Selasa, 18 Maret 2008
Senin, 17 Maret 2008
Salvia divinorum and Salvinorin A: new pharmacologic findings
The diterpene salvinorin A from Salvia divinorum (Epling and Jativa-M), in doses of 200-500 µg produces effects which are subjectively identical to those experienced when the whole herb is ingested. Salvinorin A is effectively deactivated by the gastrointestinal system, so alternative routes of absorption must be used to maintain its activity. Traditionally the herb is consumed either by chewing the fresh leaves or by drinking the juices of freshly crushed leaves. The effects of the herb when consumed this way depend on absorption of salvinorin A through the oral mucosa before the herb is swallowed.
Keywords. Salvia divinorum; Salvinorin A; Psychoactive plants; Psychoactive compounds
The diterpene salvinorin A from Salvia divinorum (Epling and Jativa-M), in doses of 200-500 µg produces effects which are subjectively identical to those experienced when the whole herb is ingested. Salvinorin A is effectively deactivated by the gastrointestinal system, so alternative routes of absorption must be used to maintain its activity. Traditionally the herb is consumed either by chewing the fresh leaves or by drinking the juices of freshly crushed leaves. The effects of the herb when consumed this way depend on absorption of salvinorin A through the oral mucosa before the herb is swallowed.
Keywords. Salvia divinorum; Salvinorin A; Psychoactive plants; Psychoactive compounds
1. Introduction
Salvia divinorum is used by the Mazatec Indians of northeastern Oaxaca, Mexico primarily for its psychoactive effects which aid in ritual divination (Wasson, 1962, 1963). It is also employed remedially to treat various health conditions (Valdes et al., 1983).
The first live specimens of S. divinorum were given to Carl Epling by R. Gordon Wasson in 1962 and were cultivated at the University of California in Los Angeles (Wasson, 1962). Cuttings of this original clone were distributed to other botanical collections over the years and most of the plants in cultivation in the USA today originated from this original clone (Valdes et al., 1987). Recently, other clones have been appearing in collections. As of this writing there are at least four different clones present in public and private botanical collections in the USA. The chemistry of this plant has been investigated several times. The diterpenes salvinorin A and salvinorin B have been identified and characterized. Salvinorin A has been shown to be active in mice while salvinorin B was inactive. No human studies with these compounds have previously been reported (Ortega et al., 1982; Valdes et al., 1984). Trace amounts of other diterpenes have been detected but have not yet been characterized (Valdes et al., 1984).
There are two methods of ingestion traditionally employed: either the fresh whole leaves are masticated and swallowed or, alternatively, the leaves are crushed to extract the juices which are then drunk. Of these two methods, chewing of the leaves is most reliable and requires a smaller quantity of leaves. The liquid preparation is often ineffective and when it does produce effects they are usually much milder than those reported for chewing, even when substantially larger quantities of leaves are used in the preparation.
When the leaves are chewed whole they must first be chewed well enough to be easily swallowed and so spend quite some time in contact with the oral mucosa. When the leaf juice preparation is consumed it can be swallowed fairly quickly and consequently spends relatively little time in contact with the oral mucosa. The level of effects reported relates quite closely to the length of time the material spends in the mouth before being swallowed.
This presentation describes the effects of salvinorin A in humans, its deactivation by the gastrointestinal system and the essential role of the oral mucosa as an absorption site for salvinorin A from orally ingested leaves.
2. Materials and methods
All plant material used in this study was propagated from the clone originally brought into the USA by R. Gordon Wasson in 1962.
2.1. Salvia divinorum leaves
In order to investigate the relative importance of the oral mucosa as an absorption site for the active principals in S. divinorum leaves, the following experiments were carried out by six volunteers using ten large fresh leaves each (approximately 30 g total) which had been homogenized with 100 ml water using a blender. Each experiment was separated by several days.
(A) The material was swallowed as quickly as possible with the intention of quickly bypassing the oral mucosa; then the mouth was immediately rinsed with water to wash away any residual material that might be clinging to the oral mucosa. None of the volunteers reported any noticeable effects when the material was ingested in this manner.
(B) The material was held in the mouth for 10 min without swallowing; then the entire contents were spit out. This method proved consistently effective with all of the volunteers reporting very definite psychoactive effects.
2.2. Salvinorin A
Salvinorin A was isolated following the method of Valdes (Valdes et al., 1984). The identity of this material was verified by comparison with an authentic sample of salvinorin A using TLC, melting point and NMR.
Salvinorin A has previously been shown to be active in mice but it has remained uncertain whether this compound is responsible for the psychoactive effects produced in humans. In order to determine this, salvinorin A was administered to a group of 20 volunteers.
When salvinorin A was encapsulated and swallowed in doses as high as 10 mg there was no detectable activity. Experiments with the leaves indicate that the active principle of the plant is deactivated by the gastrointestinal system. To test for activity of salvinorin A, alternative routes of ingestion were attempted. Salvinorin A is not water soluble so injection was not attempted.
Absorption through the oral mucosa. A 2-mg quantity of salvinorin A was dissolved in 1 ml anhydrous ethyl alcohol then sprayed on the inner surfaces of the mouth using an aspirator. The material proved to be active; however only a small percentage is absorbed this way before it gets dispersed by salivary flow. Consequently this method was inefficient and results were inconsistent.
Inhalation of the vaporized compound. The material was placed on a piece of aluminum foil. A butane micro torch was then held beneath the foil until the material was seen to vaporize. As soon as this began, the vapors were inhaled through a 15-mm glass tube.
Inhalation of the vapors produced by heating salvinorin A proved to be the most efficient method of ingestion tested. When 200-500 µg of salvinorin A is vaporized and inhaled the subjective effects produced are identical to those typically produced by the fresh herb. Doses up to 2.6 mg were tested in this manner. Typically threshold effects are noted at about 200 g.
2.3. Effects
When salvinorin A is absorbed through the oral mucosa the first effects are usually experienced in 5-10 min. The strength of the effects builds very quickly over a few minutes, maintaining a plateau for about 1 h. The effects gradually subside over another l-h period. The evolution of effects over time is identical to that of orally ingested S. divinorum leaves.
When salvinorin A is vaporized and inhaled the full effects are experienced in about 30 s. There is almost no transition period experienced. The strongest effects last 5-10 min and then gradually subside over about 20-30 min. As dosage increases above 1 mg the duration of the effects are somewhat increased. A similar evolution of effects is reported for smoked S. divinorum leaves.
The oral mucosa apparently acts as a time release buffer, slowly diffusing salvinorin A into the blood stream; hence when consumed orally, the effects begin more gradually, last longer and subside over a longer period of time than when the material is vaporized and inhaled. Although variable in duration, the effects experienced have the same overall characteristics regardless of the route of absorption used.
The nature of the effects experienced depends on many factors including dose, set and setting. Frequently people report having seen visions of people, objects, and places. With doses above 1 mg, out of body experiences are frequent. Occasionally individuals get up and move about with no apparent awareness of their movements or behavior. Some individuals speak gibberish during the most intense phase of the experience, others laugh hysterically.
Certain themes are common to many of the visions and sensations described. The following is a listing of some of the more common themes:
Becoming objects (yellow plaid French fries, fresh paint, a drawer, a pant leg, a Ferris wheel, etc.).
Visions of various two dimensional surfaces, films and membranes.
Revisiting places from the past, especially childhood.
Loss of the body and/or identity.
Various sensations of motion, or being pulled or twisted by forces of some kind.
Uncontrollable hysterical laughter.
Overlapping realities. The perception that one is in several locations at once.
Some of the effects appear to parallel those of other hallucinogens (i.e. the depersonalization experienced with ketamine, the rapid onset of effects and short duration of smoked DMT). The volunteers who were experienced with other hallucinogens all agreed that despite some similarities, the content of the visions and the overall character of the experience is quite unique.
2.4. Receptor Site Screening and MAO Inhibition
A sample of salvinorin A was submitted to NovaScreen™ for receptor site screening. At screening concentrations of 10-5 M there was no significant inhibition (i.e. 50% or less) for the following sites.
Neurotransmitters: Adenosine, alpha 1, alpha 2, beta, dopamine 1, dopamine 2, GABA-A, GABA-B, serotonin 1, serotonin 2, muscarinic 3, NMDA, kainate, quisqualate, glycine (stry sens.).
Regulatory sites: Benzodiazepine(centrl), glycine (stry insens.), PCP, MK-801.
Brain/gut peptides: angiotensin Ty2, arg-vasopressin Vl, bombesin, CCK central, CCK peripheral, substance P, substance K, NPY, neurotensin, somatostatin, VIP.
Growth factors and peptides: ANF I, EGF, NGF.
Ion channels: Calcium (type N), calcium (type T and L), chloride, potassium (low conduct).
Second messengers: Forskolin, phorbol ester, inositol triphosphate.
Monoamine oxidase inhibition: Monoamine oxidase A, monoamine oxidase B.
3. Discussion and conclusions
When S. divinorum leaves are consumed, either by chewing the fresh leaves or by retaining the leaf juices in the mouth, enough of the highly active compound salvinorin A is absorbed through the oral mucosa and into the blood stream to produce a psychoactive effect. Swallowing of the herb is unnecessary and its effects are increased by lengthening the amount of time that the herb remains in the mouth. When the leaf juices are quickly swallowed, minimizing contact with the oral mucosa, the only route of absorption is though the gastrointestinal system where salvinorin A is deactivated before entering the blood stream. When pure salvinorin A is encapsulated and swallowed it is inactive even at relatively large doses, but when absorbed through the oral mucosa or vaporized and inhaled is extremely active. It is likely that if salvinorin A were administered by injection, it would prove to be active at even lower doses than those described in this paper.
Salvinorin A is the first entheogenic diterpene reported and is active in humans at extraordinarily low doses. It does not appear to affect any of the receptor sites affected by other hallucinogens. Further research into the methods of action and possible medicinal values of this and similar compounds may prove to be quite rewarding.
Acknowledgments
I am grateful to Dr Leander Valdes III for supplying a reference sample of salvinorin A, and Dr David Nichols for his role in the receptor site screening of salvinorin A through his NIMH-funded research program.
Psychedelics and Religious Experience
The experiences resulting from the use of psychedelic drugs are often described in religious terms. They are therefore of interest to those like myself who, in the tradition of William James, (1) are concerned with the psychology of religion. For more than thirty years I have been studying the causes, the consequences, and the conditions of those peculiar states of consciousness in which the individual discovers himself to be one continuous process with God, with the Universe, with the Ground of Being, or whatever name he may use by cultural conditioning or personal preference for the ultimate and eternal reality. We have no satisfactory and definitive name for experiences of this kind. The terms "religious experience," "mystical experience," and "cosmic consciousness" are all too vague and comprehensive to denote that specific mode of consciousness which, to those who have known it, is as real and overwhelming as falling in love. This article describes such states of consciousness induced by psychedelic drugs, although they are virtually indistinguishable from genuine mystical experience. The article then discusses objections to the use of psychedelic drugs that arise mainly from the opposition between mystical values and the traditional religious and secular values of Western society.
The experiences resulting from the use of psychedelic drugs are often described in religious terms. They are therefore of interest to those like myself who, in the tradition of William James, (1) are concerned with the psychology of religion. For more than thirty years I have been studying the causes, the consequences, and the conditions of those peculiar states of consciousness in which the individual discovers himself to be one continuous process with God, with the Universe, with the Ground of Being, or whatever name he may use by cultural conditioning or personal preference for the ultimate and eternal reality. We have no satisfactory and definitive name for experiences of this kind. The terms "religious experience," "mystical experience," and "cosmic consciousness" are all too vague and comprehensive to denote that specific mode of consciousness which, to those who have known it, is as real and overwhelming as falling in love. This article describes such states of consciousness induced by psychedelic drugs, although they are virtually indistinguishable from genuine mystical experience. The article then discusses objections to the use of psychedelic drugs that arise mainly from the opposition between mystical values and the traditional religious and secular values of Western society.
The Psychedelic Experience
The idea of mystical experiences resulting from drug use is not readily accepted in Western societies. Western culture has, historically, a particular fascination with the value and virtue of man as an individual, self-determining, responsible ego, controlling himself and his world by the power of conscious effort and will. Nothing, then, could be more repugnant to this cultural tradition than the notion of spiritual or psychological growth through the use of drugs. A "drugged" person is by definition dimmed in consciousness, fogged in judgment, and deprived of will. But not all psychotropic (consciousness-changing) chemicals are narcotic and soporific, as are alcohol, opiates, and barbiturates. The effects of what are now called psychedelic (mind-manifesting) chemicals differ from those of alcohol as laughter differs from rage, or delight from depression. There is really no analogy between being "high" on LSD and "drunk" on bourbon. True, no one in either state should drive a car, but neither should one drive while reading a book, playing a violin, or making love. Certain creative activities and states of mind demand a concentration and devotion that are simply incompatible with piloting a death-dealing engine along a highway.
I myself have experimented with five of the principal psychedelics: LSD-25, mescaline, psilocybin, dimethyl-tryptamine (DMT), and cannabis. I have done so, as William James tried nitrous oxide, to see if they could help me in identifying what might be called the "essential" or "active" ingredients of the mystical experience. For almost all the classical literature on mysticism is vague, not only in describing the experience, but also in showing rational connections between the experience itself and the various traditional methods recommended to induce it-fasting, concentration, breathing exercises, prayers, incantations, and dances. A traditional master of Zen or Yoga, when asked why such-and-such practices lead or predispose one to the mystical experience, always responds, "This is the way my teacher gave it to me. This is the way I found out. If you're seriously interested, try it for yourself." This answer hardly satisfies an impertinent, scientifically minded, and intellectually curious Westerner. It reminds him of archaic medical prescriptions compounding five salamanders, powdered gallows rope, three boiled bats, a scruple of phosphorus, three pinches of henbane, and a dollop of dragon dung dropped when the moon was in Pisces. Maybe it worked, but what was the essential ingredient?
It struck me, therefore, that if any of the psychedelic chemicals would in fact predispose my consciousness to the mystical experience, I could use them as instruments for studying and describing that experience as one uses a microscope for bacteriology, even though the microscope is an "artificial" and "unnatural" contrivance which might be said to "distort" the vision of the naked eye. However, when I was first invited to test the mystical qualities of LSD-25 by Dr. Keith Ditman of the Neuropsychiatric Clinic at UCLA Medical School, I was unwilling to believe that any mere chemical could induce a genuine mystical experience. At most, it might bring about a state of spiritual insight analogous to swimming with water wings. Indeed, my first experiment with LSD-25 was not mystical. It was an intensely interesting aesthetic and intellectual experience that challenged my powers of analysis and careful description to the utmost.
Some months later, in 1959, I tried LSD-25 again with Drs. Sterling Bunnell and Michael Agron, who were then associated with the Langley-Porter Clinic, in San Francisco. In the course of two experiments I was amazed and somewhat embarrassed to find myself going through states of consciousness that corresponded precisely with every description of major mystical experiences that I had ever read. (2) Furthermore, they exceeded both in depth and in a peculiar quality of unexpectedness the three "natural and spontaneous" experiences of this kind that had happened to me in previous years.
Through subsequent experimentation with LSD-25 and the other chemicals named above (with the exception of DMT, which I find amusing but relatively uninteresting), I found I could move with ease into the state of "cosmic consciousness," and in due course became less and less dependent on the chemicals themselves for "tuning in" to this particular wave length of experience. Of the five psychedelics tried, I found that LSD-25 and cannabis suited my purposes best. Of these two, the latter—cannabis—which I had to use abroad in countries where it is not outlawed, proved to be the better. It does not induce bizarre alterations of sensory perception, and medical studies indicate that it may not, save in great excess, have the dangerous side effects of LSD.
For the purposes of this study, in describing my experiences with psychedelic drugs I avoid the occasional and incidental bizarre alterations of sense perception that psychedelic chemicals may induce. I am concerned, rather, with the fundamental alterations of the normal, socially induced consciousness of one's own existence and relation to the external world. I am trying to delineate the basic principles of psychedelic awareness. But I must add that I can speak only for myself. The quality of these experiences depends considerably upon one's prior orientation and attitude to life, although the now voluminous descriptive literature of these experiences accords quite remarkably with my own.
Almost invariably, my experiments with psychedelics have had four dominant characteristics. I shall try to explain them-in the expectation that the reader will say, at least of the second and third, "Why, that's obvious! No one needs a drug to see that." Quite so, but every insight has degrees of intensity. There can be obvious-1 and obvious-2—and the latter comes on with shattering clarity, manifesting its implications in every sphere and dimension of our existence.
The first characteristic is a slowing down of time, a concentration in the present. One's normally compulsive concern for the future decreases, and one becomes aware of the enormous importance and interest of what is happening at the moment. Other people, going about their business on the streets, seem to be slightly crazy, failing to realize that the whole point of life is to be fully aware of it as it happens. One therefore relaxes, almost luxuriously, into studying the colors in a glass of water, or in listening to the now highly articulate vibration of every note played on an oboe or sung by a voice.
From the pragmatic standpoint of our culture, such an attitude is very bad for business. It might lead to improvidence, lack of foresight, diminished sales of insurance policies, and abandoned savings accounts. Yet this is just the corrective that our culture needs. No one is more fatuously impractical than the "successful" executive who spends his whole life absorbed in frantic paper work with the objective of retiring in comfort at sixty-five, when it will all be too late. Only those who have cultivated the art of living completely in the present have any use for making plans for the future, for when the plans mature they will be able to enjoy the results. "Tomorrow never comes." I have never yet heard a preacher urging his congregation to practice that section of the Sermon on the Mount which begins, "Be not anxious for the morrow...." The truth is that people who live for the future are, as we say of the insane, "not quite all there"—or here: by over-eagerness they are perpetually missing the point. Foresight is bought at the price of anxiety, and when overused it destroys all its own advantages.
The second characteristic I will call awareness of polarity. This is the vivid realization that states, things, and events that we ordinarily call opposite are interdependent, like back and front, or the poles of a magnet. By polar awareness one sees that things which are explicitly different are implicitly one: self and other, subject and object, left and right, male and female-and then, a little more surprisingly, solid and space, figure and background, pulse and interval, saints and sinners, police and criminals, in-groups and out-groups. Each is definable only in terms of the other, and they go together transactionally, like buying and selling, for there is no sale without a purchase, and no purchase without a sale. As this awareness becomes increasingly intense, you feel that you yourself are polarized with the external universe in such a way that you imply each other. Your push is its pull, and its push is your pull—as when you move the steering wheel of a car. Are you pushing it or pulling it?
At first, this is a very odd sensation, not unlike hearing your own voice played back to you on an electronic system immediately after you have spoken. You become confused, and wait for it to go on! Similarly, you feel that you are something being done by the universe, yet that the universe is equally something being done by you-which is true, at least in the neurological sense that the peculiar structure of our brains translates the sun into light, and air vibrations into sound. Our normal sensation of relationship to the outside world is that sometimes I push it, and sometimes it pushes me. But if the two are actually one, where does action begin and responsibility rest? If the universe is doing me, how can I be sure that, two seconds hence, I will still remember the English language? If I am doing it, how can I be sure that, two seconds hence, my brain will know how to turn the sun into light? From such unfamiliar sensations as these, the psychedelic experience can generate confusion, paranoia, and terror-even though the individual is feeling his relationship to the world exactly as it would be described by a biologist, ecologist, or physicist, for he is feeling himself as the unified field of organism and environment.
The third characteristic, arising from the second, is awareness of relativity. I see that I am a link in an infinite hierarchy of processes and beings, ranging from molecules through bacteria and insects to human beings, and, maybe, to angels and gods-a hierarchy in which every level is in effect the same situation. For example, the poor man worries about money while the rich man worries about his health: the worry is the same, but the difference is in its substance or dimension. I realize that fruit flies must think of themselves as people, because, like ourselves, they find themselves in the middle of their own world-with immeasurably greater things above and smaller things below. To us, they all look alike and seem to have no personality-as do the Chinese when we have not lived among them. Yet fruit flies must see just as many subtle distinctions among themselves as we among ourselves.
From this it is but a short step to the realization that all forms of life and being are simply variations on a single theme: we are all in fact one being doing the same thing in as many different ways as possible. As the French proverb goes, plus ca change, plus c'est la meme chose (the more it varies, the more it is one). I see, further, that feeling threatened by the inevitability of death is really the same experience as feeling alive, and that as all beings are feeling this everywhere, they are all just as much "I" as myself. Yet the "I" feeling, to be felt at all, must always be a sensation relative to the "other"-to something beyond its control and experience. To be at all, it must begin and end. But the intellectual jump that mystical and psychedelic experiences make here is in enabling you to see that all these myriad I-centers are yourself—not, indeed, your personal and superficially conscious ego, but what Hindus call the paramatman, the Self of all selves. (3) As the retina enables us to see countless pulses of energy as a single light, so the mystical experience shows us innumerable individuals as a single Self.
The fourth characteristic is awareness of eternal energy, often in the form of intense white light, which seems to be both the current in your nerves and that mysterious e which equals mc2. This may sound like megalomania or delusion of grandeur-but one sees quite clearly that all existence is a single energy, and that this energy is one's own being. Of course there is death as well as life, because energy is a pulsation, and just as waves must have both crests and troughs, the experience of existing must go on and off. Basically, therefore, there is simply nothing to worry about, because you yourself are the eternal energy of the universe playing hide-and-seek (off-and-on) with itself. At root, you are the Godhead, for God is all that there is. Quoting Isaiah just a little out of context: "I am the Lord, and there is none else. I form the light and create the darkness: I make peace, and create evil. I, the Lord, do all these things." (4) This is the sense of the fundamental tenet of Hinduism, Tat tram asi—"THAT (i.e., "that subtle Being of which this whole universe is composed") art thou." (5) A classical case of this experience, from the West, is in Tennyson's Memoirs:
A kind of waking trance I have frequently had, quite up from boyhood, when I have been all alone. This has generally come upon me thro' repeating my own name two or three times to myself silently, till all at once, as it were out of the intensity of the consciousness of individuality, the individuality itself seemed to dissolve and fade away into boundless being, and this not a confused state, but the clearest of the clearest, the surest of the surest, the weirdest of the weirdest, utterly beyond words, where death was an almost laughable impossibility, the loss of personality (if so it were) seeming no extinction but the only true life. (6)
Obviously, these characteristics of the psychedelic experience, as I have known it, are aspects of a single state of consciousness--for I have been describing the same thing from different angles. The descriptions attempt to convey the reality of the experience, but in doing so they also suggest some of the inconsistencies between such experience and the current values of society.
Opposition to Psychedelic Drugs
Resistance to allowing use of psychedelic drugs originates in both religious and secular values. The difficulty in describing psychedelic experiences in traditional religious terms suggests one ground of opposition. The Westerner must borrow such words as samadhi or moksha from the Hindus, or satori or kensho from the Japanese, to describe the experience of oneness with the universe. We have no appropriate word because our own Jewish and Christian theologies will not accept the idea that man's inmost self can be identical with the Godhead, even though Christians may insist that this was true in the unique instance of Jesus Christ. Jews and Christians think of God in political and monarchical terms, as the supreme governor of the universe, the ultimate boss. Obviously, it is both socially unacceptable and logically preposterous for a particular individual to claim that he, in person, is the omnipotent and omniscient ruler of the world-to be accorded suitable recognition and honor.
Such an imperial and kingly concept of the ultimate reality, however, is neither necessary nor universal. The Hindus and the Chinese have no difficulty in conceiving of an identity of the self and the Godhead. For most Asians, other than Muslims, the Godhead moves and manifests the world in much the same way that a centipede manipulates a hundred legs-spontaneously, without deliberation or calculation. In other words, they conceive the universe by analogy with an organism as distinct from a mechanism. They do not see it as an artifact or construct under the conscious direction of some supreme technician, engineer, or architect.
If, however, in the context of Christian or Jewish tradition, an individual declares himself to be one with God, he must be dubbed blasphemous (subversive) or insane. Such a mystical experience is a clear threat to traditional religious concepts. The Judaeo-Christian tradition has a monarchical image of God, and monarchs, who rule by force, fear nothing more than insubordination. The Church has therefore always been highly suspicious of mystics, because they seem to be insubordinate and to claim equality or, worse, identity with God. For this reason, John Scotus Erigena and Meister Eckhart were condemned as heretics. This was also why the Quakers faced opposition for their doctrine of the Inward Light, and for their refusal to remove hats in church and in court. A few occasional mystics may be all right so long as they watch their language, like St. Teresa of Avila and St. John of the Cross, who maintained, shall we say, a metaphysical distance of respect between themselves and their heavenly King. Nothing, however, could be more alarming to the ecclesiastical hierarchy than a popular outbreak of mysticism, for this might well amount to setting up a democracy in the kingdom of heaven-and such alarm would be shared equally by Catholics, Jews, and fundamentalist Protestants.
The monarchical image of God, with its implicit distaste for religious insubordination, has a more pervasive impact than many Christians might admit. The thrones of kings have walls immediately behind them, and all who present themselves at court must prostrate themselves or kneel, because this is an awkward position from which to make a sudden attack. It has perhaps never occurred to Christians that when they design a church on the model of a royal court (basilica) and prescribe church ritual, they are implying that God, like a human monarch, is afraid. This is also implied by flattery in prayers:
O Lord our heavenly Father, high and mighty, King of kings, Lord of lords, the only Ruler of princes, who dost from thy throne behold all the dwellers upon earth: most heartily we beseech thee with thy favor to behold....(7)
The Western man who claims consciousness of oneness with God or the universe thus clashes with his society's concept of religion. In most Asian cultures, however, such a man will be congratulated as having penetrated the true secret of life. He has arrived, by chance or by some such discipline as Yoga or Zen meditation, at a state of consciousness in which he experiences directly and vividly what our own scientists know to be true in theory. For the ecologist, the biologist, and the physicist know (but seldom feel) that every organism constitutes a single field of behavior, or process, with its environment. There is no way of separating what any given organism is doing from what its environment is doing, for which reason ecologists speak not of organisms in environments but of organism-environments. Thus the words "I" and "self" should properly mean what the whole universe is doing at this particular "here-and-now" called John Doe.
The kingly concept of God makes identity of self and God, or self and universe, inconceivable in Western religious terms. The difference between Eastern and Western concepts of man and his universe, however, extends beyond strictly religious concepts. The Western scientist may rationally perceive the idea of organism-environment, but he does not ordinarily feel this to be true. By cultural and social conditioning, he has been hypnotized into experiencing himself as an ego-as an isolated center of consciousness and will inside a bag of skin, confronting an external and alien world. We say, "I came into this world." But we did nothing of the kind. We came out of it in just the same way that fruit comes out of trees. Our galaxy, our cosmos, "peoples" in the same way that an apple tree "apples."
Such a vision of the universe clashes with the idea of a monarchical God, with the concept of the separate ego, and even with the secular, atheist/agnostic mentality, which derives its common sense from the mythology of nineteenth-century scientist According to this view, the universe is a mindless mechanism and man a sort of accidental microorganism infesting a minute globular rock that revolves about an unimportant star on the outer fringe of one of the minor galaxies. This "put-down" theory of man is extremely common among such quasi scientists as sociologists, psychologists, and psychiatrists, most of whom are still thinking of the world in terms of Newtonian mechanics, and have never really caught up with the ideas of Einstein and Bohr, Oppenheimer and Schrodinger. Thus to the ordinary institutional-type psychiatrist, any patient who gives the least hint of mystical or religious experience is automatically diagnosed as deranged. From the standpoint of the mechanistic religion, he is a heretic and is given electroshock therapy as an up-to-date form of thumbscrew and rack. And, incidentally, it is just this kind of quasi scientist who, as consultant to government and law-enforcement agencies, dictates official policies on the use of psychedelic chemicals.
Inability to accept the mystic experience is more than an intellectual handicap. Lack of awareness of the basic unity of organism and environment is a serious and dangerous hallucination. For in a civilization equipped with immense technological power, the sense of alienation between man and nature leads to the use of technology in a hostile spirit—to the "conquest" of nature instead of intelligent co-operation with nature. The result is that we are eroding and destroying our environment, spreading Los Angelization instead of civilization. This is the major threat overhanging Western, technological culture, and no amount of reasoning or doom-preaching seems to help. We simply do not respond to the prophetic and moralizing techniques of conversion upon which Jews and Christians have always relied. But people have an obscure sense of what is good for them-call it "unconscious self-healing," "survival instinct," "positive growth potential," or what you will. Among the educated young there is therefore a startling and unprecedented interest in the transformation of human consciousness. All over the Western world publishers are selling millions of books dealing with Yoga, Vedanta, Zen Buddhism, and the chemical mysticism of psychedelic drugs, and I have come to believe that the whole "hip" subculture, however misguided in some of its manifestations, is the earnest and responsible effort of young people to correct the self-destroying course of industrial civilization.
The content of the mystical experience is thus inconsistent with both the religious and secular concepts of traditional Western thought. Moreover, mystical experiences often result in attitudes that threaten the authority not only of established churches, but also of secular society. Unafraid of death and deficient in worldly ambition, those who have undergone mystical experiences are impervious to threats and promises. Moreover, their sense of the relativity of good and evil arouses the suspicion that they lack both conscience and respect for law. Use of psychedelics in the United States by a literate bourgeoisie means that an important segment of the population is indifferent to society's traditional rewards and sanctions.
In theory, the existence within our secular society of a group that does not accept conventional values is consistent with our political vision. But one of the great problems of the United States, legally and politically, is that we have never quite had the courage of our convictions. The Republic is founded on the marvelously sane principle that a human community can exist and prosper only on a basis of mutual trust. Metaphysically, the American Revolution was a rejection of the dogma of Original Sin, which is the notion that because you cannot trust yourself or other people, there must be some Superior Authority to keep us all in order. The dogma was rejected because, if it is true that we cannot trust ourselves and others, it follows that we cannot trust the Superior Authority which we ourselves conceive and obey, and that the very idea of our own untrustworthiness is unreliable!
Citizens of the United States believe, or are supposed to believe, that a republic is the best form of government. Yet vast confusion arises from trying to be republican in politics and monarchist in religion. How can a republic be the best form of government if the universe, heaven, and hell are a monarchy? (8) Thus, despite the theory of government by consent, based upon mutual trust, the peoples of the United States retain, from the authoritarian backgrounds of their religions or national origins, an utterly naive faith in law as some sort of supernatural and paternalistic power. "There ought to be a law against it!" Our law-enforcement officers are therefore confused, hindered, and bewildered-not to mention corrupted-by being asked to enforce sumptuary laws, often of ecclesiastical origin, that vast numbers of people have no intention of obeying and that, in any case, are immensely difficult or simply impossible to enforce-for example, the barring of anything so undetectable as LSD-25 from international and interstate commerce.
Finally, there are two specific objections to use of psychedelic drugs. First, use of these drugs may be dangerous. However, every worth-while exploration is dangerous-climbing mountains, testing aircraft, rocketing into outer space, skin diving, or collecting botanical specimens in jungles. But if you value knowledge and the actual delight of exploration more than mere duration of uneventful life, you are willing to take the risks. It is not really healthy for monks to practice fasting, and it was hardly hygienic for Jesus to get himself crucified, but these are risks taken in the course of spiritual adventures. Today the adventurous young are taking risks in exploring the psyche, testing their mettle at the task just as, in times past, they have tested it—more violently—in hunting, dueling, hot-rod racing, and playing football. What they need is not prohibitions and policemen, but the most intelligent encouragement and advice that can be found.
Second, drug use may be criticized as an escape from reality. However, this criticism assumes unjustly that the mystical experiences themselves are escapist or unreal. LSD, in particular, is by no means a soft and cushy escape from reality. It can very easily be an experience in which you have to test your soul against all the devils in hell. For me, it has been at times an experience in which I was at once completely lost in the corridors of the mind and yet relating that very lostness to the exact order of logic and language, simultaneously very mad and very sane. But beyond these occasional lost and insane episodes, there are the experiences of the world as a system of total harmony and glory, and the discipline of relating these to the order of logic and language must somehow explain how what William Blake called that "energy which is eternal delight" can consist with the misery and suffering of everyday life. (9)
The undoubted mystical and religious intent of most users of the psychedelics, even if some of these substances should be proved injurious to physical health, requires that their free and responsible use be exempt from legal restraint in any republic that maintains a constitutional separation of church and state. (10) To the extent that mystical experience conforms with the tradition of genuine religious involvement, and to the extent that psychedelics induce that experience, users are entitled to some constitutional protection. Also, to the extent that research in the psychology of religion can utilize such drugs, students of the human mind must be free to use them. Under present laws, I, as an experienced student of the psychology of religion, can no longer pursue research in the field. This is a barbarous restriction of spiritual and intellectual freedom, suggesting that the legal system of the United States is, after all, in tacit alliance with the monarchical theory of the universe, and will, therefore, prohibit and persecute religious ideas and practices based on an organic and unitary vision of the universe. (11)
Footnotes
(1) See W. James, The Varieties of Religious Experience (1902). (back)
(2) An excellent anthology of such experiences is R. Johnson Watcher on the Hills (1959). (back)
(3) Thus Hinduism regards the universe not as an artifact, but as an immense drama in which the One Actor (the paramatman or brakman) plays all the parts, which are his (or "its") masks or personae. The sensation of being only this one particular self, John Doe, is due to the Actor's total absorption in playing this and every other part. For fuller exposition, see S. Radhakrishnan, The Hindu View of Life (1927); H. Zimmer, Philosophies of India (1951), pp. 355-463. A popular version is in A. Watts, The Book—On the Taboo Against Knowing Who You Are (1966). (back)
(4) Isaiah 45: 6, 7. (back)
(5) Chandogya Upanishad 6.15.3. (back)
(6) Alfred Lord Tennyson, A Memoir by His Son (1898), 320. (back)
(7) A Prayer for the King's Majesty, Order for Morning Prayer, Book of Common Prayer (Church of England, 1904). (back)
(8) Thus, until quite recently, belief in a Supreme Being was a legal test of valid conscientious objection to military service. The implication was that the individual objector found himself bound to obey a higher echelon of command than the President and Congress. The analogy is military and monarchical, and therefore objectors who, as Buddhists or naturalists, held an organic theory of the universe often had difficulty in obtaining recognition. (back)
(9) This is discussed at length in A. Watts, The Joyous Cosmology: Adventures in the Chemistry of Consciousness (1962). (back)
(10) "Responsible" in the sense that such substances be taken by or administered to consenting adults only. The user of cannabis, in particular, is apt to have peculiar difficulties in establishing his "undoubted mystical and religious intent" in court. Having committed so loathsome and serious a felony, his chances of clemency are better if he assumes a repentant demeanor, which is quite inconsistent with the sincere belief that his use of cannabis was religious. On the other hand, if he insists unrepentantly that he looks upon such use as a religious sacrament, many judges will declare that they "dislike his attitude," finding it truculent and lacking in appreciation of the gravity of the crime, and the sentence will be that much harsher. The accused is therefore put in a "double-bind" situation, in which he is "damned if he does, and damned if he doesn't." Furthermore, religious integrity-as in conscientious objection-is generally tested and established by membership in some church or religious organization with a substantial following. But the felonious status of cannabis is such that grave suspicion would be cast upon all individuals forming such an organization, and the test cannot therefore be fulfilled. It is generally forgotten that our guarantees of religious freedom were designed to protect precisely those who were not members of established denominations, but rather such (then) screwball and subversive individuals as Quakers, Shakers, Levellers, and Anabaptists. There is little question that those who use cannabis or other psychedelics with religious intent are now members of a persecuted religion which appears to the rest of society as a grave menace to "mental health," as distinct from the old-fashioned "immortal soul." But it's the same old story. (back)
(11) Amerindians belonging to the Native American Church who employ the psychedelic peyote cactus in their rituals, are firmly opposed to any government control of this plant, even if they should be guaranteed the right to its use. They feel that peyote is a natural gift of God to mankind, and especially to natives of the land where it grows, and that no government has a right to interfere with its use The same argument might be made on behalf of cannabis, or the mushroom Psilocybe mexicana Heim. All these things are natural plants, not processed or synthesized drugs, and by what authority can individuals be prevented from eating theme There is no law against eating or growing the mushroom Amanita pantherina, even though it is fatally poisonous and only experts can distinguish it from a common edible mushroom. This case can be made even from the standpoint of believers in the monarchical universe of Judaism and Christianity, for it is a basic principle of both religions, derived from Genesis, that all natural substances created by God are inherently good, and that evil can arise only in their misuse. Thus laws against mere possession, or even cultivation, of these plants are in basic conflict with biblical principles. Criminal conviction of those who employ these plants should be based on proven misuse. "And God said 'Behold, I have given you every herb bearing seed, which is upon the face of all the earth, and every tree, in the which is the fruit of a tree yielding seed-to you it shall be for meat.... And God saw every thing that he had made, and, behold, it was very good." Genesis 1:29, 31.
Minggu, 16 Maret 2008
Neuropharmacology of BZP
1-Benzylpiperazine (BZP) has a peripheral sympathomimetic action and a complex central action, both directly and indirectly acting upon on all monoamine1,2,3. There are few experiments investigating the nature of BZP's mechanism of action, and they are mainly in vitro, and on peripheral nerves. This article attempts to unify the existing research, to extrapolate the results to an in vitro, central situation and, in light of recent advances in pharmacology, clarify certain findings.
The action of BZP on the noradrenergic system has two main facets. The first is the action on the α2 adrenoreceptor, and the second is on the noradrenergic uptake carrier. The α2-adrenoreceptor is the receptor that mediates presynaptic negative feedback, both centrally and peripherally in the adrenergic system. BZP has been shown to be an antagonist at the α2-adrenoreceptor1, thus negating negative feedback at the synapse, and causing a larger stimulation-evoked release of neurotransmitter [[which one?]]. This is the same process as yohimbine, though, BZP is some 10,000 times less potent, but possibly just as efficacious1. These results were found from experimenting on peripheral nerves, not central ones, and it is possible that BZP has no α2-antagonist properties in the CNS. I find it likely that BZP's central α2 action has limited effect on the subjective experience, and mediates things like blood pressure and rate increase. BZP has also been shown to inhibit the reuptake of noradrenaline (NA)1,3. The reuptake inhibition is amphetamine-like (a theme you will come to recognize), and hence also causes the stimulation-independent release of NA1. Although the experiments which showed the stimulation-independent release of NA were done on peripheral nervous tissues, a study has been done to show that this action is probably exhibited in central nerves as well3. This amphetamine-like reuptake inhibition is probably BZP's noradrenergic action of most consequence in the CNS. In the peripheral nervous system, the α2-adrenoreceptor blockade is almost certainly responsible for most of the symptoms, as addition of clonidine (an α2 receptor agonist) blocks almost all of the effect of BZP in peripheral tissue1.
1-Benzylpiperazine (BZP) has a peripheral sympathomimetic action and a complex central action, both directly and indirectly acting upon on all monoamine1,2,3. There are few experiments investigating the nature of BZP's mechanism of action, and they are mainly in vitro, and on peripheral nerves. This article attempts to unify the existing research, to extrapolate the results to an in vitro, central situation and, in light of recent advances in pharmacology, clarify certain findings.
The action of BZP on the noradrenergic system has two main facets. The first is the action on the α2 adrenoreceptor, and the second is on the noradrenergic uptake carrier. The α2-adrenoreceptor is the receptor that mediates presynaptic negative feedback, both centrally and peripherally in the adrenergic system. BZP has been shown to be an antagonist at the α2-adrenoreceptor1, thus negating negative feedback at the synapse, and causing a larger stimulation-evoked release of neurotransmitter [[which one?]]. This is the same process as yohimbine, though, BZP is some 10,000 times less potent, but possibly just as efficacious1. These results were found from experimenting on peripheral nerves, not central ones, and it is possible that BZP has no α2-antagonist properties in the CNS. I find it likely that BZP's central α2 action has limited effect on the subjective experience, and mediates things like blood pressure and rate increase. BZP has also been shown to inhibit the reuptake of noradrenaline (NA)1,3. The reuptake inhibition is amphetamine-like (a theme you will come to recognize), and hence also causes the stimulation-independent release of NA1. Although the experiments which showed the stimulation-independent release of NA were done on peripheral nervous tissues, a study has been done to show that this action is probably exhibited in central nerves as well3. This amphetamine-like reuptake inhibition is probably BZP's noradrenergic action of most consequence in the CNS. In the peripheral nervous system, the α2-adrenoreceptor blockade is almost certainly responsible for most of the symptoms, as addition of clonidine (an α2 receptor agonist) blocks almost all of the effect of BZP in peripheral tissue1.
The action of BZP on the dopaminergic system is probably just restricted to the amphetamine-like reuptake inhibition and stimulation-independent release of dopamine (DA). This is supported by research that showed that in rats after 14 days of treatment with BZP, the amount of DA in subcortical cells is decreased, while the concentration of DA in the extracellular fluid is increased3.
The action of BZP on the serotonergic system is the most studied aspect of BZP's action, as one member of the team of experimenters who did most of the research into BZP was an employee of a drug company eager to prove the serotoninomimetic action of BZP (as this indicates more action as an antidepressant, and less possibility of abuse). Results show that BZP increases the amount of serotonin (5-HT) in the extracellular fluid surrounding subcortical neurons and decreases the amount of 5-HT in cells after 14 days of treatment, indicating that BZP exhibits the now familiar amphetamine-like inhibition of reuptake and stimulation-independent release of 5-HT3. On top of this central and probably peripheral amphetamine-like action, BZP seems to be an agonist of the 5-HT2B receptor. The logic behind the conclusion that BZP acts as a direct agonist at the 5-HT2B receptor is as follows: When BZP is applied to isolated rat stomach, it causes the smooth muscle to contract, and this contraction is blocked by methergoline, indicating the process is receptor-mediated2 (methergoline has similar pKi's for all 5ht2-receptor-subtypes). This could indicate that BZP is a direct 5-HT receptor agonist, but it could also be explained by the fact that BZP causes 5-HT to be released from nerves. BZP also causes hyperthermia in rats at high ambient temperature, an effect blocked by the 5-HT antagonist cyproheptadine, but not by amitriptyline3. Amitriptyline binds to the 5-HT reuptake carrier, probably blocking BZP's amphetamine-like action. Seeing that BZP can still exhibit a serotonergic action while the stimulation-independent release of 5-HT is blocked, it must be directly activating a 5-HT receptor, and seeing that it causes stomach contraction -- which is mediated by the 5-HT2B receptor -- it must be a direct agonist at the 5-HT2B receptor. The potency of BZP at the 5-HT2B receptor must be at least 100,000 times less that 5-HT2, meaning that functionally, it is closer to an antagonist than an agonist.
When one compares the contribution of these different neurotransmitters to the pharmacological action of BZP, it is likely that 5-HT is the major player, as BZP has the highest affinity for the 5-HT reuptake carrier (IC50 2.9 x 10-6 mol/L). It is likely that NA and DA play a roughly equal role centrally (reuptake carrier IC50 2.8 x 10-5 mol/L and 1.3 x 10-5 mol/L respectively)3. Peripherally, NA is largely responsible for BZPs peripheral effects, as NA is the main mediator of the sympathetic nervous system.
The ability for BZP to induce dependence initially looks marked, as it has a pronounced central dopaminergic action3, but if one considers all the factors, this may not be so. Tolerance to BZP's central action will develop quickly, as it probably accumulates in synaptic vesicles in the same fashion as amphetamine, while tolerance to BZP's peripheral blockade of α2-adrenoreceptors will be limited or nonexistent. This will moderate the abuse potential, since if dependence does develop it will occur along with central tolerance, and if an individual tries to up the dose of BZP to overcome the tolerance, the peripheral effects (mediated by the α2 receptor) would be intolerable.
In summary, BZP's action could be described as somewhere between amphetamine and MDMA including a yohimbine-like action as well, with limited to moderate abuse potential.
MPs vote to advance ban on party pills
A bill outlawing possession of pills containing benzylpiperazine (BZP) has been referred back to Parliament with a majority of health committee members recommending that it be passed.
Only Green Party and Maori Party members on the committee disagreed, saying party pills should be regulated rather than prohibited.
A bill outlawing possession of pills containing benzylpiperazine (BZP) has been referred back to Parliament with a majority of health committee members recommending that it be passed.
Only Green Party and Maori Party members on the committee disagreed, saying party pills should be regulated rather than prohibited.
The Misuse of Drugs (Classification of BZP) Amendment Bill will classify party pills as C1 drugs, the same as cannabis. It will be illegal to possess, use, sell, supply, import or manufacture BZP.
If the bill is passed in its present form there will be a six-month amnesty for possession of up to five grams or 100 tablets for personal use. Then BZP will become illegal. Under the Misuse of Drugs Act people possessing C1 drugs can be jailed for three months, fined up to $500, or both.
The bill was presented by Associate Health Minister Jim Anderton on the recommendation of the Health Ministry-appointed expert advisory committee on drugs. It said recent studies showed BZP was harmful and could cause fatal seizures.
Matt Bowden, chairman of the Social Tonics Association party pill industry group, said the health select committee process was a farce and if the bill was passed people were likely to use more dangerous drugs.
It was a political exercise so politicians could say they were tough on drugs, he said. "Tobacco killed 5000 Kiwis last year, alcohol killed 1000 Kiwis last year, party pills have killed zero Kiwis in the past seven years. Which one are we banning and why?"
Warning About Abuse of Benzylpiperazine
Benzylpiperazine, a chemical cousin of ecstasy, could emerge as a new drug of abuse, according to a leading toxicologist.
Benzylpiperazine, a chemical cousin of ecstasy, could emerge as a new drug of abuse, according to a leading toxicologist.
Huliq.com reported April 27 that Alison Jones, a professor at the University of Newcastle, warned that benzylpiperazine has started to show up in drug tests in the U.K. Jones co-authored a research paper detailing the drug-testing results from hospitals in London.
"This drug is currently unrestricted in the U.K.," said Jones. "Its availability and detection in patients in the UK who have come to harm, raises significant issues of clinical problems and access."
The research appears in the April 28, 2007 issue of the journal The Lancet.
Clubbers snap up new legal high
Drugs from same class as Viagra marketed as alternative to ecstasy
A new breed of stimulant drugs from the same class as Viagra but with similar effects to ecstasy are being sold through British shops and websites. The drugs, known as piperazines and marketed as p.e.p pills, are fuelling a boom in the "legal highs" trade as people search for safer, cleaner alternatives to illicit drugs that do not carry the risk of conviction.
Clubbers snap up new legal high
Drugs from same class as Viagra marketed as alternative to ecstasy
David McCandless
A new breed of stimulant drugs from the same class as Viagra but with similar effects to ecstasy are being sold through British shops and websites. The drugs, known as piperazines and marketed as p.e.p pills, are fuelling a boom in the "legal highs" trade as people search for safer, cleaner alternatives to illicit drugs that do not carry the risk of conviction.
Vendors of legal highs are always on the lookout for substances to boost sales, especially since the sale of fresh magic mushrooms was outlawed this year. Piperazines appear to be filling this void. The pills contain a blend of the stimulant benzylpiperazine (BZP) and other less potent chemicals from the piperazine family. They are becoming increasingly popular as a legal alternative to ecstasy's active ingredient, MDMA, mainly because users say they appear to work.
"I was quite surprised that a legal high could be so potent. Most usually just give you a bit of a hot flush," said Peter, 32, who has tried the pills several times. "It was a good party buzz with an ecstasy-like rush. I was up all night, feeling good, jabbering away."
"We're selling quite a lot of them," said Kieran Wilson, the manager of Spiritual High, the Middlesbrough-based company which packages and distributes the stimulant and which claims to have sold hundreds of thousands of pills. "We sell to around 150 headshops around the country, and website retailers on top of that. So we do have quite a big base for it."
The company markets a range of p.e.p pills at £5 for two or £180 for a tray of 72. Each offers a different blend of piperazines and different effect. "Stoned" is described as mild, mellow and giggly, while "Twisted" gives a "loved-up feeling with a trippy edge".
Synthesised from the pepper plant, BZP was originally used as a worming treatment for internal parasites in cattle. Taken on its own, it acts as a mild stimulant, about 10% the strength of normal "speed" or amphetamine. It causes wakefulness, euphoria and increased vigilance. But when it is mixed with other piperazines, the effects become more euphoric, even psychedelic, lasting up to eight hours. Unlike Viagra, however, BZP does not appear to have an effect on sexual performance.
Grey market
Piperazines are the latest in a stream of new or previously unknown drugs appearing on the grey market. Backroom chemists synthesise substances to exploit holes in drug laws, and the internet has made the discovery, manufacture, and sale of such chemicals too rapid for legislators to keep up with.
Alexander Shulgin, the US biochemist who rediscovered the recipe for MDMA and the inventor of more than 100 psychoactive compounds, said advances in biochemistry and pharmacological technology were making the synthesis of mind-altering drugs unstoppable: "Today there are around 200 psychoactive chemicals. By 2050 there will likely be 2,000."
Not everyone who has tried p.e.p. pills is convinced. "I didn't rate it that much. It's like they've faked some E and speed and half done the job," said Lucas, 28. "They were a bit edgy and didn't seem to mix well with alcohol, either."
Side-effects include dry mouth, restlessness and an alcohol-like hangover and headache the next day. Other users report a few amphetamine-style side-effects such as insomnia and anxiety.
In the US BZP is scheduled under class one, alongside cannabis, LSD and crack cocaine, but in the UK it remains legal. This is despite a 2002 amendment to the Misuse of Drugs Act which made Britain's laws controlling emerging drugs the strictest in the world.
But while the substance is legal across most of Europe, it is one of four piperazines banned in Denmark last week after they were detected as adulterants in batches of seized ecstasy pills. The Danish health agency declared young users were at risk of psychosis and poisoning from the drugs.
In New Zealand, however, where an estimated 5m BZP-based pills have been sold legally since 1999, a governmental select committee concluded that the drugs were low risk. It decided that regulated, lab-produced chemicals such as BZP did much less harm than black market drugs and actually diverted people from using potentially dangerous substances such as methamphetamine.
In a unique move, the New Zealand government added a new class D category to its drug laws for "non-traditional designer substances". Licensed companies are now allowed to make and sell piperazine-based highs.
Question marks
The bulk of Britain's supply is imported from New Zealand where they are packaged as a "drug harm minimisation solution". They contain vitamins and antioxidants to reduce side-effects and ease hangovers. Users are told to take no more than three at a time.
In the 80s the drug showed promise as an antidepressant, but it was subsequently shelved. Clinical evidence seems to suggest no ill effects from use. Owing to a lack of recent research, however, question marks remain over interaction with antidepressants such as Prozac and over-the-counter medicines. Those who are allergic to pepper are advised to avoid the drugs.
Worldwide there has been a single reported death associated with BZP. In Zurich in 2001 a 23-year-old took two BZP tablets alongside ecstasy and drank more than 10 litres of water in a 15-hour period. She later died from hyponatremia or water poisoning, a common cause of ecstasy-related deaths. The role of BZP was unclear.
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