The following transcript by Peter Stafford of Hofmann’s talk first appeared in Blotter #1,, a publication of the Psychedelic Education Center , Santa Cruz, CA. Only the first portion of Dr. Hofmann’s talk, given October 15, 1977, concerned with his discovery of LSD is reprinted here, due to space limitations. The later portion of his talk dealt with the magic circle of compounds which Hofmann discovered , including lysergic acid in Ololiuqui seeds of Mexican morning glories and Psilocybian in the magic mushroom.
Alexander Shulgin: I wish to welcome you all to this Colloquium tonight, and I feel very honored to have the opportunity to introduce Dr. Albert Hofmann to you. I really can’t imagine that there’s anyone here who really needs to have him introduced, so in a sense it’s sort of an exercise in futility to introduce you to the audience.
So I think in fairness it might be something of more interest to introduce the audience to you. We are a very manied group here -- many of us are artists, either with pen or with brush, and many of us have looked into the area of chemical change of state as a means of perhaps learning some of our own techniques. Many of us are sociologists and have worked very closely with people who have been involved in drug use and drug abuse, and as such they are aware of your work and are very appreciative of it.
Many of us in a sense are philosophers, are lookers to our inner self and work with ourselves as individuals. And I think you will find that a large number of the people present -- I’m introducing them to you as chemists, who have taken many of your starting spots and have gone on in other ways and chemical structures and in other chemical mysteries. Many of us are biochemists, and have looked at how these materials have acted in the body. And many of us are pharmacologists and toxicologists, who have looked as to their behavior induction in animals and in man. So there are many ways in which we are very, very different from one another, and yet are tied together in this one single thread.
And yet in many ways we are of a single thought and of a single mind in the way that we are all, indeed, students in this area of change of consciousness, and are very keenly aware of the fact that these are tools that can be used as ways of finding our own methods and our own procedures of our own mind. The second way in which we are all in common is we all bear a very, very deep respect and a deep reverence of your work and your contributions in this field.
And we are introducing ourselves to you, and I am very proud to introduce you to our audience. Dr. Albert Hofmann.
Albert Hofmann: Thank you very much, Dr. Shulgin, for a very nice introduction. And I should like to thank also Professor Bridgeman and Professor McGlothlin for their invitation to give this talk. And finally, I would like to express my best thanks to Bruce Eisner -- who was my guide, and who was coordinating this meeting.
You may be disappointed. You may have expected to meet a guru, and you meet just a chemist. If I am going to tell you in what context LSD was synthesized, and how its psychic action was discovered, I realize that I am presenting an old story. But this may be justified by the fact that quite fantastic versions of how LSD was found are current, even in professional circles. You may be interested, therefore, to hear also the true story.
It is frequently stated in the literature that LSD was discovered by chance. The following account will show that LSD was not just the fruit of chance discovery, but the outcome of a more complex process which had its beginning in a definite concept, and was followed up by an appropriate experiment during the course of which a chance observation served to trigger off a planned investigation. This then led to the actual discovery. Such a train of events may often be found to underlie what is said to be a chance discovery.
LSD had been synthesized as part of a chemical and pharmacological investigation on ergot derivatives, which I carried out in the early ‘30s in the Sandoz Laboratories which were headed at that time by Professor Stoll. Ergot is the produce of the fungus Claviceps purpurea, which grows on rye and ergagram in the air. It is a rich source of valuable medicinally useful alkaloids.
Most ergot alkaloids are derivatives of lysergic acid, and there are two types of ergot alkaloids -- alkaloids in which lysergic acid is combined with a precyclic peptide distart. As is the case in the so-called alkaloids of ergotamine and the ergotoxin group.
And there are other simple types of ergot alkaloids, where lysergic acid is combined with a simple amine -- as is the case in the alkaloid ergonomine or ergometrine, where lysergic acid is combined, connected with propylamine.
My first investigations in this field were directed toward the synthesis -- the partial synthesis -- of this compound. By means of a so-called Kirzius procedure, it became possible to recombine lysergic acid with these simple amines. By this way, when I combined lysergic acid with propynolamine, I received this compound which proved to be identical with ergometrine.
Ergometrine is oxytoxic, specific oxytoxic principle of ergotamines -- a principle which acts on the uterus, and which is used medicinally in obstetrics to stop post-partum hemorrhage. Then I did change the side-chains of this natural ergot alkaloid, using instead of propylamine, butylamine -- and then I got another compound, a new compound, named metrogine, which is used today throughout the world in obstetrics for the arrest of post-partum hemorrhage.
Whereas most of these investigations were directed toward the synthesis of oxytoxic agents, I had prepared also other compounds which -- on the basis of their structure -- could have been expected to possess other, different properties. First among other compounds, I synthesized the diethylamide of lysergic acid -- this compound -- with the intention to prepare an analeptic. That means, a compound with circulation stimulant activity.
This compound might have been expected to possess analeptic properties because of its structural relationship with the well-known circulation stimulant Nicatamide -- here -- and because the B ring, as all well-known chemists can realize, is a tetrahydranicotimic ring. And here Nicatamide is a iocylamide of Nicatinic Acid. Do you see the structural relationship?
A number of pharmacological experiments were carried out by Professor Ernst Rothlin at the Sandoz laboratory with these compounds -- with lysergic acid diethylamide -- which was given the laboratory code name “LSD-25,” because it was the 25th compound of the lysergic acid amide series. These experiments revealed a fairly marked uterotonic action, which was not unexpected in view of the close chemical relationship between LSD and the oxytoxic drugs ergometrine and metrogine.
But the compound did not seem to be of further pharmacological interest and work on LSD then fell into abeyance for a number of years. As I had a strange feeling that it would be worthwhile to carry out more profound studies with this compound, I prepared a fresh quantity of LSD five years later, in 1943.
In the course of this work, an accidental observation led me to carry out a planned self-experiment with this compound. The following is an extract of my original report on this experiment, addressed to the head of the pharmaceutical department -- at that time, to Professor Stoll. “Last Friday, April 16th, ‘43, I was forced to stop my work in the laboratory in the middle of the afternoon and to go home, as I was seized by a peculiar restlessness associated with a sensation of mild dizziness. On arriving home, I lay down and sank into a kind of drunkenness which was not unpleasant, and which was characterized by extreme activity of imagination.
“As I lay in a dazed condition with my eyes closed, I experienced daylight as specially bright. There surged up from me an uninterrupted stream of fantastic images of extraordinary plasticity and vividness and accompanied by an intense, kaleidoscopic-like play of colors. This condition gradually passed off after about three hours.”
The nature and the cause of this extraordinary disturbance raised my suspicions that some exogenic intoxication may have been involved, and that lysergic acid diethylamide -- with which I had been working that afternoon -- could have been responsible. I had separated two isomeric forms which are produced by the synthesis -- namely, lysergic acid diethylamide and iso-lysergic diethylamide.
However, I could not imagine how this compound could have accidentally have found its way into my body in a sufficient quantity to produce such symptoms. Moreover, the nature of the symptoms did not tally with those previously piously associated with ergot poisoning.
In order to get to the root of the matter, I decided to conduct some experiments on myself, with the substance in question. I started with the lowest dose which might have been expected to have any effect, namely with 0.25 milligram LSD.
The note in my laboratory journal reads as follows: “April 19th: Preparation of 0.5% aqueous solution of d-lysergic acid diethylamide tartrate.
“4:20 pm: 0.5 ml., corresponding to 0.25 mg. LSD, ingested orally. The solution is tasteless.
“4:50: no trace of any effect.
“5:00: slight dizziness, unrest, difficulty in concentration, visual disturbances, marked desire to laugh . . .”
Next slide, please. You see here crystals of lysergic acid diethylamide tartrate. Next slide. Here is a photocopy of the original inscription in my laboratory journals which I just have read in English. At this point the laboratory notes are discontinued. The last words were written with great difficulty. I asked my laboratory assistant to accompany me home as I believed that I should have a repetition of the disturbance of the previous Friday. While we were cycling home, however, it became clear that the symptoms were much stronger than the first time, and I had great difficulty in speaking coherently. My field of vision swayed before me, and objects appeared distorted like images in curved mirrors. I had the impression of being unable to move from the spot, although my assistant told me afterwards that we had cycled at a good pace. Once I was at home, a physician was called. By the time the doctor arrived, the peak of the crisis had already passed. The following were the most outstanding symptoms: Vertigo, visual disturbances. The faces of those around me appeared as grotesque colored masks. Marked, moderate unrest alternating with paralysis, intermittent heavy feeling in the head, limbs and the entire body as if they were filled with lead. Clear recognition of my condition -- in which state I realized, in the manner of an independent, neutral observer that I shouted sometimes or babbled incoherent words. Occasionally I felt as if I were out of my body, and wondered if I had already died. In contrast to my subjective feelings, a doctor found only a somewhat weak pulse -- but otherwise quite normal circulation and physical condition. The sixth hour after ingestion of the LSD, my psychic condition had already improved considerably. Only the visual disturbances were still pronounced. Everything seemed to sway and their proportions were distorted like the reflections in the surface of moving water. Moreover, all objects appeared in unpleasant, constantly changing colors -- the predominant shades being sickly green and blue. When I closed my eyes, an unending series of colorful, very realistic and fantastic images surged upon me. A remarkable feature was the manner in which all acoustic perceptions -- for example, the noise of a passing car -- were transformed into optical effects, every sound evoking a corresponding colored hallucination, constantly changing in shape and color like pictures in a kaleidoscope. At about one o’clock in the night, I fell asleep, and awoke next morning feeling perfectly well. This was the first planned experiment with LSD -- a rather dramatic one -- a horror trip, as one would say today. Because I did not know if I would return from this very strange world! Subsequent experiments on volunteer colleagues of the Sandoz laboratories confirmed the extraordinary activity of LSD on the human psyche. This showed that the effective oral dose of LSD in human beings is 0,03-0,05 mg. In spite of my caution, I had chosen for my first experiment five times the average effective dose. LSD is, by far, the most active, and most specific hallucinogen. It is about 5,000-10,000 times more active than mescaline, which produces qualitatively nearly the same symptoms. The extremely high potency of LSD is not just a curiosity. It is in many respects of the greatest scientific interest. For example, it lends support to the hypothesis that certain mental illnesses, which were supposed until then to be of purely psychic nature, had a biochemical cause. Because it now seemed feasible that undetectable traces of a psychotomimetic substance produced by the body itself might be the cause of psychic disturbances. LSD was quite unique with regard to its extremely high hallucinogenic potency, but it was not new with regard to the quality of its hallucinogenic property. As already mentioned, it produces qualitatively the same psychic effects as mescaline, a hallucinogen known long before LSD -- mescaline being the active principle of one of the ancient magic plants of Mexico.
Albert Hofmann is the retired director of research for the Department of Natural Products of Sandoz, Ltd. the pharmaceutical firm in Basel, Switzerland. Besides LSD, he has synthesized the active constituents of medicinal plants, such as ergot of rye, squill, rauwolfia, and the Mexican magic drugs. He has a doctorate in chemistry and is the author of numerous chemical and pharmaceutical research books, several books on psychedelics including LSD: My Problem Child, and has two honorary doctorates.
