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  A Note on Adverse Effects

    Lester Grinspoon & James B. Bakalar

        From: Psychedelic Reflections, ©Human Sciences Press, 1983



    While we are talking about the uses of psychedelic drugs, it is appropriate to discuss their dangers. The psychedelic voyage does produce some casualties; the question is how many and how serious they are, what causes them, and how to prevent them. This has been a matter of controversy since the 1960s. Drug users sometimes would not confess that they had any problems, because doubts and regrets were supposed to be a sign of rigidity or repression or some other inadmissible personal problem. Anti-drug crusaders sometimes would not admit that there was such a thing as a good trip or an insight to be derived from psychedelic drugs.
    The most common adverse effect is the bad trip, which takes many forms, from anxiety or panic to a (rare) psychotic state. The worst kind is a fixed intense emotion or distorted thought that can seem like an eternity of hell; for example, remorse, suspicion, delusions of persecution or of being irreversibly insane. Bad trips do not outlast the immediate effect of the drug, and recovery is usually complete. They are not adverse drug reactions in the narrow sense of something completely unintended and unexpected. Even the best trips may have moments of anxiety or depression, and every psychedelic drug user knows that eventually he may have a trip dominated by painful or frightening feelings: they are hardly more avoidable than fear when climbing a mountain or pain when running a marathon. Bad trips are sometimes regarded as more valuable than good ones, on the ground that they teach the drug taker more about himself; the suffering has the virtue of not seeming meaningless. In one study of LSD users, 24 percent of the subjects had had what they considered bad trips, and 50 percent considered the bad trips beneficial (McGlothlin & Arnold, 1971, p. 47).
    Prolonged adverse reactions to psychedelic drugs are just as varied in form as bad trips, and defy diagnostic classification just as much. In fact, one way of looking at them is as prolonged, more or less attenuated, or more or less intermittent bad trips. As the defenses of the ego are altered, repressed feelings and memories rise into consciousness, and they may create enough anxiety to disrupt the organization of the mind. Almost always, the defenses are reconstituted when the drug's influence wears off; but if the drug user's personality is unstable or the situation unsuitable—if the set and setting are wrong—the disorganization may persist or return under stress, as a kind of continuation of the unfinished psychedelic experience. The result is a great variety of altered mental states, from a mild recurrence of some drug-induced perceptual change to depersonalization or outright psychosis.
    By far the most common of these altered states is the spontaneous recurrence or flashback. By the broadest definition, a flashback is the transitory recurrence of emotions and perceptions originally experienced while under the influence of a psychedelic drug. It can last seconds or hours; it can mimic any of the myriad aspects of a trip; and it can be blissful, interesting, annoying, or frightening. Ordinarily they are only slightly disturbing, especially since the drug user usually recognizes them for what they are; they may even be regarded lightheartedly as "free trips. " Occasionally they last longer, and in a small minority of cases they turn into repeated frightening images or thoughts. Usually they quickly decrease in number and intensity. Flashbacks are most likely to occur under emotional stress or at a time of altered ego functioning; they are often induced by conditions like fatigue, drunkenness, marihuana intoxication, and even meditative states. Marihuana smoking is probably the most common single source of flashbacks.
    On a broad definition, flashbacks are very common. According to some studies, as many as a quarter of psychedelic drug users have experienced some form of flashback; about half consider them frightening and half consider them pleasant (Naditch & Fenwick, 1977). If the term is defined more narrowly for clinical purposes as "repeated intrusions of frightening images in spite of volitional efforts to avoid them, " it seems that about 5 percent of habitual psychedelic drug users have experienced them (McGlothlin, 1974, p. 27).
    Other prolonged adverse reactions are much rarer. They have been classified as chronic anxiety reactions, depressive reactions, and psychoses. One study describes 16 hospitalized patients who suffered from "philosophical delusions," intense visual hallucinations, and what the authors call a striking variety of affective and neurotic symptoms, often they had at least partial insight into the nature of their problems. Many of them received electroconvulsive therapy, and the average hospital stay was five and one-half weeks (Dewhurst & Hatrick, 1972).
    The following is an example of a chronic anxiety state produced by LSD:
    After much persuasion by his friends a twenty-year-old university student took 150 micrograms of LSD It was an "interesting but disturbing time. " Thereafter it became very difficult for him to study or concentrate, and he decided to drop out of school. He was unable to continue his part-time job as a stock clerk. There were strong feelings of the meaninglessness of life and he said that he was "philosophically confused." Some days he felt normal again for a few hours, but then the strange, moving, compressing walls and time standing still made him fear he was going crazy. He had occasional thoughts of self-destruction. He would become very upset and panicky, break out into a sweat and sometimes freeze in terror. With considerable support, strong reassurance and tranquilizer therapy, the condition subsided six months after the LSD session (Cohen, 1970 [1965], p. 92).
    Because of inadequate reporting and problems in interpreting symptoms and causes, it is hard to tell how common adverse reactions are. At Bellevue Hospital in New York from early 1965 to 1967, 200 patients appeared with complaints related to LSD—mostly panic reactions and flashbacks (Frosch, 1969). By 1969 Bellevue was seeing only one LSD reaction every 2 weeks, and most of these were thought to be borderline schizophrenics in whom the drug had precipitated a psychosis (Stern & Robbins, 1969). A 1971 Canadian government survey of the hospital records of 22,885 psychiatric patients found 67 cases (0.3 percent) where LSD was mentioned as a factor in the primary diagnosis; most of these patients had used many drugs, and the precise influence of LSD was often unclear (Final Report, 1973, p. 378).
    A questionnaire survey by J. Thomas Ungerleider and his colleagues suggests a much larger number of adverse reactions. The period covered was July 1, 1966 to January 1, 1968, and the questionnaire was sent to 2,700 physicians, psychiatrists, psychologists, and other health professionals in Los Angeles County. Of the 1,584 who replied, 27 percent (including 47 percent of the psychiatrists) had seen adverse reactions to LSD; the total number of adverse reactions was 8,958 (Ungerleider et al., 1968). Unfortunately, the definition of adverse reaction was left to the respondents, and the effect, the authors suggest, was probably to define anything that made a drug user seek professional help as an adverse reaction. The prevailing social attitudes have to be taken into account; for example, it is suspicious that in the same survey 1,887 adverse reactions to marihuana were reported. Many of the "adverse reactions" may have been nothing more than difficult moments during drug trips that were mentioned in psychiatric interviews because they seemed relevant to the problem under discussion; some may have been simply drug-induced insights that made people believe they needed help.
    Serious adverse reactions to psychedelic drugs are rare today, partly because they are being used more carefully and at smaller doses than in the first flush of psychedelic enthusiasm, and partly because LSD is no longer being unofficially promoted as a solution for emotional crises in the lives of seriously disturbed people. The most likely candidate for adverse reactions are schizoid and pre-psychotic personalities with a barely stable ego balance and a great deal of anxiety, who cannot cope with the perceptual changes, body-image distortions, and symbolic unconscious material produced by the drug. Murray Naditch has found through questionnaires that adverse reactions to LSD and marihuana (defined essentially as bad trips—strong unpleasant feelings, panic, fear of insanity or death, thoughts of suicide) are associated with high scores on psychological test scales representing schizophrenic tendencies, social maladjustment, and regression (Naditch, 1975). L.J. Hekimian and Samuel Gershon examined 47 patients admitted to Bellevue Hospital between January and July 1967 after using a psychedelic drug in the preceding 48 hours. In 31 cases psychotic conditions already present were intensified. Ultimately 32 were diagnosed as schizophrenic, 4 as schizoid, 6 as sociopaths, and 5 as depressive or neurotic. The authors were struck by the frequency of pre-existing schizophrenia (Hekimian & Gershon, 1968).
    It is certainly impossible to assume that anyone who suffers from psychosis, depression, or chronic anxiety after using a psychedelic drug would always have had the same problems in any case, but it is also wrong to suppose that these problems are likely to descend suddenly at any moment on a reasonably stable person who takes a psychedelic drug in a reasonably protected setting. The best analogy for adverse psychedelic drug reactions is psychosis precipitated by cannabis. The egos of a few people are so fragile that they can be precipitated into psychosis by any severe stress or alteration in consciousness, including surgery, an automobile accident, or alcohol intoxication; it is they who will suffer the rare psychotic reactions to cannabis. LSD and drugs like it are much more powerful mind-modifiers, and more people are vulnerable to their disruptive effects, including a few with no strong previous signs of emotional disturbance. Psychedelic drugs are capable of magnifying and bringing into consciousness almost any internal conflict, so there is no typical prolonged adverse reaction to LSD in the sense in which there is, say, a typical amphetamine psychosis (always paranoid). Instead, as many different affective, neurotic, and psychotic symptoms may appear as there are individual forms of vulnerability. This makes it hard to distinguish between LSD reactions and unrelated pathology, especially when some time passes between the drug trip and the onset of the disturbance.
    The best treatment for a bad trip is reassurance and "talking down" in a quiet, friendly setting; that is the way thousands have been handled with or without intervention by psychiatrists. Sometimes this reassurance may take the form of urging the drug user to go with it, give up resistance and allow loss of control, dissolution of the ego, and a cathartic resolution. Interpreting, judging, discussing, and being "objective" are disastrous; asking questions almost always exacerbates the problem by making impossible demands on the drug taker. Anything that might cause suspicion and paranoia, like superfluous movements or conversations, should be avoided. Use of a tranquilizer or sedative should be only a last resort, after talking down fails; diazepam (Valium) is better than anti-psychotic drugs like chlorpromazine (Thorazine), which act too abruptly and intensely. The appropriate treatment for prolonged reactions to psychedelic drugs is the same as the treatment for similar symptoms not produced by drugs: psychotherapy and drugs where necessary.
    The most important fact about chronic or long-term psychedelic drug use is that there is very little of it. Psychedelic drugs produce no psychological compulsion or craving and certainly no physical addiction. A drug that takes people into a different stretch of unfamiliar mental territory for 8 hours every time they use it is not for every day or even every weekend. Drug users soon come to understand that psychedelic trips are not to be embarked on lightly, and they tend to stop using LSD or cut down their consumption greatly after a short time.
    Nevertheless, for a few people in the late sixties and early seventies, LSD use became what H.S. Becker has called a "master trait." This kind of chronic user was known as an acidhead or acid freak, and a not very flattering composite portrait can be drawn from journalism, psychiatric papers, and other sources. He speaks softly and his manner is meek; he is passive and unwilling to take initiative. He talks a great deal about love but fears genuine intimacy and often feels emotionally lifeless. He is easily shattered by aggression or argument, finds the "hassles" of daily life an ordeal, and prefers to live in a world of drug-induced fantasy. He finds it difficult to follow an argument or concentrate on a thought; he is given to superstitious beliefs and magical practices. He does not work regularly or go to school; he rejects the accepted social forms and proselytized for LSD as a means of liberation from the standard "ego games" that constitute most people's lives, he blames society for his troubles and tends to see himself as a martyr. On the other hand, he is often at least superficially open, friendly, warm, relaxed, and uncompetitive; he is childlike as well as childish, and people often like him and feel protective toward him. But he may express aggression indirectly through his unconventional dress and manner, by absent-minded inconsiderateness, or by resentment of challenges to his unjustified conviction of superior awareness and moral insight.
    Even if no one fits this stereotype perfectly and most psychedelic drug users do not fit it at all, it does seem to have some basis in reality. K.H. Blacker and his colleagues, using a control group for comparison, studied 21 volunteer subjects who had used LSD 15 to 300 times (average 65 times), and found some of the features of the stereotypical acidhead: openness and relaxation, likeableness, passivity and introversion, occult and magical beliefs, hippie dress and hair styles. Four said they had memory blanks and sometimes found it difficult to organize thoughts and form sentences.
    On the electroencephelogram (EEG), which records brain waves, they did not have an unusually high rate of abnormalities; but they did show significantly more energy in all frequency bands than normal control subjects and psychiatric patients, and this suggested lower than usual levels of anxiety. On tests of intellectual capacity and auditory evoked response (both usually sensitive to the disorganization produced by schizophrenia) the LSD users were normal. But they were extraordinarily sensitive to visual stimuli of low intensity, which confirmed their opinion that they could observe gestures, postures, and shades of color better than most people. They also seemed to modulate and organize sensory stimuli in an unusual way, since there was no relationship between their evoked visual responses and their subjective tactile ones. The authors describe these subjects as eccentric or childlike but not schizophrenic or otherwise pathologically impaired. They emphasize that it was hard to separate the effects of the drug from those of personality and social climate.
    Psychedelic drug users have also been tested for organic brain damage. William McGlothlin and his colleagues (McGlothlin et al., 1969) compared 16 subjects who had taken LSD 20 times or more (the range was 20 to 1,100, the median was 75 times) with 16 controls; they examined the subjects clinically and also administered the Halstead-Reitan test battery. There were no clinical organic symptoms, and no scores on the neuropsychological tests that suggested brain damage; but on a test measuring capacity for nonverbal abstraction the LSD users scored lower. As in the case of Tucker's Rorschach results, the amount of LSD was not related to the score. Nevertheless, the authors conclude that continual heavy use may cause minor organic brain pathology: six of the LSD subjects, including the three heaviest users, were regarded as "moderately suspicious" in this respect. In another study, Morgan Wright and Terrence P. Hogan (1972) found no difference between subjects who had used LSD an average of 29 times and controls (matched for age, sex, education, and IO) on a variety of neuropsychological tests, including the ones used by McGlothlin. At most, these studies confirm the existence of an eccentric acidhead personality; they do not clearly imply mental illness or brain damage.
    In considering long-term psychedelic drug use, even more than in assessing acute reactions, it is hard to extricate the pharmacological contribution from the complex web of associations tying it to personality and social setting. The limitations of retrospective studies are notorious, but that is all we have. How many long-term psychedelic drug users ever were really acidheads, and how permanent is the condition? How often is psychopathology associated with psychedelic drug use, and when it is, is the drug cause, symptom, or attempted cure? In this case there is also a potential for cultural bias that creates further complications. When are eccentric beliefs and behavior pathological, and when are they simply a hippie way of life? Now that some of the social views and personal styles of the drug culture of the 1960s have become more popular, we know that they never implied a drug-induced personality change.
    Obviously many heavy drug users are seriously disturbed people, but the drug use is usually a symptom more than a cause of the trouble. If emotional problems were always a cause and not an effect of chronic psychedelic drug use, the status of acidhead would be nothing but a refuge or role-disguise for certain schizoid or inadequate personalities. But sometimes drug abuse itself, whatever the original reasons for it, becomes the central problem, notoriously so when the drug is addictive, like alcohol or heroin. The same thing may happen with LSD, but that has been rare since the 1960s and was not common even then. The best model for understanding the changes in behavior that occur after psychedelic drug use is not a drug-induced personality change or modification of the brain but the changes in one's views of self and world after a voyage to a strange country.
    A note on genetic damage and birth defects has to be added, because misconceptions about this subject still exist. Chromosome damage from LSD was first reported by Maimon Cohen and his colleagues in Science in 1967 (Cohen & Marmilli, 1967). They found a higher than normal proportion of chromosome breaks in a paranoid schizophrenic patient who had been treated with LSD 15 times, as well as with chlorpromazine and other drugs; they also found that LSD caused chromosome breaks in leukocytes (white blood cells) artificially cultured in the laboratory. In the rather overheated atmosphere of 1967, this paper gained an immediate celebrity and became the basis for a sensationalistic propaganda campaign featuring pictures of deformed children. Some LSD users switched to what they thought was mescaline or psilocybin and in fact was almost always mislabeled LSD or phencyclidine (PCP).
    Many other studies of this subject have appeared and continue to appear; it would be impossible and pointless to review them all. The literature review published in Science by Norman I. Dishotsky and his colleagues in 1971 established the reassuring conclusions that are now generally accepted. Examining nearly a hundred papers, they found that LSD was a weak mutagen, effective only at very high doses. It was not carcinogenic and did not cause chromosome damage in human beings at normal doses. One study showed that it caused no more chromosome breaks in Laboratory-cultured cells than aspirin. Illicit drug users often had more damaged chromosomes than control subjects; this was attributable not to LSD but to malnutrition, infectious disease, and general ill health as well as possible impurities in street drugs. The few available prospective studies, mostly of psychiatric patients before and after LSD use, showed no chromosome damage. There was no evidence of a high rate of birth defects in children of LSD users (Dishotsky et al., 1971). This paper is well known and adequately covers the research up to 1971; later studies have allayed persisting doubts. There is also no clear evidence that LSD or any other psychedelic drug causes birth defects in the child when it is taken by a pregnant woman. Nevertheless, pregnant women should avoid all drugs, especially in the first three months.
    To sum up, then, bad trips and mild flashbacks are common and even expected, but usually considered a nuisance—and occasionally even an opportunity—rather than a danger. More serious but relatively rare problems are recurrent frightening flashbacks, prolonged reactions (usually a few days but sometimes weeks or longer), suicides, and accidents. Thought and perception changes occur in some chronic users, but it is hard to say when these are immediate drug effects and when they are the result of reflection on the experience; in any case, they are rarely pathological and and almost never irreversible. There is no good evidence of organic brain damage or genetic alterations. The dangers are greatest for unstable personalities and in unsupervised settings. The most important limitation on the abuse of these drugs is the absence of a reliable euphoria, which means that people rarely go on using them, as they often go on using stimulants and sedatives, in spite of repeated disasters. Bad trips usually become deterrents before they become dangerous.

 

REFERENCES

Cohen, S. Drugs of Hallucination. St. Albans, England: Paladin, 1970 (orig. 1965).

Cohen, M.M., & Marmillo, M.J. Chromosomal damage in human leukocytes induced by Iysergic acid diethylamide. Science, 1967, 155:1417-1419.

Dewhurst, K., & Hatrick, J.A. Differential diagnosis and treatment of Iysergic acid diethylamide induced psychosis. The Practitioner, 1972, 209:327-332.

Dishotsky, N.I., Loughman, W.D., Mogar, R.E., & Lipscomb, W.R. LSD and genetic damage. Science, 1971, 172:431-440.

Final Report of the Commission of Inquiry into the Non-Medical Use of Drugs. Ottawa: Information Canada, 1973.

Frosch, W.A. Patterns of response to self-administration of LSD. In Roger E. Meyer (Ed.), Adverse Reactions to Hallucinogenic Drugs. Washington, D.C.: U.S. Government Printing Office, 1969, pp. 74-79.

Hekimian, L.J., & Gershon, S. Characteristics of drug abusers admitted to a psychiatric hospital. Journal of the American Medical Association, 1968, 205:125-130.

McGlothlin, W.H. The epidemiology of hallucinogenic drug use. In E. Josephson & E. C. Carrol (Eds. ), Drug Use: Epidemiological and Sociological Approaches. Washington, D.C.: Hemisphere Publishing Corp., 1974, pp. 279-301.

McGlothlin, W.H., & Arnold, D.O. LSD revisited: A ten-year follow-up of medical LSD use. Archives of General Psychiatry, 1971, 24:35-49.

McGlothlin, W.H., Arnold, D.O., & Freedman, D.X. Organicity measures following repeated LSD ingestion. Archives of General Psychiatry, 1969, 21:704-709.

Naditch, M.P. Ego functioning and acute adverse reactions to psychoactive drugs. Journal of Personality, 1975, 43:305-320.

Naditch, M.P., &Fenwick, S. LSD flashbacks and ego functioning. Journal of Abnormal Psychology, 1977, 86: 352-359.

Schwartz, C.J. The complications of LSD: A review of the literature. Journal of Nervous and Mental Disease, 1968, 146: 174-186.

Stern, M., & Robbins, E.S. Clinical diagnosis and treatment of psychiatric disorders subsequent to use of psychedelic drugs. In R. Hicks and P. Fink (Eds.), Psychedelic Drugs. New York: Grune and Stratton, 1969, pp. 55-65.

Ungerleider,J.T., Fisher, D.D., Goldsmith, S.R., Fuller, M., & Forgy, E. A statistical survey of adverse reactions to LSD in Los Angeles County. American Journal of Psychiatry, 1968, 125:352-357.

Wright, M., & Hogan, T.P. Repeated LSD ingestion and performance on neuropsychological tests. Journal of Nervous and Mental Disease, 1972, 154:432-438.


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