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Offlineclemens
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Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day"
    #18496453 - 07/01/13 10:32 AM (10 years, 8 months ago)

Very interesting article about if LSD can actually absorb through the skin. Did Albert Hofmann accidentally discover LSD's mystical phenomenon or did he have a mystical experience randomly? This posses a very interesting question.

article by: David E. Nichols who is well known for his optical isomers of psychedelic amphetamines.

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.


Overview of current research
I can't tell you all the things I do but let me just quickly give you an overview of what a hard scientist so-to-speak does, a reductionist scientist.

I look at how psychedelics affect brain chemistry. We make molecules. We make modified LSD analogues, we have a computer model of the serotonin receptor that's in the brain that we think is a target of these, computer generated that we discovered. We simulate the docking of these molecules to the receptor. We try to understand what are the amino acids in the receptor that interact with the different parts of the molecule. Then we look further in, we say when the molecule docks to the receptor, changes occur in the intercellular biochemistry. We look at the changes, how do those occur. My son who is a PhD in molecular biology doing neuropharmacology work at Vanderbilt has then looked even further and said what does LSD do to genetic regulation. He uses micro-array analysis to look at the gene expression changes following LSD in rats, and has seen changes in expression of 80 different genes. And then we have rat behavior where the rats tell us, "I think you gave me LSD" or "I don't think you gave me LSD." So we start from the design of the molecule, using computers, we synthesize the molecules, we then dock them in the receptor. We're mutating the receptor to change the amino acids so we can see how the complementary amino acids in the receptor modify the interaction with the drug. Then we look at the signaling in the receptor, what signaling pathways are turned on. And then ultimately to genetic regulation, where do protein expression changes occur.

We're looking at all the basic science -- preclinical stuff. I didn't have an MD degree so I couldn't do clinical research. This was sort of disturbing to me, but to get around it I founded the Heffter Research Institute, and they're doing all the clinical work. We're studying psilocybin -- in Zürich we have a clinical facility over there, with Franz Vollenweider. Most people know about the University of Arizona psilocybin study in OCD. Most people know about Charlie Grob's psilocybin study in terminal patients at UCLA. Those are all projects funded by the Heffter Institute.

So, we've translated everything from the basic science on into the clinical. I don't know if we can do a whole lot more. I'm doing as much as I can. We're not doing research with LSD, but I believe within a framework of 5 to 10 years, if we continue on and are successful with our psilocybin research, it will be possible to get protocols approved in the United States. We might start in Europe first but I think it will be possible to reinitiate clinical studies with LSD.


http://www.erowid.org/general/conferences/conference_mindstates4_nichols.shtml


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Take it easy dude, but take it!

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OfflineCapt. Stern
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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: clemens]
    #18496536 - 07/01/13 10:55 AM (10 years, 8 months ago)

Very interesting... :thumbup:


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Offlines240779
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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: clemens] * 1
    #18496713 - 07/01/13 11:42 AM (10 years, 8 months ago)

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."


I dunno, man, maybe he fucked something up. Mixed up the the vials in his lab or something. I'm not about to dismiss chinacat72.


http://www.shroomery.org/forums/showflat.php/Number/1335338#1335338

Quote:

chinacat72 said:
Quote:




Tell us some other stories of lost inhibitions and blissful freedom please.

   



Allright one more story tonight :grin:
This one's from a dark period of my life 'but an important night.
It's 96 and i'm livin in a hotel down on fisherman's warf in San Francisco.
I am horribly addicted to herion. Ravaged and in the grips of the beast. My friend's try everything they can to reason with me. I blow them all off and only leave my hotel room to go to the post office and western union and then down to the mission district to score my dope for the day.
One day i'm in my room in my constant nod and a good freind comes by to see me. One of the elder heads that first showed me the ropes on tour. He sit's there and cries and tells me i'm rotting away and i'm like ya ya see ya later and he leaves. A little later he calles me and say's " We love you and you need to see the light" and hang's up. I'm like whatever man and as i hang up the phone i feel it. LSD crystal doesn't require you to eat it. If you get it on your skin you get high. And as i look at my hand where i held the phone when he called me there was little specks of white fluff all over. I realized he had sprinkled it on my phone.I was like noooooooooo not now. I knew i was in for a bad trip since being a junkie you get full of bad karma. I went into the bathroom and imediatly puked everywhere. It was coming on strong and fast. I layed down and saw what a ravaged wreck of a person i had become from this evil drug. I was at the end of my rope and took off out the door and down the hall out of the hotel. Hell i was probably going to jump into the bay. As soon as i got out side there was another of my close friend's waiting casually smoking a cigarette. He flicked it and said I think it's time we got out of the city and went up into the mountain's.
That's when my healing began. I was so sick , but i was taken care of.
I havn't touched herion since. I never will.
That's the Grateful Dead family for ya :wink: 





*

Edited by s240779 (07/03/13 04:02 PM)

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Invisiblemuistrue
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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: s240779]
    #18496776 - 07/01/13 11:59 AM (10 years, 8 months ago)

Quote:

AcerolaCherryXtrct said:
I dunno, man, maybe he fucked something up. Mixed up the the vials in his lab or something. Nick Sand is fried, as revealed by his Nat Geo interview.* I'm not about to dismiss chinacat72.





You would take the word of some dude on a message board over Nick Sand? :lol:


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OfflineGreySatyr
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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: muistrue]
    #18497605 - 07/01/13 03:25 PM (10 years, 8 months ago)

I've always been curious of the whole time frame then I read "LSD: My problem child" and he mentioned mystical experiences as a child and so on an I realized that it might have been spontaneous, however, I believe it does absorb into your skin.

I don't know, maybe the whole thing was made up and Hoffman intentionally made something that could take us to the moon and back. Either way, it's incredible.


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...also, go to hell, huh?

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Offlineclemens
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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: GreySatyr]
    #18506995 - 07/03/13 01:33 PM (10 years, 8 months ago)

hofmann didn't lie he had a psychedelic experience but now there is some scientific evidence coming out to show that LSD really might not absorb through the skin.

It has not been proven as of yet, it is just a hypothesis but so far all the evidence is confusing.

I love chinacat and dont put down any of his stories but he is just a guy on a forum. I want to test for myself and see what happens, take fluff and dip a pinky finger into it and see if it works. I have ate large amounts of blotter at once and would honestly consider doing a thumbprint.

Can anyone else vouch for putting crystalline LSD on the skin and it causing psychedelic effects? Not liquid or blotter as those could be other drugs sadly but powdered LSD.


I ate alot of this at one time and had an incredibly experience, only lasted about 24 solid hours and then of course 2-3 days of a very weird period where i was still coming down. How long did chinacat say his thumbprint experience last? i will look it up


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Take it easy dude, but take it!

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OfflineCoreyRubble
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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: clemens]
    #18507090 - 07/03/13 02:01 PM (10 years, 8 months ago)

My friend told me he did a thumbprint once, it worked. He could have been blowing smoke, but I can account for hppd still being around 10 years later.

I would like to do a thumbprint, :smile:

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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" *DELETED* [Re: CoreyRubble]
    #18507203 - 07/03/13 02:30 PM (10 years, 8 months ago)

Post deleted by Blazer420

Reason for deletion: .



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~ I used to get high on life, until I realized life was cut with morons ~
* You need 2 wake up and smell the music! *
- We are all computer data in a materialistic world -
| Sometimes you have to lose yourself, to find anything |

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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: Blazer420] * 1
    #18507504 - 07/03/13 03:50 PM (10 years, 8 months ago)

Poor speculation is poor.

LSD certainly can be absorbed through skin.
Hoffman's trip lasted long enough to ride home and have a doctor visit, more than 2 hours.

The author needs to stop drinking the conspiracy koolaid and learn about Occam's bloody razor.

Quote:

I've made LSD in my lab on many occasions for research purposes, possibly in not so meticulous a manner as Albert Hofmann.



Well there's your problem!

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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: StygianKnight] * 1
    #18507606 - 07/03/13 04:19 PM (10 years, 8 months ago)

Lol at people discounting Nick Sand & Dr. Nichols.

I got a large amount of potent liquid on my skin & it had no effect whatsoever. The only way LSD is getting in is through a mucus membrane or tiny cut.


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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: Dark_Star]
    #18507620 - 07/03/13 04:23 PM (10 years, 8 months ago)

OK, this is just getting weird. Reputable people on totally opposite ends of the spectrum.

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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: s240779]
    #18507696 - 07/03/13 04:49 PM (10 years, 8 months ago)

Guys lsd does not exist. only mystical experiences do.

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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: Dark_Star]
    #18507771 - 07/03/13 05:12 PM (10 years, 8 months ago)

Quote:

Dark_Star said:
I got a large amount of potent liquid on my skin & it had no effect whatsoever. The only way LSD is getting in is through a mucus membrane or tiny cut.



Interesting.  I know people who have had the same thing happen and tripped. 
Which leads me towards the Hoffman had a small cut or roughed-up skin theory, before the random mystical experience theory.

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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: Dark_Star]
    #18508243 - 07/03/13 07:24 PM (10 years, 8 months ago)

Quote:

Dark_Star said:
Lol at people discounting Nick Sand & Dr. Nichols.

I got a large amount of potent liquid on my skin & it had no effect whatsoever. The only way LSD is getting in is through a mucus membrane or tiny cut.




Could there be a difference between getting powder LSD and liquid LSD on your skin? Also it describes Hofmann's fingertips absorbing it, maybe under your fingernails is a more direct path into your body than just your skin. I'm just speculating here, but it just doesn't make sense to me that while synthesizing one of the most potent drugs on earth, he happened to have a mystical experience that wasn't caused by the drug...

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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: StygianKnight]
    #18508282 - 07/03/13 07:34 PM (10 years, 8 months ago)

It wouldn't have been the first non-drug induced mystical experience that he'd had. He had them before, and talked about them in interviews....compared them to that experience on April 16th.


Quote:

StygianKnight said:
Poor speculation is poor.

LSD certainly can be absorbed through skin.
Hoffman's trip lasted long enough to ride home and have a doctor visit, more than 2 hours.

The author needs to stop drinking the conspiracy koolaid and learn about Occam's bloody razor.






You're confusing the April 16th incident with Bicycle Day. On the 16th he had an experience that lasted a couple hours. The infamous bike ride & doctors visit occurred on the 19th, when Albert Hoffman deliberately ingested 250 mcg of LSD to see if it had any effect.


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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: Dark_Star]
    #18508560 - 07/03/13 08:30 PM (10 years, 8 months ago)

Quote:

Dark_Star said:
It wouldn't have been the first non-drug induced mystical experience that he'd had. He had them before, and talked about them in interviews....compared them to that experience on April 16th.


Quote:

StygianKnight said:
Poor speculation is poor.

LSD certainly can be absorbed through skin.
Hoffman's trip lasted long enough to ride home and have a doctor visit, more than 2 hours.

The author needs to stop drinking the conspiracy koolaid and learn about Occam's bloody razor.






You're confusing the April 16th incident with Bicycle Day. On the 16th he had an experience that lasted a couple hours. The infamous bike ride & doctors visit occurred on the 19th, when Albert Hoffman deliberately ingested 250 mcg of LSD to see if it had any effect.




2 Legit 2 Legit

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InvisibleStygianKnight
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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: Dark_Star]
    #18508641 - 07/03/13 08:43 PM (10 years, 8 months ago)

Bah, you're right, stupid article title.

Could he have had a 'Mystical experience'?  sure, it's possible.
Of course he did also contaminate himself with a hallucinogen that can be absorbed through skin or mucous membranes in extremely small doses.  To say the only other option is mystical experience based on the hallucinations not lasting as long as expected I frankly find hilarious and sad that it's coming from a scientist.

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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: StygianKnight]
    #18508713 - 07/03/13 08:54 PM (10 years, 8 months ago)

He's not just any scientist. He's the worlds top expert on LSD. This man has been studying & working with this substance for decades. He didn't just pull this theory out of his ass. He determined through his decades of work that there is no way Albert Hoffman absorbed an active dose of LSD that day.


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InvisibleStygianKnight
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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: Dark_Star]
    #18508778 - 07/03/13 09:05 PM (10 years, 8 months ago)

:disappointedlaugh:
Titles don't make someone right.
Welcome to science, where you can be the queen of LSD and yet still wrong.  (Newton, smart guy, wrong on a bunch of things.)

Based on what evidence exactly did he determine this?  A short trip and a childhood experience... anything else?

(General note: I'm not discounting the many awesome things he's done in chemistry, but that doesn't make him automatically right.)

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Re: Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" [Re: StygianKnight]
    #18510236 - 07/04/13 03:43 AM (10 years, 8 months ago)

The fact that despite popular belief, LSD is not transdermally active. As well as the the well-earned reputation Swiss chemists have for being extremely meticulous. Coming into contact with a substance, particularly a new one, that's being synthed isn't something that they do. They're extremely careful about that shit. A dose active enough to cause the effects that Albert described lasts longer than two hours.

Dr. Nichols & his crew of grad students never got high while synthesizing LSD. Nick Sand painted a liquid solution on his body, laced with DMSO to increase the odds of absorption & it didn't work. Those are facts. You mention that you find it hilarious that a scientist would jump to a mystical experience, yet you are basing your own belief on the matter on Internet anecdotes as opposed to  those that tried real experiments with them. Two chemists say that it doesn't work. Dr. Nichols has been working with it for decades. Do yourself a favor & look up some of his work. That man has furthered our understanding about these substances tremendously. Nick Sand produced billions of doses of LSD in his day, and gave a large majority of it away for free. He knows a rung or two about it, and he says that his experiment with the solution on his skin didn't work. I personally had at least several milligrams worth of high purity LSD in liquid solution spilled & smeared all over myself, and it had no effect whatsoever.


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