Neurotoxicity and LSD treatment : a follow-up study of 151 patients in Denmark
Jens Knud Larsen
University Hospital of Aarhus, Risskov, Denmark
History of Psychiatry, 2016, Vol. 27, (2), 172–189
LSD was introduced in psychiatry in the 1950s. Between 1960 and 1973, nearly 400 patients were treated with LSD in Denmark. By 1964, one homicide, two suicides and four suicide attempts had been reported. In 1986 the Danish LSD Damages Law was passed after complaints by only one patient. According to the Law, all 154 applicants received financial compensation for LSD-inflicted harm. The Danish State Archives has preserved the case material of 151 of the 154 applicants. Most of the patients suffered from severe side effects of the LSD treatment many years afterwards. In particular, two-thirds of the patients had flashbacks. With the recent interest in LSD therapy, we should consider the neurotoxic potential of LSD.
Keywords : Denmark, LSD, LSD damages law, LSD therapy, LSD toxicity, psycholytic therapy, 20th century
Lysergic acid diethylamide (LSD)-25 was synthesized in 1938 by the Swiss chemists Albert Hofmann (1906–2008) and Arthur Stoll (1887–1971). LSD, usually written without the lysergic acid derivative series number 25, has obtained doubtful notoriety in psychiatry and society.
In 1918 in the laboratories of the pharmaceutical company Sandoz in Basel, Stoll had isolated ergotamine from ergot, which was widely used in obstetrics and migraine treatment. Hofmann asked Stoll to continue the investigations on the alkaloids of ergot to examine the stimulating potential of the derivatives on respiration and blood circulation (Hofmann, 1980: 8–12). This work led to the discovery of LSD. After a few disappointing animal experiments, further testing was discontinued (Hofmann, 1980: 13).
Hofmann did not forget (LSD)-25, and on 16 April 1943 he produced a few centigrams of the compound to give to the pharmacological department for further tests. However, in the middle of the afternoon he had to interrupt his work and go home, where he ‘sank into a not unpleasant intoxicated-like condition, characterized by extremely stimulated imagination’. He ‘perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colours. After some two hours this condition faded away …’ (Hofmann, 1980: 14).
Hofmann realized that during crystallization some of the LSD solution might have contacted his fingertips and been absorbed through the skin. On 19 April 1943, he decided to perform a selfexperiment. He took a dose of 250 micrograms of LSD diluted in water and a half an hour later experienced a very serious reaction with vivid hallucinations, intense fear and despair, out-of-body experiences and intense mortal dread. After a good night’s sleep, Hoffmann felt that he was in excellent physical and mental condition without a hangover and was able to remember the experience
of the LSD intoxication in complete detail (Hofmann, 1980: 17).
The psychic effect of LSD, later designated as the psychedelic effect, was a surprise to Hofmann, as was the small amount of the active substance needed to cause the reaction (Hofmann, 1980: 17). Perhaps he should not have been surprised, for he was well aware of the origin of ergot from the fungus Claviceps purpurea, which grows on rye and other species of grain as well as on wild grasses. In the Middle Ages, outbreaks of mass poisoning with ergot-containing bread affected and killed thousands of people, and this had been well described. One of the names of this dreadful illness was ‘St Anthony’s fire’ after the patron saint of ergotism prayers, and the order of St Anthony, which treated these patients (Alm and Elvevåg, 2013; Hofmann, 1980: 9; Siegel, 1985).
No one who sees the Issenheim Altar by Matthias Grünewald (c.1475–1528) in Colmar in Alsace can doubt that one of the figures, a man with severe ergotism, also suffered from terrifying hallucinations. However, at that time, the visions were interpreted as an assault by demons (Béguerie, 1991: 5; Nielsen, 1998: 111). This was also stated by Siegel (1985), who described hallucinations in the convulsive form of ergotism. Fuller (1968), in his account of the 1951 ergotism epidemic in France, described the presence of LSD-like hallucinations among the victims.
Hofmann wrote the foreword to a book on the history of ‘St. Anthony’s Fire in Art and Medicine’, in which the neurotoxic potential of ergot was discussed (Bauer, 1973: 58). Hofmann said: … from this research further drugs of great value have appeared; they are used in migraine treatment, in the treatment of circulatory disturbances and in geriatrics. Also drugs with such unusual effects as LSD have been found in this way. Ergot, once the cause of the feared Antonius-Fire, has thus changed from a poisonous substance into a rich gold mine of drugs … (Bauer, 1973: 6)1 LSD was marketed by Sandoz in 1947 and reached psychiatry in the 1950s. By 1965, the Sandoz company had requested that LSD should no longer be registered (Larsen, 2013: 229). It was withdrawn from the market in the mid-1960s and is now classified as a narcotic substance with severe potential of abuse. In Denmark, however, it could still be used scientifically until 1974.
In the late 1940s and 1950s, LSD was widely used to unravel the connection between behaviour and pharmacology, and early on it was often recommended as an aid to psychotherapy (Bernstein, 1988: 509). In this climate, Sandoz made the new substance available to research institutes and physicians as an experimental drug for the following purposes (Hofmann, 1980: 31):
1. Analytical psychotherapy,2 to elicit the release of repressed material and provide mental relaxation, particularly in anxiety states and obsessional neuroses.
2. Experimental studies on the nature of psychoses: by taking LSD himself, the psychiatrist is able to gain insight into the world of ideas and sensations of mental patients. LSD can also be used to induce model psychosis of short duration in normal subjects, thus facilitating studies on the pathogenesis of mental disorder.
Although the idea of the LSD reaction as a model for psychosis was rejected soon after it was proposed, psychoanalysis took LSD into its practice to accelerate the therapeutic process (Larsen, 2013: 258). In psychoanalytical circles, it was generally believed that certain drugs were able to evoke unconscious material; therefore, this material became available for interpretation and therapy. As late as 1964, the official Danish psychiatric textbook stated: ‘By using LSD, the patients may develop a psychotic-like state, in the process of which they reveal a lot of pathogenic material’ (implying that this material may be a target of psychotherapy) (Strömgren, 1964: 242; see also Larsen, 2013: 224).
In Scandinavian countries, the centres of Modum Bad in Norway and Frederiksberg Hospital in
Denmark became the leading centres of LSD research. Despite international warnings (Grinker,
1963; Rinkel, 1966) and the observation of serious side-effects, such as homicide, suicides and
suicide attempts, especially in Danish reports (Geert-Jørgensen, Hertz, Knudsen and Kristensen,
1964), the attitude towards LSD treatment in the two centres remained positive or even enthusiastic
(Geert-Jørgensen, 1968; Johnsen, 1967). Additionally, the development of persistent hallucinations,
possibly of toxic origin, following repeated administration, as reported by Rosenthal (1964),
seemed to have gone unnoticed at the two Scandinavian centres. It was reported in the Danish
study that: ‘Complications have been few and it seems absurd to have them tabulated.’ It was,
however, mentioned that: … a few patients had brief episodes of after-effects repercussion several months after the treatment had terminated, either in the form of a revival of the LSD séance or as groundless fear – in a few isolated cases … an already existing fear was seen to intensify some time after termination of treatment. (Geert-Jørgensen et al., 1964: 375)
This 1964 Danish study reported the results from a three-year period and included evaluations at three follow-up interviews (Geert-Jørgensen et al., 1964). The Norwegian report of the first 300 patients treated was evaluated many years later. The survey did not conclude that the LSD treatment had a decisive treatment effect. On the other hand, a low frequency of reported side-effects was found, which was considered to be a result of conscientious screening in the special therapeutic setting (Due-Madsen and Hoffart, 1996; Due-Madsen, Øyslebø and Hoffart, 1996).3
The Danish LSD treatment was never analysed again, until a special case 15–25 years later (see below) led to the collection of selected material on LSD-treated patients. Another 25 years has passed since this selected material became the object of analysis in the present study. Its purpose is: first, to evaluate the long-term outcome of LSD treatment in a population of Danish psychiatric patients; second, to estimate possible beneficial and damaging effects of the LSD-treatment; and finally, to find evidence for the possible neurotoxic potential of LSD.