LSD: My Problem Child
This post originally appeared on Blossom Analysis.
LSD: My Problem Child by Albert Hofmann recounts the discovery, first trip, and dissemination of LSD from the perspective of its discoverer. The book describes the chemical history, the subsequent trouble with it leaving the lab, and Hofmann’s perspective on the effects LSD elicits.
In the forward, Hofmann describes his childhood mystical experience and how it may be a solution to the spiritual crisis befalling the (Western) world.
“It is my desire in this book to give a comprehensive picture of LSD, its origin, its effects, and its dangers, in order to guard against increasing abuse of this extraordinary drug. I hope thereby to emphasize possible uses of LSD that are compatible with its characteristic action. I believe that if people would learn to use LSD’s vision-inducing capability more wisely, under suitable conditions, in medical practice and in conjunction with meditation, then in the future this problem child could become a wonder child.”
Chapter 1 – How LSD Originated
LSD was not discovered by accident, or at least not as is told in popular lore. Hofmann made the substance (LSD-25) on purpose as part of the research his lab (Sandoz) was doing. It was only by accident that he first discovered the psychedelic effects (by not carefully handling the substances).
The first chapter recounts his early work on ergots (fungi that grows on rye and similar plants). Hofmann also corrects another urban myth:
“Until recent times, epidemic-like outbreaks of ergot poisoning have been recorded in most European countries including certain areas of Russia. With progress in agriculture, and since the realization, in the seventeenth century, that ergot-containing bread was the cause, the frequency and extent of ergotism epidemics diminished considerably. The last great epidemic occurred in certain areas of southern Russia in the years 1926-27. [The mass poisoning in the southern French city of Pont-St. Esprit in the year 1951, which many writers have attributed to ergot-containing bread, actually had nothing to do with ergotism. It rather involved poisoning by an organic mercury compound that was utilized for disinfecting seed.]”
Ergots have been used as medicines since mid 1582 (first documented) but chemical analysis of the active substances took until 1907.
Hofmann’s research found it’s way to lysergic acid (“precursor for a wide range of ergoline alkaloids that are produced by the ergot fungus“). He first made LSD-25 in 1938, but based on a hunch, he resynthesized it in 1943. During this process he possibly had a bit of the substance touch his skin during crystallization. The amount of LSD needed for a subjective effect should be very small, Hofmann deduced. To investigate further her planned a self-experiment with 0.25 mg or 250 mcg/μg.
That day, 19 April 1943, he cycled home (Bicycle Day) in crisis and the report can be described as the first bad trip.
The chapter is concluded with the following observation.
“I was aware that LSD, a new active compound with such properties, would have to be of use in pharmacology, in neurology, and especially in psychiatry, and that it would attract the interest of concerned specialists. But at that time I had no inkling that the new substance would also come to be used beyond medical science, as an inebriant in the drug scene. Since my self-experiment had revealed LSD in its terrifying, demonic aspect, the last thing I could have expected was that this substance could ever find application as anything approaching a pleasure drug. I failed, moreover, to recognize the meaningful connection between LSD inebriation and spontaneous visionary experience until much later, after further experiments, which were carried out with far lower doses and under different conditions.”
Chapter 2 – LSD in Animal Experiments and Biological Research
Many experiments on animals were done to test the effects and toxicity of LSD. Hofmann notes that the effects are most pronounced in the ‘higher’ parts of the brain and significant dosages were needed to elicit effects in ‘lower’ animals. One interesting observation is that at a certain dosage the webs of spiders were better proportioned than normal, but distorted at higher dosages.
The dosage that kills half of the subjects (LD50) of LSD is 50-60 mg/kg for a mouse and 0.3mg/kg (300μg/kg) for rabbits. One elephant was given 0.3g of LSD and died a few minutes later, estimating (n=1) the lethal dosage at 60μg/kg.
Extrapolating that data to humans means that the range from effective (0.0003-0.001 mg/kg) to deadly dosage is about 300-600 fold. This low toxicity is also confirmed in a study by Haden & Woods (2020) that looked at three reports in which one person took up to 55mg (55.000μg, or 785μg/kg at 70kg) and lived to tell the tale (and even could stop a pain medication she was taking before).
LSD is absorbed completely through the gastrointestinal tract and thus injection won’t make the effects stronger. Hofmann also states that the molecules themselves are gone within a much quicker timeframe than 10-12 hours, the time the psychological/psychedelic effects persist. He states that the effects are of other mechanisms that LSD sets of. The dopamine and serotonin neurological functions are influenced by LSD.
See the research papers database on LSD for more on this topic.
Chapter 3 – Chemical Modifications of LSD
Chemical modification (looking for more valuable active properties or improved activity) was conducted on LSD. No other form was more active, most not being active at even 20 times the dosage. This was a feature that, together with the anti-inflammatory effect, led to the discovery and use of bromo-LSD (BOL-148) and Deseril/Sansert.
Chapter 4 – Use of LSD in Psychiatry
This chapter recounts the early use of LSD in psychiatry and a trip report by a self-experiment of a psychiatrist. The effects are compared to that of mescaline.
Sandoz then made LSD available under the trade name Delysid (D-Lysergsäure-diäthylamid), with the following disclaimer/description of properties:
“The administration of very small doses of Delysid (1/2-2 µg/kg body weight) results in transitory disturbances of affect, hallucinations, depersonalization, reliving of repressed memories, and mild neurovegetative symptoms. The effect sets in after 30 to 90 minutes and generally lasts 5 to 12 hours. However, intermittent disturbances of affect may occasionally persist for several days.” … “Pathological mental conditions may be intensified by Delysid. Particular caution is necessary in subjects with a suicidal tendency and in those cases where a psychotic development appears imminent. The psycho-affective liability and the tendency to commit impulsive acts may occasionally last for some days. Delysid should only be administered under strict medical supervision. The supervision should not be discontinued until the effects of the drug have completely worn off.”
The (partial) loss of ego (“egocentric problem cycle“) and heightened susceptibility to the influence of the psychotherapists were two features that made LSD a potential ally during psychotherapy. This was utilized in two different ways, 1) psychotytic therapy (Europe, moderate dosage, repeated), and 2) psychedelic therapy (US, high dose, one-time).
Another way that LSD could be used was to study psychoses. Hofmann notes that LSD doesn’t elicit a true psychosis (the effects are different), but that it may still shed light on the biochemical origin of it.
Chapter 5 – From Remedy to Inebriant
“During the first years after its discovery, LSD brought me the same happiness and gratification that any pharmaceutical chemist would feel on learning that a substance he or she produced might possibly develop into a valuable medicament. For the creation of new remedies is the goal of a pharmaceutical chemist’s research activity; therein lies the meaning of his or her work.”
Alas, after that LSD became a beacon of the counter culture and it became a ‘problem child’ for Hofmann. The widespread usage (in the millions of dosages in the US alone) was not what he expected of such a strange drug. Subsequently, he (and other labs) had to work with health authorities on work that didn’t contribute to scientific discoveries. Sandoz eventually stops its distribution of LSD in 1965.
Hofmann stresses the dangers of LSD when not used in a medical context. As noted before, the drug is not toxic by itself, but psychologically it can be very harmful when taken outside the right set and setting. And LSD made and sold outside the (official) lab isn’t always LSD (accidental or on purpose).
Hofmann profiles Timothy Leary and a meeting between the two men on September 3rd, 1971. It was amicable but the two men didn’t see eye to eye on the need for widespread use (abuse?) of LSD.
“My impression of Dr. Leary in this personal meeting was that of a charming personage, convinced of his mission, who defended his opinions with humor yet uncompromisingly; a man who truly soared high in the clouds pervaded by beliefs in the wondrous effects of psychedelic drugs and the optimism resulting therefrom, and thus a man who tended to underrate or completely overlook practical difficulties, unpleasant facts, and dangers. Leary also showed carelessness regarding charges and dangers that concerned his own person, as his further path in life emphatically showed.”
The last part of the chapter is devoted to a sample of trip reports on LSD that captures but a small part of the possible experiences one can have with the substance.
Chapter 6 – The Mexican Relatives of LSD
Psychedelic (magic, teonanácatl) mushrooms have been part of South American culture for centuries. Hofmann recounts a short history and makes the link to how Psilocybe mexicana eventually found its way to his lab.
After failing to see effects in mice or dogs, Hofmann did a self-experiment with 2.4g of dried mushrooms (a moderate/high dosage). The following trip report took on a distinctly Mexican character.
“This self-experiment showed once again that human beings react much more sensitively than animals to psychoactive substances. We had already reached the same conclusion in experimenting with LSD on animals, as described in an earlier chapter of this book. It was not inactivity of the mushroom material, but rather the deficient reaction capability of the research animals vis-à-vis such a type of active principle, that explained why our extracts had appeared inactive in the mouse and dog.”
Eventually, his lab extracted two active principles, named psilocybin and psilocin (to which the former metabolizes). There are now many more active compounds identified, of which you can find more information on Psychedelic Science Review (compounds).
Another psychedelic was investigated, seeds named ololiuhqui (morning glory seeds). After describing the origin and history, Hofmann describes their final findings:
“Lysergic acid amide, lysergic acid hydroxyethylamide, and alkaloids closely related to them chemically were established as the main active principles of ololiuhqui. Also present was the alkaloid ergobasine, whose synthesis had constituted the starting point of my investigations on ergot alkaloids. Lysergic acid amide and lysergic acid hydroxyethylamide, active principles of ololiuhqui, are chemically very closely related to lysergic acid diethylamide (LSD), which even for the non-chemist follows from the names.”
The coincidence that similar molecules were found in such different plants and fungi was something that was difficult to believe by his peers. But, me speaking here, if looked through an evolutionary lens, it may not be that unusual. Even something as complex as the eye has evolved tens of times and over the history of evolution it may be less surprising for these ‘coincidences’ to happen. For a deeper understanding on this topic I would recommend Dawkins and Dennett (amongst others) to read.
R. Gordon Wasson, whom Hofmann had been in contact since the investigations with magic mushrooms, invites him and his wife on an expedition to Mexico in the fall of 1962. On the expedition, they hope to find the plants (and molecules) behind the leaves of ‘Mary the shepherdess’ (hojas de la Pastora). It is eventually identified and named Salvia divinorum.
They eventually do and also find a curandera that is able to host a ceremony for them (as at that time it was taboo to give it to non-locals). The trip (not enjoyed by Hofmann because of an earlier upset stomach) was shorter but still similar to other psychedelics.
On the way back the party visits María Sabina, who earlier became famous after Gordon Wasson’s publication about her. There they consume the psilocybin pills they brought along and Hofmann enjoys a delayed trip with the hojas de la Pastora.
“María Sabina had said that the pills lacked the spirit of the mushrooms. I discussed the situation with Gordon, who lay beside me. For us, it was clear that absorption of the active principle from the pills, which must first dissolve in the stomach, occurs more slowly than from the mushrooms, in which some of the active principle already becomes absorbed through the mucous membranes during chewing. But how could we give a scientific explanation under such conditions? Rather than try to explain, we decided to act. We distributed more pills. Both curanderas and the curandero each received another pair. They had now each taken a total dosage of 30 mg psilocybin. After about another quarter of an hour, the spirit of the pills did begin to yield its effects, which lasted until the crack of dawn. The daughters, and Don Aurelio with his deep bass voice, fervently answered the prayers and singing of the curandera. Blissful, yearning moans of Apolonia and Aurora, between singing and prayer, gave the impression that the religious experience of the young women in the drug inebriation was combined with sensual-sexual feelings. In the middle of the ceremony, María Sabina asked for our request. Gordon inquired again after the health of his daughter and grandchild. He received the same good information as from the curandera Consuela. Mother and child were in fact well when he returned home to New York. Obviously, however, this still represents no proof of the prophetic abilities of both curanderas.”
“As we took leave of María Sabina and her clan at the crack of dawn, the curandera said that the pills had the same power as the mushrooms, that there was no difference. This was a confirmation from the most competent authority, that the synthetic psilocybin is identical with the natural product. As a parting gift I let María Sabina have a vial of psilocybin pills. She radiantly explained to our interpreter Herlinda that she could now give consultations even in the season when no mushrooms grow.”
Hofmann ends the chapter with a reflection on both the good and bad that has followed from the opening up about psychedelic compounds. On the one hand, it may/has/will help with scientific discoveries and mental health disorders. On the other hand, the tourism resulting from it hasn’t always been favorable and a part of the ancient customs may therefore get lost.
Chapter 7 – Radiance from Ernst Jünger
The last chapters of the book take a more personal tone. They describe how the substances and meetings with others on this topic have helped solve questions that Hofmann personally had.
This chapter recounts his inspiration from, and interaction with, the writer Ernst Jünger. The starting point was his book ‘Das Abenteuerliche Herz’. Subsequently, they correspond over letters and even have an LSD trip together in February 1951 and a comparison with psilocybin in 1962. On the latter, Hofmann notes: “The mushroom substance had carried all four of us off, not into luminous heights, rather into deeper regions. It seems that the psilocybin inebriation is more darkly colored in the majority of cases than the inebriation produced by LSD. The influence of these two active substances is sure to differ from one individual to another.”
Chapter 8 – Meeting With Aldous Huxley
Hofmann describes his meetings with Aldous Huxley, the author of (amongst other great books) The Doors of Perception and Heaven and Hell. They conversed about psychedelics, their usefulness, and need to differentiate them from other ‘drugs’. The book ‘Island’ was inspired (in part) by Huxley’s meeting with Hofmann.
Mirroring the death of other psychedelic pioneers, Huxley went out tripping: “In the morning, when he was already so weak that he could no longer speak, he had written on a sheet of paper: “LSD—try it—intramuscular—100 mmg.” Mrs. Huxley understood what was meant by this, and ignoring the misgivings of the attending physician, she gave him, with her own hand, the desired injection-she let him have the moksha medicine.”
Chapter 9 – Correspondence with the Poet-Physician Walter Vogt
This chapter recounts the written correspondence with the physician, psychiatrist, and writer Walter Vogt.
Chapter 10 – Various Visitors
This second to last chapter describes various interesting meetings with people Hofmann graciously received at his house. As the discoverer of LSD, he saw it as his duty to meet with those coming to find answers, relate a story, or meet the man behind the molecule. Most of those interactions were positive, as were the visitors’ experiences with LSD.
Chapter 11 – LSD Experience and Reality
“Of greatest significance to me has been the insight that I attained as a fundamental understanding from all of my LSD experiments: 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 that is ambiguous—that there is not only one, but that there are many realities, each comprising also a different consciousness of the ego.”
Hofmann states that LSD allow you to see reality from a new perspective. It allows you to change the receiver (you) as you tune into reality. And this allowed him (and millions more) to see the world not as the self (ego) being separated from the world, but as a part of the whole. Taking this other perspective, Hofmann sees how some (much?) of our industrialized wonders have also led to the destruction of nature.
This reconnection with nature is then also discussed in the light of the Eleusinian Mysteries. Rituals, probably involving psychedelics, that were held for almost two centuries.
“The cultural-historical meaning of the Eleusinian Mysteries, their influence on European intellectual history, can scarcely be overestimated. Here suffering humankind found a cure for its rational, objective, cleft intellect, in a mystical totality experience, that let it believe in immortality, in an everlasting existence.”
In the final pages, Hofmann also reflects on Christianity and meditation. Ending the book with the following: “I see the true importance of LSD in the possibility of providing material aid to meditation aimed at the mystical experience of a deeper, comprehensive reality. Such a use accords entirely with the essence and working character of LSD as a sacred drug.”