The Founder of this lecture series was described with consummate skill by Professor Aubrey Lewis in the Twenty-fifth Maudsley Lecture, before this Association. Henry Maudsley was a clinician who turned again and again to the problem I shall approach today. He even wrote a monograph under the daring title of “The Physiology and Pathology of the Mind”.

It is generally accepted that situations of danger, stress or emergency lead to an increased activity of the sympathetic system and to the discharge of adrenaline from the adrenal medulla. Until recently our knowledge was based, essentially, upon two lines of evidence; on the observation of effector organs and mechanisms, such as heart rate, blood pressure, width of skin capillaries, etc., and on the measurement of the adrenaline concentration in the suprarenals or the suprarenal veins, which contain comparatively large quantities. Lately, with the advent of more refined techniques, further methods have become available, which made it possible to estimate adrenaline in tissues other than the suprarenals, in urine and in peripheral blood. The last two methods are obviously of special importance for clinical studies.

In this paper work done in the writer's laboratory will be briefly reviewed. The first part deals with the development of a method for the estimation of adrenaline and noradrenaline in plasma and with experiments that were intended to establish the validity of the method. The concentration of adrenaline and noradrenaline, and the form of their occurrence, in plasma and CSF, will be discussed. In the second part results will be described, which suggest that there is a correlation of the blood-adrenaline level with mental activity.

I deeply appreciate the honour that the Royal Medico-Psychological Association has paid me in electing me President for this Year.

It is certainly noteworthy that, during the last few decades, whatever the contributory forces, more and more emphasis is being placed on the contention that man is a social being and that his individuality as a person is meaningful only in terms of his relations with others. Mead (1947) has shown that man as a social being is subjected “throughout his entire individual existence to systematic cultural pressures” which reinforce or intensify, elaborate or suppress his psycho-biological potentialities in a way which not only refutes the false belief in the uniformity of human behaviour but reveals also its most extreme types.

Theoretical models ranging from neurological to analytical have been introduced in the hope of providing new insights into psychopathology. The flesh and blood model is of more recent origin in this field. The experimental or model psychosis results from giving “normals” drugs which bring about a psychotic-like experience for a few hours. As is the case with theoretical models, the flesh and blood models are not accurate representations of the naturally occurring psychosis. In fact, the variability manifest in most naturally occurring psychoses makes the existence of an accurate model impossible. A model, whether carefully planned and developed or accidentally discovered, is useful to the extent that it assists us in better understanding the naturally occurring process it approximates. It is useful if it enables us to set up and test hypotheses which contribute additional knowledge about disease aetiology, mechanisms, or treatment. The model psychosis to be studied in this paper is that produced by lysergic acid diethylamide (LSD).

The hyperventilation syndrome is the name given to a distinctive group of symptoms and signs which are caused by an increase in the depth and rate of breathing. This abnormal breathing is nearly always the result of emotional stress.

Cortical undercutting, as an alternative to standard leucotomy and to the major operation of topectomy, was devised by three surgeons independently. Scoville (1949) published his preliminary results soon after McKissock had begun to do rostral leucotomies. Both have continued to use this type of operation (Scoville et al., 1951; Scoville, 1954) but Ferey (1950), the third to develop a similar technique, was disappointed with the results and soon abandoned it (Ferey, 1953). McKissock (1951) reported the initial impressions of the results in 100 cases and by the end of 1952 had operated on 240 cases. During 1953–54, 1½ to 5 years after operation, I followed up these patients, visiting 175 of them in their homes, and 35 in hospital. Personal follow up was refused or for some reason impracticable in 17 cases, including 4 whose case notes had been destroyed; 13 others had died before the survey was made.

Partridge (1950) reported a follow up study of 300 cases operated on by the same surgeon by his “standard” technique (McKissock, 1943); he had the advantage, which I had not, of being able to see his patients before operation. I have had to work retrospectively, and the case notes available, whilst often excellent, had usually not been made with the idea that they would be needed for follow-up purposes. I have not, therefore, thought it right to draw more than broad conclusions from this study.

The aim of this paper is threefold:

1. (i) To review critically the literature on the Ganser State and clarify its meaning.

2. (ii) To provide a case illustration with some hitherto unreported features.

3. (iii) To present psychological test results, which has not previously been done in a case of this kind.

This is an account of a model psychosis (6) produced by eating the seed of a tropical American plant which is known in Mexico as ololiuqui. It is only quite recently that Schultes (16) has made order from chaos in the matter of the identity of a climbing vine called Rivea corymbosa. I was introduced to ololiuqui by Mr. Leslie LeCron during a visit to Los Angeles in which he showed me Taylor's (22) article where he compares it with the peyote. Mr. LeCron discovered that seeds of Rivea corymbosa could be obtained from Dr. I. D. Clement, Director of the Atkins Gardens and Research Laboratory of Harvard University. I am indebted to Dr. Clement for sending me a supply of the seeds which would otherwise have been very difficult to obtain. It is reassuring for the investigator to know that the substances with which he is experimenting have been collected by skilled scientists who exercise meticulous care, for medical and pharmacological investigators have very often suffered from improper or imperfect botanical determination.

“Standard” leucotomy in the plane of the coronal suture is undoubtedly an effective treatment for many cases of otherwise hopeless prognosis. The main objection to its use, resulting in many “modified” operations being devised, has been the occurrence of serious personality deficits afterwards. Ström-Olsen and Tow (1949) found that these handicapped nearly three-quarters of patients with “severe neurotic depression, obsessive-compulsive neurosis and chronic tense hypochondriasis”, and though 76 per cent. were relieved of illness only 8 per cent. were in full employment. Tow (1952) has repeated his concern at the serious damage inflicted on well-preserved personalities. Partridge (1950), who has given a full account of the personality changes after McKissock's (1943) “standard” leucotomy, detected some personality deficit in nearly every case of the 300 he investigated and suspected that intellectual impairment was present in all, though he could only be sure of it in a proportion. I have elsewhere (Pippard, 1955) reported the clinical results in 240 cases followed up 1½ to 5 years after rostral leucotomy by Mr. McKissock and this paper should be consulted for details of the operative techniques and scales used for rating the results.

Our classification of the mental disorders of later life, which are becoming a social and medical problem of increasing magnitude, is still based upon the views of the great descriptive psychiatrists of half a century ago. Most of the classical accounts of mental disorder of old age (Kraepelin, 1909; Bleuler, 1916) confine themselves to the pre-senile, senile and arteriosclerotic psychoses. Their writers evidently regarded other illnesses as numerically insignificant in relation to these degenerative disorders peculiar to old age. Cases with a predominantly depressive or paranoid picture or with clouding of consciousness alone were described in these old accounts, but were attributed to an underlying cerebral illness, either of senile or arteriosclerotic type. It is consequently a long-established practice when such symptoms appear for the first time in old age, or occur in senescence after prolonged remission, to search for neurological signs, or for some evidence of a decline in intellectual efficiency which might account for the illness in terms of organic disease of the brain. Weight is thus often given to clinical findings of a quite subtle character, or the results of “deterioration tests” whose value in the early diagnosis of degenerative processes in the brain is unproven, form the basis of conclusions of doubtful validity.

It has often been said that America and Britain are separated by a common language and a similar statement might, with equal justification, be made with respect to some of the misunderstandings between psychiatrists and psychologists. Particularly in the personality field, it is quite obvious that many of the terms used are similar, that some at least of the aims of the two groups are identical, and that methods are freely exchanged. Yet, on the whole, it cannot be said that satisfactory integration has been achieved between these two disciplines.

Osmond and Smythies (1952) have given reasons for reviving the view originally put forward by Bleuler (1950) that schizophrenia is essentially a disorder of metabolism, and have suggested that some substance chemically related to mescaline might be the causative agent. Hoffer, Osmond and Smythies (1954) have begun an investigation of this hypothesis and have found that adrenochrome, an oxidation product of adrenaline which is probably a normal intermediate metabolite, has active hallucinogenic properties. These authors do not regard adrenochrome as being unquestionably the toxic agent in schizophrenia, but suggest that it or some closely related substance, having the indole ring and derived from adrenaline, is involved. They also advance the opinion that the metabolic fault consists of an overproduction of adrenochrome or similar substances. Such a view necessarily implies either overproduction of adrenaline or a blocking of one or more of the paths of adrenaline detoxification in the body which do not lead through adrenochrome. As adrenaline is derived from tyrosine the hypothesis is essentially one of abnormal tyrosine metabolism. From this hypothesis certain deductions can be made.

The importance of the psychoses of later life has been demonstrated by Cook, Dax and Maclay (1952), who found that 15 per cent. of patients admitted to mental hospitals in this country were aged 65 or over. Our own corresponding figure (derived from a Mental Hospital serving a county with a mixed rural and residential area) is 20 per cent. for the year 1953. Furthermore, it has been shown by Roth (1955) that about one-half of all admissions aged 60 and over are suffering from affective disturbances, and that of these over one-half have had no psychiatric illness before that age. Robertson and Brown (1953) report a similar proportion with late onset in their material.

Bilateral blind rostral leucotomy has been shown to be an adequate operation for the relief of many tense psychoneurotic and depressive states (McKissock, 1951; Pippard, 1955); the operation gave worthwhile results in about two-thirds of such cases in a series which included many who were unsuitable. This paper is concerned with the results in 27 cases operated on more than once.

Four patients had already had standard leucotomies with inadequate relief of symptoms; an open rostral leucotomy in one of these, a young ruminative schizophrenic, made no obvious difference. Another schizophrenic had a rostral G leucotomy to divide fibres in the inferior medial quadrant which might have been missed by the earlier standard operation (Sargant, 1953). Afterwards she no longer needed maintenance E.C.T. to keep her at a good level; reduction in tension which followed this limited incision, and the greater ease with which she could be cared for in hospital certainly suggests that a limited operation on the medial side may well be considered in some cases in which standard leucotomy has failed, and certainly before undertaking anything as drastic as Freeman and Watts' (1950) radical operation.

Another patient similarly submitted to a rostral G leucotomy had slowly relapsed after an initially successful standard leucotomy for a chronic tension state. He had, however, been left with a marked intellectual deficit and troublesome urgency of micturition and, if anything, his deficits were increased after the second leucotomy, without any useful relief of symptoms.

The study on which we are going to report has its origin in a clinical observation made twenty-six years ago (Schilderand Stengel,1928).

3,4,5-Trimethoxyphenyl-β-aminopropane (TMA) is structurally related to both amphetamine and mescaline, as is shown in Figure 1.

Because of this structural relationship of TMA and amphetamine, methedrine, and mescaline, one could anticipate a clinical response to the compound which would represent certain phenomena characteristic of each of these drugs. This presented an intriguing problem as to whether or not, in actuality, this would be the case.

In making an investigation of Huntington's Chorea in the State of Victoria, we have, so far, been able to collect 150 indisputable cases of this disease, and others. This figure includes 83 deceased, and 57 living. Out of a total of 74, who were certified to mental hospitals, 26 are still either in hospital or on trial leave. This represents ·34 per cent. of the total present mental hospital population. As regards sex distribution, our figures indicate that there were 68 females as compared with 72 males.

We all know cases who have got better and we like to think that we played a part in causing their improvement. To prove this is, however, a very different matter. We have all read the follow-up studies based on a carefully selected group of cases where the authors report on those whom they could trace—but what of the untraced? At times, an overall survey of one's case material may reveal facts unnoticed in the preoccupation with the day to day clinical work.

Delirium tremens and toxi-infective delirium are not now common diseases, but are still encountered often enough for their treatment to present problems. Delirium tremens is a medical emergency and intercurrent pneumonia is a serious complication, more likely to occur if the patient's over-activity persists. Toxi-infective delirium is less frequently accompanied by crude over-activity, but this may be a source of significant added strain in the severely ill patient, in whom it is more likely to occur. The standard treatment for delirium tremens is by sedation, and the giving of fluids and glucose. Paraldehyde seems to be the drug of choice. Opinion is divided on whether it is advisable to continue to give moderate amounts of alcohol. Sedation is the standard treatment in toxi-infective delirium, and here barbiturates tend to be used.