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Studies with Lysergic Acid Diethylamide in Regressed Schizophrenics

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Studies with Lysergic Acid Diethylamide in Regressed Schizophrenics CHAPTER 15 _ Studies with Lysergic Acid Diethylamide in Regressed Schizophrenics By FREDERICK B. CHARAT AN, M.D. OF THE MANY studies carried out with lysergic acid diethylamide in the last 15 years, relatively few have dealt with regressed schizophrenics. Most workers have used comparatively small doses of LSD. Some gave up to 600 gamma orally. Others reported the effects of up to 500 gamma intra- muscularly, 180 gamma intravenously and 60 gamma intrathecally in small series of cases. Several investigators agreed that in chronic schizophrenics higher doses of LSD than those administered to undeteriorated schizo- phrenics and nonpsychotics have been required to produce psychic effects. Apart from the slight response of chronic schizophrenics to doses of LSD which lead to marked and characteristic effects in other subjects, tolerance to the drug seems to develop in as brief a period as three days. These differences in response to LSD pose some interesting problems. Is the lack of response in chronic schizophrenics merely an apparent one caused by their inability to communicate their inner experiences? Is it due to the development of some immune state connected with biochemical alter- ations produced during the psychosis? Is it the reflection of a metabolic difference between schizophrenics and non-schizophrenics? May it be a general manifestation of schizophrenic underresponsiveness to virtually any stress, once the chronic stagnant phase of the psychosis has been reached? Clear answers to all these questions cannot yet be given. The present investi- gation was undertaken to examine further the responses of chronic schizo- phrenics to large doses of LSD and also to observe the effect of other drugs upon this response. MATERIALS AND METHODS Eight female patients were selected by the following criteria: they had all been ill for many years; they all showed well marked signs of schizophrenic deterioration; they had been under observation for at least six months in the same ward, and cared for by the same nursing staff. There are some advantages in selecting such patients. Thus, their behavior, speech and mannerisms are well known to the staff. From the Research Division, Manhattan State Hospital, Ward's Island, New York, N. Y. 195 196 BIOLOGICAL PSYCHIATRY They are very limited in their activities, which makes any departure from the usual pattern readily observed. Over a period of time ranging from several months to several years, the illness had reached a stagnant phase, and change has become a rarity. All these patients had had various treatments, including long courses of thorazine or similar drugs without improvement. One had had a topectomy. On 47 separate occasions the patients were given increasing doses of LSD by mouth and also intravenously, following which they were observed closely for six hours. Administrations were separated by at least five days to prevent the develop- ment of tolerance. The nurse also reported on the patients on the day of administra- tion and subsequently. RESULTS Oral administration. In every case, the autonomic effects were far more pronounced than the psychological, and set in 20 to 45 minutes after ingestion. Tachycardia and pupillary dilatation were seen in all patients. With the highest doses, patients became very restless, but did not speak more freely or communicate fresh material. The commonest affective changes were in the direction of an increase in hostility or depression. In five patients an unstable affective state which included weeping and sobbing was pro- duced. The LSD state showed a definite waxing and waning. By six hours, the reaction usually subsided, patients being restored to their former state on the next day. Patients were questioned directly regarding hallucinations, alterations in body image, sensory disturbances, orientation and the total experience. As these patients at their best were poorly accessible, it is not surprising that equivocal responses or no answers were given to these ques- tions. A good example of such a response was that of a patient who was clearly restless, confused, perspiring and showed marked tachycardia after LSD. When asked how she felt, she said, "I feel fine". Intravenous administration. Patients were given LSD intravenously in doses up to 400 gamma. Reactions commenced within five minutes of admin- istration and were more intense than with the same dose by mouth. Autonomic features-tachycardia, tachypnea, mydriasis, salivation-and nausea were prominent. Two patients showed pyrexia, the temperature rising 1 to 2° F. Restlessness was more marked than with oral administration. Ataxia, pseudochoreic movements and coarse tremors occurred in some patients. The same fluctuations of mood were seen. Clouding of conscious- ness and reduced accessibility were more evident. Effects of other drugs upon the LSD response. Methyl Amphetamine. Patients were premedicated with methyl ampheta- mine, 30 mg. daily, for periods of 5 to 24 days, and given the same dose of LSD intravenously as they had received previously. The effect of the methyl amphetamine on these regressed patients before LSD was very con- LYSERGIC ACID DIETHYLAMIDE IN REGRESSED SCHIZOPHRENICS 197 sistent. The patients became worse within 48 hours. They became more restless, confused, incontinent and difficult to nurse. However, no change following LSD intravenously compared with the previous reaction was seen, nor was the reaction prolonged. Intramuscular Methedrine, 15 mg. in two patients at the height of the LSD reaction, was without noticeable effect. Iproniazid. All patients were premedicated with iproniazid, 150 mg. daily, for periods of 5 to 33 days. Like methyl amphetamine, iproniazid tended to increase restlessness and regressive phenomena in these chronic schizophrenics, although to a lesser extent. The schizophrenics premedicated with iproniazid were given LSD intravenously in the same doses they had previously received. No difference in either the intensity or the duration of the reaction to LSD was observed. Diethazine. Following intravenous LSD in doses of 200 to 400 gamma, 250 mg. diethazine was given intramuscularly at the height of the reaction. In every case, the LSD reaction was terminated within one hour after the injection. Sodium amy tal explorations in chronic schizophrenics. As an aid in deter- mining whether underlying trends might be present, each patient was given a sodium amy tal exploration; 5 per cent sodium amytal was injected slowly intravenously until slight slurring of speech was apparent. Only one patient showed an increase in spontaneity, becoming more euphoric and talkative in a disorganized way, the context being about dying and being killed. The other seven patients remained empty of content. No fresh material was obtained. Changes in affect did not occur, with the exception mentioned. When questioned about topics expected to elicit responses, e.g., about children, husbands, families, ambitions, reasons for admission to the hospital, they remained apathetic and replied briefly or not at all. When thought disorder was present in the conscious state, no changes were brought about under sodium amytal. Patients' replies were "beside the point" or completely irrelevant. When asked about their thoughts or feelings they made stereo- typed responses: "I feel fine," "Nothing," or "O.K." When invited to discuss problems they remained silent. To summarize: sodium amytal gave rise to hardly any change in the psychological responses of these patients and merely highlighted the stunting and withering of their mental life. DISCUSSION Several workers have pointed out that chronic schizophrenics show reduced psychodynamic responses to LSD. Occasionally this phenomenon has been seen in normals who received up to 225 gamma. The present results are in conformity with earlier reports in which doses of LSD of up to 6 gamma per Kg. were required to produce undifferentiated emotional responses in 198 BIOLOGICAL PSYCHIATRY this schizophrenic group. It must be stressed, however, that chronic schizo- phrenics show well marked autonomic symptoms after quite small doses of LSD. Increasing the dose increases the predominantly sympathicomimetic features such as tachycardia, tachypnea, mydriasis, nausea and vomiting. With the highest doses affective instability, pseudochoreic movements and motor restlessness occur. Ideational content remains unaffected.DiMascio and co-workers have pointed out the early generalised sympathetic excitation occurring in the march of events after LSD in doses of 1 gamma per Kg. has been administered to healthy volunteers. The march of events in chronic schizophrenics halts short of discernible ideational features. One must conclude that LSD has a specific stimulating effect upon the hypothalamus-particularly those nuclei which integrate sympathetic ac- tivity. Kies and co-workers'" demonstrated an antidiuretic effect of 100 gamma of LSD in healthy subjects. Evidence for stimulation by LSD of the mesodiencephalic activating system has been provided by Himwich.F Instillation of LSD into the cerebral ventricles of cats produced minor diffuse autonomic symptoms in small doses and "sham rage" in larger doses, a sequence of events paralleling to some extent those observed in the administration of LSD to chronic schizophrenics.LSD is remarkable in causing gross changes in the affect of chronic schizophrenics who may have remained frozen for years. It is hardly necessary to recall that in- creased lability and incongruity of affect may be seen in localized sub-
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