From Royston M. Roberts, Serendipity, accidental discoveries in science (Wiley, New York, 1989), pp.130-133

The discovery of the hallucinogenic substance lysergic acid diethylamide (LSD) is one of the most frightening accounts in recorded medical history.

LSD is derived from lysergic acid, which itself is not hallucinogenic. Lysergic acid occurs along with a large number of poisonous alkaloids in the fungus ergot, which sometimes forms on rye in the field during a particularly wet season. For centuries this fungus plagued persons from Spain to Russia who, out of ignorance or hunger, ate bread baked from contaminated rye flour. Gangrene of extremities resulted from extreme constriction of blood vessels. The affliction was called St. Anthony's fire because the victims had the terrible sensation that their skin was burning, their blackened fingers and toes look charred, and they sought relief at St. Anthony's shrine. During the Middle Ages eating spoiled rye flour reportedly caused abortions, visual disturbances, and mental aberrations culminating in epidemics of madness. These symptoms were probably caused by overdoses of the poisonous ergot alkaloids combined with hysteria engendered by the rnutilating affliction rather than by lysergic acid itself. Not until Albert Hofmann, a Swiss chemist employed by the Sandoz Laboratories in Basel, synthetically attached the diethylarnide group did the acid acquire its mind-bending properties. Hofrnann was studying lysergic acid and related compounds in the hope of developing a drug to treat migraine headaches or to control bleeding after childbirth.
The following account of his experience in this research is taken from Hofrnann's own notebook as reported in The Beyond Within: The LSD Story (1970) by Dr. Sidney Cohen:

Last Friday, the 16th of April [1938], I had to leave my work in the laboratory and go home because I felt strangely restless and dizzy. Once there, I lay down and sank into a not unpleasant delirium which was marked by an extreme degree of fantasy. In a sort of trance with closed eyes (I found the daylight unpleasantly glaring) fantastic visions of extraordinary vividness accompanied by a kaleidoscopic play of intense coloration continuously swirled around me. After two hours this condition subsided.

Hofmann suspected that his unusual sensations might be due to accidentally swallowing or inhaling a minute amount of some chemical in the laboratory. His account continues:

On that Friday, however, the only unusual substances with which I had been in contact were D-lysergic acid and isolysergic acid diethylamide. I had been trying various methods of purifying these isomers by condensation, and also breaking them down into their components. In a preliminary experiment I had succeeded in producing a few milligrams of lysergic acid diethylamide (LSD) as an easily soluble crystal in the form of a neutral tartrate [a salt formed from LSD and tartaric acid]. It was inconceivable to me, however, that I could have absorbed enough of this material to produce the above described state. Furthermore, the symptoms themselves did not appear to he related to those in the ergotamine-ergonovine group. I was determined to probe the situation and I decided to experiment upon myself with the crystalline lysergic acid diethylamide. If this material were really the cause, it must be active in minute amounts, and I decided to begin with an extremely small quantity which would still produce some action in equivalent amounts of ergotamine or ergonovine.

Hofrnann therefore took 250 micrograms [0.00025 gram] of lysergic acid diethylamide. After 40 minutes he noted a "mild dizziness, restlessness, inability to concentrate, visual disturbance, and uncontrollable laughter." At this point the entries in the laboratory notebook end, and the last words were written only with the greatest difficulty. He continued his account later:

I asked my laboratory assistant to escort me home since I assumed that the situation would progress in a manner similar to last Friday. But on the way home (a four-mile trip by bicycle, no other vehicle being available because of the war), the symptoms developed with a much greater intensity than the first time. I had the greatest difficulty speaking coherently and my field of vision fluctuated and was distorted like the reflections in an amusement park mirror. I also had the impression that I was hardly moving, yet later my assistant told me that I was pedalling at a fast pace.

So far as I can recollect, the height of the crisis had passed by the time the doctor arrived; it was characterized by these symptoms: dizziness, visual distortions, the faces of those present appeared like grotesque colored masks, strong agitation alternating with paresis [partial paralysis], the head, body and extremities sometimes cold and numb; a metallic taste on the tongue; throat dry and shriveled; a feeling of suffocation; confusion alternating with a clear appreciation of the situation; at times standing outside myself as a neutral observer and bearing myself muttering jargon or screaming half madly.

The doctor found a somewhat weak pulse, but in general a normal circulation. Six hours after taking the drug, my condition had improved definitely.

The perceptual distortions were still present. Everything seemed to undulate and their proportions were distorted like the reflections on a choppy water surface. Everything was changing with unpleasant, predominantly poisonous green and blue color tones. With closed eyes multihued metamorphizing fantastic images overwhelmed me. Especially noteworthy was the fact that sounds were transposed into visual sensations so that from each tone or noise a comparable colored picture was evoked, changing in form and color kaleidoscopically.

After a good night's rest, Hofmann felt "completely well, but tired." The accidental ingestion of LSD by this perceptive chemist initiated a chain of investigation of chemically induced mental alterations that has extended into every psychiatric research center. The importance of Hofmann's discovery is not that LSD has any direct chemical relationship to a disease such as schizophrenia; its structure can hardly he expected to be synthesized by the human metabolism.

The discovery of LSD has other significant implications; it demonstrates that chemical substances in extremely minute amounts can induce mental distortions that resemble the naturally occurring psychoses. It has stimulated interest in the chemistry of the nervous system, especially the chemical transmitters across synapses, the nerve-cell connections; and it permits the laboratory study of both normal and abnormal mental processes.

Although many lysergic acid derivatives with hallucinogenic activity have been synthesized, none is as potent as LSD. Completely new and unrelated chemical groups have also been found to possess similar psychic properties. One day the chemistry of mental illness may be clear, in part, thanks to the serendipitous and terrifying experience of Albert Hofmann.

POSTSCRIPT

Because LSD was abused with such serious consequences, the Sandoz Laboratories discontinued production of the drug in 1966 and turned over all their supplies to the National Institute of Mental Health.

In a later chapter in his book, entitled "The Worst That Can Happen", Dr. Cohen comments on the possible use and abuse of LSD: "The title of this chapter is a phrase borrowed from the siren song of the LSD Religion spokesmen. 'The worst that can happen to you after taking an LSD trip' they continue to assert 'is that you will come back no better than you were.' This is as incorrect as a statement can be. You may come back much worse than you were. You may not come back."

 

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