Neurotoxicity and LSD treatment: a follow-up study of 151 patients in Denmark

This historic archive case study assessed the reports of 151 patients out of a 400 patient cohort who received treatment with LSD between 1960-73 (without psychotherapy) and who received financial compensation for LSD-inflicted harm in accordance with Danish law. The applicants reported an immediate deterioration of their condition and severe long-term effects.

Abstract

“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.”

Author: Jens K. Larsen

Summary

Neurotoxicity and LSD treatment: a follow-up study of 151 patients in Denmark

LSD was introduced in psychiatry in the 1950s, and 154 patients received financial compensation for LSD-inflicted harm. Most of the patients suffered from severe side effects many years afterwards.

Introduction

Stoll isolated ergotamine from ergot, which was used in obstetrics and migraine treatment. Hofmann asked Stoll to continue the investigation, which led to the discovery of LSD.

Hofmann did not forget (LSD)-25 and took a dose of 250 micrograms diluted in water on 19 April 1943. He experienced vivid hallucinations, intense fear and despair, out-of-body experiences and intense mortal dread and was able to remember the experience in complete detail.

The psychic effect of LSD was a surprise to Hofmann, but he should not have been surprised, as ergot, a fungus that grows on rye and other species of grain, had been well described in the Middle Ages.

Matthias Grünewald’s Issenheim Altar in Colmar in Alsace shows a man with severe ergotism who also suffered from terrifying hallucinations. However, at that time, the visions were interpreted as an assault by demons.

LSD was marketed by Sandoz in 1947 and was withdrawn from the market in the mid-1960s. It could still be used scientifically until 1974.

Sandoz made LSD available to research institutes and physicians as an experimental drug in the late 1940s and 1950s.

LSD is used in analytical psychotherapy to elicit the release of repressed material and provide mental relaxation, and in experimental studies on the nature of psychoses.

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.

Scandinavian countries became the leading centres of LSD research, despite international warnings and the observation of serious side-effects. The development of persistent hallucinations, possibly of toxic origin, following repeated administration, seemed to have gone unnoticed.

A Danish study reported results from a three-year period and included evaluations at three follow-up interviews. The study did not conclude that the LSD treatment had a decisive treatment effect.

The Danish LSD treatment was never analysed again, until a special case led to the collection of selected material on LSD-treated patients. The present study evaluated the long-term outcome of LSD treatment.

Source material

From 1959 to 1973, nearly 400 patients were treated with LSD in Denmark, mostly at Frederiksberg Hospital.

The case records from the 1960s and 1970s have not been preserved, and it is not known how many LSD-patients were treated at Frederiksberg Hospital. However, 154 patients who complained about the LSD treatment have their data preserved in the Danish State Archives.

A 23-year-old man visited a psychiatrist at Frederiksberg Hospital, experienced a severe psychotic reaction with intense anxiety and later developed a chronic psychotic illness. He again experienced LSD treatment in 1987, but his mental condition soon deteriorated again, and he died at the age of 66.

In 1972, a patient complained about the LSD treatment at Frederiksberg Hospital to the Interior Ministry. The ombudsman suggested taking a closer look at the LSD treatment at Frederiksberg Hospital, but the Interior Ministry concluded that there was no reason to pay compensation for LSD-inflicted harm.

A journalist from the Danish newspaper Information wrote an article about the state of affairs in psychiatry, and later became interested in LSD treatment. He was rewarded with the prestigious Cavling Prize in 1987.

In 1986, Denmark passed a law allowing patients treated with LSD to apply for reparatory compensation. The law defined the so-called reversed burden of proof, and stated that treatment with LSD was considered to be the cause of the damage unless it was most likely that the harm was due to another cause.

Each application was dealt with by a tribunal under the Ministry of Social Affairs, which did not include psychiatric expertise.

A total of 176 applications were received for compensation for LSD-inflicted harm. 19 applications were rejected, three applicants did not send in their application forms, and 12 applicants received free treatment.

The present study covers the case material for 151 patients being treated with LSD who applied for compensation. The tribunal made a decision on the amount of compensation and all applicants received compensation.

Methods

I was granted access to the LSD case material in the Danish State Archives and collected conventional data, as well as information on the number of treatments and the dosages used.

The indication for LSD treatment was recorded from the psychiatric diagnosis. The ICD-8 classification of diseases was used at the time of the compensation applications, but the ICD-10 classification was used in 2013.

Flashback experiences can lead to psychotic development, persistent depression, or bipolar disorder, or an anxiety disorder independent of flashback experiences, psychotic development, or depression.

I took into account any complications that were mentioned in the medical certificates, even if they were not stated in the case material.

The LSD tribunal wrote summaries and stated the reason for the amount of compensation in the conclusion for every case. In some cases, the specialist certificate could not be obtained for various reasons, so the tribunal obtained written responses from the various psychiatric departments.

The patient’s mental state was assessed before the LSD treatment, and was assessed immediately after the LSD treatment. The patient’s present mental state is different from the patient’s mental state before the LSD treatment.

In a minority of patients, psilocybin was given either alone or in combination with LSD, with similar effects as LSD.

Hospital and socio-demographic data

LSD treatment took place at Frederiksberg Hospital, and at two clinics in Copenhagen that are not mentioned in Table 1, but none of the patients applied for compensation.

The age and sex distribution of the 151 applicants shows that 25 female patients were treated at the start of treatment, compared to 14 male patients in the same age category.

91 patients were receiving invalidity pensions at the time of application for compensation. Half of these patients had severe social problems, such as inability to work, social isolation and long-lasting sick leave.

In 47 of 151 cases of mental disorder, LSD was prescribed within the first year of treatment. For 26 of these patients, LSD was the first treatment choice.

Type of consent

In 1986, the Danish NHS discussed whether LSD patients were informed according to existing laws and had consented to the treatment. It concluded that sufficient informed consent had generally been obtained.

The case material includes examples of the type of information provided, and the types of consent given, for 151 patients who received LSD treatments.

Number of LSD treatments and dosages

Figure 2 shows the number of LSD treatments for each patient. The treatment was normally given once or twice a week, often with intervals without LSD treatment.

The dosage of LSD given per session is not systematically included in the case material, but from the information available it can be inferred that the initial dose was rather low, between 25 and 50 micrograms, and the dosage was rapidly increased to a maximum of 200 – 250 micrograms.

Acute and long-term efficacy of the LSD treatment

In the follow-up study, almost half of the patients had improved and the rest were unchanged. They had completed a questionnaire, and the responses are preserved in the LSD case material.

From the analysis of 134 cases, 52 cases were improved, 34 cases were unchanged, and 48 cases were worsened by the LSD treatment.

Psychiatric diagnosis at the time of LSD treatment compared with diagnosis at the time of the compensation application

LSD was used on a wide spectrum of mental disorders and dysfunctions, and a diagnosis was given when it was considered unlikely that the mental disorder could be classified differently.

Two patients with homosexuality were unsuccessfully treated with LSD, as were one patient with gender identity disorder and one patient with sexual dysfunction.

Short-term and long-term LSD inflicted harm

The case material provides vivid descriptions of the acute LSD experiences and the revival of these in flashbacks. The experiences range from seeing snakes and reptiles to experiencing the urge to take one’s own life being multiplied.

Long-term LSD-inflicted harm was summarized in Table 4, and positive ratings were given only when documented in the medical certificate, the case notes and/or the patient’s description.

Eight patients underwent psychosurgery after being treated with LSD. The psychosurgery mostly worsened the patient’s mental state, but the treatment caused some improvement, although the patient was still severely ill.

The financial compensation for the LSD inflicted harm

The amount of compensation awarded by the LSD Tribunal was determined by the extent of the damages. Patients who underwent psychosurgery or became severely psychotic were often awarded higher compensation.

Discussion

Although many clinics in the USA and Europe used LSD in the 1950s and 1960s, very few long-term follow-up studies have been done. Early warnings and a wave of illegal use resulted in restrictions for its medical use and withdrawal from the market.

In Denmark and Norway, medical use of LSD continued until the mid-1970s, and then was gradually discontinued. Only a few complications were found in the first three years of treatment.

The results of the above study were strikingly different from the findings of the present study, which described the overall mental state of psychiatric patients approximately 25 years after they were treated with LSD. There may be many explanations for these discrepancies, including the small sample size.

The lack of psychotherapy with the LSD treatment at Frederiksberg Hospital is often cited as a reason why patients deteriorate and suffer from severe side-effects. Nevertheless, no one applied for compensation.

LSD treatment failed to cure stuttering in two patients and resulted in long-lasting side-effects in both cases. Moreover, deterioration of the mental state was observed independently of the diagnosis, even in patients with obsessive-compulsive disorder.

The high number of patients with LSD inflicted problems found 25 years after the treatment may reflect the natural course of these disorders, independently of the treatment.

At the time of LSD treatment, flashbacks were considered to be rare side-effects. They were not observed in many international studies.

Flashbacks and anxiety symptoms were the rule rather than the exception in studies on LSD. They were not well understood at that time, but were related to the number of LSD exposures and severe psychopathology.

In some early studies, it was considered that flashback experiences were not caused by psychedelic drugs as a true drug effect. However, later reviews undoubtedly accepted the potential of LSD to create flashbacks.

In the study of a group of alcoholics by Ditman et al. (1962), a high percentage of patients claimed improvement after six months of LSD treatment, but none maintained their sobriety.

The early enthusiasm for LSD therapy was probably due to reports of an acute therapeutic effect on a variety of mental disorders. However, the scientific paradigm shifted to necessitate randomized clinical trials, which were never conducted with LSD treatment.

The findings in the 1964 Danish follow-up study may be explained by the acute stimulating effects of LSD, which also interacts agonistically and antagonistically with dopamine D1 and D2 receptors.

Recent studies have suggested that LSD therapy may be effective for treating anxiety associated with life-threatening diseases, and may be used as an antidepressant.

In the light of the findings of the present study, clinical use of LSD seems frightening. It is better tolerated by individuals without severe psychopathology, and selection criteria before treatment should focus on recognizing the acute effects of LSD as unwanted.