Karger Gazette No 71> Swiss Pioneers in Science and Medicine
The chance discovery of LSD's psychotropic effects unleashed a controversy that continues to this day.
D. Paterson
In northwestern Switzerland, where the river Rhine turns right to begin the important business of separating France from Germany, sits the city of Basel. The peaked roofs and church spires of its old town center are an unlikely backdrop for the birth of one of the most controversial drugs of the 20th century, but just beyond the medieval cathedral and city hall stand the chimneys and office blocks of the city's globally important pharmaceutical industry. It was in one of these buildings in 1938 that the chemist Albert Hofmann first synthesized a compound called lysergic acid diethylamide, a compound that would come to be known as LSD.
In the 1930s Hofmann was working for the pharmaceutical division of Sandoz (now part of Novartis), which was investigating the ingredients of traditional remedies to isolate and synthesize their active components. Hofmann was looking at the fungus ergot of rye (Claviceps purpurea), which had been used to induce childbirth since the 16th century. Ergot's alkaloids, which were based around a lysergic acid core, were known to have physiological activity, so Hofmann began synthesizing lysergic acid derivatives. In 1938 he synthesized his 25th lysergic acid amine - in German called Lysergsäure-diäthylamid-25, or LSD-25. From its structure Hofmann thought it might have activity as a circulatory respiratory stimulant, but Sandoz's pharmacologists found nothing remarkable and so LSD-25 was quietly filed away.
But it was not forgotten. Hofmann had what he termed a 'peculiar presentiment' and, in 1943, on a hunch that LSD-25 could have secrets it did not yield on first inspection, he decided to take another look.
Bicycle Day
Hofmann returned to LSD-25 in the hope of finding some physiological property that could hint at a medicinal use for the drug. What he found was one of the most powerful psychoactive drugs ever created by man - and he found out firsthand. During his second synthesis of LSD-25, a small amount of it somehow came into contact with his skin, and Albert Hofmann became the first person in history to go on an acid trip. He quickly entered a dreamlike state, which he described as 'an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors.'
After he had recovered his senses, Hofmann realized that LSD-25 had strange and powerful properties. Fascinated by his experience, three days later he began what he thought would be a controlled LSD experiment on himself. Unaware of the drug's extreme potency, Hofmann swallowed 0.25 mg of LSD, a huge overdose by today's standards, and sat down to record his experiences in his laboratory journal. This attempt at scientific rigor was wildly optimistic: Hofmann wrote only a few words before being overwhelmed by the effects of the drug. He became anxious, started experiencing paralysis and began seeing things. Hofmann's presumably alarmed lab assistant then had the unenviable task of getting his delirious boss home on a bicycle (wartime petrol rationing precluding the use of infinitely more practical forms of motorized transport).
Once home, the turmoil in Hofmann's head intensified, and he experienced a succession of delusions that ranged from acute irrational fears to rather pleasant tableaus of colorful images. Remarkably, a doctor could find nothing physically amiss, except Hofmann's by then extremely dilated pupils. Even more incredibly, when Hofmann awoke the next morning, he felt fine and could remember everything.
Albert Hofmann showing a model of the molecule LSD (ca. 1950). Courtesy of
Norvartis Company Archives.
Psychedelic Dream
Sandoz quickly realized that such a drug could have therapeutic potential in psychiatry and soon made LSD available to clinical researchers. From today's standpoint, in a world where governments speak of LSD in the same breath as heroin, it seems remarkable that it was first greeted by the mental health community as a potential therapy or useful research tool.
Psychiatrists saw in it the potential to bring about a 'model psychosis' in healthy patients that could be used to study schizophrenia, while psychoanalysts became interested in its apparent ability to give insights into a person's unconscious.
During the 1950s several hundred research articles on LSD appeared in the medical literature, most of them positive and reporting few ill effects. Some research groups even saw startlingly strong results in using LSD to treat alcoholism.
However, this period in the sun would not last long. Lacking today's strict controls on clinical trials, LSD soon found its way out of the research setting and into recreational use, first among artists and intellectuals - notably Brave New World author Aldous Huxley, a personal friend of Hofmann - and then on university campuses. By the 1960s a thriving black market in LSD had sprung up and newspapers began running lurid stories of mayhem wrought during uncontrolled LSD binges. By the middle of the decade Sandoz had ended production of the drug and, in 1966, the death-knell for legitimate LSD use was sounded when the USA, UK, Netherlands, France and Canada banned it.
When Hofmann discovered LSD's properties he had hoped it would find use as a therapy. He was also interested in its ability to induce a transcendental state and was open to the possibility of using it to gain new perspectives on the world. But Hofmann never thought LSD would become popular as a party drug and he frowned upon what he termed this 'profane application'. Speaking in 1993 at a symposium to mark the 50th anniversary of LSD, he said: 'What I never would have expected for the future of LSD was that it would ever find application as a pleasure drug on a large scale, considering the demonic, terrifying effects I had also experienced in my first self-experiment.'
Throughout his life Hofmann maintained an interest in the powerful effects of psychoactive drugs, particularly those used in ancient cultures. He became interested in the sacred drugs of pre-Columbian Mexico and found both the 'magic' mushroom teonanacatl and ololiuqui, the Aztec name for seeds from the morning glory plant family, contained compounds structurally similar to LSD.
Flashback to the Future
Although LSD has now been in the scientific wilderness for more than 40 years, Hofmann lived to see the first tentative signs of a government re-think before his death at the age of 102. Organizations such as the Multidisciplinary Association for Psychedelic Studies in the USA and the Beckley Foundation in the UK pressure governments to alter their outright bans on LSD and allow its use in medicinal research. In the last few years they have seen their first successes.
Amanda Feilding, Lady Neidpath, who is director of the Beckley Foundation, says: 'I visited Albert Hofmann when he was 99 and promised him that for his 100th birthday I would give him a present worthy of such an occasion: approval for the first scientific research on LSD using human subjects.'
The foundation did not quite make that date, but in 2007 it, together with the University of California Berkeley, received the go-ahead to start limited LSD research. The Beckley Foundation is currently supporting two studies, one in the USA looking at the effect of LSD on brain connectivity and creativity, and one in Switzerland looking at the use of LSD to ease anxiety among the terminally ill.
Among the aims of the foundation are the re-establishment of LSD as a tool for exploring consciousness and as a possible treatment for conditions such as cluster headaches. Lady Neidpath adds: 'Most medical practitioners still view LSD with suspicion, but there seems to be a stirring of interest in some quarters.'
Further Reading
Engel G, Herrling P (eds): Exploring the Frontiers: in Celebration of Albert Hofmann's 100th Birthday. Basel, Schwabe, 2006.
Hofmann A: LSD: My Problem Child. Santa Cruz, MAPS, 2005.
Pletscher A, Ladewig D (eds): 50 Years of LSD: Current Status and Perspectives of Hallucinogens. New York, Parthenon, 1994.
David Paterson is an editor of the Karger Gazette
| Testing the Acid: The Unlikely Birth of LSD  Albert Hofmann (1906–2008) |  |
D. Paterson
In northwestern Switzerland, where the river Rhine turns right to begin the important business of separating France from Germany, sits the city of Basel. The peaked roofs and church spires of its old town center are an unlikely backdrop for the birth of one of the most controversial drugs of the 20th century, but just beyond the medieval cathedral and city hall stand the chimneys and office blocks of the city's globally important pharmaceutical industry. It was in one of these buildings in 1938 that the chemist Albert Hofmann first synthesized a compound called lysergic acid diethylamide, a compound that would come to be known as LSD.
In the 1930s Hofmann was working for the pharmaceutical division of Sandoz (now part of Novartis), which was investigating the ingredients of traditional remedies to isolate and synthesize their active components. Hofmann was looking at the fungus ergot of rye (Claviceps purpurea), which had been used to induce childbirth since the 16th century. Ergot's alkaloids, which were based around a lysergic acid core, were known to have physiological activity, so Hofmann began synthesizing lysergic acid derivatives. In 1938 he synthesized his 25th lysergic acid amine - in German called Lysergsäure-diäthylamid-25, or LSD-25. From its structure Hofmann thought it might have activity as a circulatory respiratory stimulant, but Sandoz's pharmacologists found nothing remarkable and so LSD-25 was quietly filed away.
But it was not forgotten. Hofmann had what he termed a 'peculiar presentiment' and, in 1943, on a hunch that LSD-25 could have secrets it did not yield on first inspection, he decided to take another look.
 Ergot of rye: © Novartis Company Archives. |
Bicycle Day
Hofmann returned to LSD-25 in the hope of finding some physiological property that could hint at a medicinal use for the drug. What he found was one of the most powerful psychoactive drugs ever created by man - and he found out firsthand. During his second synthesis of LSD-25, a small amount of it somehow came into contact with his skin, and Albert Hofmann became the first person in history to go on an acid trip. He quickly entered a dreamlike state, which he described as 'an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors.'
After he had recovered his senses, Hofmann realized that LSD-25 had strange and powerful properties. Fascinated by his experience, three days later he began what he thought would be a controlled LSD experiment on himself. Unaware of the drug's extreme potency, Hofmann swallowed 0.25 mg of LSD, a huge overdose by today's standards, and sat down to record his experiences in his laboratory journal. This attempt at scientific rigor was wildly optimistic: Hofmann wrote only a few words before being overwhelmed by the effects of the drug. He became anxious, started experiencing paralysis and began seeing things. Hofmann's presumably alarmed lab assistant then had the unenviable task of getting his delirious boss home on a bicycle (wartime petrol rationing precluding the use of infinitely more practical forms of motorized transport).
Once home, the turmoil in Hofmann's head intensified, and he experienced a succession of delusions that ranged from acute irrational fears to rather pleasant tableaus of colorful images. Remarkably, a doctor could find nothing physically amiss, except Hofmann's by then extremely dilated pupils. Even more incredibly, when Hofmann awoke the next morning, he felt fine and could remember everything.
Albert Hofmann showing a model of the molecule LSD (ca. 1950). Courtesy of
Norvartis Company Archives.
Psychedelic Dream
Sandoz quickly realized that such a drug could have therapeutic potential in psychiatry and soon made LSD available to clinical researchers. From today's standpoint, in a world where governments speak of LSD in the same breath as heroin, it seems remarkable that it was first greeted by the mental health community as a potential therapy or useful research tool.
Psychiatrists saw in it the potential to bring about a 'model psychosis' in healthy patients that could be used to study schizophrenia, while psychoanalysts became interested in its apparent ability to give insights into a person's unconscious.
During the 1950s several hundred research articles on LSD appeared in the medical literature, most of them positive and reporting few ill effects. Some research groups even saw startlingly strong results in using LSD to treat alcoholism.
However, this period in the sun would not last long. Lacking today's strict controls on clinical trials, LSD soon found its way out of the research setting and into recreational use, first among artists and intellectuals - notably Brave New World author Aldous Huxley, a personal friend of Hofmann - and then on university campuses. By the 1960s a thriving black market in LSD had sprung up and newspapers began running lurid stories of mayhem wrought during uncontrolled LSD binges. By the middle of the decade Sandoz had ended production of the drug and, in 1966, the death-knell for legitimate LSD use was sounded when the USA, UK, Netherlands, France and Canada banned it.
When Hofmann discovered LSD's properties he had hoped it would find use as a therapy. He was also interested in its ability to induce a transcendental state and was open to the possibility of using it to gain new perspectives on the world. But Hofmann never thought LSD would become popular as a party drug and he frowned upon what he termed this 'profane application'. Speaking in 1993 at a symposium to mark the 50th anniversary of LSD, he said: 'What I never would have expected for the future of LSD was that it would ever find application as a pleasure drug on a large scale, considering the demonic, terrifying effects I had also experienced in my first self-experiment.'
Throughout his life Hofmann maintained an interest in the powerful effects of psychoactive drugs, particularly those used in ancient cultures. He became interested in the sacred drugs of pre-Columbian Mexico and found both the 'magic' mushroom teonanacatl and ololiuqui, the Aztec name for seeds from the morning glory plant family, contained compounds structurally similar to LSD.
Flashback to the Future
Although LSD has now been in the scientific wilderness for more than 40 years, Hofmann lived to see the first tentative signs of a government re-think before his death at the age of 102. Organizations such as the Multidisciplinary Association for Psychedelic Studies in the USA and the Beckley Foundation in the UK pressure governments to alter their outright bans on LSD and allow its use in medicinal research. In the last few years they have seen their first successes.
Amanda Feilding, Lady Neidpath, who is director of the Beckley Foundation, says: 'I visited Albert Hofmann when he was 99 and promised him that for his 100th birthday I would give him a present worthy of such an occasion: approval for the first scientific research on LSD using human subjects.'
The foundation did not quite make that date, but in 2007 it, together with the University of California Berkeley, received the go-ahead to start limited LSD research. The Beckley Foundation is currently supporting two studies, one in the USA looking at the effect of LSD on brain connectivity and creativity, and one in Switzerland looking at the use of LSD to ease anxiety among the terminally ill.
Among the aims of the foundation are the re-establishment of LSD as a tool for exploring consciousness and as a possible treatment for conditions such as cluster headaches. Lady Neidpath adds: 'Most medical practitioners still view LSD with suspicion, but there seems to be a stirring of interest in some quarters.'
Further Reading
Engel G, Herrling P (eds): Exploring the Frontiers: in Celebration of Albert Hofmann's 100th Birthday. Basel, Schwabe, 2006.
Hofmann A: LSD: My Problem Child. Santa Cruz, MAPS, 2005.
Pletscher A, Ladewig D (eds): 50 Years of LSD: Current Status and Perspectives of Hallucinogens. New York, Parthenon, 1994.
David Paterson is an editor of the Karger Gazette
 © 2010, S. Karger AG, Basel. All rights reserved. |
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