgesics, or euphoriants; or rather they can be all or none of these. The various names proposed for them reflect the hopes and fears of investigators as much as their analytical methods. In the absence of any clear definition of the drugs' pharmacological nature or psychological effects, their names often represent attempts to say how they should or should not be used; none of them has satisfied a majority of researchers. One popular term, commonly used in experimental investigations in the 1950s and still favored by some researchers, is "psychotomimetic," which implies that the drug reaction resembles natural forms of psychosis and may be a clue to their causes and treatment. What began as a discussion among physicians and psychiatrists turned into a political debate in the 1960s, when Timothy Leary and other advocates of psychedelic philosophy and religion declared that use of words like "psychotomimetic" was an attempt to suppress the drugs by giving them a bad name, denying the true significance of the experience by labeling it as obviously undesirable. Further complications were introduced when R. D. Laing and his followers rejected the usual implications of the term "psychosis" itself and promoted a new view of schizophrenia as a harrowing but revelatory and potentially restorative mental journey with some of the same virtues as an LSD experience. The relationship between drug-induced states, schizophrenia, and other unusual forms of consciousness is still an open question and an important one, but even those who continue to use the term "psychotomimetic" now generally agree that the drug effect is not the same as schizophrenia or any other naturally occurring psychosis. We will have more to say about this, but it is enough for now to point out that the term "psychotomimetic" is both too limiting and misleading, although many symptoms of the drug reaction at times resemble the symptoms of schizophrenia or other functional psychoses.

"Hallucinogen" is the designation used by the U.S. government in its drug laws and also the most common term in medical research. It fixes on the sensory distortion and enhancement, especially visual, that is one of the most striking effects of some of these drugs at low doses, in the early stages of intoxication, or during the first few drug experiences. The point is that most drug-induced hallucinations are effects of overdose, associated with metabolic disturbances, major autonomic changes (in heart rate, blood pressure, breathing, and so on), delirium, and eventual stupor or amnesia; drugs like LSD produce perceptual changes without these side effects, and can therefore be defined as primarily hallucinogenic. Even Humphry Osmond, the inventor of the word "psychedelic," eventually adopted "hallucinogen." Nevertheless, there are several objections to the term. By referring only to perceptual effects, it understates the importance of mood and thought changes; and the implication of disease or deleteriousness that it inescapably conveys creates a tendency to prejudge the value of the experience. The word "hallucination" has narrowed in meaning. It is derived through Latin from the Greek aluein, "to be distraught," a term used for sorcerers' voyages and other mental wanderings. Now it is usually taken to mean perceiving imaginary objects as real ones, but that is rare with or without drugs. Used to describe the estheticized perception or fascination effect, enhanced sense of meaningfulness in familiar objects, vivid closed-eye imagery, visions in subjective space, or visual and kinesthetic distortions induced by drugs like LSD, "hallucination" is far too crude. If hallucinations are defined by failure to test reality rather than merely as bizarre and vivid sense impressions, these drugs are rarely hallucinogenic. In one study, experimental subjects given a choice of eighteen categories to describe their experience placed "hallucinations" last (Ditman and Bailey 1967). The awkward terms "pseudohallucinogenic" (referring to images in subjective space or otherwise distinguishable from external reality) and "illusionogenic" have been proposed as substitutes. But many of the most powerful and sought-after effects can be called hallucinations or illusions only by stretching definitions to the breaking point or imposing a questionable social judgment. It is inaccurate to describe in this way experiences like intense emotional reaction to slight gestures, enhanced empathy, deep introspective reflection, reliving of old memories or participation in symbolic dramas, loss of the unity of body and self, quasi-religious exaltation, or ecstatic union with other people or the cosmos. Finally, some drugs that we intend to discuss (and which are classified as hallucinogens under federal law), like MDA, MMDA, and DOET, can enhance self-awareness and intensify feelings or restore memories without producing sensory distortions at all.

The 'term "psychodysleptic" (mind-distorting or mind-disrupting), introduced in 1959 (Brimblecombe and Pinder 1975, p. 4), has been popular in Europe and Latin America. Although it is more comprehensive (or vaguer) than "psychotomimetic" or "hallucinogenic," it is subject to some of the same objections. In any case, its unfamiliarity in this country makes it inappropriate for our purposes. Another term that conveys the range of feeling and thought produced by the drugs and also has a pleasantly poetic ring is "phantastica" (or, in the English adjective form, "phantasticant"), invented by one famous student of psychoactive drugs, Ludwig Lewin, and endorsed by two others, Albert Hofmann and Richard E. Schultes (Schultes and Hofrnann 1973, p. 7). "Oneirogenic" (causing dreams), a term first used by the nineteenth-century physician Moreau de Tours in his study of hashish, has not become popular, although it is more accurate than "hallucinogenic" as a description of some aspects of the experience. Among words less committed to a specific descriptive content than "psychotomimetic" and "hallucinogenic," only "psycholytic" and "psychedelic" have gained any currency. "Psycholy-ic" is derived from Greek roots meaning "mind loosening- and has become associated with a form of therapy in which small doses of LSD, mescaline, or psilocybin are used to aid in psychoanalysis and psychoanalytically oriented psychotherapy, presumably by breaking down ego defenses and bringing up repressed feelings and thoughts from the unconscious. It is inappropriate for us to use the term because, like "psychodysleptic," it is unfamiliar in the United States, and also because it has become too closely associated with the models and therapeutic methods of psychoanalysis to serve as a neutral descriptive classification. It identifies a kind of therapy more than a class of drugs; like "psychotomimetics," it has come to imply a recommendation about how the drugs should and should not be used.

We are left with the unsatisfactory but unavoidable "psychedelic," from the Greek psyche (mind) and delos (clear or visible), invented by the psychiatrist Humphry Osmond during a correspondence with the novelist Aldous Huxley in 1956. Osmond introduced the word because it had never been used for anything but the drug experience and therefore was uncontaminated by other associations; it is usually interpreted to mean "mind manifesting" or "mind revealing." Although Osmond did not intend it as a judgment on the value of the experience—that was his objection to "hallucinogenic" and "psychotomimetic"—it was quickly taken up by drug enthusiasts who played on the religious implications of words like "manifestation" and "revelation" and made it a weapon in the cultural propaganda war of the 1960s. From this history many objections to the word are derived: that it is a means of self-congratulation for drug users, that it ignores all but the religious or mystical aspects of the experience, that it overrates the drugs' significance, that it is the central idea of an absurd and offensive intellectual system and world view. (A minor annoyance for scrupulous etymologists is that the word is derived improperly. By the rules for combining Greek roots, it should be "psychodelic"; this was the form Huxley always used.) "Psychedelic" also suffers by associations with "consciousness expending,'' since one person's expansion is another's inflation, dilution, and distortion. In general, it has been objected that the wrong people use (or have used) the word for the wrong kind of purpose. But this feeling is best ignored. We are not obliged to give the same meaning to "psychedelic" that leaders of drug cults give it, any more than we are obliged to give the same meaning to "democracy" that the governments of Eastern Europe give it. In any case, the cultural conflict that raged so fiercely in the 1960s is over, or at least a partial armistice has been declared, so "psychedelic" need no longer be treated as a war cry. It has become part of the common language—the favorite popular term where "hallucinogenic" is the favorite academic term—and we can use it as Osmond intended, without assuming anything about the value of what is manifested or revealed.

The drugs usually called psychedelic have no chemical structure in common; their pharmacological mechanisms are poorly understood; and as we pointed out, their effects are diverse and can be produced in other ways as well. It may seem unfair or unreasonable, then, to deny a place in the (sacred or infernal, depending on one's point of view) psychedelic kingdom to opium dreams, drunken ecstasy, amphetamine hallucinations, shamanistic trances induced by coca or tobacco, and so on, simply because they were not objects of a cult in America in the 1960s; certainly they are all drug-induced manifestations or revelations of mental powers and states not ordinarily experienced. A definition that provides a basis for excluding these drugs and some others that we will mention is as follows: a psychedelic drug is one which, without causing physical addiction, craving, major physiological disturbances, delirium, disorientation, or amnesia, more or less reliably produces thought, mood, and perceptual changes otherwise rarely experienced except in dreams, contemplative and religious exaltation, flashes of vivid involuntary memory, and acute psychoses.

But this is no more than a rough guide; in the end, no definition is adequate, because the psychedelic drugs have a vague family resemblance rather than an easily described set of common features. Besides, it is somewhat misleading to exclude the cultural component that can make all the difference. The alcohol drunk by bacchants in the rites of Dionysus in ancient Greece might be called a psychedelic drug; the alcohol drunk by the American sports enthusiast as he sits in front of his television set watching a football game is not. Tobacco as used by a South American Indian witch doctor may resemble LSD more than it resembles the tobacco consumed by the Marlboro man. But if we overemphasize cultural context, the topic becomes broad and diffuse beyond all reasonable bounds. Some compromise between comprehensiveness and precision is necessary. One useful way to identify the topic of discussion is by reference to a central or prototype drug: d-lysergic acid diethylamide. It is the most powerful as well as the most famous (or notorious) psychedelic drug, capable of producing almost all the effects that any of the others produce, and at much smaller doses. Whether a drug should be regarded as psychedelic or not can be said to depend on how closely and in what ways it resembles LSD; the resemblance must be judged by the drug's cultural role as well as by its range of psychopharmacological effects. From this point of view, the group of psychedelic drugs has a clearly defined center and a vague periphery; the fewer of the family features a drug has, or the less likely it is to be used by the same people or at the same places and times as LSD, the less social and psychopharmacological claim it has to be called psychedelic. Unavoidably, the necessary exclusions and inclusions will be somewhat arbitrary.

The drugs we regard as central can be divided according to their chemical structure into two categories: indole derivatives and phenylalkylamines. The indoles, with more than one carbon ring, include lysergic acid amides, tricyclic carbolines (harmala alkaloids), ibogaine, and substituted tryptamines (psilocin, psilocybin, DMT, and others). The phenylalkylamines, with only one carbon ring, belong to two groups: phenylethylamines, of which the only important representative is mescaline; and phenylisopropylamines or amphetamines, including MDA, MMDA, DOM, and many others.*

LSD

Chemical structure and source: The structural formula is as follows:

* There are several systems of chemical nomenclature. We have used one that is common in the psychiatric and the pharmacological literature. In the chemical literature, terminology may be different; for example, phenylethylamine is called 1-amino-2-phenyl ethane.

The "d" stands for dextrorotatory: turning the plane of polarized light to the right. To convey some idea of the specificity of the chemical action, it is worth noting that there are three other stereoisomers of LSD, all containing the same number and kinds of atoms but in different spatial arrangements. These are the optical mirror-image (levorotatory) /-LSD, d-iso-LSD, and /-iso-LSD; all are pharmacologically inactive. The active stereoisomer d-LSD is the one that corresponds to natural lysergic acid. Several other lysergic acid amides do have effects like those of LSD, although most of them are much weaker. The most potent is 1-acetyl-LSD (called ALD-52), which has 91 percent of the strength of LSD and is sometimes sold on the illicit market as a substitute that is   not so indisputably illegal; another is 1-methyl-LSD (called MLD-41), 36 percent as potent as LSD.

LSD is synthetic, but it is derived from the natural substances known as ergot alkaloids, which are produced by ergot (Claviceps purpurea), a fungus that grows on rye, and also by certain members of the Convolvulaceae or morning-glory family, notably Rivea corymbosa, Ipomoea violacea or Ipomoea tricolor, Ipomoea carnea, Argyreia nervosa (Hawaiian baby woodrose); and Merremia tuberosa (Hawaiian woodrose). Bread made from rye infected with the fungus causes a disease known as ergotism with hallucinatory as well as physiological symptoms. A drink containing the powdered seeds of the morning glories produces LSD-like experiences along with nausea, diarrhea, and other toxic side effects from the many alkaloids present. Morning glories that produce ergot alkaloids grow in many parts of the world, but they have been traditionally used as drugs only in Mexico and possibly Central America. The divine plant ololiuquiof the Aztecs has been identified as Rivea corymbosa, and another traditional Mexican Indian drug, tlitliltzin or badoh negro, is derived from Ipomoea violacea. Both of these species are now cultivated in several ornamental horticultural varieties including Heavenly Blue, Pearly Gates, and Flying Saucers—names that took on new implications in the late 1960s when the seeds were being used for purposes unrelated to gardening. The psychoactive principles of these plants are several forms of lysergic acid amide, chiefly ergine (d-lysergic acid amide) and isoergine (d-isolysergic acid amide), which are 5 to 10 percent as strong as LSD. It is estimated that 100 o/o/iuqui seeds or four to eight Hawaiian baby woodrose seeds are equivalent to 100 micrograms of LSD. LSD in the form of the water-soluble tartrate salt is manufactured from lysergic acid, which can be produced either by hydrolysis of ergot alkaloids or directly in certain cultures of the ergot fungus.

Dose: LSD is one of the most powerful psychoactive drugs known. As little as 10 micrograms (ten millionths of a gram or .01 milligram) produces some mild euphoria, loosening of inhibitions, and empathetic feeling. The lowest psychedelic dose is 50 to 100 micrograms, and the intensity and profundity of the effects increase up to about 400 or 500 micrograms, with individual variations; higher doses may prolong but do not further alter the experience (Klee et al. 1961). Only a tiny proportion of the drug actually reaches the brain. The lethal dose in man is unknown. One person is said to have taken 40 mg and survived (Barron et al. 1970); in the only reported case of death possibly caused by overdose, the quantity of LSD in the blood suggested that 320 mg had been injected intravenously (Griggs and Ward 1977). Tolerance (resistance to the drug effect) develops quickly—within two or three days—and disappears just as fast.

Physiological effects: These are extremely variable and more or less independent of dose. The most common effects are especially conspicuous in the first hour, before the psychological effects become obvious: dilation of the pupils (the most nearly universal symptom); increase in deep tendon reflexes; increased heart rate, blood pressure, and body temperature; mild dizziness or nausea, chills, tingling, trembling; slow deep breathing; loss of appetite; and insomnia. Most of the symptoms are sympathomimetic; they indicate activation of the sympathetic nervous system, which prepares the body physiologically for emergencies. But none of these symptoms is always present; their opposites may even appear instead. LSD probably produces a broader spectrum of physical symptoms than any other drug, almost all of them secondary effects of the complex psychological changes. Most physiological measures—liver function, serum cholesterol, urine, and so on—are unaffected. LSD is almost completely metabolized in the body; very little is excreted unchanged in the urine.

Psychological effects: This topic has supplied volumes of eloquence. The enormously variable effects have been described as an unspecific intensification of mental processes. They can be classified, roughly, as changes in perception, changes in feelings, and changes in thought—although carving up any experience in this way is somewhat arbitrary, and although this particular experience of ten has the special property of making such distinctions seem meaningless. Perceptually, LSD produces an especially brilliant and intense impact of sensory stimuli on consciousness. Normally unnoticed aspects of the environment capture the attention; ordinary objects are seen as if for the first time and with a sense of fascination or entrancement, as though they had unimagined depths of significance. Esthetic responses are greatly heightened: colors seem more intense, textures richer, contours sharpened, music more emotionally profound, the spatial arrangements of objects more meaningful. Other effects include heightened body awareness and changes in the appearance and feeling of body parts, vibrations and undulations in the field of vision, heightened depth perception and distortions of perspective, proiongation of afterimages, the appearance of physiognomies and expressions in inanimate objects, and synesthesia (hearing colors, seeing sounds, etc.). Time may seem to slow down enormously as more and more passing events claim the attention, or it may stop entirely, giving place to an eternal present. When the eyes are closed, fantastically vivid images appear: first geometrical forms and then landscapes, buildings, animate beings, and symbolic objects.

The emotional effects are even more profound than the perceptual ones. The drug taker becomes extraordinarily suggestible, reacting with heightened sensitivity to faces, gestures, and small changes in the environment. As everything in the field of consciousness assumes unusual importance, feelings become magnified to a degree of intensity and purity almost never experienced in daily life; love, gratitude, joy, sympathy, lust, anger, pain, terror, despair, or loneliness may become overwhelming. Hidden ambivalent emotion becomes fully conscious, so that two seemingly incompatible feelings may be ex-perienced at the same time. It is possible to achieve either unusual openness and emotional closeness to others or an exaggerated detachment that makes others seem like grotesque puppets or robots. The extraordinary sensations and feelings may bring on fear of losing control, paranoia, and panic, or they may cause euphoria and even bliss. Short-term memory is usually impaired, but forgotten incidents from the remote past may be released from the unconscious and relived. Introspective reflection with a sense of deep, sometimes painful insight into oneself or the nature of man and the universe is common; often the experience is considered somehow more real or more essential than everyday life, and the drug user feels himself to have transcended the trivial and absurd preoccupations of his fellows—the "game world" of ordinary consciousness. There are also profound changes in the sense of self: the ego may separate from the body so that one's feelings and perceptions seem to belong to someone else or to no one; or the boundary between self and environment may dissolve so completely that the drug user feels at one with other people, animals, inanimate objects, or the universe as a whole.

Advanced states of intoxication produce transformations in consciousness that affect thought, perception, and feeling at once. The drug user becomes a child again as he relives his memories, or he projects himself into the series of dreamlike images before his closed eyelids and becomes the protagonist of symbolic dramas enacted for the mind's eye. Actions, persons, and images in this dreamworld or even in the external world may become so intensely significant and metaphorically representative that they take on the character of symbols, myths, and allegories. The drug user may feel that he is participating in aribient rites or historical events that occurred before his birth; sometimes he interprets these as memories of a past incarnation. Users may also believe that they are perceiving normally unconscious physiological processes oi experiencing themselves as nerve cells and body organs. They may identify themselves with animals, or feel themselves to be reliving the process of biological evolution or embryonic development. They may experience loss of self as an actual death and rebirth, which they undergo with anguish and joy of overwhelming intensity. They may believe that they are encountering gods or demons, or that they have left the body and can look down on it from above or abandon it to travel instantly to a faraway place. The many degrees of mystical ecstasy culminate in what Hindu theology has described as sat-chit-ananda, being-awareness-bliss; here for an eternal moment all contradictions are reconciled, all questions answered, all wants irrelevant or satisfied, all existence encompassed by an experience that is felt to define ultimate reality: boundless, timeless, and ineffable.

Some of these effects are more common than others, but few of them occur with any reliability. One person may feel only nervousness and vague physical discomfort from a dose that plunges another into paranoid delusions and a third into ecstasy; and the one who feels ecstatic joy now may experience infinite horror or grief the next time, or even the next moment. For this reason people who advocate the use of LSD always rightly emphasize appropriate set (mood, personality, expectation) and setting (physical, social, and cultural environment). But the drug—or rather the character and emotional state of the drug user whose perceptions, feelings, and memories it intensifies—is so unpredictable that even the best environment and the highest conscious expectations are no guarantees against a painful experience.

Duration of action: Begins forty-five minutes to an hour after the drug is taken by mouth, reaches a peak at two to three hours, and lasts for eight to twelve hours, often ebbing and returning several times. The half-life of LSD in blood plasma is about two hours.*

*For a detailed discussion of lysergic acid derivatives, see Sankar 1975.

Harmala Alkaloids

Chemical structure and source: These are cyclic tryptamines of the kind called beta-carboline derivatives. The structural formulas are as follows:

Before the alkaloids were isolated, the mixture that constitutes the active principle of the plants from which they are derived was called banisterine, yageine, or sometimes, because of an alleged capacity to induce extrasensory perception, telepathine. The harmala alkaloids are 7-methoxy-beta-carbolines; other psychoactive beta-carbolines are 6-methoxy-dihydroharman and 6-methoxy-tetrahydroharman. The harmala alkaloids are found in the seeds of the Near Eastern shrub Peganum harmala (Syrian rue), in the bark of South American vines of the Banisteriopsis genus (especially B. caapi, B. inebrians, and B. quitensis), and also in another vine belonging to the same family, Tetrapterys methystica. Harmine is the major alkaloid. From the inner bark of the vines a drink known in various parts of the western Amazon basin as ayahuasca ("vine of souls"), caapi, natema, pinde, yagé, nepe, or kahi is made.

Dose: Little reliable information is available. In some reports harmaline is said to be active at 70 to 100 mg intravenously or 300 to 400 mg orally; harmine is about half as potent, 1/8000 the strength of LSD (Naranjo 1967, p. 387; Hollister 1968, p. 47; Brown 1972, p. 91). Other reports state that harmine and harmaline have the same strength and are active orally at 200 mg, which amounts to 30 inches of B. caapi vine (Stafford 1977, p. 279).

Physiological effects: The South American drinks and snuffs often cause nausea, vomiting, sweating, dizziness, lassitude, tremors, and numbness, and so does pure harmaline. Muscles are usually relaxed.

Psychological effects: Withdrawal into a trance with dreamlike imagery. Open eyes see imaginary scenes superimposed on surfaces and vibrations in the visual field. When the eyes are closed, long sequences of vivid cinematic images appear: especially circular patterns, sardonic masks, dark-skinned men, tigers and jaguars, birds, and reptiles; also, visions of spirit helpers, demons, deities, and distant events. The images are often colored blue, purple, or green. There may be a sense of suspension in space or flying, falling into one's body, or experiencing one's own death. The images often become mythical symbols or archetypes expressing themes of sexuality and aggression. The dreamlike sequences are sometimes said to be longer, more vivid, and more realistic than those produced by mescaline or LSD. Since both Amazon Indians and middle-class Chileans are said to see similar visions, possibly these drugs produce a special kind of imagery; but evidence is scarce, and the potential influence of previous knowledge and suggestion great, so the effect may be cultural rather than chemical. Ecstasy, dread, exaggerated empathy or detachment, synesthesia, change in time sense, color enhancement, and body-image distortion occur more rarely. Emotion may or may not be strongly affected. The drug taker often wants to be alone with his thoughts and has no desire to communicate with others.

Duration of action: Four to eight hours when taken orally.*
*For further information see Harner 19736, Naranjo 1967, Naranjo 1975 (1973), and Stafford 1970.

Ibogaine

Chemical structure and source: Resembles the harmala alkaloids. The chemical formula is:

It is one of twelve alkaloids extracted from the root of the West African plant Tabernanthe iboga. Africans use the root as a stimulant and aphrodisiac at low doses and ritually at higher doses.

Dose: From 200 to 400 mg produce psychedelic effects orally.

Physiological effects: Resembles the harmala alkaloids; can cause paralysis, convulsions, and death at high doses.
 

Psychological effects: Little is known, but the available reports suggest that it is like harmaline but less purely visual and symbolic. The images are often of fountains, tubes, marshy creatures, white and blue light, and rotating motion. Explosions of rage directed against the images of persons and situations from the past are reported. Childhood fantasies are reenacted, and a sense of insight and heightened emotion often accompany the images. The drug taker concentrates on his inner world and personal past. The effect is easily distinguishable from that of LSD.

Duration of action: Eight to twelve hours.*

*For further information see-Naranjo 1975 (1973).

Psilocin and Psilocybin

Chemical structure and source: These are substituted tryptamines. The structural formulas are:

Psilocin is 4-hydroxy-N,N-dimethyltryptamine and psilocybin is the phosphate ester of psilocin; in the body it is broken down into psilocin and takes effect in that form. The synthetic N,N-diethyl homologues, known as CEY-19 and CZ-74, are also psychedelic but shorter-acting (three to four hours). Psilocybin and, in smaller quantities, psilocin have been found in about ninety mushroom species, and more are constantly being discovered. Most of them belong to the genera Psilocybe, Conocybe, Gymnopilus, Panaeolus, and Stropharia, all members of the family Agaricaceae. Psilocybe mexicana and Stropharia cubensis (Psilocybe cubensis) are probably the most important; others are Panaeolus campanulatus, Panaeolus cyanescens, and Psilocybe semilanceata (known in the Pacific Northwest as "liberty caps"). Psilocybin mushrooms grow in many parts of the world, including the United States and Europe, but until recently they were eaten mainly in Mexico and Central America, where they used to be called by the ancient Aztec name of teonanacatl ("flesh of the gods)," a term now rendered nanacatl in Mexico.*

Dose: Estimates vary, but the psychedelic effect of psilocybin seems to begin at 4 to 6 mg; the usual dose is 10 to 20 mg, or 5 to 10 grams of dried Stropharia cubensis. It is about thirty times stronger than mescaline and slightly less than 1 percent as potent as LSD. Psilocin is 1.4 times as strong as psilocybin. Tolerance develops as with LSD, and there is also cross-tolerance with LSD (Rech et al. 1975).
 

Physiological effects: Like LSD but gentler.
 

Psychological effects: Very similar to LSD; the experience is sometimes said to be more strongly visual, less intense, and more euphoric, with fewer panic reactions and less chance of paranoia. Drug users often prefer it, especially in the natural mushroom form.

Duration of action: Four to six hours.

*On the identification and cultivation of these mushrooms, see Schultes and Hofmann 1973, Haard and Haard 1975, Pollock 1976, Lincoff and Mitchel 1977, and the references in Stafford 1977, pp. 253-254,

Other tryptamines supply the active components of several South American psychedelic snuffs and drinks. The chief of these is 5-methoxy-N,N-di-methyltryptamine (5-Me0-DMT):

It resembles DMT (see p. 19) in its effects, and is produced, along with other active tryptamines, by the trees Virola calophylla, Virola calophylloidea, Virola theiodora, Anadenanthera peregrina (Piptadenia peregrina), Psychotria viridis, and others. From the bark resin of the Virola trees Indians make a snuff called yakee or yako in Colombia and epéna or paricà in Brazil. From the seeds of Anadenanthera peregrina they make another snuff called yopo or paricà in the valley of the Orinoco and cohoba in the West Indies; vilca or cebil, a snuff prepared from the seeds of Anadenanthera colubrina, was formerly used in southern South America. Bufotenine (5-hydroxy-N,N-dimethyltryptamine), a better-known substance produced by some of the same plants as well as in the skin of toads, is not clearly psychoactive, apparently because it does not pass the barrier between the bloodstream and the brain; 5- methoxy-N,N-DMT itself is about as potent as psilocybin but inactive orally. Harmala alkaloids have also been extracted from Virola resin; they allow the tryptamines to take effect orally by acting as inhibitors of the enzyme monoamine oxidase, which would otherwise destroy them. Several hydroxytryptamine derivatives have strong effects on animals but are untested in man.*

*For further information see Brimblecombe and Pinder 1975, p. 108, p. 112, and the table on p. 117; see also Gillin et al. 1976.

DMT

Chemical structure and source: This is the prototype member of the tryp-tamine subclass of indole derivatives. The structural formula is:


The drug is a constituent of many of the same South American snuffs and drinks that contain other psychedelic indole derivatives; it is often found in the same plants as 5-MeO-DMT, and Indians add a substance containing it to drinks containing harmala alkaloids. DMT is the major constituent of the bark of Virola calophylla, mentioned above; it is also found in the seeds of Anadenanthera peregrina; in the seeds of the vine Mimosa hostilis, used in eastern Brazil to make a drink called ajuca or jurerna; in the leaves of Banisteriopsis rusbyana, which are added to the harmaline drinks derived from other plants of the Banisteriopsis genus to make oco-yagé; and in the leaves of Psychotria viridis, also added to the Banisteriopsis drinks. Like 5-MeO-DMT, DMT must be combined with monoamine oxidase inhibitors to become active orally.

Dose: First strong effects are felt at about 50 mg, whether it is smoked or injected. Tolerance develops only after extremely frequent use—injections every two hours for three weeks in rats; at that dose frequency, but not otherwise, there is also cross-tolerance between DMT and LSD (Rosenberg et al. 1964; Kovacic and Domino 1976).

Physiological effects: Resembles LSD, but sympathomimetic symptoms like dilated pupils, heightened blood pressure, and increased pulse rate are more common and more intense.

Psychological effects: Like LSD but often more intense. Since it is not taken by mouth, the effects come on suddenly and can be overwhelming. The term "mind blowing" might have been invented for this drug. The experience was described by Alan Watts as like "being fired out of the muzzle of an atomic cannon" (Leary 1968a, p. 215). Thoughts and visions crowd in at great speed; a sense of leaving or transcending time and a feeling that objects have lost all form and dissolved into a play of vibrations are characteristic. The effect can be like instant transportation to another universe for a timeless sojourn.
 

Duration of action: When DMT is smoked or injected, effects begin in seconds, reach a peak in five to twenty minutes and end after a half hour or so.

This has earned it the name "businessman's trip." The brevity of the experience makes its intensity bearable, and, for some, desirable.*

*For further information see Szara 1956; Szara et al. 1966; Leary 1968a, pp. 264-269; Stafford 1971, pp. 211-218; Stafford 1977, pp. 282-305.

At least two synthetic drugs in which the methyl group of DMT is replaced by a higher radical are psychedelic:

The drug DET is active at the same dose as DMT and the effects last slightly longer, about one and a half to two hours. DPT is longer-acting still and has fewer autonomic side effects. In therapeutic experiments its action continues for one and a half to two hours at the lowest effective dose, 15 to 30 mg,, and for four to six hours at doses in the range of 60 to 150 mg. Both DET and DPT are milder than DMT. The drug 6-FDET (6-fluorodiethyltryptamine) resembles DET in its effects. All these drugs, like DMT, are inactive orally and must be smoked or injected. Dibutyltryptamine (DBT) and higher substitutions are inert, but other synthetic drugs related to DMT may be psychoactive.*

*See Szara et al. 1966; Szara 1967; Faillace et al. 1967.

Mescaline

Chemical structure and source: The largest group of psychedelic compounds is the phenylalkylamines, with a one-ring chemical structure. The simplest of these and the only one so far discovered in nature is 3, 4, 5-trimethoxyphenylethylamine, or mescaline:


Mescaline is found in several species of cactus that grow in northern South America, Mexico, and the southwestern United States. Best known are Lophophora williamsii (formerly called Anhalonium lewinii), the peyote or peyotl cactus, and Trichocereus pachanoi, the San Pedro cactus of Peru. Mescaline is the only one of more than thirty alkaloids and protoalkaloids in the peyote cactus that is known to have psychedelic characteristics, but the rest have not been studied thoroughly and may be responsible for some of the effects.
A few synthetic phenylethylamines are also psychedelic (Brimblecombe and Finder 1975, p. 60; Shulgin 1978, pp. 268-272).

Dose: The effective dose is about 200 mg or three to five peyote buttons (cactus tops). Mescaline has 1/3000 to 1/4000 the strength of LSD. Tolerance develops as with LSD and psilocybin; there is cross-tolerance between any two of the three drugs in all sequences of administration (Rech et al. 1975).

Physiological effects: Resembles LSD. The peyote cactus is bitter and nauseating, and pure mescaline can also cause nausea and vomiting. It is sometimes said to produce more intense autonomic (sympathomimetic) symptoms than LSD. Although it takes 30 or 40 times as much mescaline as psilocybin to produce psychedelic effects in human beings (effective dose in man), it takes only 2.5 times as much to kill mice (lethal dose).

Psychological effects: Similar to LSD, but sometimes reported to be more sensual and perceptual, with less change in thought, mood, and the sense of self. It may be too physiologically toxic at high doses to produce the most profound effects very often. In spite of these reports, however, subjects apparently cannot distinguish mescaline from LSD at appropriate doses in double-blind clinical trials (Hollister and Sjoberg 1964).
 

Duration of action: About the same as LSD.

Methoxylated Amphetamines

Phenylalkylamines in which the ethyl group is replaced by an isopropyl group are usually called amphetamines, after the common name for the simplest member of the class, the stimulant phenylisopropylamine or Benzedrine. The amphetamines are a very large group of synthetic drugs with effects that vary according to molecular structure. Some are relatively inactive, some produce effects like those of Benzedrine (euphoric stimulation, and sometimes a paranoid psychosis after prolonged use or at high doses), and some are psychedelic or have both psychedelic and stimulant properties. An important subgroup is the amphetamine analogues of the methoxylated phenylethylamine, mescaline. Out of more than a thousand of these methoxylated amphetamines, several dozen have been tested on human beings and another hundred or so on animals. Although many methoxylated amphetamines are not psychedelic, most known psychedelic amphetamines are methoxylated. Chemists find them easier to work with than tryptamines, because their structure is simpler, so they have become the richest source of new synthetic psychedelic drugs and also of speculation on the exact relationship between molecular structure and psychedelic properties.*

*The most detailed survey of these drugs is Shulgin 1978

The chemical skeleton of the methoxylated amphetamines is as follows:

Several series of drugs result when different groups of atoms are substituted for "R" in different places. Their psychedelic potency is measured in mescaline units (M.U.), defined as the effective dose of mescaline divided by the effective dose of the compound being evaluated. (Anything under 1 M.U. is likely to be more toxic than psychedelic.) The most important series studied so far are the dimethoxyamphetamines, the trimethoxyamphetamines, the methylenedioxyamphetamines, and the 2,5-dimethoxy-4-alkylamphetamines. Some of these drugs are listed in the following table:

The compound TMA is somewhat unusual. At 50 to 100 mg it is like a small dose of mescaline, but at high doses (250 mg and up) anger, hostility, and megalomania predominate (Peretz et al. 1955; Shulgin et al. 1961). Two other drugs ought to be mentioned. The first, DOB, or 4-bromo-2,5-DMA, in which a bromine atom is substituted for the 4-methoxy group of TMA-2, is the strongest of all known methoxylated amphetamines at 150 M.U.; only a few lysergic acid derivatives have greater psychedelic potency (Shulgin et al. 1971). The second, paramethoxyamphetamine or 4-methoxyamphetarnine (PMA), with a strength of 5 M.U., produces paranoid reactions and is physically poisonous at relatively low doses; it was sold on the streets for a short time in 1973 as MDA and is said to have been responsible for several deaths wrongly attributed to that drug (see Anonymous 1973). The list given here is far from exhausting all the amphetamines known to be psychedelic, and there are also many still untested.

The methoxylated amphetamines are chemically related to the essential oils of nutneg, mace, sassafras, and other spices, from which they can be manufactured. Nutmeg (from the East Indian tree Myristica fragrans) in large doses produces mild psychedelic effects like those of cannabis but also nausea, dizziness, headaches, and other side effects; it is not considered a highly desirable drug but is sometimes used by prisoners. The main active principle is a component of the essential oil myristicin, which can be made into MMDA by adding an amine (NH2) group; nutmeg also contains elemicin, which is related to TMA in the same way, and safrole (the major component of sassafras oil), which is related to MDA. Another essential oil from which a psychedelic methoxyamphetamine (TMA-2) can be derived by amination is asarone, found in the root of Acorus calamus (sweet flag or sweet calomel), which is also said to produce psychedelic effects at high doses. The pharmacology of these substances remains unclear. Possibly the oils are partly transformed in the body into the corresponding methoxylated amphetamines, but there is no solid evidence of this.*

*For further information see Hoffer and Osmond 1967, pp. 47-55; Shulgin et al. 1967; Weil 1971; Stafford 1977, pp. 307-314.

Several drugs that have been studied in human subjects are particularly in-teresting because of their qualitative peculiarities: MDA, MMDA, DOM, and DOET.

MDA

Chemical structure and source: The structural formula is:

The drug is synthetic but related to safrole, which is contained in oil of sassafras and oil of camphor as well as in nutmeg. It has been available on the illicit market since 1967. Derivatives that sometimes appear on the street are MDM (N-methyl-MDA) and MDE (N-ethyl-MDA).

Dose: Characteristic effects begin at about 50 mg, but the usual street dose is 100 to 150 mg. Potency is 3 to 4 M.U. but comparison is difficult because of qualitative differences.

Physiological effects: Variable and not very important at doses normally used; the psychological effects are usually associated with a feeling of relaxation and physical well-being. Sometimes there is sweating, tension in the jaw and facial muscles, or skin reactions; these occur in 10 percent of subjects at doses of 150 to 200 mg (Naranjo 1975 [1973], p. 71). There have been reports of death and serious injury from high doses, but this issue is complicated by drug mixtures and substitutions in the illicit traffic (Richards 1972; Stafford 1977, p. 313).

Psychological effects: At moderate doses MDA resembles neither of the two types so far discussed—the LSD type and the harmaline type; sometimes called "the love drug," it produces feelings of esthetic delight, empathy, serenity, joy, insight, and self-awareness without perceptual changes, loss of control, or depersonalization. It seems to eliminate anxiety and defensiveness; it has been described as inviting self-exploration where LSD demands it and as reducing the need to aggrandize the ego. Like LSD, MDA brings back lost childhood memories and also produces the condition that has been described, in a phrase borrowed from hypnosis, as age-regression: the MDA user actually feels himself to be a child and relives childhood experiences in full immediacy, while simultaneously remaining aware of his present self and present reality. The user often feels affectionate and wants to be close to others, talk to them and touch them; a pleasant feeling that the boundaries of the self are melting is common. In the illicit market MDA may be preferred to LSD and other drugs because it distorts perception less and causes fewer unpleasant emotional reactions, yet at high doses (150 to 200 mg) some users report it to be very much like LSD.

Duration of action: The peak is one to two hours after the drug is taken; it lasts eight to twelve hours.*

*For further information see Richards 1972; Zinberg 1974; Turek et al. 1974; Weil 1976; Yen-sen et al. 1976.

MMDA

Chemical structure and source: Synthetic but related to myristicin. The structural formula is:

The drug MMDA-2 (2-methoxy-4,5-MDA) has similar effects.
 

Dose: The threshold dose is 75 mg orally. An effective dose is 120-150 mg. Physiological effects: Similar to MDA.
 

Psychological effects: According to the few available reports, it produces drowsiness and relaxation, closed-eye imagery, intensification of moods (euphoria or anxiety), more sensory and less verbal and abstract thinking, coming into consciousness of unconscious desires. The effects are mild and controllable. The experiences, like those produced by MDA, are personal rather than symbolic, but with more emphasis on the present moment as opposed to the past (Naranjo 1975 [1973]; Shulgin et al. 1973; Shulgin 1976).

Duration of action: The peak is one hour after the first symptoms appear; the effects last three to four hours.

DOM

Chemical structure and source: Synthetic. The structural formula is:

It is an analogue of TMA-2. A slang term for it is STP, after the petroleum additive. It was first synthesized in 1963 and has been available on the illicit market since 1967.

Dose: At doses under 5 mg, effects resemble those of DOET (see below); at 5 mg and above, it resembles LSD. Potency is 50 to 100 M.U. Some tolerance develops, and there is partial cross-tolerance with LSD, mescaline, and psilocybin.

Physiological effects: Sympathomimetic action like amphetamine or LSD.

Psychological effects: As used on the street in the 1960s, in doses of 10 to 30 mg, it is like amphetamine combined with LSD but longer-lasting than either. The effects continue for so long, ebbing and returning, that the user may think he will never recover. It seems that DOM produces more adverse reactions, including flashbacks and prolonged psychosis, than most other LSD-like drugs. At doses of 5 to 8 mg used experimentally, the effects are much milder and not nearly so long-lasting.

Duration of action: At high doses, sixteen to twenty-four hours or even more. At lower laboratory doses, six to eight hours.*

*For further information see Snyder et al. 1968; Shick and Smith 1972; Stafford 1977, pp. 354-356.

DOET

Chemical structure and source: Synthetic. The structural formula is:

Dose: Slightly stronger than DOM: 1.5 mg has the same effect as 2 to 3 mg of DOM.

Physiological effects: Dilates the pupils but affects pulse rate, blood pressure, and breathing very little at psychedelic doses.

Psychological effects: Resembles MDA: mild euphoria, enhanced self-awareness, insight, body-image awareness, some closed-eye imagery, talkativeness. No perception disturbance or cognitive impairment even at 4 mg. The difference between the effective dose and the dose at which perceptual and thought disturbances begin (if there is such a dose) is greater than for DOM.

Duration of action: Five to six hours.*

*For further information see Snyder et al. 1968.

A number of other drugs are often called psychedelic, hallucinogenic, or psychotomimetic and have been used ritually or recreationally for their mind-altering powers. They lie at the periphery of the psychopharmacological and cultural region centered on LSD.

Muscimole

Chemical structure and source: Muscimole is the chief of three related alkaloids known as isoxazoles (the others are ibotenic acid and muscazone) found in the fly agaric mushroom, Amanita muscaria, which, despite its name, contains only minute amounts of the common mushroom poison muscarine. A related species, Amanita pantherina, contains the same alkaloids in greater concentration but is rarer. Both are slightly toxic, but they are not to be confused with the deadly Amanita phalloides, Amanita verna, and a dozen other highly poisonous species of this genus. The Amanita mushrooms grow in high temperate latitudes all around the world. The structural formula is:

Dose: Six mg of pure muscimole produces discernible effects; the usual dose is 7 to 20 mg. Ibotenic acid is a fifth to a tenth as strong. One large and two small dried mushrooms supply the needed amounts (Stafford 1977, p. 369).

Physiological effects: Muscle spasms, trembling, nausea, loss of equilibrium, dizziness, and numbness in the limbs have been reported.

Psychological effects: One common pattern is a half-sleep, trance, or stupor with visions lasting two hours, followed by elation, a feeling of lightness and physical strength, heightened sense perception, synesthesia, and changes in the body image. The effects are variable but are perceived as stronger and more dangerous than those of psilocybin: at high doses delirium, coma, and amnesia have been reported.

Duration of action: About six hours.*

*For further information see Waser 1967; Waser and Bersin 1970; Wasson 1972b; Pollock 1975b, Ott 1976; Lincoff and Mitchel 1977.

THC

This is the familiar active principle of the hemp plant (Cannabis indica, Cannabis sativa, Cannabis ruderalis), which is smoked or eaten all over the world as bhang, kif, hashish, ganja, marihuana, dope, grass, and so on. Tetrahydrocannabinol is chemically unusual because it contains no nitrogen and is therefore not classified as an alkaloid. Psychopharmacologically and culturally it has some claim to be called psychedelic, although its effects at the doses normally used are milder and more controllable than those of most other drugs we have discussed. Marihuana has been compared to walking a foot off the ground as opposed to the intergalactic voyage produced by LSD, or likened to a pony in contrast with the locomotive of mescaline. In one comparative clinical trial, 30 to 70 mg of oral THC (an average dose of high-quality smoked cannabis might contain 10 to 20 mg) proved to be very much like 100 to 200 micrograms of LSD or 6 to 20 mg of psilocybin. The main differences were more persistent euphoria, a strong sedative effect, and shorter time of action. THC produced fewer visual distortions than LSD and more dreamlike image sequences (Hollister and Gillespie 1969).

Physiologically, THC is not sympathomimetic. It is sedative, has little effect on blood pressure, increases appetite, and does not dilate the pupils.

There is no cross-tolerance between THC and LSD, mescaline, or psilocybin. Although THC is actually more potent weight for weight than mescaline, cannabis is sometimes called a "minor" psychedelic, possibly because it is rarely used in amounts large enough to produce the most intense effects and possibly because of its soporific qualities. There are several practical reasons for not including it in this study: for one, the experimental, clinical, anthropological, and historical literature is already enormous; for another, cannabis apparently does not produce any psychological effects not also occasionally produced by other drugs. Even drug users in our society do not place marihuana in the same class as more powerful psychedelic drugs with respect to strength, safety, and predictability; and in other social and cultural settings the effects are often perceived quite differently. In some places it is used daily at work, unlike the psychedelic drugs that are almost always reserved for special ritual, medicinal, or recreational occasions. Even large doses of THC (up to 420 mg a day in Jamaica) taken habitually in this way may serve only as a mild stimulant, euphoriant, or tranquilizer.*

*For further information see Tart 1971; Rubin and Comitas 1975; GHrinspoon 1977.

Anticholinergic Deliriants

These drugs are not usually regarded as psychedelic, although they have a great deal in common historically, culturally, and pharmacologically with other drugs taken for their mind-altering powers. They are called anticholinergic because they block the action of acetylcholine, a nerve transmitter substance that controls the contraction of skeletal muscles and also plays an important role in the chemistry of the brain. They are called deliriants because their effects at high doses include incoherent speech, disorientation, delusions, and hallucinations, often followed by depression and amnesia for the përiod of intoxication. The classical anticholinergic deliriants are the belladonna alkaloids:

These tropane derivatives, the most powerful and important of which is sc polamine, are found in differing concentrations in various plants of the Nightshade Family or Solanaceae, among them deadly nightshade (Atropa belladonna), mandrake (Mandragora officinarum), black henbane (Hyoscyamus niger), jimsonweed (Datura stramonium), and over twenty other species of henbane and datura. Of all psychoactive drugs, only alcohol has been in use for so long over such a large part of the world. For thousands of years on all inhabited continents the belladonna alkaloids have been a tool of shamans and sorcerers, who take advantage of the sensations they evoke to leave their bodies, soar through the air, or change into an animal in imagination. They also produce toxic organic symptoms like headache, dry throat, loss of motor control, blurred vision, and greatly increased heart rate and body temperature; death from paralysis and respiratory failure may occur. The belladonna alkaloids are so terrifying and incapacitating—the physical effects often so unpleasant, and the loss of contact with ordinary reality so complete—that they are used only with great caution and rarely for pleasure. For the same reasons, ironically, they are not regarded as a drug abuse problem and can be bought in small doses on prescription or in over-the-counter sedatives and pills for asthma, colds, and motion sickness (Heiser 1969; Weil 1977b; Hall et al. 1977).

A number of synthetic esters of benzilic and glycolic acid used in medicine for the treatment of Parkinson's disease and the Parkinsonian side effects of antipsychotic drugs occasionally produce effects like those of the belladonna alkaloids, apparently by the same anticholinergic mechanism. The prototype is Ditran (JB-329), N-ethyl-3-piperidylcyclopentonylglycolate; others are Artane (trihexphenydil), Cogentin (benztropinmesylate), benactyzine (2-diethylaminoethylbenzilate), JB-318, and JB-336 (N-ethyl and N-methyl-3-piperidyl benzilate).*

*For further information see Wilson and Shagass 1964; Brimblecombe and Pinder 1975, pp. 188-190; Garcin et al. 1974, pp. 33-37.

Dissociative Anesthetics

This is the name usually given to a class of synthetic drugs (arylcyclohexylamines) whose most interesting representatives are phencyclidine, or PCP, and ketamine. They are useful in medicine as analgesics and anesthetics that produce no respiratory or cardiovascular depression. Their effects have been likened to sensory deprivation: dreamlike visions, a sense of isolation, and often the feeling that the self or soul has separated from the body. It has been suggested that they stimulate the central nervous system while disturbing the centers where sensory impulses are relayed to the cerebral cortex. They are sometimes said to be intermediate in their effects between the anticholinergics and LSD.

PHENCYCLIDINE

The common designation -PCP- is derived from the chemical name. The drug was patented in 1963 as a surgical analgesic and anesthetic under the name of Sernyl, but withdrawn for use on human beings in 1965 because of delirium, agitation, and disorientation reported on emergence from anesthesia. Since 1967 it has been marketed under the name Sernylan as a tranquilizer and anesthetic for animals. It first appeared on the street that same year and has since been sold as "crystal,'' "angel dust,'' "super weed,'' "rocket fuel," and "hog," and also deceptively labeled as THC, "synthetic grass," mescaline, psilocybin, or other drugs. It is easy to synthesize and the precursors are readily available, so it has become one of the most popular illicit drugs; some people are reported to have taken it daily for several years.

Phencyclidine can be taken orally or intravenously or snuffed (snorted), but it is usually sprinkled on marihuana or parsley and smoked. Less than 5 mg is considered a low dose, 5 to 10 mg moderate, and more than 10 mg high. As it is used on the street, PCP should probably be described as a tranquilizer, analgesic, or euphoriant rather than a psychedelic drug. Vivid visual imagery is rare; common reported effects are relaxation, warmth and tingling, physical and emotional numbness, floating sensations, a feeling of emotional or sensory isolation ("sheer nothingness"), changes in body image and space and time judgment. Phencyclidine raises heart rate and blood pressure but does not affect breathing. The effects last four to six hours, and a mild irritable depression may follow; sometimes residual effects continue for up to twenty-four hours. It remains in the blood and urine for as long as a week.

Overdose can produce stupor, coma, and even death; there is also a danger of accidental death, because both judgment and motor coordination are severely impaired. But the most important adverse effect is a psychotic reaction; phencyclidine is much more unpredictable and dangerous in this respect than LSD and other psychedelic drugs. The symptoms vary greatly; they may include manic excitation, depression, catatonic immobility, severe anxiety, sudden mood changes, inappropriate laughter and crying, blank staring, disordered and confused thought, delusions and paranoid thoughts, fear of dying, and unpredictable violence. Some common physical symptoms are nystagmus (vertical and/or horizontal), high systolic blood pressure, sweating, vomiting, muscular rigidity in the face and neck, opisthotonic posturing, drooling, and repetitive movements. The psychosis may last for as little as a few hours to as long as two weeks, and it is often followed by partial or total amnesia for the period since taking the drug. The best treatment in an emergency is to put the patient in a quiet, dark room, with one person watching. Reassurance or talking down, a procedure that often works with adverse reactions to marihuana and LSD, is usually ineffective in PCP psychoses. Phenothiazines are not recommended while PCP is still in the body, because they intensify its anticholinergic effects. Diazepam may be used for sedation, or if necessary haloperidol.

Long-term use of PCP is becoming more common, and the effects of it have not been studied adequately. Chronic users are sometimes described as "crystallized"- suffering from lethargy, memory and concentration difficulties, and dulled thinking and reflexes. PCP does seem to produce psychological dependence and some tolerance; withdrawal symptoms have also occasionally been reported. There is no evidence of permanent brain damage.

An analogue known as TCP (1-(1-(2-thionyl)cyclohexol)piperidine) with similar but stronger effects has been synthesized, and other analogues may be developed.*

*For further information see Rosenbaum et al. 1959; Ban et al. 1961; Chen 1973; Burns et al. 1975; Showalter and Thornton 1977; and Petersen and Stillman 1978.

KETAMINE

Ketamine is chemically related to phencyclidine and was first synthesized in 1962 at Parke-Davis laboratories in a search for phencyclidine substitutes. The hydrochloride has been available on prescription since 1969 as Ketalar and is used as an anesthetic or analgesic in children to avoid cardiovascular depression. It has a greater anesthetic potency, a shorter time of action (one to two hours), and fewer residual effects than phencyclidine; and the ratio of lethal to effective dose is high. The dose used for general anesthesia is about 10 mg per kg of body weight intramuscularly or 1 to 3 mg per kg intravenously, but at a tenth of this dose it produces strong analgesia and psychedelic experiences. The effects resemble those of phencyclidine or LSD, with a tendency toward a sense of disconnection from the surroundings: floating, suspension in outer space, becoming a disembodied mind or soul, dying and going to another world. Childhood events may also be relived. The loss of contact with ordinary reality and the sense of participation in another reality are more pronounced and less easily resisted than is usually the case with LSD. The dissociative experiences often seem so genuine that afterward users are not sure that they have not actually left their bodies.

Although ketamine has excited the interest of adventurers in exotic realms of consciousness, it is not a common street drug, and few adverse reactions have been reported. However, John Lilly's account of his involvement with the drug (Lilly 1978) suggests that prolonged and frequent use can cause some of the same problems as PCP, including psychological dependence, psychotic reactions, and a gradual loss of contact with the everyday world.*

*For further information see Domino et al. 1965; Collier 1972, Johnstone 1973; Khorramza-deh and Lofty 1973, Perel and Davidson 1976; Moore and Alltounian 1978

General Anesthetics

The extraordinary psychological effects of the common general anesthetics have been recognized ever since their discovery in the eighteenth century. In contrast with previously discussed complex alkaloids and synthetic compounds, they have a rather simple molecular structure and take the form of volatile liquids or gases. Diethyl ether (CH,CH2OCH,CH2), chloroform (CHC13), and nitrous oxide (N20) all produce experiences that could be described as psychedelic or hallucinogenic. Ether inhalation was the source of Dr. Olfver Wendell Holmes' "anesthetic revelation"; chloroform, nitrous oxide, and other anesthetics have also been used as recreational drugs.

The least toxic of these drugs, nitrous oxide, is now regaining a following among drug users. It is a sweet-smelling gas produced by heating ammonium nitrate. Inhaled from a tank, an aerosol can, or a balloon, it induces exhilaration and euphoria, with involuntary laughing and loss of pain sensations. Sounds become distant and distorted, and there may be sensations of floating or flying great distances. Visual hallucinations or pseudohallucinations like brightly colored patterns or broken dream sequences often occur as normal consciousness returns. The high point of the experience is a moment of transcendence in which the user passes out of the everyday world into a paradisiacal egoless state in which he believes he has attained some ultimate revelation about the nature of mind and the universe, expressible only in phrases like "Everything is as it is,'' "All is one," "Opposites are the same," and so on. This revelation fades when the drug effect wears off, leaving only the memory of its intensity and bewilderment about its meaning. The whole experience lasts only two or three minutes, and memory of its details is usually poor; often for an hour or two afterward minor tensions, anxieties, pains, and depression disappear in a feeling of general well-being. Physically, nitrous oxide is relatively safe (except for pregnant women) and can be inhaled over and over again at intervals for a long time if oxygen is mixed with it or the user stops for deep breaths of air. Anoxia (failure of oxygen supply to the brain) and physical injury from temporary loss of motor control are the main dangers. It has few significant physiological effects; heart rate and pupil size, for example, are not changed.*

The fact that a simple compound like nitrous oxide as well as the complex organic molecule of a drug like LSD can produce a kind of psychedelic mystical experience suggests that the human organism has a rather general capacity to attain the state and can reach it by many different biological pathways. It should be clear that there is no simple correlation between the chemical structure of a substance and its effect on consciousness. The same drug can produce many different reactions, and the same reaction can be produced by many different drugs. For example, a number of substances we have not mentioned produce effects that in some circumstances approach the psychedelic, usually by way of a delirium that is a by-product of a physically toxic overdose: carbon dioxide, carbon tetrachloride, volatile solvents, airplane glue, gasoline fumes, heavy metals, insulin, cortisone, tetracyclines, narcotic antagonists, quinine, digitalis, and so on. There are also many similar experiences not produced by drugs but possibly associated with the same kinds of chemical changes in the body and brain. These include not only the involuntary states occurring in dreams and in extreme situations like psychosis, starvation, isolation, and high fever, but also the many techniques for altering consciousness that have been elaborated, tested, and passed on by tradition for thousands of years: hypnotic trance, repetitive chanting, prolonged wakefulness, revivalist exhortation, song or dance, fasting, hyperventilation, special postures, exercises, and techniques for concentrating attention. One of the most interesting aspects of the study of psychedelic drugs is the light it throws on these other unusual states of mind—a subject to which we will return after examining the drugs themselves.

*For further information see Steinberg 1955; Lynn et al. 1972; Shedlin and Wallechinsky 1973.