LYSERGIC ACID DERIVATIVES

THE BEST KNOWN of the lysergic acid derivatives is lysergic acid diethylamide (LSD-25) , a compound which has created. an aura of excitement and magic from the moment of its discovery. Indeed, some element of its "mind-expanding" property may have been acting on Albert Hofmann on April 16, 1943, when he was able to distinguish "a peculiar sensation of vertigo and restlessness" and being "unable to concentrate"' from an ordinary case of Friday afternoon doldrums. In so doing, he was to discover a heretofore unknown property of a drug and initiate a new era in the continuing effort to understand the underlying mechanisms which control human behavior. Hofmann had, in fact, accidentally ingested minute quantities of one of the most powerful of drugs. A few years later, this potency in producing bizarre psychic phenomena, plus a lack of addictive and toxic properties, and the minimal side effects, were to impress and excite many behavioral scientists who were concerned with mental illness, particularly schizophrenia. There was a reawakened interest in the possibility of natural chemical activators in the schizophrenic process. Among the concepts re-introduced was the possibility of using drugs to initiate so-called model psychoses. Advocates reasoned that compounds such as LSD-25 could be used to induce a "schizophrenic-type" state analogous to a natural psychosis; biochemical and physiological mechanisms of the drug action could provide clues to mechanisms involved in schizophrenia; drugs counteracting the drug-induced psychoses could provide a therapeutical approach to schizophrenia. The underlying premise of these ideas is that natural psychoses could be caused by the production of a minute, perhaps undetectable, amount of aberrant metabolite by the organism.

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The model psychoses theory, attractive in its simplicity, resulted in a deluge of publications, but has produced neither a cure for nor a better understanding of the causes of schizophrenia. Although it was not completely discarded, it was rapidly displaced by a more pervading, insidious, and much more difficult to evaluate concept, namely, that LSD-25 and other hallucinogens can be used for constructively expanding one's mental existence and of permanently altering human personality and behavior, ostensibly for the better. As Hollister2 has so aptly observed, what was once regarded as insanity was now heralded as insight. The change in emphasis seemed to parallel the degree to which observers became participants in the LSD experience. Justification for this view is expressed by Blum3 who noted:
It was when people shifted from using the drug to see what it was like or what it could do, to using it to see what they themselves were like or what they could do, that LSD use rather than LSD effects became an intriguing subject for investigation.
As will be shown on the following pages, neither the model psychoses theory nor the expanded psyche concept can be proved or disproved by the investigative methods and/or philosophy that are presently available to the biochemist or to the behaviorist.


Lysergic acid compounds, which can be chemically manipulated to yield various hallucinogens, are found as natural molecular components of ergot. The latter has had an intriguing history of mixed horror and magic in its own right.' Ergot is a biological product of a growing fungus, specifically Claviceps purpura, which parasitizes cereal grains. Various types of grains can be affected, but the history and distribution of ergot parallels that of its favorite host, which is rye. Rye was introduced into Southern Europe by the Teutons in the early Christian era. During the Middle Ages, rye bread was eaten largely by the poor, since wheat at that time, because of vicissitudes in agricultural conditions, was regarded
as a luxury crop. Rye and ergotism were largely restricted to districts of poor soil and poorer people.

The first description of ergot as such was made in 1582 along with a description of its use by women in producing pains of the uterus. Although ergot had been used as an oxytocic agent for centuries by European midwives, its use for that purpose was introduced into modern medicine in 1808 by an American physician, Dr. John Stearns. In his scholarly and exhaustive monograph on ergot, Bargee credits a "New World" freedom from prejudice for the eventual, but belated, recognition of ergot as a useful medicinal agent. This view would be hotly contested in the "New World" of today. But he also recognized that the Old World had suffered much from the toxic properties of ergot; its good had been obscured more by pain, suffering and ignorance than by any prejudice against its use by the medical fraternity.

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During the middle ages and after, infected rye was used in bread and animal feed and caused major widespread epidemics of ergotism in both people and livestock. Ergot poisoning was of two types, gangrenous and convulsive. The early symptoms of gangrenous ergotism were tingling in the fingers and toes, vomiting, and diarrhea. These were followed by a dry type of gangrene in the extremities, affecting the entire limb which would separate spontaneously at the joint without pain or loss of blood.4 In convulsive type, early symptoms were much the same, but were followed by painful contractions and distortions of the limbs, and by convulsions. If the victims survived either type, they were left mentally incompetent. Although there were cases of ergotism reported in the early 1900's, improved agricultural methods, coupled with governmental regulation and inspection of grains, has made it an insignificant modern disease. Ergot is grown commercially now in most countries of the world and processed for medicinal purposes. Spain and Portugal are among the world's major producers.