The inventor of ibuprofen tested the drug on his own hangover | Hacker News Reader

The inventor of ibuprofen tested the drug on his own hangover

smithsonianmag.com

168 pointsthrusong196 comments

Ibuprofen is a true miracle drug. The team that discovered it routinely tested candidates on themselves. This wasn't uncommon in medicinal chemistry. My dad and his colleagues did it at Merck in the '70s. In one case, he and his lab partner took a candidate appetite suppressant (serotonergic) and went out for Chinese. They ate like kings and concluded it didn't work.

That's one way to get a free lunch paid by the company.

I wonder if the decline of this style of testing is one reason the rate of progress is lower today.

Possibly, also possible this type of testing worked great when the low hanging fruit was available. When there was easier discovery of miracle molecules.

It's almost certainly a factor, in the same way that improvements in safety standards and stronger adherence to them have slowed progress and increased cost in construction (and many other fields).

I don't think it's controversial to state that. Where it gets controversial is in what value judgements you place on it, because to a large extent it boils down to 'how much human life are you willing to risk for how much progress?'.

Less of an issue if it's an individual choosing freely to risk their own neck, but hard to distance even that from whatever safety culture and norms surround them. Perhaps less people take these risks today because it's no longer the norm in their field.

Of course if it goes really bad(fatal or stroke or something), you just lost years of expensive science education just to test a drug that's not gonna work. Sure it's faster if you get it right, but the if you do the math on doing this as the standard method it would quickly be fae too costly to society.

At least that's my take on why this is perhaps not the most ideal methodology in terms of opportunity cost.

Definitely shouldn't be considered "standard", the value judgement would be left to the inventor who decides whether or not to take it.

This. I live in Africa where I estimate we have at a minimum a few decades to go to catch up with the world when it comes to everyone having a decent house to live in. Trouble is in the towns some of the modern construction rules have slowed things down considerably. No I am not advocating for having no rules but I contend that when the more advanced countries started building hundreds of years ago they didn't have to contend with modern building laws we are having to contend with.

What is interesting is that there are no building codes to conform to in the village. So you can build as you please.

New construction slowing down isn't too much of a problem if the construction lasts longer and costs less to maintain.

When you a few hundred years behind most of the world it is a problem. I don't know of any building in sub Saharan Africa that predates the colonialists. I know Egypt and North Africa do have old buildings but not where I am from.

Result is overcrowding and people living in shacks.

great zimbabwe and other ruins in southern africa predate the colonists others like benin city were destroyed by the colonists

I get your point but I was specifically refering to houses in cities that people live in. The majority of houses were mud huts in Zimbabwe and these were not dwellings passed on from generation to generation. This is contrast to cities like London were some buildings have been standing for hundreds of years. This means new generations are not starting building from scratch.

What makes you think new construction would last longer? If anything, new innovations in building techniques and materials are optimized to be cheap and last just long enough.

Lots of great stuff in the pipeline right now, including for obesity.

The difficulty of progress depends on what you try to treat. Otherwise healthy people get pain and swelling. Otherwise healthy people get HIV (my dad is on the patent for one of the world's best-selling HIV drugs). If you concentrate research on afflictions of the dying, progress is harder.

You have nothing to support your claim of "rate of progress" and drug safety is significantly improved from fifty years ago when drugs would turn out to have mutagenic effects on unborn kids and such.

Not really because any good scientist knows a unblinded, uncontrolled sample of 1 doesn’t tell you much.

A not uncommon scenario. Here's how the first "upper endoscopy" was performed in the 1950s, after a GI fellow at the University of Michigan read a foundational paper about fiberoptic cable in Nature:

Hirschowitz, like a lot of fellows and young researchers in science, first tested the device on himself in February 1957. He managed to control his own gag reflex, passed through his esophagus and looked around in his own stomach. He then scoped a patient indicated on the slide as patient #2. A most remarkable aspect of this discovery was that it was not supported by grants and was carried out by a GI fellow, and two physicists who worked very hard to create this incredible advance.

The same talk also notes the Australian researcher who discovered the role of Helicobacter pylori in curing stomach ulcers tested the culture on himself:

He stated that his halitosis was so bad, that his wife told him that he had to sleep on the couch. After the infection was established he treated himself with the anti-Helicobacter therapy and completely recovered.

https://blogs.harvard.edu/lamont/2020/01/30/advances-gastroe...

Yeah, a genius heroin addict friend of mine drew a molecular structure for a new opioid[0] on the back of a napkin and sent it off to a synthetic chemist in China to be synthesised. To my infinite horror I actually tried a dose of what came back, at the same time as he took his dose, and in the recommended (high!) dosage of what I think was a decent chunk of a gramme. Luckily it worked. I can well see how someone could have the confidence to try something as mild as ibuprofen.

[0] Or pseudo-opioid, I'm not sure. He's a biologist and I'm not a natural scientist at all. All I recall is that it was a positive allosteric modulator of the mu opioid receptor, which, by and large, may as well be Greek to me.

Pseudo-opioid sounds right to me. Typically opioids are agonists at MOR, i.e activate the receptor on their own. Whereas a PAM binds to a separate binding site, and increases the effect of binding by the endogenous neurotransmitter(hence it positively modulates it).

How the increased effect actually happens depends on the receptor and can get pretty complicated so I won't go into it since I'd have to google quite a bit.

I'm pretty sure the Hamilton Morris podcast would like to interview your friend. Anonymously, of course. https://www.patreon.com/HamiltonMorris

Not to forget about the first heart catheterization done by Werner Forstsmann on himself and awarding him the Nobel prize. https://en.m.wikipedia.org/wiki/Werner_Forssmann

Worth noting that the two great psychedelic alchemists - Albert Hofmann and Sasha Shulgin - conducted human tests with their own persons. It couldn't be otherwise..."Uh, Someone Who Isn't Me and their dog report that this stuff is pretty interesting..."

Ah, "Sasha" aka "Alexander" Shulgin, who died in 2014. His obituary [1] is worth a read. The book Phenethylamines I Have Known And Loved: A Chemical Love Story by Alexander and Ann Shulgin, his wife, documents their experiences with lots of drugs, and at various dosages, that he created. The book also contains instructions for synthesis etc. It's still in print, and a version of the second part - dealing with the chemicals, but not the experiences - is freely available online at [2].

EDITED to amend the above to clarify that link [2] contains only the second part of the book, and to add that the full book can be downloaded via [3]. FURTHER edited to add download links from Z-library [4].

[1] https://www.theguardian.com/science/2014/jun/03/alexander-sh...

[2] https://erowid.org/library/books_online/pihkal/pihkal.shtml

[3] https://libgen.is/search.php?req=PiHKAL%3A+A+Chemical+Love+S...

[4] https://b-ok.cc/s/?q=%22PiHKAL%3A+A+Chemical+Love+Story%22

They also wrote an equivalent book on tryptamines. Same name and url except p -> t.

Another note: IIRC, I believe it wasn't just Shulgin and his wife who tested the drugs, but also a small group of friends that he'd give samples.

Cheers.

> ... it wasn't just Shulgin and his wife who tested the drugs, but also a small group of friends ...

Yes, indeed - also tested with friends, and some of those accounts are included in part one of the book. Thanks for the correction.

Huh? Halitosis can also be caused by gastric issues? Thanks for the info! I thought it was purely a dental / oral issue and have been trying to tackle it like that. Perhaps I should pay a visit to a general physician.

Yes, if you have H.Pylori it can cause all sorts of problems, acid reflux, bad breath, gastritis, ulcers, etc. I'm no doctor but I have been tested for this in the past; I think it was just a blood test, nothing invasive, and it's curable.

Better to get it sorted sooner than later. That GP visit can also be a good time to ask about all sorts of other small issues, and a blood test is a good idea at least every year or two. Ask about hormone levels, iron, vitamins, everything; for you it's just a lab visit.

I can't wait until it's possible to get these tests a few times a year and have all the values charted somewhere tied into the personal health ecosystem. Ironically, as someone interested in online privacy, I find the medical data the least concerning; I'm willing to let all of that go if it means I can get back some good answers or better healthcare. I can understand why some people aren't, of course, and they should always have the right to it; and it's good that this medical industry privacy situation is influencing other industries as well. But still! Imagine if some ML system with access to the data of a million people like me could show me exactly what I should stop eating, or exactly what supplement I need more of....

Please don't take this as criticism, but your last paragraph sounds similar to the initial vision behind Theranos. That's not meant to imply that it's a bad idea.

I'm referring to the "testing several times a year, and using ML on the aggregated data"

Yeah, I do an annual health checkup every year. (Healthcare is thankfully cheap for me in India).

> ...I have been tested for this in the past; I think it was just a blood test...

Since you are interested in this subject - Have been reading on this and apparently a blood test for H.Pylori is no longer suggested as it only tests for anti-bodies which can be still be present after the infection is over. So a stool test is now the recommended way to find if you still have that particular germ inside you.

Oh, I remember the case. Nobody believed Barry Marshal and he had to use radical method of getting solid proof - infect and cure himself. I admire the man.

This reminds me of chloroform.

Some scientists were hanging out “experimenting” with substances they made (presumably huffing things and getting high?) when they apparently realized chloroform could have medical applications.

So, one of them used it on a patient a couple days later.

They claimed they had discovered this property of chloroform independently, but it had been described as an anaesthetic a couple years earlier.

Regardless, medicine in the 1800s was pretty fast and loose.

I love reading old medicine books, they include stuff like wine pairings for medications

These days, I'd use Reddit for that.

Same with old bird books, some of the originals have tasting notes for each of the birds they described.

Love me some red sparrow at the top o' the mornin'.

With a nice Cabernet

I found a "Backwoods Surgery and Medicine" book from 1910 at my grandparent's house. Half of the pain-related guidance involved cocaine in some form.

If people didn't enjoy it so much, it would probably be an impressively flexible medication.

If we ever legalized it it would probably replace or augment caffeine in just about everything overnight.

But aren’t there probably long term harmful consequences of cocaine even in small doses?

Pure cocaine? Maybe? But many people do smaller amounts for years and we don’t know about it.

What I‘ve always wondered what drugs is it that burn people out in that recognizable way. And what ones are fairly recoverable.

indiginous people have been consuming coca leaves with no bad effects for thousands of years. the dose makes the poison.

by comparison, if you snorted pure caffine powder. you'd literally die

Have a source/pictures you can link to?

My grandfather was given a Guinness daily when he was in the hospital recovering from colon surgery in the 1960s. It was thought the iron in it was helpful.

Now I'm just imaging seeing a hospital bill were they charged me $20 for a Guiness or something.

Complimentary healthcare as it should be! Now I'm not sure if an Ibuprofen will be $70 or $500

Depending on the bar and the city, a $20 Guinness is readily achievable today.

Hospitals can do better!

$270, negotiated down to $120 billed to insurance. You pay $15. Bill received in 6-9 months. Thank you for your business.

> You pay $15

Only if you complain and ask for a detailed list.

This reads like my Cigna explanation of benefits

In VA hospitals it was not uncommon to give a patient N beers per day to match their typical consumption to avoid them going into alcohol withdrawal during their stay.

I don't know what VA is but in the UK they will attempt to maintain any addictions so the withdrawal does not affect the patient.

For example, if you're a smoker I guess they give you nicotine patches or something.

VA is veterans' services in the US. I can't remember what the A stands for

Veterans Affairs

Cigarettes were often prescribed for depression in the 60's I'm told. Nicotine is an anti depressant.

My mother was prescribed a glass of Guinness a day by her Ob/Gyn when she was pregnant with me in the 70s for the same reason.

> Regardless, medicine in the 1800s was pretty fast and loose.

There's a good series about the early days of modern medicine:

https://www.imdb.com/title/tt2937900/

Look up "hysteria" and how 1800's doctors thought about the womenfolk. And the prescribed treatment was pretty eyebrow raising as well.

Nitrous oxide was a recreational drug for 40 years before someone had the bright idea to use it during surgery.

One interesting non-obvious use for ibuprofen is that it'll relieve some sore throat symptoms. I discovered this when I took some for a headache while I had a cold some years back.

Or maybe that was only non-obvious to me, but I sure wish somebody had told me about that 15-20 years earlier.

You wanted to be told what, exactly? That an anti-inflammatory reduces inflammation?

Isn't a bit of inflammation and fever actually healthy ? By cancelling them I would have guessed that you partially disable the immune reaction ?

I wonder about this, and for antihistamines as well.

This is a well documented warning of antihistamines; if you have an infection you should not use them.

And you should definitely not continue use after 3 days with no improvementn in symptoms.

You also should avoid using steroids when you have an infection (many antihistamines are steroids) (unless you're fighting the immune response). The risks increase more with fungal infections than bacterial or viral. (So much that it was a popular trope in House MD that if it was fungal or the infection was causing sepsis then the steroids would kill the patientl https://www.healthline.com/health-news/overuse-of-steroid-me...

Rarely, if ever.

There's at least some hints that short term inflammation might be good, and not something you always want to suppress with ibuprofen etc.

https://www.sciencealert.com/intriguing-study-suggests-infla...

From what I understand, inflammation is a side effect of the process.

Fever yes. You shouldnt generally cancel it (except it goes over 40.5). If you do, disease lasts longer and there is also evidence it helps with cance.

I mean, maybe it's just me, but I always figured a sore throat was more like an itchy skin rash than a stiff swollen knee. I'd only take ibuprofen for the swollen knee.

IANAD, if that's not obvious by now: https://xkcd.com/2647/

Yes, my heuristic for ibuprofen vs. acetaminophen is whether there is swelling involved. Ibuprofen helped me a bit to manage a sore, swollen throat due to COVID. (But the corticoids I was prescribed are what really did the trick.)

[Edit: IANAD]

Could that be because swelling is an inflammation and ibuprofen is an anti-inflammatory drug ("AID" part of "NSAID"), whereas acetaminophen is not an NSAID?

[IANAD]

Of course, but as parent comment suggests, not everyone knows this.

I usually just take both, and even then, I sometimes wonder if they actually do anything or if it's just a mass scale placebo conspiracy.

My personal experience is that ibuprofen has no effect whatsoever in any situation, and acetaminophen quickly brings me back from near death when I have a fever.

Interesting. My experience is the opposite. Aspirin and Tylenol never seemed to do anything for me, but Ibuprofen will rid me of a headache usually withing about 45 minutes. I still remember thinking the first time I tried it, "holy shit! This actually does something!"

I use it for sunburn. Another less commonly associated ailment that it works great with.

It seems like pain killers work differently on different people. I wonder if there is data on this? For me, ibuprofen always helps with any type of pain or itching/irritation.

Most people who end up needing a lot of painkillers end up choosing one favorite. For my migraines it's ibuprofen, my dad swears by celebrex, some people prefer naproxen sodium, etc.

The frustrating thing when traveling is that a ton of countries are very heavily invested into acetaminophen. That stuff is toxic, has a nasty overdose profile, and doesn't really work at all for me, but sometimes it's all you can find.

As European, it's mind-boggling when I see those 1,000 tab containers at Walgreens, given that I usually buy them in a pack of 12 and only take them very selectively as a last instance. You know, side-effects and stuff.

If you’re willing to share, what side effects do you get from ibuprofen? I have none, or at least the side effects are not noticeable in comparison to the pain I’d otherwise be in.

That concerns not only ibuprofen but it may cause heart or kidney issues. I think it can't hurt trying to only take it as a last resort.

The dose where those are an issue are way above the "maximum dose" noted on the OTC posology

Doctors routinely tell patients to use way above the maximum OTC dose when instructing them on how to treat difficult muscle problems like back problems. (Please don't do that except under specific instruction).

Not good for the liver, kidneys in the long term I guess (if you take it daily)

Apparently there are people who will add Tylenol or ibuprofen or aspirin to their daily cocktail of pills even if they don’t feel bad at all. Amazes me.

Low doses of asprin are (were?) sometimes used as prophylactic treatment for people at high risk of stroke or heart disease.

It's not a panacea--and more recent data suggests that it's probably overused--but the idea itself isn't bonkers.

Low dose aspirin daily is recommended by cardiologists in my country as a preventative/protective measure against heart disease.

You're thinking of paracetamol / acetaminophen. Ibuprofen has little effects on the liver / kidneys.

I'm sorry

ibuprofen is ignored by the liver which says a lot about its safety.

Nah, Ibuprofen definitely affects the kidneys. It's on my mental list of medications never to try again. It always leaves me writhing in pain (thought it was my lower back that was on fire, turns out it was my kidneys).

Have you ever tried dipyrone? Never had issues with kidneys with Ibuprofen, mostly noticed it with the stomach, but dipyrone was very noticeably affecting my kidneys.

Nope. Along with GI bleeds, kidney toxicity is an issue.

https://www.uptodate.com/contents/nsaids-acute-kidney-injury

(European here as well, so I'm referring to way lower dosages compared for example to the US)

I don't have any 100% proof of it being caused by painkillers, however years ago I took Ibuprofen based painkillers on unusual higher dosage for some time to fight against pretty nasty back pains (driving exclusively bikes for 38 years comes at a price). After some time I developed some strong anemia, which scared me a lot for having a bad family history (some cancer cases, and my father died of leukemia); by my doctor's advice I did repeated blood tests and stopped taking painkillers for a while (and later never get again to that dosage) while starting a cure with iron and folate. Red blood cells took a while to fully recover but ultimately they did.

About backpains, I later learned with immense relief that in many cases postural training will lead to results that painkiller can only dream of: I still have my back problems, and after a motorcycle accident also a stabilized column with screws et al, but no need for painkillers: I keep them for headaches or other things, but my back has never been so damaged and so pain free (touches various things...:).

> what side effects do you get from ibuprofen

What if I use it more than a two days straight there is something really wrong with me, so I should drop everything and start emergency recovery procedures, involving a visit to a doc or seek an emergency care

Ibuprofen or other NSAIDs taken in high enough concentrations for long enough can lead to peptic ulcers, and depending on the person those concentrations can be within the recommended dosing limits.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478398/

I've given myself a peptic ulcer while awaiting a root canal. I had odd eating habits (especially in hot periods) and also like beers... bad combo with handfuls of Advil.

full body hives (about 2% of population has allergy to ibuprofen)

Regular use of Ibuprofen is not good for the gastric mucosa, overuse can lead to gastritis and stomach ulcers.

I was surprised like you too, but later I realized that people were popping pills at that rate because it is used as substitute for primary care which is both expensive and sometimes not easy to schedule, unless it ER getting an appointment can take a lot of time here .

Took me a week to a see a dentist, I popped more pills than last 10 years to keep going for a week before I could get prescriptions that actually solved the problem.

No, really, it's safe, and it's a good painkiller and that's it.

The Europeans have it wrong on this one.

There's no reason not to have regular dose variations at the drug store.

Long term use of NSAIDs may (probably?) contribute to chronic pain:

https://bgr.com/science/nsaids-like-ibuprofen-may-actually-b...

(Original paper: https://www.science.org/doi/10.1126/scitranslmed.abj9954)

Yes, but that's not a reason to have anything fundamentally different.

I do think maybe some things, he 'first time you buy' you should have the pharmacist spell it out for you. Or it's even 'behind the counter' and you just have to ask for it i.e. 'controlled substance'.

But I'm not sure if effectively it would make a change, other than the way it's sold in 'huge quantities' makes people believe they can just eat it up willy nilly.

It may be safe in by itself, but using a painkiller only masks the pain, the underlying issue is addressed later or never and that can create problems for you.

Also when the body signals with pain, that needs attention and treatment, taking painkillers frequently may make one ignore a real problem, which perhaps had it been taken more seriously and treated earlier may save lives.

The US has an opiate epidemic in no small parts due to a overprescription and "just medicate the problem away, can't take a day off" mentality.

A while ago there was a very relevant article about this on HN, an American woman moved to Germany and had some surgery done. She had pain after the surgery, and from her American experiences she expected to be given heavy painkillers.

Instead the doctors prescribed her ibuprofen and told to rest well. At first she felt that was barbaric, but the article described how actually taking a rest to heal up, completely changed her view and how ultimately she was very glad not having had to depend on opiates to get trough that.

I wish I could find that article again, but sadly I couldn't, maybe somebody else remembers it and can share the link.

Ibuprofen is not addictive, it's in the same class as Tylenol, really. It's just not a problem. It doesn't make you high either.

"It was later renamed ibuprofen and is now one of the world’s most popular nonsteroidal anti-inflammatory drugs (NSAIDs) under the brand names of Brufen, Advil, Motrin, Nurofen and others. It is estimated that one package of the product is sold every three seconds in the United States."

Combined paracetamol and ibuprofen is king Ive found and they both work well together and dont seem dangerous. If you follow the dosage. Combine with Caffeine too.

>It's safe to take ibuprofen with paracetamol or codeine.

https://www.nhs.uk/medicines/ibuprofen-for-adults/taking-ibu...

For those who don't know, paracetamol is also known as acetaminophen.

Goody's is my go-to for headaches and minor aches and pains. It's sold in powder packs here in the US with some optional flavoring added and contains acetaminophen, aspirin, and caffeine.

I believe that's what Excedrin is as well (as a tablet of course)

Paracetamol is also a leader in deadly prescription drug overdoses.

This is because of Percocet and Tramadol that combine opiates and paracetamol.

Paracetamol is easy to overdose on because the opiate is lower in those.

paracetamol is perscription free.

Tramadol is the opiate itself, it does not have paracetamol. There are other brand pills that contain both.

Paracetamol does not contain an opiate. It is a different substance from opiates. It is, however, dangerous to the liver in large amounts.

Because it affects the liver thus large quantities are dangerous and having it with alcohol is dangerous.

This is why ibuprofen is so miraculous; you can take it with alcohol lol.

> Paracetamol poisoning is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia, and New Zealand.

https://en.wikipedia.org/wiki/Paracetamol

> Analysis of national mortality files shows about 450 deaths occur each year from acetaminophen-associated overdoses; 100 of these are unintentional.

https://www.acsh.org/news/2017/09/11/tylenol-far-most-danger...

edit: https://www.propublica.org/article/tylenol-mcneil-fda-use-on...

Almost sounds like a knockoff ECA stack.

Paracetamol and Ibuprofen is a magic mix - and it's safe to throw Codeine on top as well.

From personal experience I've never been wowed by Paracetamol in tablet form, however after experiencing it in liquid form via IV - wow; it's a surprisingly capable analgesic.

I'd also point out that whilst Ibuprofen and other NAISDs can be great for short term inflammation, it can lead to worst long-term healing/outcomes. Depending on how you've damaged yourself (I shattered both my heels) it might actually be more beneficial long term _not_ to use it.

Fun fact, if you're having a lot of headaches and take pain killers daily you can start suffering rebound headaches.

Basically a highly painful headache caused by the pain killers. This creates a nasty feedback loop.

If your suffering head pain try and rotate pain killers and have days of no pain killers.

Of course you should be trying to find out the reasons for the pain so you can stop taking them.

I never would take painkillers daily unless prescribed! That is dangerous and I know it. Why would you think/do this?

> Combined paracetamol and ibuprofen is king Ive found and they both work well together and dont seem dangerous. If you follow the dosage. Combine with Caffeine too.

The way this was worded didn't make it unreasonable to assume you often take painkillers...

Well, I don't think so and I don't? _So...

It's fine that you don't think so, but that's how it was worded.

"Casual" painkiller users tend to take what's on hand and aren't trying to build three medication stacks with caffeine.

When I am in pain I want it to go away. This is what I found works best over the years. Last time I used it getting Covid vaccine after effects fever. So awhile ago.

Excedrin is a stack of acetaminophen, aspirin, and caffeine, I’ve even been prescribed different combinations a few times, and I’ve had more than one doctor tell me how to rotate painkillers to safely maximize the effect and tell me to drink an energy drink with painkillers to make them work better.

I think it’s that doctors are honestly just excited to tell you the fun trivia.

You're being very defensive as if the person who started their comment with "fun fact" had instead started it with "you're an idiot doing wrong things" - nobody was criticising you, nor claiming they knew your frequency of use. They were sharing useful information on a public forum that, if not useful to you, would still be useful to other people who read your first comment.

Because, i believe, the parent comment included ibuprofen into their definition of painkillers. And there are tons of people who take ibuprofen daily.

>And there are tons of people who take ibuprofen daily.

Not me.

Then the comment is for others, not you.

Just because you yourself might be physically fit, that doesn't mean we don't have an obesity epidemic in NA. Apply this same principle to my earlier statement about ibuprofen.

How dangerous though? As someone who has persistent back pain, Ibuprofen seems a lot safer than Codamol

Paracetamol and Ibuprofen is a magic mix - and it's safe to throw Codeine on top as well if the pain warrants it.

From personal experience I've never been wowed by Paracetamol in tablet form, however after experiencing it in liquid form via IV - wow; it's a surprisingly capable analgesic.

edit: spelling

> From personal experience I've never been wowed by Paracetamol in tablet form, however after experiencing it in liquid form via IV - wow; it's a surprisingly capable analgesic.

Part of this is because the oral route is very damaging to some types of substances, I.e. molocules are getting digested before they even reach the liver - where paracetamol/acetaminophen is metabolized and becomes bioavailable.

If I recall correctly, the maximum dosage on the bottle is typically the maximum under the assumption that all of the medicine hits the liver. Because everyone’s gut biomes and digestive enzymes are slightly different, everyone has a different amount that actually reaches the liver. Taking it IV skips the harsh environment of the stomach and doctors can give you the maximum safe dose which ends up being way more than you can get via the oral route at the same level.

> I’d also point out that whilst Ibuprofen and other NAISDs can be great for short term inflammation, it can lead to worst long-term healing/outcomes

I wish this was more studied because, while this is true, there is way more nuance that they’ve been able to capture. My partner is allergic to paracetamol/acetaminophen and stronger pain relievers get compounded with that so she has to get it compounded with ibuprofen. After a surgery she had however, there were few options because her surgeon did not want her to take any kind of blood thinners. Luckily, she is sensitive to the numbing effects of ibuprofen so she takes a low dose (200-400mg vs 800-1200mg) and he gave her the clear to have up to 400mg every 6 hours.

There is also the danger of ulcers developing because it affects the stomach pH drastically, but can be mitigated with large quantities of water or food to help buffer it.

I get migraines (not as frequently as when I was young, but still quite often) and caffeine is key—my pediatrician told my mom to get me a Coke if I was coming on with a migraine, which I was of course thrilled about as a kid.

I also find that combined ibuprofen and acetaminophen has the best results, though if I had to choose one for a desert island I’d take Advil Liqui-Gels since they don’t hurt my stomach if I haven’t eaten/am unable to eat.

Yep, that's the NSAID-acetaminophen-caffeine trifecta that Excedrin uses (and it's generic counterparts, of course).

Last time I had COVID the doctor literally recommended ibuprofen+ paracetamol and caffeine together lol. Not gonna lie, definitely a good cocktail.

So I thought it was unsafe to take for hangovers due to the risk of stomach bleeding… or is it just a matter of waiting long enough after you’ve stopped drinking?

Its amazing how many people eat Ibuprofen like candy. My friend ended up with holes in her stomach, despite the warnings she thought there was little risk (even took Ibuprofen for stomach pain).

It also increases the risk of stroke and heart attack[0]. After finding that out, I don't take it quite as liberally.

[0]https://www.health.harvard.edu/blog/fda-strengthens-warning-...

They really need to quantify this risk. Simply saying it 'increases the risk' is just scaremongering.

Yep, I think most would agree that traveling by car significantly increases the risk of being in a fatal car accident, yet this does not deter people on a daily basis.

A lot of these “X increases the risk of Y” might be true on the whole, but there are so many variables that are not captured and can very drastically affect individual outcomes.

She probably has an underlying condition that's not being addressed. Autoimmune is quite common, but could be lots of things. Diet changes are sometimes enough.

Sometimes a massage gun and Bob and Brad youtube channel will fix muscle knots that are the real issues.

It's not a surprise if you look at the Ibuprofen packaging used in US supermarkets... There's a picture in the article of such a supermarket aisle. You can buy a 750- or even 1000-pack for a few dollars. WTF, how is it a good idea to sell painkillers in such quantities in supermarkets?

If you sell drugs like candy people will eat it like candy.

Or, hear me out, they are less than pennies to produce and don't expire, and I can buy that one bottle for basically many years, for multiple people

Yep. My grandchildren will inherit my Costco bottles of meds.

> If you sell drugs like candy people will eat it like candy.

Even candy shouldn't be eaten like, well, candy.

As a German it's super surreal to me. Ibuprofen are only sold in dedicated pharmacies here, behind the counter, the higher dosages ones even require a prescription from a doctor.

I don't even understand why/how somebody can take/need so many of them in such high dosages. Usually half a 400 mg pill will deal with any headache I occasionally have.

Took higher doses regularly due to problems with my teeth, which had a noticeable bad effect on my stomach. Do people just medicate that away too?

Definitely a better choice than paracetamol, which is metabolized by the liver...

Yeah, don't take paracetamol if your liver is already busy getting rid of the alcohol. However, both alcohol and ibuprofen increase the risk of stomach bleeding, so don't overdo it with ibuprofen either. I'm sometimes shocked how nonchalantly people mix residual alcohol with drugs without checking side effects.

PS: Paracetamol is a drug with pretty low side effects, but the dosage is really important. Even just doubling or tripling the dose can cause acute liver failure.

Paracetamol and alcohol is actually not a dangerous combination at all as far as the liver is concerned. That is why there is no warning against combining the two in the information leaflet that comes with it. Paracetamol is not toxic, but its intermediate metabolite NAPQI is. The enzyme that converts paracetamol into NAPQI is the same that breaks down alcohol, and it has a higher affinity for alcohol meaning that it will be too busy working on the alcohol to turn the paracetamol into toxic NAPQI.

Long-term alcohol abusers will develop more of this enzyme, so they are more likely to get liver damage from paracetamol though.

It's not just ulcers, you can get serious liver damage from combining alcohol and ibuprofen:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921853/#:~:tex....

It is wildly superior to the other option (acetaminophen) which is both ineffective on hangovers and damaging to your liver which is already dealing with the alcohol. Alcoholics may have issues with the stomach lining that can be exacerbated by ibuprofen, but people who are just drinking don't typically have that problem.

It's more a matter of not abusing it. Because it's relatively safe, many people take much, much more than the recommended dose.

How could the inventor of the drug have known at the time? That seems like something that would be discovered later.

That’s true, I was more surprised that the article didn’t have even a passing mention of “hey don’t do this”.

The major part of hangovers is dehydration, try hydrating up, with electrolytes, before going to bed, maybe pop an aspirin if you already feeling the headache come on.

Does ibuprofen actually help with alcohol induced headaches? I've found the only things that can cure a hangover are time or more alcohol.

Works well for me although the best remedy I’ve found is a few rounds of sparkling water at the end of the night

Are you speculating that the carbonation is helping in some way? Otherwise, hydrating to counter dehydration sounds like a reasonable approach.

Perhaps it is the fizzy feeling of the drink that makes it more palatable when you are drunk and your throat is dry after a night of partying.

I think that carbonation actually helps, yes.

It has a positive affect on an irritated stomach lining, I've found. This is easy for me to explain when it's slime/phlegm doing it, as the bubbles helping enzymes and stomach acid dissolve the goo.

I'm seldom enough drunk to have a good sample, but liquor isn't good for the stomach, and I've cautiously drunk a pint of sparkling water with complete success, while knowing that still water would have come back up within five minutes.

Maybe the stimulation of the bubbles promotes the lining to exude what it's supposed to, which alcohol strips away? No idea but I do think it materially helps.

Kind of… For me a cold glass of sparking mineral water tastes a lot better than tap, so I’m far more likely to drink it.

Plus mineral water does contain far more electrolytes than tap which I think has a non-zero effect

works for me too, but vitamin c powder (emergenC or whatever) seems like magic to prevent one before I go to sleep, along with lots of water. I'd love to know why that works so well.

Next time try lots of water, without adding the vitamin C. I got absolutely blasted at my brother's wedding a few months ago, blasted as in I lost an entire hour of dancing and attempting to win an auction of whiskey that I don't even drink. My parents and family were astonished when I woke up the next morning at like 10am, very very groggy but with no headache and actively shoveling greasy hotel breakfast into my stomach to prepare for a 6 hour drive home.

My secret? I was far too drunk to sleep when we got to the hotel so I stayed up drinking about 100oz of water over the course of an hour or so, while sobering up. Just drink water, you probably don't need the vitamin C, or if you somehow messed up your "electrolytes" or something, just sip gatorade.

Most of a hangover is dehydration, or not having enough excess water in your blood to easily expel the literal vinegar the metabolism of ethanol creates.

Yeah massive amounts of water os of course the standard. But the vitaminc/d powder really does do something extra. Its consistent and after a friend told us about it both my wife and I have had success with it after making a dilly mistake like have drinks on an empty stomach or not paying attention to the abv on a bottle. I have no hypothesis why it might work, but I'm absolutely convinced it does so, and well, vs water chugging. Its mainly just the headache you skip. It doesn't replace hydration or speed up metabolism of the alcohol. I think it may speed up conversion of alcohol metabolism byproducts, but I don't know why that would be the case.

According to https://en.wikipedia.org/wiki/Ethanol_metabolism#Acetaldehyd... it seems the ascorbic acid MAY help neutralizing free radicals produced when Acetaldehyde breaks down, though that paragraph seems to be in the context of a pregnant person metabolizing alcohol for some reason.

Same. Though, the article says he took, "a handful" which is a bit more than I'm willing throw down at once.

IDK what a handful means in this case, but 800mg will knock out any headache I have. Obviously I don't take it very often.

800mg is prescription strength, granted I usually just take 2 500mg and a cup of coffee any time I have a headache. IDK if it is the caffeine or the ibuprofen, but any headache will usually be gone within 30 minutes.

My wife's doctor said the optimal does for an average adult is 600 mg (typically 3 pills) - he warned that going below that won't product the same results. When it's been prescribed, it's always 800 mg.

> 800mg is prescription strength

Makes sense that my dr/nurse friends are the ones that told me to do 800mg when I use it (and it worked much better). I typically don't take painkillers, and ibuprofen isn't something to be taken everyday anyway.

Ibuprofen has a really high LD50, at higher dosages it becomes anti-inflammatory.

Lots of water to rehydrate and fresh ginger for the nausea. Ibuprofen only works for the headache, you still need to fix the rest.

Lots of water before going to bed (or ideally, combined with the alcohol intake, 2 glasses of water for every glass of alcoholic drink) is the best preventive measure I know. I guess drinking afterwards might also help.

I don't know how well they work (if at all) but there's quite a market for 'hangover cure' drinks in Japan[0], and I've heard of a tradition of drinking citrusy supplements or anything high in Vitamin C in Japan. It always sounded off to me, but I suppose it would help with mineral depletion.

[0] https://jobsinjapan.com/working-in-japan/japans-famous-anti-...

I wonder if they work because they make it easier to consume a lot of water, just due to the taste

I'm a believer. I don't care if it's superstition, I'll take a gram of C at the drop of a hat. I love the Japanese hangover drinks, E-Mergen-C is not quite as tasty but 30 of them take up the volume of 3 bottled C drinks, for the small kind.

Works better before, but will improve disposition the morning of as well.

I've noticed this as well. I feel like staying awake very late, eating and drinking as I sober a little before going to sleep drunk helps too

Can confirm that. If you're drunk, drink as much water as you can, expel it and drink again; this will help a lot to soften and shorten the hangover, effectively reducing the amount of alcohol in the blood.

Also: salty/"consistent" food. Think burger/ramen. Prevents hangover 100% of the time.

It works because it increases your water retention!

This is the method that works for me. If I go heavy on water between alcoholic drinks I can avoid having a hangover entirely, or at least reduce it to a very mild headache that Ibuprofen can deal with.

The only downside is you will have to use the bathroom a lot.

> I've found the only things that can cure a hangover are time or more alcohol.

Hangovers are due to the aldehydes accumulated IIRC when your body clearance process for alcohol is overrun.

NAC before alcohol or even better, Emoxypine prevents that. Other things might work (vitamin C, glycine) but are less efficient.

Emoxypine is really a miracle cure!

I’ve never heard of NAC or Emoxypine - but here’s what Wikipedia says about the latter:

“In Russia, emoxypine has a wide range of applications in medical practice. It purportedly exercises anxiolytic,[4][5] anti-stress, anti-alcohol, anticonvulsant, nootropic, neuroprotective and anti-inflammatory action.[citation needed] Emoxypine presumably improves cerebral blood circulation, inhibits thrombocyte aggregation, lowers cholesterol levels, has cardioprotective and antiatherosclerotic action.”

Preloading on NAC does seem to work somewhat, will have to try Emoxypine sometime.

It definitely helps with the associated upper back pain that gets amplified when I indulge too much...

> I've found the only things that can cure a hangover are time or more alcohol.

It's called the hair of the dog (that bit you):

https://en.wikipedia.org/wiki/Hair_of_the_dog

I’ve found it pretty effective. Usually I’ll wake up with a headache and pop 400mg advil with a lot of water and that’s good enough.

Other times when the headache starts in the gap between drinking and sleeping I find that the same dosage works there too.

I’m only talking 2-3 drinks here. I don’t drink often and am a lightweight:)

I have not had success with Ibuprofen and hangovers. My goto is water and 3x Aspirin.

An acquaintance who likes to party a lot, and have a job related to medicine, have small bottles of some B vitamins to inject themselves when they are pretty bad. AFAIK those are the medicine ER gives you when you have a really bad alcohol intoxication, so I believe this works.

Yes. In my experience, they don't fix the headaches, but they certainly take the edge off in a way other painkillers don't.

Yes, nsaids thin your blood and vadodilate dehydrated blood vessels in your head, this may also help reduce acetate toxins.

Caffeine as a mild stimulant then increases blood pressure and gives some adrenal pain relief (and was combined in Excedrin)

Alcohol (hair of the dog) also vasodilates and provides some pain relief.

Hydration is ultimately important.

Acetaminophen (Tylenol) should not be taken as it increases your liver load.

https://journals.plos.org/plosone/article?id=10.1371/journal...

It helps a little.

Having a cold beer within minutes of waking up works a lot better IMO, followed by a greasy breakfast and the painkillers.

“He never mentioned that he was the inventor and listened patiently when the person selling it would ask if he had taken it before."

Oh my god he was a saint. If I were in his shoes, the question, "Have you taken Ibuprofen before?" would instantly lead to "Well yes, I invented it.".

Ok well I respect it but at the same time he's no Albert Hofmann https://en.wikipedia.org/wiki/Albert_Hofmann#Discovery_of_LS... "Three days later, on 19 April 1943, Hofmann intentionally ingested 250 micrograms of LSD."

> While the drug had been tested for pain in clinical trials, no one had yet tried it on an alcohol-induced headache.

The otherwise interesting article treats it as a discovery that headache is a type of pain. Sure, it should not be taken for granted which kinds of pain (both by symptoms and their etiology) can be alleviated with a given drug, but still.

"Ibuprofen became an effective treatment for the disease, but it was no cure." Perfect, says the pharmacist.

its well worth the effort to learn about the life of experimental chemist Alexander (Sasha) Shulgin who famously would design then create in his backyard lab hundreds of permutations of various molecules ... Sasha would take the creation and if it had potential would share with his wife and friends ... fascinating storyteller taboot

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