The Work of Albert Hofmann

The Swiss chemist Albert Hofmann (1906- ) is often referred to as the inventor of LSD, as if he had set out with the intent of creating a hallucinogenic drug that would sweep the Western world. He was the first to synthesize the molecule Lysergic acid diethylamide, but it was not until five years after its first synthesis that the hallucinogenic properties of the drug were discovered.

On the other hand, the drug was hardly stumbled upon by accident, which is another common misconception. It was quite intentionally and systematically synthesized, Hofmann makes clear. The real accident was the discovery of its hallucinogenic properties, five years later.

There have been claims by drug enthusiasts that LSD’s discovery was a sort of predestined event designed to bring the world out of its social ‘Dark Ages’ and into a new era of mind. Although Hofmann points out some coincidences that led to the synthesis of LSD, the strength of his claims fall far below that of the drug advocates of the sixties.

The story begins at the Sandoz Company’s pharmaceutical-chemical research laboratory in Basle, Switzerland. Here, Albert Hofmann chose to work after completing his higher education at the University of Zurich. He chose Sandoz because he could work with natural chemicals as opposed to synthetic ones.

Hofmann requested to work with the ergot alkaloids in 1935. Much work was being done with ergot in England and America and he wished to keep Sandoz at the head of the race. After being warned that ergot alkaloids are very difficult substances to work with, his wish was granted and his work begun with them.

Ergot is produced by a lower fungus called Claviceps purpurea. It grows parasitically on rye and other wild grains and grasses but the variety used medicinally is that which grows on rye called Secale cornutum. In the Middle Ages this fungus would cause mass poisonings whose effects were dramatic causing convulsions and gangrene. A religious order was formed specifically to treat ergot poisoning, the cause of which was unknown at the time. The patron saint of this order was St. Anthony, and for this reason the affliction came to be called St. Anthony’s Fire. Eventually when the it became known that eating rye bread with the fungus growing on it was the cause, the incidence of poisonings nearly disappeared.

Ergot was also used medicinally to precipitate childbirth. This was dangerous to the baby, however, for in high doses it could cause uterine spasms. Because the dosage of alkaloids within an organic material is always uncertain to some degree, this use was discontinued. It’s use became confined to lessening bleeding after childbirth.

Hofmann set out to artificially synthesize ergobasine, the ergot alkaloid useful in obstetrics. This he accomplished. It was a profitable success because it made accessible in great quantities that which was only minimally available in nature. Next he went on to improve the effectiveness of ergobasine by slightly altering its make-up. This he also accomplished and the altered ergobasine became widely used under the trade name Methergine.

After these achievements Hofmann decided to produce new lysergic acid compounds--lysergic acid being the nucleus common to all ergot alkaloids. On the grounds of their chemical structure, they could be expected to have other useful pharmacological properties. Based on the chemical structure of each lysergic acid, each one was synthesized for a specific purpose. In 1938 Lysergic acid diethylamide, abbreviated LSD-25 because it was the twenty fifth compound produced in this series, was synthesized with the intent of obtaining a circulatory and respiratory stimulant.

When tested on animals, this compound was found to have no useful properties. It had a strong effect on the uterus, about 70% that of ergobasine. Additionally noted was that while under the effects of the drug, animals became restless. Since ergobasine was already in use, and restlessness was nothing special, the testing of this drug was discontinued.

During the next five years, Hofmann continued his experiments with ergot and made some useful discoveries and significant breakthroughs; LSD-25 was not involved in any of these. After a compound is found to have no pharmacological value, time is no longer wasted on it.

However, Hofmann could not seem to forget this unexciting compound. Despite the taboo against re-testing useless compounds, Hofmann took it upon himself to synthesize another sample of LSD-25 for further tests. On April 16, 1943 during the final step of the synthesis, Hofmann noticed some strange effects which forced him to discontinue his work and go home to rest. These effects included dizziness, restlessness, extremely stimulated imagination, extraordinary brightness of daylight, and hallucinations on closed eyelids.

After contemplating how his unusual state could have arisen, he could only come to the conclusion that he had absorbed some of the LSD-25 through his skin. Despite the meticulous precautions he had taken as a chemist dealing with a highly toxic substance, this was possible, although unlikely. Hofmann decided that there was only one way to ascertain whether Lysergic acid diethylamide was the culprit. He would perform a self-experiment.

This experiment took place three days later in his laboratory, his assistant being well informed of the experiment. He orally took .25 mg of diethylamide tartrate, a crystalline form of LSD-25, diluted in 10 cc of water. Forty minutes later he reported similar symptoms to those he experienced three days prior: dizziness, anxiety, visual distortions, symptoms of paralysis and the desire to laugh. He is barely able to take notes by then and asks to be taken home by his assistant, where he endures a “most severe crisis.” (see Appendix I)

Albert Hofmann was completely astonished by the effects of the psychoactive substance Lysergic acid diethylamide. What is refreshing about his view of the now famous hallucinogen LSD is that his perception of it was completely unbiased. He was the first person to feel the effects of it and his judgment of them was without any prior knowledge of hallucinogens. He had no idea that it would become a pleasure drug, abused by the masses, and thus he could see nothing inherently wrong with it. It was a frightening experience for him to be under the influence of LSD and he couldn’t imagine someone wanting to do this recreationally.

Hofmann’s first idea was that LSD-25 was be of tremendous value to the psychological and neurological fields. Because it affected the cognitive processes in such drastic and fundamental ways, the study of how it worked could inevitably lead to a greater understanding of how our minds worked in the first place.

When Hofmann tried to tell his colleagues about his discovery of the psychoactive effects of LSD-25, they didn’t believe him; this was due to the immense potency of the drug. That any drug should produce such profound effects in such a small dose--.25 mg--was utterly unbelievable. They urged him to check his measurements again and again, which Hofmann did, always obtaining the same results. Their doubts were finally satisfied when they each tried a sample of the drug, in only a fraction of amount Hofmann tried, and still got remarkable results. LSD was once again admitted into the experimental trials.

Some of the effects of LSD in the body can be measured. But the exact mechanism by which LSD affects thought processes is not well understood.

LSD is absorbed completely within the gastrointestinal tract. The lowest concentration of all the bodily organs is found in the brain, surprisingly, since this is where most of its action is observed. The psychic effects of LSD are present long after the drug can no longer be detected in the body--2 hours max., for the small intestine. Hofmann inferred that the drug is not active in and of itself, but that it triggers other mechanisms in the body that provoke such a condition which can continue after the instigator LSD is gone.

Pupilary dilation, increase in body temperature and rise in the blood-sugar level are also noted as physical effects of the drug, as well as uterine-constricting, which was known prior to extensive testing. LSD also blocks serotonin functioning in the brain. This was thought to be the explanation for the psychic effects of LSD for some time because serotonin plays an important role in emotions and psychic functions. However, there are other drugs which also display serotonin-blocking activities which have none of the psychic effects LSD does. That was therefore ruled out as a mechanism by which LSD works.

Once a chemical is found to have advantageous properties, a chemist must them synthesize various derivatives of that compound to search for other useful molecules. This is what was done with ergobasine which led to the synthesis of LSD. Next, this was done with LSD itself. Since it is impossible to tell if a substance is hallucinogenic or not from observing the effects on animals (although this can give indirect clues, no conclusive data is available by this means), Hofmann sacrificed once again--he and his colleagues performed more self-experiments. This had an edge of danger to it, naturally, because these were substances they knew nothing of, except what their chemical structure implied. None of them turned out to be poisonous, fortunately. None of them turned out to be as potent as LSD either. Several were hallucinogenic in much higher doses, but with different qualities to their narcosis. Still others had no noticeable effect.

One such derivative was found that had no hallucinogenic effects, but a much higher serotonin-blocking effect. Because serotonin is involved in the generation of a migraine, this derivative, bromo-LSD or BOL-148, is now used as a medicine for the treatment of migraines and is known as Sansert.

How did LSD become Albert Hofmann’s “problem child?” It had potential for psychotherapy uses and, from a purely academic point of view, it was a very interesting drug with unusual properties, worthy of study. How did its use get so out of hand?

One of the reasons is that it was such an unlikely candidate for abuse. It slipped in through the keyhole. Hofmann and others did not even conceive that it would be swept up in the mania of inebriating drug use because the effects it produced were so unlike other drugs abused at the time. It was not even taken into account that the general public would want to use for recreation a drug that caused such extreme mental disturbances.

What Hofmann had expected was curiosity from the artists of the community. Because this drug was so effectual at stimulating the imagination, he concluded that the painters, writers and performers would find most use of LSD. This prediction proved accurate. Besides that, mescaline had been in use in artistic and literary circles before the discovery of LSD and mescaline produces similar effects.

However, the stage was set when LSD came into being for it to become the drug of choice, as the media reported it to be. Drug use was on the rise and the hippie movement was up and coming. Albert Hofmann put the catalyst for widespread LSD use as materialism, alienation from nature through industrialization, purposelessness in a wealthy, saturated society, and other deep-rooted sociological problems that exist within the society at the time.

On top of this, the psychological testing of LSD was highly sensationalized by the media, reports being published in magazines and newspapers instead of scientific journals. The use of LSD by movie stars in theraputical settings was also widely reported and added to the allure of the drug.

But mostly, Tim Leary and Richard Alpert were the inciters of LSD use by the masses. Tim Leary encouraged kids to “Tune in, Turn on, and Drop out.” He was essentially urging youth to take LSD, discover their unity with the universe and drop out of society, abandoning their schooling and/or employment. Although Hofmann agreed with the usefulness Leary found in LSD, he wholly disapproved of his irresponsible distribution of LSD to the young and eager.

Adding to the problem of general, uninformed public use of LSD was that a lot of the LSD the public was using was black market LSD. LSD bought on the street in pills and crystals could be anything from PCP to cocaine. Often, many of the reports of bad trips and mishaps that were attributed to LSD may actually have been from impure black market LSD, which may not have been LSD at all.

Besides all this, LSD is a dangerous drug. Hofmann interprets it as an intensifier of psychic states already present. Therefore, people in unpleasant psychic states such as depression or fear can have intensely horrific experiences which can be ghastly and feel as if the psyche is on the brink of destruction, a type of psychic breakdown which can even lead to suicide.

LSD is also very dangerous for young people who have not fully developed their concepts of reality. When LSD challenges their underdeveloped concepts it introduces the threat of a person never maturing and acquiring a grip on what is real and what is not. This could leave juveniles feeling insecure and lost, Hofmann concludes.

Because of the above mentioned factors a virtual LSD hysteria ruled. Sandoz, being the corporate, responsible party for the public availability of the original LSD had to make a statement on the drug. It was their responsibility to act as the accountable party, and to give the final word on this drug that had caused such a mania in the public. This would release them from any obligation to people affected by the drug, by arresting its production and condemning its use by the public. On August 23, 1965, nearly 25 years after Albert Hofmann first synthesized what was thought to be a drug that would bring guidance and support to the psychology field, LSD’s production was halted (see Appendix II).

Hofmann’s experience with LSD could be likened to how a shaman in the rainforest would stumble onto a hallucinogenic plant. Both are analyzing the plants around them to see if they have healing properties. The fact that he always tested his medicaments on himself first also runs parallel to the experience of a shaman, who must go to the other side and back before he can heal the people on this side. Hofmann was looking for the good in the drugs he was synthesizing. Such a powerful drug to him must have looked like a powerfully healing drug. That it turned into his problem child was an unfortunate occurrence.

Thus Albert Hofmann’s tryst with LSD is brought to a close. His entanglement with hallucinogens was far from confined to LSD, however. Being an expert in the chemical structure of indole compounds, which are common to many hallucinogenic drugs, his knowledge was of use to others researching hallucinogens.

In 1966 a query came to Sandoz which inquired about their interest in carrying out the chemical investigation of Mexican hallucinogenic mushrooms. Research of the Mexican hallucinogenic mushroom teonanacatl was going on in the US and France, but these attempts to isolate the hallucinogenic compound were unsuccessful. Sandoz was asked, of course, because of their prior experience with the hallucinogenic drug LSD. Hofmann was eager to start on this work. This was the only other naturally occurring hallucinogen known to him at the time besides mescaline, as LSD is not found in plant tissue, to date.

Since he was the head of the natural products department at Sandoz, he wanted to assign the work to one of his coworkers, that he might oversee the research. No one, however, wanted to touch this assignment. Because of the bad reputation hallucinogens had gotten as a street drug, top management did not look highly upon that. Hofmann was of the opinion that enthusiasm is needed for a project to be successful, so he undertook the assignment himself.

Hofmann had a sample of mushrooms that had been cultivated in the laboratory. He and his assistant had no clues as to the what the active chemical was, so they were going on only what the effects of different extracts were on animals. Since the effects of hallucinogens on animals can be quite difficult to ascertain, Hofmann wasn’t even sure if the mushrooms they were administering were active at all. So, true to his image of a good research scientist, he performed a self-experiment, to certify whether the mushrooms were active or not.

Lo and behold, the mushrooms were active. After ingesting 2.4 grams of dried mushrooms Hofmann experienced a hallucinogenic state that lasted several hours, shorter than an LSD intoxication. Recognizing the fact that in order to determine if there were any other hallucinogenically active compounds within the mushrooms, the extracts would likewise have to be tested on human subjects. Wanting to continue his research, Hofmann accepted volunteers, coworkers and colleagues, to participate in the tests.

In 1958, the results of the investigations were published, including the identification of the active principles--psilocin and psilocybin and their respective chemical structures. Their synthetic synthesis was also published as it is much more efficient to synthesize these compounds that to extract them from mushrooms.

Psilocin and psilocybin are both very similar in structure to LSD and serotonin. They both block the action of serotonin as LSD does. In fact, their pharmacological effects in general are very similar to LSD, except for the dosage. LSD is much more potent than either psilocin or psilocybin and nearly 100 times the amount of LSD needs to be taken of psilocybin in human subjects to experience the same intensity of experience.

Soon after the chemical make-up of teonanactl had been demystified, Hofmann became interested in the elucidation of the chemical makeup of another Mexican hallucinogenic drug called ololiuhqui. Ololiuhqui is the Aztec name for the seeds of Turbina corymbosa or Ipomoea violacea, the morning glory.

Embarking on this study in 1959, Hofmann started with the hypothesis that the active chemical in the morning glory seeds would be in the group of the indole compounds as LSD, psilocybin, and psilocin were. Since this is only one group out of many, this idea was far from probable, and was in fact unlikely. This could be tested quite easily with the colorimetric reactions. With certain chemicals, indole compounds will turn bright blue. They performed the test, got a bright blue mixture, and showed that indole compounds were present.

Skilled in isolating these compounds from his experience with the ergot alkaloids, Albert Hofmann took no time at all to isolate the indole compounds and discern their identity. What he found was astonishing; the active principles in the seeds were lysergic acid derivatives that had already been tested and self-experimented with by Hofmann himself: lysergic acid amide, lysergic acid hydroxyethylamide, and alkaloids closely related to them.

When he presented these findings to the International Union for Pure and Applied Chemistry in 1960, nobody believed him. This was too much of a coincidence. Two factors were brought up against his findings. These were: (1) that it was likely that the ergot in his laboratory had contaminated the samples of ololiuhqui he had been testing and (2) that it was believed that the ergot alkaloids were restricted to the lower fungi. Hofmann admits, “It is indeed a very rare exception to find a characteristic group of substances [the ergot alkaloids] occurring in two divisions of the plant kingdom broadly separated in evolutionary history.”

Needless to say, but unexpected to Dr. Hofmann, after this discovery was published, sales of morning glory seeds boomed. It didn’t last long, however, because the effects were not as agreeable as the LSD had been, producing sensations of mental emptiness and often anxiety and depression.

At this juncture, Hofmann’s chemical studies of hallucinogen’s came to a logical conclusion, in his opinion. Having started off studying ergot alkaloids and ultimately synthesizing LSD in his own laboratory, he finally came to finding one of the very alkaloids he synthesized in the laboratory, in nature. The circle had closed.

His adventures were not over, however. Hofmann’s interest had been sparked by the use of hallucinogens by ancient cultures. He had his own ideas of the usefulness of hallucinogens in the proper setting, but in the use of teonanacatl and ololiuhqui he found this practice embedded in the culture for years past.

In 1962, in order to experience this first hand, he goes to Mazatec Country in Mexico to pursue the magic plant Ska Maria Pastora with his wife and Gordon Wasson, Hofmann’s colleague and a mushroom expert. All they knew of the plant was information that Wasson had obtained: the juice of leaves of a plant called Ska Maria Pastora (leaves of Mary the shepherdess) were expressed and were used among the Mazatec in medico-religious practices.

They met in Mexico city and set off to the Mazatec village of Jalapa de Diaz. After traveling several days on mules they arrived at Ayautla where they met a woman who was able to obtain for them samples of the plant. However these samples were incomplete and not suitable for botanical identification. Finally, in San Jose Tenango they met with another woman who was able to get them a bundle of the desired plant. Natividad Rosa, who had given them the plants would not agree to perform a ceremony, however, claiming to be too old to endure the effects of the plants. At least now they had a botanical specimen.

It was clear the plant was part of the Salvia genus. Because they knew the juices of the leaves contain the active principles, in good ethnobotanical fashion they preserved these chemicals by crushing the leaves on a stone plate, diluting the juice with alcohol and holding them in flasks till they could be studied later.

Before they had to leave, but long after they thought they would ever be lucky enough to be able to attend a ceremony involving this plant, they made a contact. A native woman brought them up a hill one night to take part in the ceremony. This had to be done under the cover of night so that no one would see them. It became obvious that the reason they had not been given the opportunity to see a ceremony was because it was taboo--even worthy of punishment--to divulge the secrets of this sacred custom.

The curandera’s, or medicine woman’s, name is Consuela Garcia and she invited them in her hut to take part in the ceremony. Wasson was to take part in the intoxicant part of the ceremony but Albert Hofmann, fond as he was of self-experimenting, could not participate as he had a stomach ache and was ill. His wife substituted for him.

The leaves were crushed and rinsed with water and the mix was drunk after answering affirmatively that the ceremony was holy and truthful. Some ceremonial recitations were spoken and prophetic questions were asked of the curandera. The ceremony was short, but before they left a thunderstorm broke out that delayed their departure. Finally they left, still shrouded by the cloak of night.

Taking part in this ceremony was the culmination of their field study of this plant. It confirmed that the plant was used in divination in much the same way that teonanactl was used. They also had obtained sufficient plant material for analysis and identification. Also, the inebriation of the drug was reported to be distinctly hallucinogenic by the experimenters, although its qualities differed from both psilocybin and LSD.

Next they visited Maria Sabina in Huautla. She had been the curandera with whom Wasson had first experienced teonanactl. With her they would have a mushroom ceremony using synthetically produced psilocybin in the form of pills containing 5.0 mg a piece. One pill, thus, was equal to eating two mushrooms.

The curandera would take the pills instead of real mushrooms in this ceremony so that it could be determined if the pills produced effects identical to the mushrooms; to see if the spirit of the mushrooms was present also in pills containing what the mushrooms contained.

Maria rationed out the pills, 2 pairs to herself and a few others who could take such a high dose. Others got one pair including Wasson, while his wife and another woman got only one pill. Because Hofmann was well by now, he wanted to experience the Ska Maria Pastora that he had not been able to at the previous ceremony, so this mixture was made and he took it.

After about a half an hour of waiting, Maria Sabina murmured that the pills lacked the spirit of the mushroom. Wasson and Hofmann could deduce that the pills took longer to produce an effect because an unmasticated pill was not as easily processed by the stomach as chewed up mushrooms in which some chemicals are even absorbed through the saliva in the mouth. For the pills it would just take a little longer. But rather than try to explain this complex process in a language native to neither of them, they decided to act. They gave her more pills, 2 more, her dosage now 30 mg. Just as predicted, after another fifteen minutes the drugs did start to take effect. Singing and prayer ensued for most of the night. Maria answered prophetic questions and the efficacy of the pills was proven.

Maria confirmed this when their party was departing. The pills had the same power as the mushrooms, she said. There was no difference.

Albert Hofmann’s journey with psychedelic drugs does not end here. He performs many more self-experiments, comparing the effects of LSD and psilocybin. He corresponds with artists and writers concerning the psychedelic experience. In short, the psychedelic experience is something that has made him think a lot about reality. He considers his discovery of LSD to be integral to the way he views life.

After much contemplation, Hofmann offers the most valuable realization he gained from experimenting with hallucinogens: “what one commonly takes as ‘the reality,’ including the reality of one’s own individual person, by no means signifies something fixed, but rather something the is ambiguous--that there is not only one, but that there are many realities, each comprising also a different consciousness of the ego.”

His experiments with LSD and other hallucinogenic drugs have brought Hofmann to rethink some basic concepts his reality was based on. His experiences with these drugs have significantly affected his life. He is 92 years old today and alive to see the repercussions of his work in society. Although similar compounds did exist before he came upon LSD, it is unlikely they would have received such wide attention as they did in the Western world. Although LSD brought many problems to our society today it also produced insight in people like Albert Hofmann, Aldous Huxley, Alan Watts and many other artists and writers alike. As hallucinogens instigated many art forms in Mexico, so they did in America and Europe. Although controversial, Albert Hofmann’s work was influential to our society today.

The Albert Hofmann Foundation was established in 1988 with the intent to preserve the earliest records of psychedelic activity, mainly highlighting the research of Dr. Albert Hofmann. They are a nonprofit, educational and research organization that hopes to open a library where all of the research done by Albert Hofmann and other scientists studying hallucinogenic drugs will be available to the public. In this way, the important information uncovered by Albert Hofmann will be accessible to every person so that they might be transported to that fateful day when he first experienced the effects of hallucinogenic drugs. In this way, every human is given the opportunity to see through his eyes the uncloaking of a substance whose power, for better or for worse, has yet to be fully tapped.







Bibliography

Hoffman, Albert “LSD: My Problem Child” St. Martin’s Press: New York 1983.

Schultes, Richard Evans and Albert Hofmann “The Botany and Chemistry of Hallucinogens” Charles C. Thomas Publisher: Springfield, IL 1980.

“Postulated Mechanisms of LSD” by Ian Leicht. http://www.cs.hmc.edu/~ivl/text/lsd/

Albert Hofmann Foundation. Robert Brettin, President. http://www.hofmann.org








Appendix I

Albert Hofmann’s self report of self experiment with LSD-25 from “LSD: My Problem Child” pp. 16-19

Here the notes in my laboratory journal cease. I was able to write the last words only with great effort. By now it was already clear to me that LSD had been the cause of the remarkable experience of the previous Friday, for the altered perceptions were of the same type as before, only much more intense. I had to struggle to speak intelligibly. I asked my laboratory assistant, who was informed of the self-experiment, to escort me home. We went by bicycle, no automobile being available because of wartime restrictions on their use. On the way home, my condition began to assume threatening forms. Everything in my field of vision wavered and was distorted as if seen in a curved mirror. I also had the sensation of being unable to move from the spot. Nevertheless, my assistant later told me that we had traveled very rapidly. Finally, we arrived

at home safe and sound, and I was just barely capable of asking my companion to summon our family doctor and request milk from the neighbors.

In spite of my delirious, bewildered condition, I had brief periods of clear and effective thinking - and chose milk as a nonspecific antidote for poisoning.

The dizziness and sensation of fainting became so strong at times that I could no longer hold myself erect, and had to lie down on a sofa. My surroundings had now transformed themselves in more terrifying ways. Everything in the room spun around, and the familiar objects and pieces of furniture assumed grotesque, threatening forms. They were in continuous motion, animated, as if driven by an inner restlessness. The lady next door, whom I scarcely recognized, brought me milk - in the course of the evening I drank more than two liters. She was no longer Mrs. R., but rather a malevolent, insidious witch with a colored mask.

Even worse than these demonic transformations of the outer world, were the alterations that I perceived in myself, in my inner being. Every exertion of my will, every attempt to put an end to the disintegration of the outer world and the dissolution of my ego, seemed to be wasted effort. A demon had invaded me, had taken possession of my body, mind, and soul. I jumped up and screamed, trying to free myself from him, but then sank down again and lay helpless on the sofa. The substance, with which I had wanted to experiment, had vanquished me. It was the demon that scornfully triumphed over my will. I was seized by the dreadful fear of going insane. I was taken to another world, another place, another time. My body seemed to be without sensation, lifeless, strange. Was I dying? Was this the transition? At times I believed myself to be outside my body, and then perceived clearly, as an outside observer, the complete tragedy of my situation. I had not even taken leave of my family (my wife, with our three children had traveled that day to visit her parents, in Lucerne). Would they ever understand that I had not experimented thoughtlessly, irresponsibly, but rather with the utmost caution, and that such a result was in no way foreseeable? My fear and despair intensified, not only because a young family should lose its father, but also because I dreaded leaving my chemical research work, which meant so much to me, unfinished in the midst of fruitful, promising development. Another reflection took shape, an idea full of bitter irony: if I was now forced to leave this world prematurely, it was because of this Lysergic acid diethylamide that I myself had brought forth into the world.

By the time the doctor arrived, the climax of my despondent condition had already passed. My laboratory assistant informed him about my self experiment, as I myself was not yet able to formulate a coherent sentence. He shook his head in perplexity, after my attempts to describe the mortal danger that threatened my body. He could detect no abnormal symptoms other than extremely dilated pupils. Pulse, blood pressure, breathing were all normal. He saw no reason to prescribe any medication. Instead he conveyed me to my bed and stood watch over me. Slowly I came back from a weird, unfamiliar world to reassuring everyday reality. The horror softened and gave way to a feeling of good fortune and gratitude, the more normal perceptions and thoughts returned, and I became more confident that the danger of insanity was conclusively past.

Now, little by little I could begin to enjoy the unprecedented colors and plays of shapes that persisted behind my closed eyes. Kaleidoscopic, fantastic images surged in on me, alternating, variegated, opening and then closing themselves in circles and spirals, exploding in colored fountains, rearranging and hybridizing themselves in constant flux. It was particularly remarkable how every acoustic perception, such as the sound of a door handle or a passing automobile, became transformed into optical perceptions. Every sound generated a vividly changing image, with its own consistent form and color.

Late in the evening my wife returned from Lucerne. Someone had informed her by telephone that I was suffering a mysterious breakdown. She had returned home at once, leaving the children behind with her parents. By now, I had recovered myself sufficiently to tell her what had happened.

Exhausted, I then slept, to awake next morning refreshed, with a clear head, though still somewhat tired physically. A sensation of well-being and renewed life flowed through me. Breakfast tasted delicious and gave me extraordinary pleasure. When I later walked out into the garden, in which the sun shone now after a spring rain, everything glistened and sparkled in a fresh light. The world was as if newly created. All my senses vibrated in a condition of highest sensitivity, which persisted for the entire day.

Appendix II

Decision Regarding LSD-25 and Other Hallucinogenic substances

More than twenty years have elapsed since the discovery by Albert Hofmann of LSD 25 in the SANDOZ Laboratories. Whereas the . fundamental importance of this discovery may be assessed by its impact on the development of modern psychiatric research, it must be recognized that it placed a heavy burden of responsibility on SANDOZ, the owner of this product.

The finding of a new chemical with outstanding biological properties, apart from the scientific success implied by its synthesis, is usually the first decisive step toward profitable development of a new drug. In the case of LSD, however, it soon became clear that, despite the outstanding properties of this compound, or rather because of the very nature of these qualities, even though LSD was fully protected by SANDOZ-owned patents since the time of its first synthesis in 1938, the usual means of practical exploitation could not be envisaged.

On the other hand, all the evidence obtained following the initial studies in animals and humans carried out in the SANDOZ research laboratories pointed to the important role that this substance could play as an investigational tool in neurological research and in psychiatry.

It was therefore decided to make LSD available free of charge to qualified experimental and clinical investigators all over the world. This broad research approach was assisted by the provision of any necessary technical aid and in many instances also by financial support.

An enormous amount of scientific documents, published mainly in the international biochemical and medical literature and systematically listed in the "SANDOZ Bibliography on LSD" as well as in the "Catalogue of Literature on Delysid" periodically edited by SANDOZ, gives vivid proof of what has been achieved by following this line of policy over nearly two decades. By exercising this kind of "nobile offlcium" in accordance with the highest standards of medical ethics with all kinds of self-imposed precautions and restrictions, it was possible for many years to avoid the danger of abuse (i.e., use by people neither competent nor qualified), which is always inherent in a compound with exceptional CNS activity.

In spite of all our precautions, cases of LSD abuse have occurred from time to time in varying circumstances completely beyond the control of SANDOZ. Very recently this danger has increased considerably and in some parts of the world has reached the scale of a serious threat to public health. This state of affairs has now reached a critical point for the following reasons: (1) A worldwide spread of misconceptions of LSD has been caused by an increasing amount of publicity aimed at provoking an active interest in laypeople by means of sensational stories and statements; (2) In most countries no adequate legislation exists to control and regulate the production and distribution of substances like LSD; (3) The problem of availability of LSD, once limited on technical grounds, has fundamentally changed with the advent of mass production of lysergic acid by fermentation procedures. Since the last patent on LSD expired in 1963, it is not surprising to find that an increasing number of dealers in fine chemicals are offering LSD from unknown sources at the high price known to be paid by LSD fanatics.

Taking into consideration all the above-mentioned circumstances and the flood of requests for LSD which has now become uncontrollable, the pharmaceutical management of SANDOZ has decided to stop immediately all further production and distribution of LSD. The same policy will apply to all derivatives or analogues of LSD with hallucinogenic properties as well as to Psilocybin, Psilocin, and their hallucinogenic congeners.