the discovery of the drug lsd -- 9/4/19

Today's selection -- from How to Change Your Mind by Michael Pollan. The story of LSD's discovery:

"As a young chemist working in a unit of Sandoz Laboratories charged with isolating the compounds in medicinal plants to find new drugs, [the Swiss chemist Albert] Hofmann had been tasked with synthesizing, one by one, the molecules in the alkaloids produced by ergot. Ergot is a fungus that can infect grain, often rye, occasionally causing those who consume bread made from it to appear mad or possessed. (One theory of the Salem witch trials blames ergot poi­soning for the behavior of the women accused.) But midwives had long used ergot to induce labor and stanch bleeding postpartum, so Sandoz was hoping to isolate a marketable drug from the fungus's alkaloids. In the fall of 1938, Hofmann made the twenty-fifth mole­cule in this series, naming it lysergic acid diethylamide, or LSD-25 for short. Preliminary testing of the compound on animals did not show much promise (they became restless, but that was about it), so the formula for LSD-25 was put on the shelf.

"And there it remained for five years, until one April day in 1943, in the middle of the war, when Hofmann had 'a peculiar presenti­ment' that LSD-25 deserved a second look. Here his account takes a slightly mystical turn. Normally, when a compound showing no promise was discarded, he explained, it was discarded for good. But Hofmann 'liked the chemical structure of the LSD molecule,' and something about it told him that 'this substance could possess prop­erties other than those established in the first investigations.' An­other mysterious anomaly occurred when he synthesized LSD-25 for the second time. Despite the meticulous precautions he always took when working with a substance as toxic as ergot, Hofmann must somehow have absorbed a bit of the chemical through his skin, because he 'was interrupted in my work by unusual sensations.'

"Hofmann went home, lay down on a couch, and 'in a dreamlike state, with eyes closed . . . I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors.' Thus unfolds the world's first LSD trip, in neutral Switzerland during the darkest days of World War II. It is also the only LSD trip ever taken that was entirely innocent of expectation.

Dr. Hofmann, date unknown, with a chemical model of LSD.

"Intrigued, Hofmann decided a few days later to conduct an exper­iment on himself -- not an uncommon practice at the time. Proceed­ing with what he thought was extreme caution, he ingested 0.25 milligrams -- a milligram is one-thousandth of a gram -- of LSD dis­solved in a glass of water. This would represent a minuscule dose of any other drug, but LSD, it turns out, is one of the most potent psychoactive compounds ever discovered, active at doses measured in micrograms -- that is, one thousandth of a milligram. This sur­prising fact would soon inspire scientists to look for, and eventually find, the brain receptors and the endogenous chemical -- serotonin ­-- that activates them like a key in a lock, as a way to explain how such a small number of molecules could have such a profound effect on the mind. In this and other ways, Hofmann's discovery helped to launch modern brain science in the 1950s.

"Now unfolds the world's first bad acid trip as Hofmann is plunged into what he is certain is irretrievable madness. He tells his lab assis­tant he needs to get home, and with the use of automobiles restricted during wartime, he somehow manages to pedal home by bicycle and lie down while his assistant summons the doctor. (Today LSD devotees celebrate 'Bicycle Day' each year on April 19.) Hofmann describes how 'familiar objects and pieces of furniture assumed gro­tesque, threatening forms. They were in continuous motion, ani­mated as if driven by an inner restlessness.' He experienced the disintegration of the outer world and the dissolution of his own ego. '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.' Hofmann became convinced he was going to be rendered permanently insane or might actually be dying. 'My ego was suspended somewhere in space and I saw my body lying dead on the sofa.' When the doctor arrived and examined him, however, he found that all of Hofmann's vital signs -- heartbeat, blood pressure, breathing -- were perfectly normal. The only indication something was amiss were his pupils, which were dilated in the extreme.

"Once the acute effects wore off, Hofmann felt the 'afterglow' that frequently follows a psychedelic experience, the exact opposite of a hangover. When he walked out into his garden after a spring rain, 'everything glistened and sparkled in a fresh light. The world was as if newly created.' We've since learned that the experience of psychedelics is powerfully influenced by one's expectation; no other class of drugs are more suggestible in their effects. Because Hofmann's experiences with LSD are the only ones we have that are uncontam­inated by previous accounts, it's interesting to note they exhibit neither the Eastern nor the Christian flavorings that would soon become conventions of the genre. ...

"Hofmann came back from his trip convinced, first, that LSD had somehow found him rather than the other way around and, second, that LSD would someday be of great value to medicine and especially psychiatry, possibly by offering researchers a model of schizophre­nia. It never occurred to him that his 'problem child,' as he eventu­ally would regard LSD, would also become a 'pleasure drug' and a drug of abuse."




Michael Pollan


How to Change your Mind


Penguin Books


Copyright 2018 by Michael Pollan


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