The present analysis pertains to the experiment reported by Brengelmann, Pare and Sandler (15) to assess the effect of 5-hydroxytryptophan (5-HTP) on lysergic acid diethylamide (LSD) by means of psychological tests. In the following, problems of measurement and validity of the LSD- “psychosis” are discussed.

It seems to me proper to stress from the beginning that there are various types of depressions. Often they are ill-defined, while at other times they fit into the clinical entities of manic-depressive reactions or later-life (involutional) groups. In addition, psychoneurotic depressions are also recognized. However, the essential nature of all these types of depressions is still poorly understood. Treatment therefore cannot be based on an aetiological concept or be specific for depression, but must be based on the psychopathological data.

Among factors held to be causally related to suicide are: (i) social isolation (1); (ii) social degeneration (2); (iii) parental deprivation (3, 4, 5). If these factors are aetiologically related to suicide, they should present prominently in that minority of depressive patients who attempt suicide. On the other hand, these factors should be found less frequently in non-suicidal depressive patients. The hypothesis that a factor is causally related will not be supported if it is found to occur as frequently among non-suicidal depressive patients as among those showing both depression and suicidal behaviour.

It is good to be back in the serenity of this assembly after an interval of ten years, but I must ask your forbearance in view of the fact that the topic assigned me today is rather similar to the one I discussed here in 1947.

In the investigation described, the hypothesis was tested that 5-hydroxytryptamine (5HT) acts to reduce the psychological effects of lysergic acid diethylamide (LSD). The method was to inject 5-hydroxytryptophan (5HTP) prior to LSD and to compare the results of psychological tests performed after these injections. Placebo controls were used.

It has been stated too frequently that new therapeutic developments in psychiatry are revolutionizing the field. While this did not turn out to be true for any of the treatment procedures, it can well be stated that those of us who entered psychiatry more than 25 years ago, lived through a period in which psychiatry changed from a specialty known for its therapeutic nihilism to a field of almost feverish therapeutic activity. Undoubtedly the physical treatments have played a decisive role in this change. They have also clearly changed the attitude on the part of the individual psychiatrist to his specialty. Our teachers were primarily concerned with attempts to organize and systematize our knowledge, while our generation, perhaps because too pragmatic, may easily be blamed for failure to link the newly-acquired information with the basic concepts developed by them, concepts which were neither confirmed nor disproved by our new knowledge. When I think of my own development as a neuropsychiatrist, I remember that I started out in psychiatry, but temporarily turned to neurology because at that time neurology seemed to give much greater therapeutic possibilities. It was only in the middle nineteen-thirties that this changed radically, and that so many more therapeutic possibilities developed in psychiatry that it became a challenge to return to this field. The introduction of the various physical treatments in close succession was an amazing coincidence. Although met by some with scepticism and even ridicule, and by others with unjustified over-enthusiasm or a competitive attitude improper for scientific progress, the new treatments evoked a beneficial optimism among psychiatrists. They helped to change the attitude of the mental hospitals in all countries and gave an entirely new impetus to the general public to become interested in matters concerning the mentally sick. It may also be said that the physical treatments gave a new stimulus to efforts at psychological and social treatments of the psychotic patient, and I dare say that the improvements in mental hospital management which are so conspicuous in your country could not have progressed so fast and met with so much public support if the physical treatments had not helped to improve the adaptability of patients in these hospitals. It is a historical fact which can be easily proved, especially in England, that those hospitals which are now the showplaces for modern hospital treatment, with open wards and social and recreational activities for almost every single patient, are also the ones in which pioneer work was done with insulin coma treatment, convulsive treatments and psychosurgery. I am going to discuss these treatments, while the newest approach, pharmacotherapy, will be left to another report and be mentioned only as far as it influences the application and indications of the other treatments.

I should like to discuss some of the clinical aspects of the tranquillizing drugs, but without going into great detail as to the many theoretical considerations in biochemistry, physiology, pharmacology, etc. which have been ventilated so often in connection with this form of treatment.

It is presumptuous for a clinician to embark on this subject, and I hasten to apologize for my boldness in doing so. My excuses are many. The first comes from clinical experience. Since my student days, when I observed malignant schizophrenia in a young girl for the first time, and watched its relentless progress despite all therapeutic efforts, I came to the belief that this was an illness of body as well as of mind, and this belief has led me to maintain a continuing interest in the medical, as distinct from the purely psychological, investigations of this disease throughout my professional years. Next has been the observation of experimental or model psychoses produced by drugs. An LSD or mescaline psychosis is not schizophrenia, any more than curare poisoning is myasthenia gravis, but there is enough similarity between the dissociation states produced by psychotomimetic drugs and the real thing to stimulate one's curiosity, at least.