Dr. FRASER. I would not say that they would never be lowered. I would say they usually would not. Senator DANIEL. Now, we have heard testimony that they go to sleep. Dr. FRASER. Yes. Senator DANIEL. And are not able to work or do anything. They have their mental reflexes dulled or lessened to a certain extent. Dr. FRASER. Please don't interpret my answer as meaning that drug addiction is a desirable phenomena. I was responding only to a question respecting the reactions of the man to drive an automobile. In general, a person on drugs is a definitely defective individual functionally, but that is primarily because his motivations have been reduced. He doesn't have the desire to work nor the motivation to work. Senator DANIEL. Would he have the same desire to avoid hitting an automobile or a pedestrian that you and I would have in driving down the street? Dr. FRASER. Well, I don't know that I can answer that question. Senator DANIEL. You would rather drive with me than with a drug addict, wouldn't you? Dr. FRASER. I have never been driving with a drug addict, and I could only answer experimentally. In other words, when you test them experimentally, you can't bring up defects of coordination unless you give larger doses. Senator DANIEL. That is exactly what I asked a minute ago. You are talking about a drug addict on the minimum amount to keep him comfortable. Dr. FRASER. Yes. Senator DANIEL. Now, then, suppose he is on a larger dose than what is the minimum amount to prevent withdrawal symptoms? Dr. FRASER. If he is on a larger amount, he will still function very well unless he took a dose, he was just beginning his addiction and took an excessive dose. Senator DANIEL. Do you think a man who is a drug addict, we will say who is on his usual amount of drugs, could work, hold down a job, just as easily as other people who had equal intelligence and ability? Dr. FRASER. It's possible, but in practice they don't do it. Senator DANIEL. They don't do it? Dr. FRASER. Experimentally, we have found a lot of changes in these individuals. For example, apparently the activity of their adrenal glands is impaired, and they do not respond to stress as well. They are indifferent to their situation. Senator DANIEL. Aren't they indifferent to fears, the normal fears that you and I have? Dr. FRASER. That's right. Senator DANIEL. Aren't they indifferent to the normal fears of getting hurt or hurting other people? Dr. FRASER. I would rather say they are less acutely aware of those. Senator DANIEL. Less acutely aware. And you are talking about this from a scientific and theoretical standpoint? Dr. FRASER. Yes. Senator DANIEL. Actually the way it works out, most drug addicts just simply are not able to hold down jobs and to work like normal people, while they are on drugs. Dr. FRASER. That's correct. It is a matter of motivation, rather than ability to perform a particular task. Senator DANIEL. What do you think of this plan that has been advocated to give drug addicts, at free or little cost, injections in clinics or through doctors to keep them comfortable at their regular level, give them the necessary amount of drugs to take care of their addiction, and let them go in and out and try to hold down jobs? Dr. FRASER. Well, to begin with, I certainly wouldn't want to be involved in trying to administer it from a medical point of view. Senator DANIEL. Do you think the medical profession in general would want to try such a thing? Dr. FRASER. I would be very doubtful that they would want to, and I would personally not want to be involved in it, because I think it would be very difficult to administer. Second, the mere fact that you gave the addict drugs, I don't believe, as this testimony has brought out, is going to solve the problem, because the individual while on drugs is not a normal individual, and he won't be nearly as good or as responsible a citizen as when he is off drugs, so the object of the doctor should not be to keep him on drugs, but to get him off drugs. Senator DANIEL. Now, for those reasons, then, you would not think that such a plan as I have mentioned to you would be practical? Dr. FRASER. That's right. Senator DANIEL. Doctor, do you have any other suggestions to make to the committee? Is there anything that we should know or anything that we should do, as far as the treatment of either the drug addict or the barbiturate addicts are concerned? Dr. FRASER. No additional recommendations other than those already made. Senator DANIEL. Now, the barbiturate addicts cannot be admitted to Lexington, if they have addiction to barbiturates alone; is that right? Dr. FRASER. That's correct. Senator DANIEL. Do you think the law should be changed so that they could be admitted? Dr. FRASER. Now, when you ask me that question, then you immediately become involved in whether you build 2 or 3 other institutions or not. Senator DANIEL. In other words, the present institutions are not able to hold all of the narcotics addicts; is that right? Dr. FRASER. We have difficulty keeping up with it. Senator DANIEL. Do you think some other method of treatment probably should be established by the States and the cities for the barbiturate addicts? Dr. FRASER. Well, I would rather pool the alcoholic and barbiturate cases together and provide institutions for treatment of that class. Senator DANIEL. Do you think that they could be treated together for the reasons you have given in your paper? Dr. FRASER. That's right. Senator DANIEL. Rather than mixing them up with the narcotic addicts in the hospitals? Dr. FRASER. That's correct, Mr. Chairman. Senator DANIEL. Now, do you have some material for the record there? What about the joint paper by you and Dr. Harris Isbell? May we make that a part of the record? Dr. FRASER. Yes, sir. Senator DANIEL. All right. That will be received and made a part of the record at this point. (The document entitled "Chronic Barbiturate Intoxication" is as follows:) [From the AMA Archives of Internal Medicine July 1954, vol. 94, pp. 34-41] CHRONIC BARBITURATE INTOXICATION 1 Further Studies by H. F. Fraser, M. D.; Harris Isbell, M. D.; Anna J. Eisenman, Ph. D.; Abraham Wikler, M. D., and F. T. Pescor, Lexington, Ky. Isbell and coworkers, in 1950, showed that the behavior and neurological status of 5 patients experimentally intoxicated with large amounts of barbiturates for 92 to 144 days resembled that of patients chronically intoxicated with alcohol. Also, convulsions and/or a delirium followed abrupt withdrawal of barbiturates from these chronically intoxicated persons. The purpose of the present communication is to extend the series of Isbell and coworkers, from 5 to 19 cases, in order that the variations in the clinical picture of barbiturate addiction, withdrawal, and recovery can be more completely delineated. In addition, a larger series would provide sufficient controls to permit evaluation of therapeutic regimens. SUBJECTS AND METHODS Five of the subjects included in this study were those used by Isbell and coworkers, and they have been identified in both reports by the same code numbers, S1, S2, P3, P4, and A5. Fourteen additional male volunteers in general good physical state were selected for study shortly after their admission to the United States Public Health Service Hospital, in Lexington, Ky. All gave histories of addiction to opiates and chronic intoxication with large amounts of barbiturates, but, after the study was completed, patients 7, 11, and 16 retracted the history of barbiturate intoxication prior to admission. None of the patients studied had personal or familial histories of epilepsy or psychoses. The patients were continuously observed in a special closed ward throughout the study. The precautions taken have been described by Isbell and coworkers.2 Since the patients were all addicted to opiates as well as being chronically intoxicated with barbiturates, it was necessary to convert their mixed addictions to a chronic intoxication with a single barbiturate. Following transfer to the special ward, secobarbital was administered orally six times daily in the highest dosage compatible with safe ambulatory management. Secobarbital was chosen as the drug to be used in these investigations because our patients seem to prefer this barbiturate to all others. Methadone was substituted for whatever opiate the patient had been using, and then it was gradually withdrawn over a period of 10 to 14 days; thereafter, no opiates were prescribed. Administration of secobarbital was continued at the same level during and after withdrawal of methadone. The nutritional status of all patients was evaluated. All received supplements of milk and fruit juice in addition to a liberal hospital diet and, when indicated, multivitamin capsules (hexavitamin, U. S. P.) were prescribed. None of the patients was considered to have any significant nutritional impairment at the time barbiturates were withdrawn. Dosage. The average daily dosages of barbiturates and the length of the intoxication period are shown in table 1. The table also gives an estimate of the number of days the patients had been consuming barbiturates prior to admission to the hospital. RESULTS Chronic intoxication. The signs and symptoms of maintained barbiturate intoxication resembled those of intoxication with alcohol. The symptoms included confusion, difficulty in thinking, impairment of judgment, marked swings in mood with alternation between elation and depression, increased irritability, 1 From the National Institute of Mental Health Addiction Research Center, Public Health Service Hospital. 2 Isbell, H.; Altschul, S.; Kornetsky, C. H.; Eisenman, A. J.; Flanary, H. G., and Fraser, H. F.: Chronic Barbiturate Intoxication: An Experimental Study, Arch. Neurol. & Psychiat. 64:1-28 (July) 1950. and decreased ego control (fighting, weeping, etc.); marked regression in behavior was the rule. The patients neglected their persons and living quarters, and some became infantile and had to be fed by the attendants. The neurological signs included dysarthria, nystagmus, ataxia in gait and station, past-pointing, and diminished or absent skin reflexes. The amount of sleep in 24 hours was not excessive, averaging 7.7 ± 1.37 hours per day during the last 30 days of intoxication. No great changes in weight were observed. TABLE 1.-Summary of dosage during chronic barbiturate intoxication 1 Cases S1, S2, P3, P4, and A5 were observed for an extended period without drugs prior to experimental chronic barbiturate intoxication. In cases 6 to 19, inclusive, the figures represent an estimate of the number of days which these patients were continuously chronically intoxicated prior to admission to the hospital. The history and tolerance of the patient for barbiturates were used in arriving at this estimate. In case 12 the history was too unreliable to permit an estimate of prior intoxication. Marked variation in the degree of intoxication and tolerance was observed in different persons. Thus, patient 14 could consume 2.2 grams of secobarbital daily and, even with this enormous intake, was able to converse coherently and to walk about without staggering. Patient 12, on the other hand, was extremely drunk and frequently semicomatose on a dosage of only 1.0 gram daily. In most instances, a "ceiling" dosage of barbiturate could be established for each person, which could not be exceeded by even 0.1 gram of barbiturate daily without the degree of intoxication becoming dangerously increased. Frequently, the ceiling dosage declined after completion of opiate withdrawal. Withdrawal.-Withdrawal of barbiturates was abrupt and complete, and no treatment whatever was administered except in cases S1 and 6. These two patients became so exhausted during the withdrawal delirium that their lives were judged to be in danger, and reintoxication with barbiturates followed by slow withdrawal was carried out. The clinical signs and symptoms observed in these patients following withdrawal can be classified as "major" (convulsions and delirium) and “minor." Only 3 of the 19 patients escaped both convulsions and delirium. Taken together, the "major" and "minor" symptoms form a very clearcut clinical entity. In the first 8 to 12 hours after the last dose of barbiturates, the degree of intoxication gradually declined and the patients appeared to be improving. Between the 8th and the 36th hour the minor symptoms appeared and increased in intensity. These included (in rough order of their appearance) anxiety, involuntary twitching of muscles, coarse tremor of hands and fingers on intention, progressive weakness, dizziness, distortions in visual perception (walls seem curved, etc.), nausea, vomiting, insomnia, weight loss, and precipitous drops in blood pressure on standing, or even on sitting. All patients lost weight; the minimum loss was 0.5 kilogram, and the maximum loss, 7.2 kilograms. A subject was judged to have insomnia when he slept 2 hours or less out of a 24-hour period. If this criterion is used, only 4 of the 19 patients did not have this symptom. Subject 6 went without sleeping for 8 consecutive days. Not all patients, of course, exhibited all these minor signs and symptoms, but all the subjects in this series had 5 or 6 of those listed above. The minor signs usually reached maximum intensity in the second day of abstinence and, thereafter, gradually declined over the course of the following 2 to 15 days. Convulsions of grand mal type developed in 15 of the 19 patients, an incidence of 79 percent. The earliest convulsion occurred 24 hours, and the latest, 115 hours after the last dose of barbiturates. All but 2 of the 33 seizures experienced by these patients occurred within 78 hours after secobarbital was withdrawn. The greatest number of convulsions observed was four. Following the convulsive phase, 12 of the 19 patients (63 percent) developed a psychosis which resembled alcoholic delirium tremens. The delirium was preceded by insomnia and was characterized by disorientation in time and place but usually not in person and by hallucinations which were predominantly visual. The delirium tended to begin and to be worse at night. It usually terminated spontaneously with sleep which lasted several hours. During the delirium, rectal temperature was usually elevated to about 38.1 C. (100.6 F.). The intensity and duration of the delirium varied widely; some patients were delirious for only 1 day, others for as long as 8 days. Some patients reacted quietly to their hallucinatory experiences, sat quietly, held conversations with imaginary persons, etc. In such patients, very close observation was necessary to establish that a delirium was present. Other patients were agitated, screamed repeatedly, and attempted to escape from imaginary tormentors. Psychological studies.-Psychological tests were conducted during addiction, withdrawal, and recovery, to assess quantitatively the coordination, reaction time, and motivation, or "set," of 11 of these 19 patients who were intoxicated with secobarbital. Tests were performed 4 hours after administration of barbiturates, when the acute effects of intoxication usually had subsided. In comparison with a control group of persons who were no longer addicts and were not under the influence of drugs, barbiturate addicts had a severe impairment of coordination, as reflected by increased reaction time and a decreased ability to maintain a "set" or readiness to respond. Such persons would be very unsafe operators of automobiles or other potentially dangerous machines. These studies have been reported in detail elsewhere by Hill and Belleville.3 TABLE 2.-Incidence of major symptoms which followed abrupt withdrawal of barbiturates Severity of delirium is graded 1 to 4 as follows: 1, disorientation in place or time and/or hallucinations (visual or auditory) occurring briefly and at widely separated intervals, with complete insight; 2, disorientation in place and time, with visual and auditory hallucinations occurring every hour or so, with transient loss of insight; 3, disorientation in place and time, with visual and auditory hallucinations constantly present; patient preoccupied with hallucinations; no insight but patient not agitated; 4, disorientation in place, time, and occasionally, in person; constant vivid, frightening hallucinations; complete loss of insight; great agitation. 2 Withdrawal was terminated during the psychotic phase by reintoxication with barbiturates, since the life of the patient was considered in danger. Hallucinations with insight but no disorientation. Hill, H. E., and Belleville, R. E.: Some Effects of Chronic Barbiturate Intoxication on Motivation and Muscular Coordination, A. M. A. Arch. Neurol. & Psychiat. 70: 180-188 (Aug.) 1953. |