It has repeatedly been mentioned in the literature that LSD might have carcinogenic potential. This speculation appeared for the first time in the paper by Cohen, Marinello and Back. (22) The authors drew this conclusion from their findings of a markedly increased frequency of chromosomal breakage and a quadriradial chromosome exchange figure in a patient with paranoid schizophrenia who had undergone extensive LSD psychotherapy. This is a combination occurring in three inherited disorders: Bloom's syndrome, Fanconi's anemia and ataxia teleangiectatica. These disorders are connected with a high incidence of leukemia and other neoplastic diseases. The authors also pointed out that cells of neoplastic origin show a variety of chromosomal aberrations, many of which are not unlike those they had found in subjects after ingestion of LSD. In addition, some of the agents known to produce similar chromosome aberrations, such as radiation and various viruses, are known carcinogens.
The carcinogenic hypothesis was supported by the finding of Irwin and Egozcue (57) that nine subjects who had taken illicit LSD had chromosomal fragments resembling the so-called Philadelphia (Phi) chromosome, often associated with chronic granulocytic leukemia. Grosshard et al. (46) found a Phi-like chromosome in all thirty-five peripheral leucocytes from an individual who had used illicit LSD and other drugs and who later developed acute leukemia.
Several serious objections can be raised against this hypothesis. First, the evidence that pure LSD causes chromosomal aberrations is rather problematic and inconclusive. Second, the cause of the chromosomal lesions in the above mentioned inherited disorders is not known, nor has it been established whether these lesions have any relation to subsequent neoplastic developments. There exist many chromosome breaking agents which are not associated with leukemia, and quadri-radial and other rearrangement figures have also been found in the white blood cells of normal individuals. Third, Cohen's comparison of the effects of LSD with those of radiation does not seem to be well substantiated by experimental and clinical findings. According to Dishotsky et al., (28) long-term chromosomal damage following LSD injection has been reported in three retrospective studies. In two reports of subjects studied before and after they took LSD (prospective approach), the occasional damage that was found was without exception transitory, suggesting a reversibility of effect unlike that associated with radiation. Fourth, the Phi-like chromosome was reported in only two studies; in both of them it was found in peripheral leucocytes. In chronic granulocytic leukemia, the Phi chromosome is characteristic only of myeloid and erythroid cells, which normally do not divide in peripheral blood. Dishotsky et al. (28) quote Nowell and Hunger-ford (84) who initially described this lesion: "A chromosome compatible with the Phi would have to be observed in blood cells other than lymphocytes to be relevant to the question of chronic granulocytic leukemia."
Only two cases of leukemia have been reported in individuals who were treated in the past with pure LSD. (41, 108) In both of thein it remains to be established whether the association represents a causal relation or a coincidence. In one of these cases, reported by Garson and Rohson, (41) there was a "remarkable incidence of childhood malignancies strongly suggestive of a familial predisposition to malignant disease." At the present time the carcinogenic hypothesis seems to be rather poorly supported by experimental and clinical data and remains in the realm of pure speculation. There appears to be no definite evidence that LSD is a carcinogenic agent.
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