LSD

105. One of the most remarkable and controversial drugs known today is d-lysergic acid diethylamide-25, better known as LSD or simply 'acid'. LSD is capable of producing profound and unusual psychological changes in almost infinitesimal doses, with relatively little general physiological effect and, along with other related drugs, has exerted noticeable influence in a variety of aesthetic, scientific, philosophic, religious and social areas over the past two decades. LSD is often considered the prototype of the drug class we have labelled Psychedelic-Hallucinogens, although there are a great number of less potent synthetic and naturally occurring substances with somewhat similar psychopharmacological properties. To date, almost 3,000 articles on LSD have been published in scientific journals, although many of these reports do not meet adequate scientific standards.

106. LSD was developed in 1938 by Hofmann and Stoll, in Switzerland, as part of a research programme investigating potential therapeutic uses of certain ergot compounds. LSD is a semi-synthetic derivative of lysergic acid, an ergot alkaloid produced by a parasitic fungus, or 'rust', sometimes found on rye or other grains. Closely related substances are also produced in the seeds of certain varieties of morning glory. Most ergot alkaloids are not particularly psychoactive, although some may have a variety of powerful, and often toxic, physiological actions, and have been used for centuries for medical purposes.

107. Since LSD appeared to be relatively uninteresting, physiologically, in animal studies, it received little attention until Hofmann unwittingly ingested a minute quantity some years after its original synthesis. He subsequently described his experience as follows:102

In the afternoon of 16 April 1943, when I was working on this problem, I was seized by a peculiar sensation of vertigo and restlessness. Objects, as well as the shape of my associates in the laboratory, appeared to undergo optical change. I was unable to concentrate on my work. In a dreamlike state I left for home, where an irresistible urge to lie down overcame me. I drew the curtains and immediately fell into a peculiar state similar to drunkenness, characterized by an exaggerated imagination. With my eyes closed, fantastic pictures of extraordinary plasticity and intensive colour seemed to surge towards me. After two hours this state gradually wore off.

To confirm his suspicion that LSD was responsible for this effect, Hofmann investigated further:

However, I decided to get to the root of the matter by taking a definite quantity of the compound in question. Being a cautious man, I started my experiment by taking 0.25 mg of d-lysergic acid diethylamide tartrate, thinking that such an extremely small dose would surely be harmless, and bearing in mind that the natural ergot alkaloids produce toxic symptoms in man only with doses exceeding several milligrams. After 40 minutes I noted the following symptoms in my laboratory journal: slight giddiness, restlessness, difficulty in concentration, visual disturbances, laughing.

And later:

I lost all count of time. I noticed with dismay that my environment was undergoing progressive changes. My visual field wavered and everything appeared deformed as in a faulty mirror. Space and time became more and more disorganized and I was overcome by a fear that I was going out of my mind. The worst part of it being that I was clearly aware of my condition. My power of observation was unimpaired. . . . Occasionally I felt as if I were out of my body. I thought I had died. My ego seemed suspended somewhere in space, from where I saw my dead body lying on the sofa.... It was particularly striking how acoustic perceptions, such as the noise of water gushing from a tap or the spoken word, were transformed into optical illusions. I then fell asleep and awakened the next morning somewhat tired but otherwise feeling perfectly well.

108. Since various aspects of the experience were thought to resemble symptoms of naturally occurring schizophrenia, many investigators became interested in using LSD as a tool for producing an artificial or 'model psychosis' in the laboratory. The possibility of gaining insight into psychiatric disorders by the study of the LSD-induced state stimulated considerable activity in medical and scientific communities, and the terms psychotomimetic (psychosis-mimicking) and psychotogenic (psychosis-producing) were coined. The subsequent discovery that the LSD experience is, in fact, generally different from natural psychoses has lessened interest in this aspect of its use. The descriptive label hallucinogenic (hallucination-producing) has gained wide acceptance, in spite of the fact that true hallucinations do not commonly occur with LSD. The term illusinogenic (illusion-producing) is probably more appropriate.

In the 1950s the exploration of LSD as an aid to psychotherapy began. Much of the early work, in Canada, investigating the use of LSD in the treatment of alcoholics, was conducted under the direction of Dr A. Hoffer at the University of Saskatchewan, In 1957, after reviewing the various descriptive names given LSD and related drugs, Dr H. Osmond, then Superintendent of the Saskatchewan Hospital, suggested the terms psycholytic (mind-releasing) or psychedelic (mind-manifesting) as more appropriate general labels.174 For various reasons the latter has gained world-wide usage, although its common application has strayed considerably from its original context, and it may now denote general styles of art, fashion and music which are, in some sense, felt to reflect, enhance, or substitute for the psychedelic drug experience.

109. While LSD has had a rather short, and somewhat stormy history, numerous naturally occurring substances with apparently similar psychological effects have been used in the Western Hemisphere for centuries. Perhaps the most widely known are mescaline, from the peyote cactus (lophophora williamsii), psilocybin, one of the active principles in 'sacred mushrooms' (teonanactl), and the Mexican morning-glory 'ololiuqui' (Rivea Corymbosa). In addition, DMT (dimethyltryptamine) and the related DET (diethyltryptamine) are found in special snuffs used for centuries by certain South American Indians. Some of these botanical substances were considered divine by the ancient Aztecs and played an important role in religious ceremonies long before the Spanish invaded the land. In spite of the Conquistadors' attempts to destroy the culture and its historical and religious underpinnings, the sacramental use of peyote spread to the Mexican Indians and, later, in the nineteenth century to certain North American tribes. Today, peyote is used in religious ceremonies by the Native American Church which has over 200,000 Indian members in Canada and the United States.

110. Until recently, psychedelic drugs received little general public attention, even though some had been intensively explored over the past century by various writers, scientists and 'adventurers'. Based on his mescaline experimentation, Aidous Huxley106 presented, in his twin volumes The Doors of Perception and Heaven and Hell, one of the most lucid and perceptive analyses of some of the possible personal, philosophical and social implications of the psychedelic experience.

Non-medical interest in LSD and related drugs began to grow during the 1950s, although such use was apparently largely restricted to a few professional, academic, and artistic experimenters. The drug gained continental notoriety in the early 1960s as a result of experimentation by two Harvard University psychology professors, Drs Alpert and Leary, who invited other 'explorers' to 'Turn on, tune in, and drop out' of the existing social institutions. Their unorthodox religious orientation to the LSD experience is presented in The Psychedelic Experience128 (a manual based on the Tibetan Book of the Dead), which became one of the 'bibles' of the psychedelic drug movement. Another significant influence, with considerably less religious orientation was writer Ken Kesey's group, the adventures of which are well documented in The Electric Kool-Aid Acid Test .247

111. Since 1963, the Canadian Government has controlled the medical and scientific use of LSD, and in 1969 the possession of LSD without governmental authorization was made a criminal offence. Regulation of the legal supply of LSD has apparently had little effect on 'street' use, however, since essentially all of the drug so used has come from clandestine laboratories. Although the constituent chemicals are not readily available and some sophisticated apparatus is necessary for its proper synthesis, LSD can be produced by individuals without extensive training in chemistry. Since it is odourless, colourless and tasteless in solution, and active in almost invisible quantities, effective legal control of its transportation, distribution and use has been extremely difficult.

In recent years, several new synthetic drugs with effects similar to LSD have appeared on the black market. These include MDA (alphamethyl-3,4-methylene - dioxyphenethylamine), STP or DOM (2,5-ditnethoxy-4-methyl-amphetamine), and PCP or Sernyl* (phencyclidine).

Medical Use

112. There is currently no widely accepted medical use of LSD, although it may be employed experimentally for therapeutic purposes. There have been numerous impressive reports of LSD successes in the treatment of alcoholics, opiate narcotic dependents, criminals and various psychiatric patients.101, 129 LSD has also been used with patients dying of cancer, to alleviate their anxiety and pain, and to help them adjust to the prospects of death.176 Many of these leads have not been followed up with adequate scientific investigation, however, and several recent controlled studies have not substantiated the claim that LSD adds to the effectiveness of conventional psychotherapy.205

113. Two basic forms of psychological treatment with LSD have developed: psycholytic therapy, which uses small or moderate doses on repeated occasions, sometimes over a period of several months; and psychedelic therapy which calls for higher doses and a more profound acute effect and is, as a rule, given only once or twice. While some investigators claim that LSD, itself, is more effective than psychotherapy, others claim that its usefulness is mainly limited to the removal of therapeutic 'blocks' which may occur at times in the course of psychotherapy, and still others feel that LSD has no useful contribution to make to psychiatric treatment. Most clinicians who have had experience with this form of therapy, stress the need for a careful selection of patients and for special qualities and experience in the therapist.

More sophisticated scientific investigations of possible therapeutic uses of LSD are now underway and may help clarify some of these issues. It seems justified to say at this time, however, that the general medical effectiveness of LSD has not yet been adequately demonstrated. It may well be another decade before definitive evidence will be available.

Administration, Absorption, Distribution and Physiological Fate

114. LSD is usually taken orally, and may be sniffed in powdered form or injected in solution. While it is available in ordinary capsules or tablets, LSD is often impregnated in such innocuous substances as sugar cubes, candies, biscuits, and cloth or blotter sections for oral use. It is well absorbed from the gastro-intestinal tract, is distributed in the blood and easily diffuses into the brain, and in pregnant females crosses the placental barrier into the foetus. Although only a tiny portion actually reaches the central nervous system, LSD is one of the most potent biologically active substances known and, in some individuals, exerts a noticeable psychological effect with quantities as low as 20 to 30 micrograms (millionths of a gram). Customary doses are usually around 200 mcg and some individuals have taken up to several thousand micrograms.

Taken orally, LSD effects usually occur within an hour but may be much faster; response to intramuscular injection usually appears within ten minutes; and if the intravenous route is used, the latency may be only a few minutes or less. The duration of the action depends to a certain extent on the amount taken, and with a customary dose, major effects usually last 8-12 hours or more with gradual recovery over a similar period. Essentially all of the LSD in the body is metabolized into an inactive substance in the liver and excreted.

Psychological Effects

115. The psychological effects of LSD are not readily predictable, and are determined to a considerable degree by various personality factors in the individual, his past history and experiences, his attitudes, expectations, and motivations, the general setting in which the drug is taken, persons accompanying the 'trip' and external events occurring during the experience. While the psychological response is to some extent dose-related, certain effects appear to be relatively independent of dose over a considerable range. Increased quantities often seem to affect the duration more than the intensity or quality of the 'trip'.

116. Subjective psychological effects of LSD are extremely difficult to describe and many scientists are quite pessimistic about the possibility of presenting an objective list of responses which in any way communicates the essence of the experience. The intensely personal nature of the effects further limits description and generalization. Pahnke and Richards177 have described several major types of psychological experience which have been reported with psychedelic drugs. The outline presented below is based on, but is not identical to, that proposed by these researchers. While the list is certainly not exhaustive and does not describe necessarily discrete or non-overlapping categories, it provides a convenient basis for the discussion of LSD effects. It should be noted that not all of the experiences listed happen in all sessions or in all individuals, although several may occur in varying degrees, in sequence or simultaneously, within a 'trip'.

117. First is the psychotic adverse reaction, or 'freak-out' which may be characterized by an intense negative experience of fear or nightmarish terror to the point of panic, complete loss of emotional control, paranoid delusions, hallucinations, catatonic features, and, perhaps, profound depression and sense of meaninglessness. Such states are usually acute, although pro1onged reactions have been noted.

118. Second is the non-psychotic adverse reaction in which the person may experience varying degrees of tension, anxiety and fear, unpleasant illusions, depression and despair. Inappropriate or disordered social behaviour may occur. This kind of reaction may differ from the first in the intensity of the experience and in the degree of control and 'reality contact' expressed by the individual. Such unpleasant experiences are commonly labelled 'bad trips' or 'bummers'.

119. Third is the psychodynamic psychedelic experience characterized by a dramatic emergence into consciousness of material which had previously been unconscious or suppressed. Strong emotional feelings can accompany what may be experienced subjectively as a reliving of incidents from the past or a symbolic portrayal of important conflicts. Such effects are often sought in LSD psychotherapy.

120. Fourth is the cognitive psychedelic experience characterized by an impression of astonishingly lucid thought. Problems may be seen from a novel perspective and the interrelationships of many levels of meaning and dimensions may be sensed simultaneously. The relationship between this experience and naturally occurring insight and creativity has been the subject of considerable interest and speculation.

121. Fifth is the aesthetic psychedelic experience characterized by a change and intensification of all sensory impressions, with vision often most affected. Fascinating alteration in sensation and perception may occur; synaesthesia or crossing-over of sensory modalities may be produced (music and other sounds may be 'seen'); objects such as flowers or stones may appear to pulsate or 'become alive'; ordinary things may seem imbued with great beauty; music may take on an incredible emotional power; and visions of beautiful colours, intricate geometric patterns, architectural forms, landscapes and 'almost anything imaginable' may occur.

122. The sixth type of psychedelic experience has been called by such names as psychedelic-peak, cosmic, transcendental, or mystical. Some of the psychological phenomena which are said to characterize this experience, are: a sense of unity or 'cosmic oneness' with the universe; a feeling of transcendence of time and space; a deeply felt positive mood of joy, blessedness, love, and peace; a sense of sacredness, awe and, wonder; a feeling of profound theological or religious awareness; a feeling of insight into reality at an intuitive, nonrational level; an awareness of things which seem logically contradictory and paradoxical; and a belief that the experience is beyond words, non-verbal and impossible to describe. The full peak experience, in its entirety, does not occur in the majority of individuals, is usually transient, and does not last for long in its full intensity, although it may have persisting effects on attitudes and behaviour.

123. With few exceptions, little general information can be given as to the relative frequency of occurrence of these various types of psychedelic drug reaction, since the response is largely determined by such variable factors as the particular individual involved, his set and the setting. As is often the case in science, techniques designed to measure the effects of LSD may greatly influence or distort the phenomenon under study. Savage198 has pointed out that unless the LSD experience takes place '. . . in a secure setting, with sufficient emotional support where S (the subject) feels safe to encounter the bizarre and often powerful manifestations of his own mind unharassed by tests, interpretations, and the coldly precise scientific analytic attitudes, the only result can be confusion and paranoia'.

Reports of 'objective' study of LSD's subjective effects considerably in content and often appear to be as much a function of the individual scientist's conceptual orientation and experimental methods as they are of the subjects and the drug itself. Some researchers report that LSD experiences in their subjects, are definitely unpleasant and anxiety-ridden, and that subsequent sessions are uniformly avoided, while other scientists claim that anxiety is infrequent and that subjects generally enjoy the sessions and are eager to participate further.228 Experiences in non-supervised and indiscriminate settings are undoubtedly even more variable.

124. It is generally reported that LSD has deleterious effects on performance in tests requiring a high degree of attention, concentration or motivation. It is often difficult to get meaningful data from such measurements, since subjects frequently become engrossed in the subjective aspects of the drug experience and lose interest in the tasks presented by the investigators. Psychological tests are often seen as absurd or irrelevant by the subjects. Performance on standard tests of intelligence, learning, memory and other cognitive functions, as well as certain psychomotor tasks generally show impairment and sometimes lack of change and, rarely, improvement.205 Certain types of conduct by some persons under the influence of LSD indicate gross impairment of judgement. Recall of events occurring during the drug experience is generally good, however. Effects on driving skills have not been systematically investigated, although available related data, and reports by users, as well as certain eye witness accounts, suggest that driving ability is usually drastically reduced by the acute effects of LSD. There is no evidence that the drug has been a significant factor in automobile accidents, however.

True hallucinations, where false sensory signals are believed to be physically real, are rarely reported, although pseudohallucinations and other perceptual distortions and illusions are frequently noted. One of the most uniformly cited and significant subjective effects is the alteration of ordinary temporal perception, or time-sense. Moments may seem like hours, and time may seem to be transcended. Pleasant experiences may extend indefinitely or, on the other hand, bad trips can become an interminable horror.

125. Current arguments as to whether LSD is truly 'consciousness-expanding' as its proponents contend or 'consciousness-constricting' as its opponents assert, will probably not be resolved by science in the near future, since it seems unlikely that such hypotheses can be put to adequate empirical test given the current state of technology.

Contentions are often made that LSD can elicit new levels of spontaneity, insight, problem-solving and creativity.214 These claims are very difficult to assess, since the effects described are often highly subjective and personal, and are hardly amenable to empirical validation. The problems of studying creativity in the laboratory are considerable, and little is known of the basic psychology of such cognitive processes. A generally agreed upon definition of the concept of creativity has eluded investigators so far, and few meaningful tests are available. Studies of the effects of psychedelic drugs on allegedly creativity-related behaviours have produced inconsistent results. Often performance does not reflect the subjective impressions of the drug experience. Although sophisticated scientific investigation in this area is only just beginning, it is already obvious that LSD will not perform the miracle of turning an uninspired and untalented individual into a creative genius. The question of more subtle effects on creative activity in certain individuals must be answered by future research.

126. Most authorities agree that LSD does not have a specific aphrodisiac or sex-drive stimulating effect. Some users indicate an enhanced appreciation of sexual experience, while many others report a total disinterest in sex while on a 'trip'. Some increase in sexual behaviour may occur as a result of a lessening of inhibitions and an increase in emotionality, tactile appreciation, and interpersonal contact. LSD has been used in the treatment of sexual disorders of psychological origin (e.g. frigidity and impotence) although its general usefulness has not been clearly demonstrated in this area.

127. An LSD-induced 'bad trip' may range from a mildly negative or ambivalent experience to an episode of intense terror and nightmarish panic. Such adverse reactions often seem to focus on the fear of death, fear of permanent insanity, basic sexual conflicts, and fear of legal repercussions in illicit users, or may be precipitated by an objective 'hassle' or problem of real or imagined significance. Under the influence of LSD, it is often difficult to cope with immediate problems which arise, and emotional vulnerability may be increased. 'Bad trips' seem to occur most often when the individual is poorly prepared, alone, or in an otherwise unprotected or unsupervised setting. While an experienced 'guide' or therapist can often help prevent or alleviate negative reactions, this is no guarantee against an unpleasant experience. Neither are earlier positive experiences - severe 'bad trips' have been noted in individuals who had previous long histories of unequivocally pleasant psychedelic experiences. Certain tranquillizers can be of assistance in reducing the unpleasantness of the experience, often by terminating the drug effect non-chemical, personal supportive guidance is most important in treating negative reactions.

Although most negative LSD experiences appear to be of short duration, prolonged psychotic episodes lasting months or even years have been elicited by LSD.50 Many investigators contend that such extreme experiences occur only in individuals already predisposed to psychotic reaction, and are simply precipitated by the stress of a 'bad trip'. On the other hand, numerous examples have occurred in persons without obvious prior pathology, and it would appear that there is no satisfactory method for predicting who might suffer a serious adverse reaction.

128. Prolonged psychoses are quite rare in clinical or experimental settings, even when psychiatric patients are used as subjects. Cohen49 surveyed 44 investigators who had given LSD or mescaline to approximately 5,000 persons a total of about 25,000 times, and found that psychotic reactions lasting over 48 hours occurred in 0.18 per cent of the psychiatric patients studied and 0.08 per cent of the experimental subjects. There were four suicides in the patients, all occurring months after the LSD experience, and none among the experimental subjects. Whether these deaths can be attributed to LSD use is not certain. Similar incidents of adverse reaction under controlled circumstances have been reported by others and the use of LSD in medically supervised settings has been considered by many investigators to be comparatively safe from a psychiatric point of view.65, 132

These findings do not provide a satisfactory basis for estimating the effects of illicit use, however, since set, setting, purity and quantity of drug, and consequently, the quality of the trip, are all apt to be quite different in these situations. The frequency of bad trips among street LSD users is unknown, although many such cases have come to the attention of medical authorities and certainly cannot be considered uncommon. Solursh2l3 reports that in one series of street users studied retrospectively, 'freak-outs' occurred in 24 of 601 'acid trips', Furthermore, impressionistic accounts from individuals in close contact with the 'drug-scene' suggest that the incidence of 'bad trips' is steadily increasing. Ungerleider229 studied 70 individuals who required hospitalization in a Los Angeles Medical centre after illicit LSD use. One-third of these admissions were diagnosed psychotic and two-thirds were hospitalized for more than a month.

129. Usually neither the therapist nor the patient is certain as to the identity, purity or quantity of the drug involved in 'street' cases and records are further complicated by the fact that there is considerable discrepancy among reporters as to what exactly constitutes an adverse reaction. Furthermore, it would appear that many 'bad trips' are treated by friends and never come to the attention of the medical authorities. In addition to personal support and assistance in these situations, tranquillizers (and niacinamide) are available legally and on the black market for such emergencies. Even if some accurate estimate could be made of the number of negative reactions occurring, it would not be possible to assess the relative significance of the figures, since we have little idea as to the overall frequency of illicit LSD use in the general population.

130. Illicit users of LSD commonly voice the opinion that bad trips are caused by bad drugs and that 'pure acid' is relatively free from adverse reactions. These claims are rarely based on chemical analysis, and although contaminants and other drugs reported to appear in black market LSD can undoubtedly affect the experience, it is uncertain what proportion of the negative reactions can be accounted for by contaminants. It is certain that well-documented 'freak-outs' have occurred with clinically pure LSD.

131. Although suicide may be rare among illicit as well as medically supervised LSD users, a few cases have been documented. Attempts at self-mutilation have also been reported on rare occasions. Accidental deaths are somewhat more common and a number of cases of fatality or serious injury have been noted as a result of a loss of critical judgement or attentional processes. For example, some individuals have jumped from buildings or trees apparently under the delusion that they could fly or were indestructible. Stories of numerous persons who had become permanently blind while staring at the sun during LSD trips were generated by a state official in the United States and widely circulated in the public media. These reports were subsequently shown to be a hoax and no such cases are on record.170'b'

132. Although fear, panic and aggression may result from a 'freak-out', homicides associated with LSD use are rare and only a few have been documented. Reports of violence occurring while under the influence of LSD have generally not been supported,78 although there may be some significant exceptions. The majority of non-drug arrests associated with LSD use seem to be in the order of 'disturbance of the peace' offences and there is little evidence that LSD plays a significant role in major crimes.

Recurrence of certain aspects of LSD experiences ('flashbacks' or 'echoes') of varying duration and intensity have been reported over periods ranging from a few months to more than a year after last (or only) LSD use.189 The quality of these experiences, which usually last only a few minutes or less, may depend on as many factors as the original trip. They may be triggered or precipitated by seemingly irrelevant stimuli or events, by other drugs, or may appear spontaneously. We have no good information as to frequency of these recurrences, although they appear to occur most often in heavy users and could clearly be unpleasant or dangerous in certain circumstances.

133. The possible religious significance of psychedelic drug experiences has been the subject of heated controversy for centuries. While many authorities have pointed out basic similarities between drug-induced feelings of transcendental or mystical awareness and the satori or kensho of Zen Buddhism, the samadhi of Hinduism or the beatific vision of Christianity, others have been outraged by the suggestion that such 'instant mysticism' could be produced chemically. It is quite apparent, however, that a considerable degree of religiosity has pervaded the psychedelic drug movement of the 1960s and has played a major role in the use of such drugs in other cultures.

The major theoretical positions and scientific research in this area have been reviewed by several investigators208, l47 and these reports provide experimental support for the notion that drug-evoked experiences may have religious significance for certain individuals. Perhaps the most rigorous scientific evidence comes from Pahnke's175 controlled psilocybin experiment with seminary graduate students conducted in the setting of a Good Friday religious service. He notes that: 'Those subjects who received psilocybin experienced phenomena which were indistinguishable from, if not identical with, the categories defined by our typology of mysticism.' The religious aspects of the psychedelic experience apparently depend a great deal on the individual, his values and expectations, and the setting involved, and do not normally occur with great intensity in most persons or in most situations. Masters and Houstonl47 report that 6 out of 206 of their subjects attained a mystical experience, while other researchers report no such events and still others, a much higher incidence. Differences in semantic meaning, definition and criteria may account for part of these discrepancies. The 'objective validity' of drug-elicited religious experiences, however, is by nature untestable in the scientific sense, and the area will doubtless remain in a storm of controversy.

134. Numerous claims have been made by various LSD users, psychotherapists and scientists that LSD can produce long-lasting beneficial effects on personality and behaviour. On the other hand, many observers feel that chronic use of LSD may result in a lessening of work output and a deterioration of social behaviour, a general 'amotivational syndrome' in some individuals. Both types of allegation are difficult to evaluate, since few adequately controlled investigations have been done on the long-term effects of either medically supervised or non-medical LSD use.

Physiological Effects

135. LSD exerts its most significant physiological effects on and through the central nervous system, although the exact mechanism by which this occurs is not yet known. As a result of its potent general arousal or activation capacity. LSD may produce a variety of autonomic nervous system (sympathomimetic) actions, considered to be of little clinical significance at normal doses. Commonly reported are: widened pupils, increased heart rate and blood pressure, sweating, increased body temperature, chills, increased blood sugar level, 'goose pimples', flushing of the facial skin, increased urination, headache, and rarely nausea and vomiting. It generally increases the activation of the brain (as indicated by the EEG), produces alertness, blocks sleep, decreases appetite, may induce tremors and reduce coordination, changes respiration patterns, and facilitates certain simple reflexes.138 In a few instances convulsions have occurred. LSD has remarkably low physiological toxicity and, to date, no human deaths have been reported due to overdose. Although the evidence is not clear, psychological indications of minor brain damage may be present in chronic heavy users of LSD.152

l36. In the past few years, considerable controversy and sensational publicity has arisen around the possibility that LSD may affect hereditary transmission through chromosomal alterations, produce changes in white blood cells resembling leukemia and adversely affect the developing human focus.48 Relevant studies involving test-tube preparations of human live animal and insect experiments, and examinations of illicit LSD users, have been contradictory to date and provide no clear answers to these important questions.105 The relationship between in vitro (test-tube) and in vivo (living organism) effects is rarely straightforward, and generalizations from one species to another are difficult. Furthermore, studying the users of 'street' drugs gives little information regarding specific compounds, since such individuals may use a variety of drugs and neither the investigator nor the subject can be sure of the purity, quantity or identity of substances obtained from the illicit market. In the few controlled studies in which chromosomes were examined in humans before and after clinically supervised administration of known doses of pure LSD, little evidence of significant change was noted.125,58 The effects of prolonged regular use of LSD have not been carefully investigated, however, and the presence or absence of alterations under such conditions can not be completely predicted on the basis of present information.

Research in this area is complicated by the fact that temporary or permanent chromosome breakage is not an uncommon response to a variety of non-drug experiences, and can be produced by nuclear radioactivity, many pollutants, X-rays, fever and a number of virus infections. Furthermore, there is evidence that such frequently used drugs as caffeine and aspirin may cause chromosome breaks in certain cells.122 It should be noted that chromosome damage per se does not necessarily affect either the individual or his offspring, although the possibility must be considered.

137. High doses of LSD administered at certain times early in pregnancy have been shown to produce deformities in the offspring of some animal species and not others. No unequivocal evidence of such teratogenic LSD effects in humans has been reported, although there have been a few widely publicized instances of abnormalities in babies born of mothers who had used LSD. Whether such anomalies occur more frequently in LSD users than in the normal population is uncertain. Most investigators feel that the possibility of chromosome or foetal damage in humans forbids the use of LSD for either medical or non-medical purposes, by women who are either pregnant or expect to become so in the near future.

Tolerance and Dependence

138. Tolerance to the psychological and physiological effects of LSD develops on repeated use, although the form of psychological tolerance is unusual in several respects. Tolerance to most drugs can be overcome and effects of full intensity obtained by simply increasing dosage. With LSD, often a period of three or four days or longer must separate 'trips' if the full effects are to be obtained, regardless of dose. A second unusual quality of LSD tolerance is the rapidity with which it develops and dissipates. A reduction in effects may occur after only one or two consecutive administrations. Furthermore, when LSD is used intermittently many users report, a 'reverse' tolerance, or increased sensitivity to the drug and may, after experience, use less to achieve the desired effects. These factors suggest that the pharmacological mechanism underlying LSD tolerance may be quite different from those seen with most other psychoactive drugs.

139. Physical dependence does not develop to LSD, even in cases in which the drug has been used more than two hundred times in a single year.51 Psychological dependence has been reported to occur in certain individuals who become preoccupied with the drug experience and feel emotionally depressed and unsatisfied without it. Normally, however, LSD use is intermittent and periods of weeks or months may separate 'trips' in even 'confirmed' users,

LSD and Other Drugs

140. It appears that many LSD users will also experiment with other psychedelic drugs. Cross-tolerance occurs among some of these substances and an individual who has recently taken LSD will generally show reduced response to mescaline and psilocybin, but not to cannabis or phencyclidine (PCP). It should be noted that mescaline and psilocybin are rarely found in Canada and no such black market samples have been verified by chemical analysis.

Other drugs, such as atropine or amphetamines, are reported to be sometimes added to LSD to intensify, prolong or otherwise alter the experience. Strychnine (a stimulant once commonly used in medical practice) is rumoured to have also been employed for such effects. In spite of such stories, black market products purported to contain mixtures of LSD and other drugs have rarely been found on analysis to be as represented. Such combinations appear to be infrequent in Canada. Unsuccessful attempts at LSD synthesis may produce a variety of other ergot alkaloids with possibly unpleasant or dangerous pharmacological properties in high doses. Samples of such concoctions have been obtained from black market sources.144

Chlorpromazine (Largactil*), a major tranquillizer, usually blocks LSD effects, although in rare instances it paradoxically potentiates the original drug response. In addition certain sedatives and niacinamide (nicotinamide) may also reduce some of the effects of LSD.