This talk will describe the early career of Albert Hofmann, his accidental discovery of the hallucinogenic properties of LSD-25, his legendary bicycle ride home from work during an LSD trip, and the legacy of his discovery.
Industrial accidents ancient poisoners poison prevention this is toxic history I’d like to now introduce Dr Hannah bungan who is a graduate of the UCLA Ronald Reagan all of view emergency Medicine Residency and is a currently a senior toxicology fellow at Banner University Medical Center in Phoenix
Well thank you so much for having me today we’ll be talking about bicycle day and Albert Hoffman and his discovery of LSD so first I would like to make it clear that this lecture is about the bicycle day that falls on April 19th it’s not to be confused with the world
Bicycle day which the UN General Assembly has recognized as June 3r so I apologize for any cycling off fici and AOS out there the first time I heard about bicycle day was sometime during my sophomore year of college in Upstate New York uh a group of friends and I were
Sitting around somebody’s dorm discussing how 420 became the national Stoner holiday when my friend Joe soln cut in he’s like dude forget 420 the real holiday is on 419 bicyle day and Joe proceeded to Enlighten us I don’t remember the exact version of the story he told but most
Circulating versions of the popular Legend go something like this on April 19th 1943 a Swiss chemist named Albert Hoffman gets exposed to lysergic acid diamide a compound he’s been working on in his lab while he’s riding his bicycle home the LSD starts to kick in and he experiences the world’s first Acid trip
And from that trip a social movement is born by and large this version of events isn’t all that far off from the truth with a few notable exceptions but there is a lot more to the story my objective today is to convince you that the bicycle trip isn’t even the most
Interesting part some of the things we’ll talk about today include snail juice the creepiest looking fungus I know what an analeptic is and why Hitler’s doctor always had a syringe full at the ready and why milk isn’t always the answer with that let’s begin so today we take for granted the
Existence of psychedelic drugs that produce non-ordinary States Of Consciousness dropping acid or having a bad trip are phrases that are so ingrained in pop culture even the most straight edged people mostly know what they mean but in the early 20th century there was not much mainstream cultural awareness about this kind of departure
From a normal state of being hallucinogenic experiences were largely confined to the realm of the religious or ulst Dr Weiss was just discussing Outsiders rarely sought involvement in these ceremonial intoxication rituals and the use of substances like masculine or iasa wasn’t widely recognized outside of anthropology circles other plants however were
Gaining interest with the medical community for their pharmaceutical properties many researchers at the time were trying to isolate specific components of plants to identify targets for drug development digitalis the active component of the Fox Glove flower was a prime example although it had had been used medically to treat various
Heart failure related conditions for centuries no one knew its exact structure how to reliably synthesize it doing so would allow for more precise standardized dosing and lucrative profits for the company that figured out how to do it this was the historical context during which a bright young chemist
Named Albert Hoffman had just completed his chemistry studies at the University of Zurich his thesis was about figuring out the structure of kiten which is the molecule that gives exoskeletons and fungal cell walls their rigid structure did this by studying the gastric juice of Vineyard snails and he earned his doctorate degree with
Distinction after completing his snail thesis Hoffman took a job with the basil based pharmaceutical company Sandos in its chemical research lab Hoffman’s background purifying and figuring out the structure of an unknown compound was exactly what Sandos wanted him to do for medicinal plant matter and thus Hoffman
Got what in my opinion was a promotion from snails to squill seill or dmia maritima is a plant that contains members of the same family of cardioactive glycosides that are found in Fox Glove or digitalis Hoffman’s job was to isolate a more stable version of these molecules that could theoretically
Be turned into Pharmaceuticals kind of like how digitalis was turned into dexin a once widely prescribed drug for heart failure in 1935 After figuring out the structure of the squill glycosides he decided it was time for a change specifically hofman was interested in working with a group of substances called Urgot alkaloids it’s
Worth taking a minute to discuss Urgot which could be a lecture of its own and was the topic of Trevor serb’s excellent talk about the relationship between Urgot and the Salem Witch Trials on toxic history episode number 21 Urgot is the common name for a fungal disease that affects wheat rye and other
Grain crops infected grains get these disturbing looking purple brown growths that look like something straight off the set of The Last of Us it’s caused by the fungal genus claviceps peria and it has caused multiple outbreaks of mass poisoning throughout history surprisingly though it has also been
Used as a medicine since at least the 1500s to help augment labor and control bleeding after childbirth don’t ask me how they first figured that out Hoffman’s Mentor stole had done some work in the 1910s with Urgot alkaloids and Hoffman felt like it was worth giving them another look some prominent
American scientists had just isolated one of the backbone structures of Urgot which they were calling lysergic acid Hoffman envisioned building on that backbone to make more potent or efficacious Pharmaceuticals Stole was less than enthusiastic about the idea of working with Urgot again quote I must warn you of the
Difficulties you face in working with the Urgot alkaloids these are exceedingly sensitive easily decomposed substances less stable than any of the compounds you have investigated in the cardiac gide field but you are welcome to try unquote and try Hoffman did he set out trying to synthesize a series of
Lysergic acid derivatives for animal testing many Urgot derivatives had already been tried as drug to control postpartum bleeding but Hoffman had his sight set on a slightly different use his theory uh for those of you who are watching here his theory was that adding this specific ethyl these this diethyl
Functional group to the lysergic acid backbone would create a drug like coramine coramine was the brand name of nikethamide which was a drug being used at the time as an analeptic analeptic isn’t a term you hear often in medicine anymore for a number of reasons mainly because it’s
Imprecise it describes a wide array of drugs that through some mechanism or another stimulate breathing and reverse coma this was from a time when we knew just enough to know how to sedate people with drugs like barbituates but we weren’t great at waking them back up
Again coramine was the kind of thing you might find in use long before we had the standard things we use for comos talkx patients today like Naran and just intubating them a historical side note Adolf Hitler’s personal physician was known to carry Coran around and used it
Anytime the fur got a little bit too deeply sedated on barbituates to wake him up it turns out this was a fairly regular occurrence because this physician Dr Theodor Morell used barbituates anytime he overdid it on the IV cocaine and methamphetamine injections he was also administering to Hitler in fact Morel regularly injected
The fear with an absolutely wacky smorgus Board of substances including testosterone sugar stimulants and sedatives as the time of day required I suspect the only reason Morell didn’t kill Hitler outright was because there were unfortunately often other more competent doctors around anyway this functional group attracted Hoffman’s attention so he synthesized the diamide
Version of lysergic acid it was known in his Shand as LSD 25 because it was the 25th lysergic acid derivative he produced as a drug candidate Hoffman first synthesized lsd2 in 1938 and as was the drug development protocol they first tested it on animals so technically the first LSD trip was
Experienced by a lab rabbit in 1938 and I have no way of proving it but animal experimentation being what it was at the time I suspect it was a terrifying experience the animal researchers charged with documenting the effect of lsd2 on rabbits merely noted that the animals became restless but it quote
Aroused no special interests in our pharmacologists and Physicians testing was therefore discontinued unquote after the lackluster rabbit trials in 1938 nothing more was heard of lsd2 for the next 5 years Hoffman busied himself by synthesizing a drug called hydren an Urgot derivative that was used for dementia treatment it was thought to
Dilate cerebral blood vessels and it was actually the 11th most widely prescribed drug at in the world at one time in the 80s but its use fell off when people realized it didn’t really work this brings us to the biggest mystery of the story about five years after abandoning LSD as a potential
Pharmaceutical Hoffman decided to make it again why no one really knows returning to substances that had already been tested and discarded as drug candidates was almost unheard of all Hoffman had to say about it was that he had a quote peculiar presentiment so it seems like the disc discovery of LSD as
A hallucinogen and the Psychedelic social movement at Birth all came down to a hunch kind of makes you wonder what other substances have been written off in the annal of pharmaceutical history so we returned to the spring of 194 three shortly after Hoffman’s peculiar presentent led him to try
Working with LSD 25 again he got to work synthesizing a new batch and at the final step of the synthesis he started to feel weird quote last Friday April 16th 1943 I was forced to interrupt my work in the laboratory in the middle of the afternoon and proceed home being
Affected by a remarkable restlessness combined with a slight dizziness at home I lay down and sank into a not unpleasant intoxicated like condition characterized by an extremely stimulated imagination in a dreamlike state with eyes closed I perceived an uninterrupted stream of fantastic pictures extraordinary shapes with intense kaleidoscopic play of colors after some
Two hours this condition faded away it is this account and not the story of his legendary bicycle ride the following Monday that describes the first time a human experienced the effects of LSD before we get to Bicycle day and we’re almost there I promise Hoffman’s first
Mini trip begs the question how did he absorb it this question has actually been discussed in psychedelic pharmacology circles because the idea that he absorbed it through intact skin is not really feasible all accounts of Hoffman’s work habits describe him as meticulously neat moreover there are many accounts from chemists who have
Synthesized LSD that refute the idea that it’s easy to accidentally absorb some through intact skin Dr David Nichols a chemistry and pharmacology professor at Purdue University addressed this question during a 2003 lecture at a psychedelic pharmacology conference quote I’ve made LSD in my lab on many occasions for
Research purposes possibly in not so meticulous a manner as Albert Hoffman nothing ever happened I had several graduate students who made lsds an intermediate for projects no accidental ingestion of LSD ever occurred a technician in my lab makes it routinely because we use it as a drug to train our
Rats he’s learned by experience that he never gets high nothing ever happens unquote tragically Nichols does not describe what he was training the rats to do on on LSD but he does go on to relate the story of a colleague who painted a solution of LSD in DMSO which
Is a solvent that enhances dermal drug absorption onto his skin and still experien no effects so overall I think it’s unlikely that Hoffman’s first exposure came from an accidental spill the LSD solution probably had to come into contact with mucous membranes or a break in his skin to get absorbed my
Guess is that he may have rubbed his eye or touch something he ate with contaminated hands but at the end of the day this is all pure conjecture and no one really knows knows whatever the mechanism of his accidental exposure Hoffman spent the weekend after that Friday thinking about
His experience he concluded that this substance must be active at an extremely low dose to cause such profound effects with presumably minimal exposure so he decided to test his theory with a self- experiment he was aiming for the minimum dose that would cause any noticeable effect and he settled on 250 micrograms
Ironically 77 years later some researchers did a dose finding study at the University of basil and the maximum dose they wanted to test on healthy humans was 200 micrograms which is shown here in for those of you that can see in the blue bars on this graph they showed
That this dose caused profound effects in terms of oceanic boundlessness as you can see here on the y- axis before I found the study I did not even know that Oceanic boundlessness was a scale that could get reported in a legitimate scientific journal and and just to
Clarify for the eagley viewers the black bar here denoted as 200 micrograms Plus K represents a group that got both LSD and ketanserin simultaneously ketan serin is a serotonin receptor antagonist since LSD works by activating the type 2A serotonin receptors co-administering it with a serotonin antagonist canceled
Out the effect so all this is to say that Hoffman had no idea of knowing it at the time but 250 micrograms is actually not a low dose the resulting experience now commemorated every April 19th as bicycle day is is described in Hoffman’s contemporaneous notes as follows as you
Will see he wisely waited until the end of his workday to conduct the self- experiment quote for 1943 at 4:20 in the afternoon 0.5 cc’s of half promil aquous solution of diamine tartrate orally take and diluted with about 10 cc’s of water tastless 1700 beginning of dizziness feeling of anxiety visual dis
Distortions symptoms of paralysis desire to laugh supplement of 421 home by bicycle from 1800 to about 2000 most severe crisis c special report his notes were short because he started to have difficulty riding fortunately an assistant in his office was available to escort him home by bicycle Hoffman later
Described the ride home quote 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 unquote he didn’t have much more to say about the 4 kilometer Journey from the Sandos lab to
His home in basil but it’s clear that when he got home he was in pretty bad shape he described his surroundings as having taken on a very Sinister quality at first he thought he had gone permanently insane a bit later he concluded he was dying and he started
Lamenting the hardships in store for the young family he was to leave behind in desperation he decided to try drinking milk as a non-specific detox iic an and in an act not dissimilar to Modern fraternity hazing rituals he chugged about 2 liters of milk over the course
Of the evening a physician summoned to attend to Hoffman noted that he had dilated pupils but otherwise physically seemed completely fine the doctor had Hoffman lie in bed at which point Hoffman finally realized he wasn’t dying and so reassured by this physician he closed his eyes and even briefly began
To enjoy the experience he described swirling and playful kaleidoscopic images and felt like he could see the sounds of the ambient city noise outside his window eventually he fell asleep and when he woke the next day to his astonishment he felt fine almost immediately after this experience Hoffman realized that this
Substance had great potential for medicinal use though initially his thoughts were more along the lines of a medical model of psychosis as opposed to a therapeutic tool he told his boss stole about his self- experiment and sto’s immediate reaction was that Hoffman must have miscalculated the dose
Because no substances at the time had known psychoactivity at fraction of a milligram doses the the director of the Sandos pharmacology Department agrees agreed with sto’s appraisal until both he and stole conducted their own self- experiments at even lower Doses and concluded that Hoffman was right thus began a new area of pharmacologic
Research into LSD the rest as they say is history LSD caught on quickly in the world of Psychiatry trials were undertaken to study the use of LSD in the reliving of repressed memories and Sand’s package insert even had a section that recommended that psychiatrists use it themselves to experience the world of
Model psychosis that they would be subjecting their patients to weirdly it was also piloted on schizophrenic patients a decision that is now widely recognized as a bad idea most of the non- schizophrenic experimental subjects who are given LSD exhibited much more euphoric reactions than Hoffman initially had early proponents of the
Use of LSD in Psychotherapy tried to clearly maintain that it was supposed to be an adjunct to psychoanalysis and not a cure in and of itself some more Fringe psychoanalysts even became adamant that LSD was a tool for reliving childbirth either way LSD enjoyed about a decade of therapeutic experimentation before it
Caught on as a drug of abuse Hoffman later came to think of LSD as his problem child as reports of L people experimenting with LSD reach frenzy levels in the media Sandos had to cease manufacturing LSD for research due to the abundance of negative PR it was attracting even though LSD is remarkably
Safe from a therapeutic index perspective even as Hoffman reflected on his life’s work decades later his attitude towards his own creation was mixed and he clearly struggled with the fact that his legacy of developing therapeutic drugs became so intertwined with illicit drug use in the counterculture Community nevertheless he continued to
Take LSD throughout his life his last trip was at the age of 97 and he passed away in 2008 at the age of 102 I think he would probably take great encouragement from the renewed Interest being enjoyed by multiple psychoactive substances including LSD as therapeutic tools today and with that here are my
References and thank you so much for having me here today