Adverse Reactions to Hallucinogenic Drugs

Foreword

The National Institute of Mental Health through its Center for Studies of Narcotic and Drug Abuse serves as the focal point for support of research into the problems of drug abuse. The growing problem of hallucinogenic drug usage has been of great concern to the staff of this Center. In the midst of reports of the spreading epidemic of drug misuse and its sequelae, the National Institute of Mental Health has sought to clarify the many questions and myths that have arisen in both the lay and

scientific press.

Consistent with this effort, the Center for Studies of Narcotic and Drug Abuse sponsored a meeting of scientists in September 1967 to discuss the psychological and biological sequelae of LSD use. This volume consists of the proceedings of that meeting, plus significant background papers which were available to the participants in advance of the meeting. While few definitive answers emerged from the discussions, the major questions were clearly defined and some research strategies were proposed. This book, in a way, serves as a bench mark of our knowledge at that time. The geneticists were as keenly interested in the deliberations of the psychiatrists and psychologists as the latter were intrigued by the findings of the former. Subsequent to the meeting, the efforts of a number of people were responsible for its preparation in readable form. Miss Arlene Jaffe and Miss Eleanor Carroll, of the Center for Studies of Narcotic and Drug Abuse, and Miss Marilyn Wilhelms of the Office of Communications, NIMH, greatly assisted in the editing of the manuscript.

[List of conference participants and the twelve individual clinical, genetic, and epidemiological presentations that follow (pp. v-53) omitted.]

Summary of the Conference

The extent and characteristics of hallucinogenic drug abuse among middle class young adults is at this time unknown. Preliminary reports of grant-supported surveys in the spring of 1967 indicated that 15 to 20 percent of the college population had used marihuana and approximately u to 8 percent of this same population had used LSD (and/or other hallucinogenic drugs). Much of this could be characterized as "experimentation." Within hippie gathering places, however, drug use more clearly approximates drug abuse with persons regularly taking multiple and more dangerous compounds. Some clinical and research observers of the LSD scene have observed a discrete pattern of psychopathologic behavior among chronic users of LSD and persons on "bad" trips. These professionals have been concerned about possible outbreaks of new forms of organic psychosis related to hallucinogenic drug use. Preliminary reports from various biological laboratories have also suggested the possibility that LSD may be implicated in serious chthmosomal aberrations. These observations have led some to conclude that LSD may be leukemogenic and/or teratogenic. Concerned with these reports of psychological and biological damage, the Center for Studies of Narcotic and Drug Abuse on September 29, 1967, convened a meeting of leading research investigators in this area. This report summarizes the proceedings of this meeting. Most participants deplored the complication of reasonable research deliberation by exaggerations in the popular press and the tendency to draw conclusions from preliminary data. Some participants confirmed the spread of intravenous methedrine abuse in some of the hippie communities and described the outbreak of STP use which took place early in the summer of 1967. The original reports which had indicated that chlorpromazine potentiated STP trips in a dangerous manner were specifically refuted by several participants. This drug (STP) was felt to be more typically adrenergic, consistent with its chemical structure.

Evidence of pert:sti-;:i psychological damage from chronic LSD a;.12.aiiiisirk-Con was minimal. This negative finding may be "real" or may reflect a lack of sophistication in out measuring instruments. While some psychological tests done on persons who have used LSD many times suggest borderline evidence of organicity, electroencephalographic findings subsequent to LSD administration (but not during the LSD trip) are generally normal. Dr. Julian Silverman, reporting on a study done with eight chronic LSD users at the National Institute of Mental Health, indicated that amplitudes of EEG evoked responses (secondary to photic stimuli) were elevated in some ch-onic LSD users (while not under LSD) . These higher amplitudes paradoxically returned to normal levels when 50 micrograms of LSD was administered. Of some interest was the observation that these chronic users (when not on LSD) showed uniformly lower thresholds to auditory stimuli, and that these thresholds resembled those of Addisonian patients being withdrawn from steroid maintenance. This suggests the possibility that sensory overload may be a problem for some chronic LSD users, even when they are not on the drug. It was speculated that, in some way, this phenomenon may be related to the absence of goal-directed behavior among the chronic users of LSD. Dr. Humphrey Osmond of the New Jersey Neuropsychiatric Institute and a pioneer in early research efforts with LSD confirmed some of Dr. Silverman's findings by his own observations at the New Jersey Neuropsychiatric Institute. Other participants focused on the treatment of the "bad" trip. Some noted that chlorpromazine has been ofttimes ineffective and, that in some centers, routine sedation and psychological support is the preferred treatment. Most participants agreed, however, that the psychiatric community should gain increasing familiarity with this new syndrome and that each psychiatrist should develop familiarity with a treatment pro-

gram that could include phenothiazines and/or the use of sedative drugs and psychological support. Several clinicians present noted that "bad" trips are seen almost exclusively among persons in the 15 to 25-year age group. One postulated that this relationship might represent the potentiation, by LSD, of adolescent adju3tment problems into severe acute crises. Several participants described the phenomenon of recurring psychedelic experience without recurrent ingestion of the drug. Of particular concern were descriptions of recurrent paranoid episodes, at times accompanied by vivid hallucinations, in some users of LSD. There were neither psychological nor pharmacological explanations of this phenomenon, but the LSD experience generates powerful emotions and any effectively rich experience is bound to recur in the mental life of the individual. Dr. William Frosch, of Bellevue Hospital in New York, reported the continuing admission of two patients per week to the Psychiatric Service secondary to LSD use. Dr. Thomas Ungerleider of UCLA indicated that the large number of LSD admissions to the emergency room at UCLA caused the Psychiatric Service to close its doors to those experiencing "bad" trips. While some have reported that the frequency of "bad" trip admissions to general hospitals and other institutions has been decreasing, it appears that this is still a continuing problem for mental health professionals. Additionally, a number of participants pointed to the phenonenon of depression among chronic users of LSD. This depression has been particularly refractory to traditional psychiatric treatments and the participants were not agreed on the nature or treatment of the phenomenon. Unfortunately, many chronic LSD users have turned to amphetamines in an effort at self-treatment of the depression. Relative to the question of leukemogenic or teratogenic properties of LSD, Drs. Maimon Cohen and Kurt Hirschhorn summarized their data relative to LSD and in vivo and in vitro chromosomal aberrations. Since their initial report in Science 62 they have also observed chromosomal damage secondary to chlorpromazine and certain other tranquilizing drugs. They noted, however, that these aberrations were not as severe as the dislocations and translocations observed secondary to LSD administration. Dr. David Hungerford of the Cancer Research Institute in Philadelphia also reported investigat-

ing the circulating lymphocytes of some hippies in the Philadelphia area but failed to confirm Dr. Cohen's findings. On the other hand, Dr. Hermann Lisco of Harvard University observed similar chromosomal changes in persons who had been given psilocybin in a psychological experiment. Persons attending this meeting were unclear as to the ultimate significance of these findings. Dr. Robert Miller of the Epidemiology Branch, National Cancer Institute, noted that time would be the significant factor in observing the evolution of possible leukemia-type syndromes. Underlying all of the discussion was the concern that these reported chromosomal changes have also been observed in survivors of the Hiroshima attack and other persons exposed to high doses of ionizing radiation, all of whom have an increased likelihood of developing leukemia-type syndromes. Early reports from Dr. Auerbach 413 at the University of Wisconsin noting teratogenic effects of LSD administered to mice (plus an increase in the rate of spontaneous abortions) were not confirmed in studies done on rats by Dr. Josef Warkany of the Children's Hospital, Cincinnati. Subsequent reports of teratogenic effects in the hamster suggest species differences in fetal response to LSD. Some reports cubsequent to this meeting suggest that the chromosomal changes secondary to LSD may be transient phenomena similar to those observed in viral illness and therefore not analogous to the chromosomal changes observed after radiation exposure (which are permanent). At this time our information about the biological hazards of LSD and other hallucinogenic drugs must be considered incomplete. One observer at the meeting said that he almost wished that some of these reports about chromosomal damage were true so that we could stem the increase in illicit hallucinogenic drug use. But the jury is still out. We would certainly continue to warn potential mothers about the possible hazards of LSD exposure; being always clear about our facts while avoiding scare techniques. The group was unanimous in feeling that scare techniques only alienate the drugusing community so that they may not at some future time listen to scientific facts about confirmed hazards of hallucinogenic drug use.

62 Cohen, see footnote 2, page 1. 63 Auerbach, see footnote 37, page 40.

[The Appendix (seven background papers reprinted from professional journals, plus a bibliography, pp. 57-116) omitted.]