About this Document

  
GENERAL
conferences
Modern humans must learn how to relate to psychoactives
responsibly, treating them with respect and awareness,
working to minimize harms and maximize benefits, and
integrating use into a healthy, enjoyable, and productive life.
MindStates IV LSD Panel:
Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day"
with brief overview of current research
BY DAVID NICHOLS
May 24, 2003
Transcription & Editing by Erowid.
Adapted from transcript of presentation given at Mindstates IV, Berkeley, CA
Citation: Nichols, David. "Hypothesis on Albert Hofmann's Famous 1943 'Bicycle Day'" Adapted from a presentation given at Mindstates
IV.Erowid.org/general/conferences/conference_mindstates4_nichols.shtml. May 24 2002.
Editor's Introduction
At Mindstates IV, Dr David Nichols, chemist and pharmacologist, professor of medicinal chemistry and molecular pharmacology at Purdue University,
proposed a novel alternate reading of Albert Hofmann's famous 1943 "Bicycle Day" and a brief overview of his research.
Presentation
I'm here to give you a report from the institutional research division of your community. If you pay taxes to the IRS, you support my research to
understand how psychedelics affect brain chemistry; thank you.
Since we're just a slight bit past the 60th anniversary of the discovery of LSD, I thought I would have a little audience participation fun, and give
you a little insight into how the scientific process works. Because, often times in this community, "scientist" has somewhat of a pejorative
connotation. I want to show you how we're not so different, and do a little experiment.
You know the way science works. We make observations, we develop or formulate a hypothesis that is consistent with those observations, and then we
attempt to carry out experiments to test the hypothesis. I don't think we'll be able to carry out the experiments to test the hypothesis, but what I
want to do is develop a hypothesis today that I think you'll find very interesting. But the first thing we need to know is what kind of a database
we're working with. What I'd like you to do is raise your hand if you have read Albert Hofmann's account of the discovery of LSD.
[nearly everyone in the conference hall raises their hand]
"The only hypothesis I can come up with that's consistent with all of these facts is that on April 16, 1943, Albert Hofmann did not get LSD in his
body at all. He had a spontaneous mystical experience!"
Ah, just as I suspected. So we have a good database, and probably an educated database.
What I want to do now is another experiment. I want you to raise your hand and hold it in the air as long as I am stating things that you hold to be
true, and when I say something you believe not to be true, then put your hand down.
So, the first thing I'm going to say, if you believe it to be true, raise your hand, and keep it up there until I say something you disagree with.
On April 16, 1943, when Albert Hofmann accidentally ingested LSD, he ingested at least 25 micrograms. Now keep your hand up until I say something you
disagree with.
[most people in the audience raise their hands]
On that same date in 1943, Albert Hofmann ingested at least 50 micrograms of LSD.
[a few people put their hands down]
On that same date in 1943, Albert Hofmann ingested at least 75 micrograms.
[several more people put their hands down]
And then again, on that date in 1943, Albert Hofmann ingested at least 100 micrograms.
[more people put their hands down]
On that same date, Albert Hofmann ingested 150 micrograms.
[only a few people still have their hands still up]
Well I think I've already proved the point. I think there's a consensus that Albert Hofmann must have ingested at least 50 to 75 micrograms, and there
are people in here who believe he must have ingested 100 or 150 micrograms. Now we've estimated, with this educated database, approximately how much
LSD he must have accidentally gotten inside himself.
Now, we'll do the same thing again. In April 1943, after his accidental ingestion, how many people believe that Albert Hofmann would have experienced
the effects of LSD for at least 10 hours, based on that dose?
[Several people put their hands up]
Now if we believe he took LSD, and if we believe he took 50 to 75 micrograms -- that's the context -- how many people believe the effects should have
lasted at least 8 hours. [many more hands go up] How many believe the effects would have lasted at least 6 hours? [more hands go up] How believe the
effects would have lasted at least four hours? [nearly all hands are up at this point]
Now, how many people believe that the effects of a 50-75 microgram dose of LSD would only have lasted two hours? [nearly all hands go down]
We read from his account:
"I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two
hours(emphasis added) this condition faded away." (Hofmann, 1983).
Well now, that was a conundrum for me. I read that and I thought, "gee I'm a scientist, and this doesn't make sense with what I know." And for most of
you, I think, that doesn't make sense either. So, the question: how can we formulate a hypothesis consistent with this observation? We need to
consider a few things.
We know that Albert originally synthesized LSD in 1938 as part of an ambitious program to make a number of lysergamides. LSD-25 was only the 25th in
the series. I actually don't know how many of those compounds he made, but let's assume he only made 30. So we had up to 30 in the series. He may have
made many more actually, but at least say 30. And they were all tested; he sent the pharmacology department LSD-25, 24, 23... and so forth. They then
say, "LSD-25: not interesting." The assays of that day really didn't provide much information; they were very unsophisticated. But five years later,
Albert has a hunch that the pharmacology department missed something on this 25th in the series.
Now that's kind of peculiar. I'm familiar with the drug industry, and I've actually started a small company myself. Imagine you're a musician, and
you've created this musical piece. It's really wonderful; it's one of the best pieces you've ever written; you play it for people, they think it's
great. And this one artist comes down. He's very creative but he has no musical talent at all, really tone deaf, he listens to your music and he says,
"Man that sucks. You missed something. There's something missing." Now you as a musician are probably going to have some sort of a gut reaction to
that. And even though the pharmacologist at Sandoz was probably a friend of Albert's, can you imagine this chemist coming down the hall and saying,
"You know, I made this compound five years ago, out of this whole series, and there's this one compound, LSD-25, that you said was uninteresting...
but you must have missed something. I just have this 'peculiar presentiment,' this strange hunch that you missed something." You're going to look at
Albert and say, "You know, really, I'm an expert in pharmacology Albert. We tested it very well."
The Germans and the Swiss are very precise chemists, and pharmacologists, and scientists. There wouldn't have been any question about this being
somehow mis-analyzed the first time.
This is another interesting point. Why the 25th? We know that only the 25th in the series was active. Any other compound that he made -- and I've made
many of them, we've tested many of them -- none of the others approach LSD, either in its sophistication or in its potency. Only the 25th. And this is
unusual. In pharmacology often you have a regular series. If we think of things like DOB, and DOI, there's a kind of regular progression. They all fit
into a kind of subgenus. And LSD doesn't. We don't call the other members of the series Albert made as LSD something or other, but if we had LSD-23,
24 and 26, they would all be one-tenth the activity of LSD-25. Peculiar presentiment indeed!
As I've said, Swiss and German chemists have a reputation -- today and back then -- for being absolutely meticulous. If we had gone into Albert's lab
at Sandoz in 1943, we would probably have found everything in its place, organized in an obsessively neat manner. No dirty glassware, no trash on the
floor, meticulous. How in the world did a meticulous Swiss chemist get 50 to 75 micrograms or more of LSD into his body? We don't know.
Another fact: I've made LSD in my lab on many occasions for research purposes, possibly in not so meticulous a manner as Albert Hofmann. Nothing ever
happened. I had several graduate students who made LSD as 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. And
yesterday I was talking to Nick Sand, and Nick said, "I made a solution of LSD in DMSO…" -- DMSO (dimethyl sulfoxide) is a chemical that greatly
enhances absorption of other chemicals through the skin -- he says, "…I painted it on my skin. Nothing happened." A concentrated solution and
nothing happened! How did this very meticulous Swiss chemist get the LSD into his body? I don't know.
The other fact we need to think about is when Albert was a child, he had a spontaneous mystical experience. Now depending on whether you're a
psychologist or a psychiatrist or whatever, we could say that Albert had a predisposition to altered states of consciousness.
So what facts do we know? I'm going to formulate a hypothesis. He took a dose that by your consensus should have lasted certainly more than two hours,
but it only lasted two hours. He was a meticulous chemist -- a Swiss chemist. Anyone I know who's worked with LSD -- and Nick Sand painted a solution
of it on his arm -- didn't get high. This doesn't make sense. And what is this peculiar presentiment? Why the 25th in the series? Inexplicable! And,
he was predisposed to altered states of consciousness.
The only hypothesis I can come up with that's consistent with all of these facts is that on April 16, 1943, Albert Hofmann did not get LSD in his body
at all. He had a spontaneous mystical experience!
Now if I were working in the lab with a new chemical, and I started having kaleidoscopic visions of wonderful colors and patterns, my first thought
wouldn't be that I was having a spontaneous experience. My first thought would be, "What was that new chemical I was working with? I need to tell
Sasha about it." [laughter]
I think that's what happened, that's the hypothesis. We can't test that hypothesis, but when I saw Albert in Basel a couple years ago, I presented
that particular hypothesis to him and said, "What do you think?" He said, "It's entirely possible." So, that's our little experiment, and I think most
of you really didn't think seriously about the discovery of LSD, but it puts a different light on it.
Now one aside to that we could then bring up is this. If the force that caused him to have this peculiar presentiment -- and very peculiar it is -- is
the same force that induced him to have this mystical experience, which caused him to focus on this chemical, we can hope it might happen again.
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