Spiritual - Nichols on Hofmann: Trip or mystical experience?

[grandbaby]

Here's a page copied from Erowid. I was wondering if anyone had thoughts about it.

From http://www.erowid.org/general/confer..._nichols.shtml
(Thanks to hyperreal for the link)

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. http://www.erowid.org/general/confer..._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]

1. 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." (Hofman, 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.


****

My take on this is somewhat different than Nichols'. I agree that it's a little odd that Hoffmann's experience lasted only "about two hours", but I think a more plausible explanation is that the visuals only lasted about two hours, and when they went away, Hoffman counted the experience as "over." Given that Hoffmann had no experience with the drug and absolutely no expectations about it, he wouldn't have been looking for the reasonably subtle mental change that characterizes a 50-75ug LSD experience.

He was probably thinking "What the &*&@^# was that?" and trying to puzzle it out. Low to medium doses of psychedelics can often simply resemble intense states of baseline experience, IME -- that there isn't necessarily a qualitative difference between a low-level trip and a charged creative or intellectual state.

On the questions of how a meticulous scientist happened to ingest some of his "problem child", and the more vexing question of what called Hoffman to that particular chemical, I don't know. Hoffmann's account is slightly less dismissive of the results of preliminary testing of LSD-25 than is Nichols'. Viz:

I had planned the synthesis of this compound with the intention of obtaining a circulatory and respiratory stimulant (an analeptic). Such stimulating properties could be expected for lysergic acid diethylamide, because it shows similarity in chemical structure to the analeptic already known at that time, namely nicotinic acid diethylamide (Coramine). During the testing of LSD-25 in the pharmacological department of Sandoz, whose director at the time was Professor Ernst Rothlin, a strong effect on the uterus was established. It amounted to some 70 percent of the activity of ergobasine. The research report also noted, in passing, that the experimental animals became restless during the narcosis. The new substance, however, aroused no special interest in our pharmacologists and physicians; testing was therefore discontinued.
(from "LSD: My Problem Child" by Albert Hoffmann, natch)

Possibly something in the behaviour of the dosed animals stirred a chord in Hoffmann, if during the testing he was around at all. Maybe he got a touch of a "contact high" or recognized, subconsciously, that the animals were not behaving "normally" - or even behaving abnormally in a fashion that didn't conform to patterns that one would expect.

He may have had no contact with dosed animals, which makes the "peculiar presentiment" more mysterious; however, in his book he doesn't mention the results of animal testing of any of the other isomers of LSD - did they cause "strong effects on the uterus" or any other activity? The noted results could well have been strikingly different from LSD-1 to 24, etc. Strictly working from Hoffmann's account, though, we have nothing to base speculation on.

I'm not trying to completely discount Nichols' argument, but it seems like a bit of a straw man to me... and a bit farther-fetched than I'm willing to go. Nonetheless, it's delicious food for thought - & discussion?

Reputation Comments on this post:

	Great post
	nice input - article and personal approach
	Thanks for posting this!
	a most excellent post
	nice find with stimulating ideas, and thoughtful discussion of the quote

[IHrtHalucingens]

Good post! Very interesting and definately something to think about. But i would have to agree with you that he only noted the visual portion of his low dose experience as the actual experience. I know that SWIM would probably not realize that he was accidently intoxicated with LSD until the visuals. The rest of the effects could be explained by a normal day to day reaction to some sort of common stimulus.

[enquirewithin]

I have read Nichol's theory before. It's quite possible.

[raven3davis]

SWIM to has read this article and it is an excellent piece of work that is conductive the the theory that lsd was a gift from some higher power. SWIM has heard a few dead head raimbow types on various boards claim that lsd is a gift from god given to us at a time when it was needed most. It was after all the one drug that persuaded the masses from a generation to "drop out." SWIM has never had an experience that came close to matching the divine nature of a large dose lsd trip.

Whatever the case, it is an interseting theory. The discovery of lsd will always be the topic of conspiracy. Lsd is a molecule that will go down in the history of mankind. Ask your average joe what 2c-e, DOC, or 4-ho-mipt are and they will look at you like you are a nucking fut, but ask them about LSD and chances are 99% they will be able to give you a breif explination of what it is (hallucinogen).

A trip with the described visuals should definitely have lasted longer than 2 hours.

[enquirewithin]

SWIM has heard a few dead head raimbow types on various boards claim that lsd is a gift from god given to us at a time when it was needed most. It was after all the one drug that persuaded the masses from a generation to "drop out."

If that's true, it doesn't seem to have have done much good!

[Silence_Inc]

swim has had an uknown ingetsing of lsd one time. it took him 2 hours he thinks to really become aware of it. but the experience lasted as long as normal ... so in a way - when you are aware of what you took - and the ego thinks "this will last ... time" you'll probaboy will experience it. the first two hours swim started noticing something was diffrent - but more because the world seem to go more rapid and he was slowing down.

sdo indeed - i follow your personal approuch - that when you don't know - you can miss out on what is really happening.

[Expat98]

This is a fascinating hypothesis indeed. I'm bumping this because with the timing of Dr. Hofmann's passing last week, people may be interested in reading about the discovery of LSD now.

[Shampoo]

An interesting theory for promoting a continuously striving mysticism-theory of LSD discovery, however I have to agree with grandbaby's original points regarding Nichols' fallacy:

Originally Posted by grandbaby

I agree that it's a little odd that Hoffmann's experience lasted only "about two hours", but I think a more plausible explanation is that the visuals only lasted about two hours, and when they went away, Hoffman counted the experience as "over." Given that Hoffmann had no experience with the drug and absolutely no expectations about it, he wouldn't have been looking for the reasonably subtle mental change that characterizes a 50-75ug LSD experience.

Considering the profound intensity of the initial peak of a powerful psychedelic experience for a first time user, especially one without expectations or planning, it seems certainly possible that he considered the effects following the peak to be the physical and psychological aftermath of the trauma, just like the weak knees and stumbling speech so often encountered for sometimes many hours after a vivid experience like a car accident or waking up from a terrifyingly realistic dream.

Additionally, Hoffman's statement that Nichols uses as proof for the 'two hour' concept could just as easily have been interpreted as,

"I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away."

And regarding his 'peculiar', mystical attraction to the 25th isomer in the series

Originally Posted by grandbaby

he doesn't mention the results of animal testing of any of the other isomers of LSD - did they cause "strong effects on the uterus" or any other activity? The noted results could well have been strikingly different from LSD-1 to 24, etc.

Does anyone have any more information on the activity of the other LSD isomers? I have heard many times, and from Nichols above, that only the 25th in the series was active, but does that mean psychoactive or active? In other words, were those judgments of 'inactivity' made after the discovery of LSD-25's true psychedelic power in comparison? or were they based on the same criteria by which the initial LSD-25 would have been considered active (restless animals and uterine activity)?

[Expat98]

Although it may not have been a "spontaneous mystical experience" as Nichols put it, I'd say Jung's concept of synchronicity is highly relevant to the way events panned out.