5 ms·

I wonder why so many HN readers are interested in phenethylamine-type chemicals. Sure, there will be a small percentage who will be consumers of said chemicals

I wonder why so many HN readers are interested in phenethylamine-type chemicals. Sure, there will be a small percentage who will be consumers of said chemicals who've a vested interest and no doubt there are organic chemists who will have a professional interest in said molecules even if they're never likely to work with them in person, but that still leaves many interested bystanders who've more than just a casual interest. Even I—who is far too timid to take anything that doesn't come out of a reputable pharmaceutical company let alone ever risk manufacturing any of these chemicals—have an interest and can pretty much instantly recognize one of these molecules the moment I see its skeletal formula—even if I can't necessarily remember which specific one it is. So what is the principal interest among the mere curious—is it cultural, or the fact that society has gone to great lengths to ban them, or is it just a technical curiosity about the effect they have on humans? There's little doubt there’s much interest among HN readers in the subject as this is the second article to appear on HN's same page-one only three stories removed from the first, the earlier one being Derek Lowe's article The Uselessness of Phenylephrine (science.org). At the time of this post that article had received 559 comments. In my comment to Lowe's article, I referred to an older HN article of similar nature posted at the end of November last year on the availability of the precursor phenylacetone—aka phenyl-2-propanone, P2P—and that story also had a large number of comments—361 in total. Incidentally, my post to Lowe’s article was, I thought, a pretty innocuous one wherein I essentially agreed with Lowe’s comments and provided the link to the older HN P2P story that essentially backed up what Lowe was saying, nevertheless it received a number of down-votes without any explanation. It seems such stories are still quite divisive on HN.

dylan604 5y ago
>come out of a reputable pharmaceutical company Please, name one of these reputable companies for me. One that does not push pills based on their bottom line but for actually improving the health of users. One that has not been known for rewarding doctors for pushing their pill over a competitors pill. One that does not have advertisments on TV/print/internet that talk about a side effect might be death, but still encourage random people to push their doctors.
- hilbert42 5y ago
  "...name one of these reputable companies for me." You're right of course, I cannot (and I fully agree with your points and sentiments). What I should have said is 'pharmaceutical companies that employ proper industrial control processes to ensure that what's inside the box is the same as printed on the packet' but that seemed a bit long-winded. In hindsight, putting 'reputable' in quotes would have been a better option. Apologies for the following rave but I'm likely a stronger advocate on these points than you are. ;-) In my defense I would let you know that if you were to look back into the archives of my HN posts—mind you, I'm not suggesting that you waste time actually doing so—then you would note that I've been one of the most outspoken, voracious and unquenchable critics of the Sackler family and Purdue Pharmaceuticals to post on HN. I consider what happened over the opioid epidemic not only an unforgivable failure on the part of the Sacklers and Purdue and that they have essentially gotten away with murder—the settlement being an unmitigated damn farce—but also a major systemic failure of Government (of the regulators/FDA) and of the medical profession in general. How 150-plus† years of knowledge about opiates and opiate addiction—basic info that's a compulsory default requirement in 101 pharmacy/medicine—can be chucked out and ignored by the regulators and the medical profession alike simply defies adequate description let alone understanding. How the fuck did this happen, why have others, regulators, guilty MDs, etc., also not been brought to task over the matter? After all, everyone knows that outside certain radioactive nuclides and chemical weapons, VX etc., opiates are the most controlled and regulated chemicals on earth and have been governed by international treaties for going on 100 years. We still don't know how this happened and we still need a full and better accounting of what exactly went wrong. Moreover, I've been an advocate for much tighter government control and regulation of drug companies and have held this view long before the Purdue incident. Similarly, I believe that we need to review drug patent laws to stop pharmaceutical companies exploiting consumers—I could write pages on this but I'll spare you the details. I'd also ban drug advertisements, especially so those that are aimed at the public. I have a particular concern over the continued promotion of drugs on TV and elsewhere, especially so the promotion of the coal-tar antipyretic class of drugs—the NSAIDs such as ibuprofen, paracetamol (acetaminophen), etc. as being safe, fix-all painkillers (even if not mentioned, that's the effect of such promotions). They aren't as safe as made out in ads, and they're especially dangerous with long-term use, but drug companies promote them as safe and governments continue to allow such promotions without warnings and caveats. (Incidentally, expert medical knowledge isn't necessary to determine the dangers of using these drugs as their dangers are well documented in any number of pharmacopeias, even Wiki has their side-effects well covered.) These antiquated 19th-Century drugs [paracetamol possibly made as early as 1852—see Wiki] are more dangerous than even many medicos think (the possible exception being the salicylates (aspirin) but even it has dangers). We have been progressively eliminating numbers of these ancient NSAIDs from the pharmacopeia since the 1930s—that is whenever we realize their kill-rate has become unacceptably high we move on to the next least dangerous one on the list instead of banning all of them outright (the last of the old ones still standing is paracetamol, its immediate forerunner, phenacetin, having since fallen). For example: acetanilide, pyrazolone, phenazone, amidopyrin (pyramidon), phenacetin, phenylbutazone (butazolidin) all derive from the 19th C. or from precursors that do. All have been progressively banned over a 30-40 year period (or in some instances their use limited to very specific applications), however it was obvious early on that these drugs were very dangerous and should not have been put in service (or at least withdrawn much earlier). Back in the late 1950s and 1960s there was a huge kerfuffle over the dangers of use of phenacetin, especially so when mixed with aspirin and caffeine in a combination known as 'APC'—a concoction which had been in prior use for some 40 or so years. There were many thousands of cases of rotted-out kidneys as a result of their use. What's not generally understood is that phenacetin is metabolized into paracetamol and it's the paracetamol that provides the pain relief (but paracetamol can easily be life-threatening and kills many people every year). Wiki states that phenacetin was withdrawn in Canada in 1973 and by the U.S. FDA in 1983. Why the delay of some 10 - 20 years after it was known for certain that phenacetin was dangerous, even carcinogenic? I know this delay to be factual because I can remember the widespread publicity about the dangers of phenacetin as a kid in the 1960s. (Incidentally, in recent years I've had both a pharmacist and a medico tell me that I could use paracetamol over long periods without any ill-effects and that combining it with aspirin was no problem so long as I didn't exceed the recommended maximum daily dose (exceeding the dose is extremely injurious to the liver). The pharmacist even suggested it was one of the safest drugs known. (Despite warnings in almost every pharmacopeia about the dangers, unfortunately it seems that lessons from the phenacetin incident haven't been well learned—if anyone knows the reasons for this then we ought to know about it.) Moreover, nothing changed with the introduction of the newer COX-2 selective NSAIDs, rofecoxib (Vioxx), etc. The pharmaceutical companies were still up to their usual deceptive tricks, in this instance Merck was the main culprit in that it deliberately withheld important information about dangers of the drug. Quoting Wiki: "Merck withdrew the drug after disclosures that it withheld information about rofecoxib's risks from doctors and patients for over five years, allegedly resulting in between 88,000 and 140,000 cases of serious heart disease." The utter fucking hide of Merck! I recall this well: in the early 2000s I read an article in Science mag that provided graphic stats that rofecoxib was causing heart attacks. It was of particular interest to me as I was taking the drug for my sore back. At the time I remember thinking that the drug would soon be banned even if it turned out that the article's data was found to be exaggerated (the damaging stats were too bad to think otherwise). That said, rofecoxib wasn't banned immediately despite overwhelming evidence against it; in fact, it took about three years from the publication of the Science article before Merck withdrew the drug from the market. That delay was unforgivable. If ever there were a case to regulate these pharmaceutical bastards tightly then the Vioxx/rofecoxib incident is a quintessential example. __ † The problems of opiate addiction became widely understood by the medical profession in the light of the US Civil War when the hypodermic needle first came into widespread use to administer opiates on the battlefield.
pmoriarty 5y ago
"I wonder why so many HN readers are interested in phenethylamine-type chemicals." First, MDMA is a phenethylamine, and it's one of the most popular psychedelics. Second, if you look at the trip reports of the "magical half-dozen"[1], they sound amazing, so they're pretty interesting just for that. Third, even if one never does any of the phnethylamines in PiHKAL (I personally haven't, except for MDMA once many decades ago) they're still fascinating in terms of their effects, the potential for research and further development, and PiHKAL the book is interesting and admirable for the wealth of information it revealed on previously unknown compounds, the story of how they came to be, and all the self-experimentation Shulgin and his friends did. [1] - https://en.wikipedia.org/wiki/PiHKAL#Magical_half-dozen https://en.wikipedia.org/wiki/PiHKAL#Magical_half-dozen
- jobs_throwaway 5y ago
  reading about the magical half-dozen is one of my favorite internet rabbit holes. None are easy to come by, but if I ever get my hands on STP I'd love to give it a try.
  - hilbert42 5y ago
    You're right, I too have a high level of curiosity and interest in phenethylamines even if I'm not taking or making them. My interest centers around two main reasons, the first is that such simple molecules can have such a dramatic effect on the brain and that relatively few changes to the basic amphetamine molecule can elicit such large changes in one's perception (i.e.: from one molecule to the next). The second is that I'm always been surprised about how little of these chemicals are needed to have an effect - we never talk in grams, which itself is a small enough unit, but rather always in milligrams. It's not only drugs but also poisons where milligrams can kill within minutes or even seconds - we all know how deadly chemicals with the structure x-CN are and how little of them is needed. I see an analogy between these chemicals and electronics. They act somewhat like high gain amplifiers with control circuits attached - that is they have gain as well as great specificity of action. I don't take a huge interest in how individual phenethylamines are made but rather the fact that there are so many of them and that there are so many ways of synthesizing each one. As soon as some precursor becomes difficult to get then some ingenious chemist finds a substitute together with a new method of synthesis. I'd say I'm more curious about chemists who are even more ingenious than those mentioned - those who break new ground in chemistry. Especially so when it comes to the synthesis of iconicially difficult molecules such as strychnine. This notorious and highly toxic poison (I know, as an evil bastard poisoned my dog with it when I was a kid and I watched horrified as he died in agony) - is also notoriously difficult to synthesize and has always been a challenge for chemists. It's the go-to molecule to synthesize if one wants a challenge, its synthesis challenged the greatest of chemists until the legendary Robert Woodward and his team managed to do so in 1954: https://en.m.wikipedia.org/wiki/Strychnine_total_synthesis https://en.m.wikipedia.org/wiki/Strychnine_total_synthesis. I'd reckon, even today, if one came up with a new synthesis for it then one would be recognized to be at the very top of the profession. You say reading about phenethylamines is one of your favorite internet rabbit holes. Whilst it's mine and obviously that of many others too, I'm somewhat paranoid at spending too much time doing so for fear of attracting too much attention. I had this feeling the last time phenethylamines came up on HN some five months ago, especially so after I followed a poster's link to Uncle Fester's (aka Steven Preisler) Secrets of Methamphetamine Manufacture which turned out to be on Wikileaks (I later learned it's also on the Internet Archive which is perhaps somewhat more innocuous (but likely not given the book's notorious content)). BTW, I think that Preisler's publication of this document was irresponsible for all concerned - not for publication of the chemistry per se but rather the huge amounts of volatile chemicals he recommends without giving all the necessary warnings. Some novice could easily kill himself and others around him if Preisler's directions were followed (the quantities he suggested were more in keeping with those of a registered pharmaceutical lab than a backyard chemist). You can't blame responsible people for being concerned with such publications and I said so in a follow-up post at the time.
ipnon 5y ago
That Silicon Valley is down the road from San Francisco is the simplest explanation. The computer revolution and the psychedelic revolution happened almost concurrently in nearly the same place. N+1 Magazine had a great article called Googlebang, which I cannot find now, describing the phenomenon of the Internet being a radical space filled with pornography, occultism, and drug information because the Internet inherited the culture of Northern California where it was born instead of the rest of the world where it spread.
- pmoriarty 5y ago
  I'm not sure if that alone explains it as there are probably plenty of people in the SF Bay Area that have never tried and have no interest in psychedelics. I wish it wasn't so, but except maybe during the heyday of psychedelia in the 60's when LSD was legal, psychedelic users even in the SF Bay Area have probably been in the minority. My guess is that it takes a certain type to have tried psychedelics after they were made illegal and before the Psychedelic Renaissance. It took a certain amount of curiosity, daring, and non-conformity that most people don't have.
tlb 5y ago
I'm extremely interested in the mind and how it works. The ways that it can work differently under chemical stimulus seems helpful to understanding it better. It hints at a few dimensions of the vast parameter space that alternative (biological, alien, or AI) minds could exist in.

dylan604 5y ago

>come out of a reputable pharmaceutical company Please, name one of these reputable companies for me. One that does not push pills based on their bottom line but for actually improving the health of users. One that has not been known for rewarding doctors for pushing their pill over a competitors pill. One that does not have advertisments on TV/print/internet that talk about a side effect might be death, but still encourage random people to push their doctors.

hilbert42 5y ago
"...name one of these reputable companies for me." You're right of course, I cannot (and I fully agree with your points and sentiments). What I should have said is 'pharmaceutical companies that employ proper industrial control processes to ensure that what's inside the box is the same as printed on the packet' but that seemed a bit long-winded. In hindsight, putting 'reputable' in quotes would have been a better option. Apologies for the following rave but I'm likely a stronger advocate on these points than you are. ;-) In my defense I would let you know that if you were to look back into the archives of my HN posts—mind you, I'm not suggesting that you waste time actually doing so—then you would note that I've been one of the most outspoken, voracious and unquenchable critics of the Sackler family and Purdue Pharmaceuticals to post on HN. I consider what happened over the opioid epidemic not only an unforgivable failure on the part of the Sacklers and Purdue and that they have essentially gotten away with murder—the settlement being an unmitigated damn farce—but also a major systemic failure of Government (of the regulators/FDA) and of the medical profession in general. How 150-plus† years of knowledge about opiates and opiate addiction—basic info that's a compulsory default requirement in 101 pharmacy/medicine—can be chucked out and ignored by the regulators and the medical profession alike simply defies adequate description let alone understanding. How the fuck did this happen, why have others, regulators, guilty MDs, etc., also not been brought to task over the matter? After all, everyone knows that outside certain radioactive nuclides and chemical weapons, VX etc., opiates are the most controlled and regulated chemicals on earth and have been governed by international treaties for going on 100 years. We still don't know how this happened and we still need a full and better accounting of what exactly went wrong. Moreover, I've been an advocate for much tighter government control and regulation of drug companies and have held this view long before the Purdue incident. Similarly, I believe that we need to review drug patent laws to stop pharmaceutical companies exploiting consumers—I could write pages on this but I'll spare you the details. I'd also ban drug advertisements, especially so those that are aimed at the public. I have a particular concern over the continued promotion of drugs on TV and elsewhere, especially so the promotion of the coal-tar antipyretic class of drugs—the NSAIDs such as ibuprofen, paracetamol (acetaminophen), etc. as being safe, fix-all painkillers (even if not mentioned, that's the effect of such promotions). They aren't as safe as made out in ads, and they're especially dangerous with long-term use, but drug companies promote them as safe and governments continue to allow such promotions without warnings and caveats. (Incidentally, expert medical knowledge isn't necessary to determine the dangers of using these drugs as their dangers are well documented in any number of pharmacopeias, even Wiki has their side-effects well covered.) These antiquated 19th-Century drugs [paracetamol possibly made as early as 1852—see Wiki] are more dangerous than even many medicos think (the possible exception being the salicylates (aspirin) but even it has dangers). We have been progressively eliminating numbers of these ancient NSAIDs from the pharmacopeia since the 1930s—that is whenever we realize their kill-rate has become unacceptably high we move on to the next least dangerous one on the list instead of banning all of them outright (the last of the old ones still standing is paracetamol, its immediate forerunner, phenacetin, having since fallen). For example: acetanilide, pyrazolone, phenazone, amidopyrin (pyramidon), phenacetin, phenylbutazone (butazolidin) all derive from the 19th C. or from precursors that do. All have been progressively banned over a 30-40 year period (or in some instances their use limited to very specific applications), however it was obvious early on that these drugs were very dangerous and should not have been put in service (or at least withdrawn much earlier). Back in the late 1950s and 1960s there was a huge kerfuffle over the dangers of use of phenacetin, especially so when mixed with aspirin and caffeine in a combination known as 'APC'—a concoction which had been in prior use for some 40 or so years. There were many thousands of cases of rotted-out kidneys as a result of their use. What's not generally understood is that phenacetin is metabolized into paracetamol and it's the paracetamol that provides the pain relief (but paracetamol can easily be life-threatening and kills many people every year). Wiki states that phenacetin was withdrawn in Canada in 1973 and by the U.S. FDA in 1983. Why the delay of some 10 - 20 years after it was known for certain that phenacetin was dangerous, even carcinogenic? I know this delay to be factual because I can remember the widespread publicity about the dangers of phenacetin as a kid in the 1960s. (Incidentally, in recent years I've had both a pharmacist and a medico tell me that I could use paracetamol over long periods without any ill-effects and that combining it with aspirin was no problem so long as I didn't exceed the recommended maximum daily dose (exceeding the dose is extremely injurious to the liver). The pharmacist even suggested it was one of the safest drugs known. (Despite warnings in almost every pharmacopeia about the dangers, unfortunately it seems that lessons from the phenacetin incident haven't been well learned—if anyone knows the reasons for this then we ought to know about it.) Moreover, nothing changed with the introduction of the newer COX-2 selective NSAIDs, rofecoxib (Vioxx), etc. The pharmaceutical companies were still up to their usual deceptive tricks, in this instance Merck was the main culprit in that it deliberately withheld important information about dangers of the drug. Quoting Wiki: "Merck withdrew the drug after disclosures that it withheld information about rofecoxib's risks from doctors and patients for over five years, allegedly resulting in between 88,000 and 140,000 cases of serious heart disease." The utter fucking hide of Merck! I recall this well: in the early 2000s I read an article in Science mag that provided graphic stats that rofecoxib was causing heart attacks. It was of particular interest to me as I was taking the drug for my sore back. At the time I remember thinking that the drug would soon be banned even if it turned out that the article's data was found to be exaggerated (the damaging stats were too bad to think otherwise). That said, rofecoxib wasn't banned immediately despite overwhelming evidence against it; in fact, it took about three years from the publication of the Science article before Merck withdrew the drug from the market. That delay was unforgivable. If ever there were a case to regulate these pharmaceutical bastards tightly then the Vioxx/rofecoxib incident is a quintessential example. __ † The problems of opiate addiction became widely understood by the medical profession in the light of the US Civil War when the hypodermic needle first came into widespread use to administer opiates on the battlefield.

pmoriarty 5y ago

"I wonder why so many HN readers are interested in phenethylamine-type chemicals." First, MDMA is a phenethylamine, and it's one of the most popular psychedelics. Second, if you look at the trip reports of the "magical half-dozen"[1], they sound amazing, so they're pretty interesting just for that. Third, even if one never does any of the phnethylamines in PiHKAL (I personally haven't, except for MDMA once many decades ago) they're still fascinating in terms of their effects, the potential for research and further development, and PiHKAL the book is interesting and admirable for the wealth of information it revealed on previously unknown compounds, the story of how they came to be, and all the self-experimentation Shulgin and his friends did. [1] - https://en.wikipedia.org/wiki/PiHKAL#Magical_half-dozen https://en.wikipedia.org/wiki/PiHKAL#Magical_half-dozen

jobs_throwaway 5y ago
reading about the magical half-dozen is one of my favorite internet rabbit holes. None are easy to come by, but if I ever get my hands on STP I'd love to give it a try.
- hilbert42 5y ago
  You're right, I too have a high level of curiosity and interest in phenethylamines even if I'm not taking or making them. My interest centers around two main reasons, the first is that such simple molecules can have such a dramatic effect on the brain and that relatively few changes to the basic amphetamine molecule can elicit such large changes in one's perception (i.e.: from one molecule to the next). The second is that I'm always been surprised about how little of these chemicals are needed to have an effect - we never talk in grams, which itself is a small enough unit, but rather always in milligrams. It's not only drugs but also poisons where milligrams can kill within minutes or even seconds - we all know how deadly chemicals with the structure x-CN are and how little of them is needed. I see an analogy between these chemicals and electronics. They act somewhat like high gain amplifiers with control circuits attached - that is they have gain as well as great specificity of action. I don't take a huge interest in how individual phenethylamines are made but rather the fact that there are so many of them and that there are so many ways of synthesizing each one. As soon as some precursor becomes difficult to get then some ingenious chemist finds a substitute together with a new method of synthesis. I'd say I'm more curious about chemists who are even more ingenious than those mentioned - those who break new ground in chemistry. Especially so when it comes to the synthesis of iconicially difficult molecules such as strychnine. This notorious and highly toxic poison (I know, as an evil bastard poisoned my dog with it when I was a kid and I watched horrified as he died in agony) - is also notoriously difficult to synthesize and has always been a challenge for chemists. It's the go-to molecule to synthesize if one wants a challenge, its synthesis challenged the greatest of chemists until the legendary Robert Woodward and his team managed to do so in 1954: https://en.m.wikipedia.org/wiki/Strychnine_total_synthesis https://en.m.wikipedia.org/wiki/Strychnine_total_synthesis. I'd reckon, even today, if one came up with a new synthesis for it then one would be recognized to be at the very top of the profession. You say reading about phenethylamines is one of your favorite internet rabbit holes. Whilst it's mine and obviously that of many others too, I'm somewhat paranoid at spending too much time doing so for fear of attracting too much attention. I had this feeling the last time phenethylamines came up on HN some five months ago, especially so after I followed a poster's link to Uncle Fester's (aka Steven Preisler) Secrets of Methamphetamine Manufacture which turned out to be on Wikileaks (I later learned it's also on the Internet Archive which is perhaps somewhat more innocuous (but likely not given the book's notorious content)). BTW, I think that Preisler's publication of this document was irresponsible for all concerned - not for publication of the chemistry per se but rather the huge amounts of volatile chemicals he recommends without giving all the necessary warnings. Some novice could easily kill himself and others around him if Preisler's directions were followed (the quantities he suggested were more in keeping with those of a registered pharmaceutical lab than a backyard chemist). You can't blame responsible people for being concerned with such publications and I said so in a follow-up post at the time.

ipnon 5y ago

That Silicon Valley is down the road from San Francisco is the simplest explanation. The computer revolution and the psychedelic revolution happened almost concurrently in nearly the same place. N+1 Magazine had a great article called Googlebang, which I cannot find now, describing the phenomenon of the Internet being a radical space filled with pornography, occultism, and drug information because the Internet inherited the culture of Northern California where it was born instead of the rest of the world where it spread.

pmoriarty 5y ago
I'm not sure if that alone explains it as there are probably plenty of people in the SF Bay Area that have never tried and have no interest in psychedelics. I wish it wasn't so, but except maybe during the heyday of psychedelia in the 60's when LSD was legal, psychedelic users even in the SF Bay Area have probably been in the minority. My guess is that it takes a certain type to have tried psychedelics after they were made illegal and before the Psychedelic Renaissance. It took a certain amount of curiosity, daring, and non-conformity that most people don't have.

tlb 5y ago

I'm extremely interested in the mind and how it works. The ways that it can work differently under chemical stimulus seems helpful to understanding it better. It hints at a few dimensions of the vast parameter space that alternative (biological, alien, or AI) minds could exist in.