The Weird Link Between Bicycles, Obstetrics, and LSD

5–22–17

April 19 is Bicycle Day. What is it and who celebrates it? To answer that, we need to travel back to the 1940s. Spoiler alert for Adil: it has nothing to do with your home for the past year.

At ~400 deaths per 100,000 live births, the mortality rate of all women during pregnancy was still unacceptably high in the 1940s in the US (for comparison, today it is ~10 per 100,000). Even worse, this rate was actually double for african american women. These might seem like relatively small numbers, but it translates to ~10,000 women dying from childbirth in 1940. This was, in fact, a huge incentive for pharmaceutical companies and other medical innovators. Because one of the major causes of death during pregnancy at the time was post-partum hemorrhage, many pharma companies began searching for drugs to stop the bleeding. Sandoz Pharmaceuticals was one of those companies.

Arthur Stoll

At the time, Dr. Arthur Stoll was leading the pharmaceutical research team at Sandoz. His claim to fame was isolating ergotamine, a drug from the ergot fungus that was subsequently used to control uterine bleeding post-partum.

ergotamine

Bonus FF: ergot is a poisonous fungus found in rye that caused ergotism, also known as “St. Anthony’s Fire” (extra bonus FF: ergotism can be gangrenous or convulsive. “Convulsive ergotism is characterized by nervous dysfunction, where the victim is twisting and contorting their body in pain, trembling and shaking, and wryneck, more or less fixed twisting of the neck, which seems to simulate convulsions or fits. In some cases, this is accompanied by muscle spasms, confusions, delusions and hallucinations. “ This was so disturbing that a number of scholars believe it to be the catalyst for accusations of being a witch, and there are various studies that have correlated years of rye famine with increased numbers of witch accusations, as people would become more willing to eat poisoned grain during a famine). ANYWAY, despite all this, it was still used in folk medicine to stop bleeding after deliveries, often at the expense of the mother. That was the impetus to isolate the active molecule, which was Stoll’s accomplishment.

Hofbro

Fast forward a couple years and they hire a yung Albert Hofmann, PhD. Dr. Hoffman was working on creating amide derivatives of lysergic acid — the characteristic nucleus of ergotamine — to see if he could create something with similar properties without the side effects or to identify new uses for the drugs entirely. After 24 other attempts, he created lysergic acid diethylamide, abbreviated to LSD-25.

Comparison between structure of ergotamine and LSD

Testing was performed on animals and there was a series of weird symptoms that included animals becoming oddly excited; beyond that, however, the drug showed no promise to the pharmacologists on staff at the time, and testing was discontinued.

A couple years went by with no thought of LSD-25, but five years later, in what Hofmann described as “a peculiar presentiment — the feeling that this substance could possess properties other than those established in the first investigations,” he resynthesized the drug. (upon recalling the urge later on, Hofmann claimed “I did not choose LSD; LSD found and called me.”

April 16, 1943 would go down in history as a case study of self-experimentation and is now known affectionately as “Bicycle Day.” I don’t want to ruin the experience of hearing this from the horse’s mouth, so here are the notes from Hofmann’s notebook itself:

April 19, 1943: Preparation of an 0.5% aqueous solution of d-lysergic acid diethylamide tartrate. 
 
4:20 P.M.: 0.5 cc (0.25 mg LSD) ingested orally. The solution is tasteless. 
 4:50 P.M.: no trace of any effect. 
 5:00 P.M.: slight dizziness, unrest, difficulty in concentration, visual disturbances, marked desire to laugh…

“At this point the laboratory notes are discontinued: The last words were written only 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. 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 the physician was called.” Hence, the origin of “Bicycle Day.” Also, note that he took .25mg of LSD and that he did it at 4:20pm ( ͡° ͜ʖ ͡°)

By the time the doctor arrived, the peak of the crisis had already passed. As far as I remember, the following were the most outstanding symptoms: vertigo, visual disturbances; the faces of those around me appeared as grotesque, colored masks; marked motoric unrest, alternating with paralysis; an intermittent heavy feeling in the head, limbs and the entire body, as if they were filled with lead; dry, constricted sensation in the throat; feeling of choking; clear recognition of my condition, in which state I sometimes observed, in the manner of an independent, neutral observer, that I shouted half insanely or babbled incoherent words. Occasionally I felt as if I were out of my body.

In his book, LSD: My Problem Child, he has another brilliant description of his trip:

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 … 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 relentlessness. 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 … 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 a wasted effort. A demon had invaded me, had taken possession of my body, mind, and soul … 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?
Back to his lab notes:
The doctor found a rather weak pulse but an otherwise normal circulation…. Six hours after ingestion of the LSD my condition had already improved considerably. Only the visual disturbances were still pronounced. Everything seemed to sway and the 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 in upon me. A remarkable feature was the manner in which all acoustic perceptions (e.g., 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 I fell asleep and awoke next morning feeling perfectly well.

Hofmann was fascinated and experimented further…on his friends. He found some “volunteer colleagues” from Sandoz and tested out the activity of the drug, eventually identifying the effective dose as .03-.05mg (Hofmann yolo took five times the average effective dose when he first tried it…whose mans is this????)

As you can imagine, Hofmann earned a great deal of fame from this exploration, and was subsequently understood as the patron scientist of all things hallucinogenic. Ultimately, researchers from around the world sent him all kinds of drugs characterize.

His other prized ~trippy~ research include identifying the active molecules in 1) magic mushrooms

shrooms

(psilocybin…turns out it’s more economical to synthesize psilocybin than to collect it from mushrooms nowadays, and this ultimately led to Hofmann taking synthetic psilocybin pills with a wise curandera, Maria Sabina during a holy mushroom ceremony. She claimed that there was no difference in her experience between mushrooms and the pills, which Hofmann claimed was the ultimate sign of success)

ololiuqui

and 2) ololiuqui (a Mexican plant whose seeds people ate to trip). After isolating the active molecules in the ololiuqui plant, Hofmann was shocked to find an organic source of lysergic acid derivatives!

I think Hofmann described this coincidence best:

The aim of my chapter is to describe an unusual cycle of chemical research, full of coincidences, a kind of magic circle, which started with the synthesis of various Iysergic acid amides and the discovery of the extraordinary psychotomimetic potency of Iysergic acid diethylamide (LSD), which led to the investigation of the sacred Mexican mushrooms, the isolation of psilocybin, and ended with ololiuqui, where lysergic acid amides were again encountered, thus closing the magic circle.

TL;DR, Women dying from childbirth →poisonous fungi →trippy drugs →more trippy drugs

Sources:

https://en.wikipedia.org/wiki/Mar%C3%ADa_Sabina

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