In study, acetaminophen makes risky moves seem less dangerous | Hacker News Reader

In study, acetaminophen makes risky moves seem less dangerous

news.osu.edu

157 pointshliyan133 comments

For those not recognizing the title, I know it as paracetamol (or tylenol in movies).

The article reports on several studies of various sizes where, indeed, people all took a pill (some placebo and some not) and those with the real thing rate activities as less risky or underestimate the risk of the balloon bursting by adding one more pump. Of course, the article mentions the ongoing pandemic where those on this drug may perceive meeting people to be less risky.

Another thing I found interesting in the article is that "nearly 25 percent of the population in the U.S. [takes] acetaminophen each week". I wouldn't know where to find numbers for other countries, I'm curious if it follows a similar pattern as opioid usage (or even the "opioid epidemic", as Wikipedia's article is titled) in the USA versus other countries, but regardless, this stuns me.

I too come from a country where this is called paracetamol, and here too, over the counter usage is very common. I'm surprised more people are not worried about the alcohol interaction.

In Germany they always (n=2) act surprised when I ask for more than a single box. I don't even take it myself, my girlfriend uses one dose (usually 2x0.5g before going to sleep) maybe every tenth day or so; I myself might use it once a year. But the stuff lasts for years and I don't fancy running out or not having some with me when I (or someone near me) needs it, so we just buy it in bulk and replace when empty or after the expiry has sufficiently passed. I get a lecture from the apothecary every time. Does nobody else buy ahead, especially in the pandemic?

They just want to protect you from yourself, do not take it personal.

I don't really, and I am polite and do thank them for the info they give / the concern they express. It just surprises me a little that they don't consider this normal.

In the UK, paracetamol and ibuprofen are sold in supermarkets, but you're limited to buying two packs of 16 pills per visit. Of course, you can easily build up a stash over time.

That’s really interesting. I have a bottle of probably 300 acetominophen caplets from Costco, it’s my go-to hangover cure. Ibuprofen and acetaminophen are incredibly common in the US.

Yeah, US bottles seem crazy to me, for drugs where overdose is lethal. I think the theory behind the UK pack size restriction is that suicide attempts are often spontaneous, so it's life-saving not to have a lethal amount in the house. Also, accidentally popping hundreds of pills out of the blister packaging (rather than a bottle) is pretty unlikely. The restrictions seem to work, with a 40% reduction in paracetamol-related deaths: https://www.nhs.uk/news/medication/smaller-paracetamol-packs...

What’s really funny is that if you go to Amsterdam, you can get paracetamol in a quick dissolving pill that works much faster than the really hard ones you get in the states, but it’s in a bubble package and fewer doses so it’s harder to commit suicide with. But in the states you only get the hard pills, which are harder to crush and use to make illicit drugs out of, but in unlimited amounts. So.. we don’t care if you kill yourselves, as long as you don’t have any fun doing it?

> we don’t care if you kill yourselves, as long as you don’t have any fun doing it?

This is actually a good summary. As mentioned in sibling threads, most pharmaceuticals that could potentially be enjoyable are formulated stateside in combination with things that will either make you feel terrible or outright kill you at high enough doses.

I'd say if you need that much tylenol for your hangovers, the alcohol consumption is a far bigger worry than the side effects of the tylenol.

You're missing the necessary information to make that assumption. Though the temptation to judge others is an inherent human trait of sanctimony.

I bought a massive sack of kosher salt because it was a good deal. It's a stupid amount. Doesn't mean I overdose on salt with every meal, it's going to last me a long, long time. Might become a family heirloom.

You'd be silly to lecture me about salt intake.

To add, people respond to alcohol differently due to genetics, metabolism, etc. I can wake up the next day with a ponding headache even after a seemingly small amount of drinks to some people, especially if I’m poorly hydrated in general,

A couple glasses of water before bed works at least as well as a pill the next morning, in my experience. Hangovers are one of the main ways I feel myself getting old! Haha

Bit confused by your comment—Costco is a big box store. I paid maybe $10 for the bottle. I’m not taking it daily, nor do I take more than a standard amount. I was just commenting that it’s sold in much larger quantities here, not that I’m abusing acetaminophen or alcohol.

Are you sure it's safe? Paracetamol has high hepatotoxic effects when taken with (or soon after consumption of) alcohol. It's probably best to ask a doctor when you have a chance.

I take a standard adult dose in the morning, 6-8 hours after I stop drinking and after plenty of water. I’m not worried about it. Also, to be fair, I usually take ibuprofen. Acetaminophen hits different though, sometimes it’s what you need.

In Canada don't think there is a limit.

I buy Costco's kirkland branded acetaminophen and ibuprofen. it's like 500 pills in a 2 pack, 500mg pills (extra strength) like every 1-2 years

You can purchase over the counter, most grocery stores and gas stations carry it. Pick it up at the "dollar mart" too.

I was taking 2000mg of each at the same time, for bad tooth pain for a week.

It's the #1 cause of acute liver failure in the US, I always find it shocking that the British take it like we take aspirin.

The issue with it is that people unknowingly take does. You may pop a Tylenol for a fever, then take it again in your NyQuil and not realize it.

It’s a well tested and safe drug. Both aspirin and ibuprofen have significant risks if used daily. Aspirin causes stomach bleeding, and ibuprofen causes significant kidney issues over time.

For this reason I try my hardest to buy single-active-ingredient versions of everything. I can keep a list of what pill combos combine into nyquil/mucinex/whatever, and can avoid doubling up on anything unintentionally.

It drove me crazy that in Japan OTC painkillers had a minimum of 4 active ingredients and up to 6 in one case. I could not find any that did not contain caffeine, for example.

The pharmacist explained that caffeine reduces headaches. Well that's great, but I didn't have a headache, I had muscle aches, and I was trying to sleep. He looked at me like I was crazy.

> The pharmacist explained that caffeine reduces headaches.

Also, IIRC, caffeine specifically has been identified to help with migraines, not headaches more generally.

My headaches (and I guess many others) are often caused by caffeine withdrawal. Taking caffeine without a painkiller usually solves the problem.

One meta-theory I had is that the caffeine has been determined to help with headaches only because studies done on it are for people who are ill and need pain management, and ill people tend to change their coffee habits.

When I'm healthy and working, I regularly drink about three espresso shots a day. If I'm sick, that plummets to zero while I'm lying in bed and feeling miserable. Invariably, I'll get a killer headache, which the paracetamol alone doesn't fix. I know this, and either I just ignore the headache or make myself some instant coffee at home.

But a badly run scientific study would not control for this quantifiable effect: Sick people get headaches, and dosing them with caffeine reduces the headaches! Ergo... caffeine reduces headaches.

However, I very much doubt that caffeine has a headache reducing effect in sick people that aren't also having caffeine withdrawal.

Imagine a world where most office workers would regularly partake in, say, Opiates to "take the edge off" their stressful jobs. In that world, researchers would confidently conclude the OTC pain relief medication should include Naloxone!

This isn't even that outlandish a scenario. There are countries where people living at high altitude habitually chew Coca leaves to counteract altitude sickness. Should OTC pain killers in those countries include Propranolol? Is it right to force tourists wanting ordinary Paracetamol to also take drugs for acute Cocaine withdrawal just because most locals feel better if they get it?

It's absurd to mix drugs like this, if you think about it a little...

My understanding is that this is also to prevent abuse / recreational use. For example OTC cough pills containing dihydrocodeine (an opiate), but with enough caffeine and others to make recreational doses of the opiate unpleasant even for those with high caffeine tolerance. Or DXM, which is only found with enough guanfecine (IIRC) to make you feel like crap if you take too much. Kind of like how industrial ethanol is mixed with things that would make you vomit.

Or so my pet monkey told me.

This is something that really irks me. The reason you always get paracetamol packaged with codeine is to prevent abuse of the codeine. They'd literally rather you destroy your liver and die than risk getting addicted to codeine.

Wonderful. Caffeine (and many stimulants) either give me panic attacks or trigger manic episodes.

A cup of green tea is enough to ruin my day and possibly the next week.

> caffeine

I had a chat with my chemist about why a small bit of caffeine was in the more expensive brands of acetaminophen / paracetamol. I asked if it was used as a kind of pick me up to feel more awake.

He said that the dose of caffeine was very very small and not for that, but it actually helps the paracetamol work better or faster.

They way OTC medications are packaged and marketed drives me bonkers. I take a sleeping pill every once in a while. I was at the store once comparing two boxes of pills. One was marked "Sleep Aid", and was $8 or so. The allergy medication nearby was the same count, same dosage, and only $5.

They were both diphenhydramine HCL, 25mg. Both tablets. The only differences were the labels, the pill colors (blue for ZZZZ, pink for allergy), and the price.

And the other benefit to stocking single-drug medications is more flexibility. I imagine some hapless guy whose has pain in the morning, but sees only "Advil PM" in the medicine cabinet.

If I need Advil PM, I'll take a regular ibuprofen and a regular diphenhydramine.

Ugh yup. Extra hard trying to explain this to a demented family member who just wanted to sleep... diphenhydramine worsens alzeimer's. :(

Keep in mind that taking higher doses of DPH has the opposite effects, i.e. you will definitely NOT sleep from it. See "anticholinergic toxicity". When I was younger I thought taking more of it is going to help me sleep better, but I ended up with auditory hallucinations, tachycardia, and the like. I was hospitalized for it, albeit left untreated, or rather, treated as a junkie and they threw me into a detox room, but that is a different issue.

I could not edit my comment, so here it is: I forgot to include a relevant symptom I had, which is delirium. I was in a delirious state for many hours, and it left me in a disassociated state for some time afterwards.

Just to add, most nootropics are cholinergics in some way or another. Take a look at choline supplements, or racetams (from Wikipedia: "Racetams are understood to work by activating glutamate receptors that are colocalized with cholinergic receptors, thus increasing the frequency of activation of the latter."). They are supposed to help people with Alzheimer's disease, improve their memory and whatnot. There are many studies around to support this. There is also Huperzine A that has been investigated as a possible treatment for Alzheimer's disease and there was a meta-analysis that found it efficacious in improving cognitive function (see https://en.wikipedia.org/wiki/Huperzine_A for more).

But yeah, anticholinergics are known to be bad for people with Alzheimer's disease, and some cholinergics are known to be effective in improving cognition of those who have it. Of course there are other medications that are supposed to be avoided, here is more about it for the curious (it mentions DPH, too): https://www.mind.uci.edu/medications-and-patients-with-alzhe...

Could the dissolution rates of the tablets be different?

Was in Er for an optical migraine, they gave me a dose Of diphenhydramine.

It took everything I had to not start literally climbing up the walls. My anxiety and energy level skyrocketed.

One of kids is the same way on Benadryl.

Apparently 5% have such a reaction.

I got tired of explaining the reaction to doctors and nurses, (got called a liar several times). Although I had one nurse almost in tears as she had same reaction, but no one would believe her.

So on forms I put I’m allergic to allergy medication.

Ya, and it's way cheaper that way. Especially if you buy the basics in bulk at a big box store.

Acetomeniphin Ibuprofen Benadryl Pseudoephedrine

Covers almost all of the many combinations for sale at the drug store.

Not as many as glycerine!

>For this reason I try my hardest to buy single-active-ingredient versions of everything.

Yes, but according to the post, the single-active-ingredient version of acetaminophen might make you less cautious and more risky, and lead you to buy multiple-action drugs!

:-)

I've made this mistake - I thought I was alternating between paracetamol and ibuprofen preparations, but I'd accidentally used a paracetamol-containing version of the second product. Fortunately it was a manageable acute/one-off dose for my body weight (8g/24hrs - the A and E doctor ran a blood paracetamol level test as a precaution, but they didn't expect any issues), but it's an easy mistake to make.

There is a version of Nyquil without it. Nyquil Cough, I think. Also has HFCS instead of sucralose like some of the others (tastes less gross). Seems much harder to find, though. I've only seen it in cherry, so if you want it, probably avoid anything berry.

Aspirin. Nobody sane takes that in 2020. It thins your blood out and can cause major havoc also in healthy individuals.

Are you kidding?

Safety margin on aspirin is huge, you tend to notice your blood is very thin before you get any worse symptoms. Massive doses of aspirin have also been used to treat various illnesses.

Ask your doctor and don't self medicate on Aspirin. The 80s are over.

Until you get to your doctor, be in the know, read these:

https://www.healthline.com/health/aspirin-overdose

https://www.mayoclinic.org/drugs-supplements/aspirin-oral-ro...

Yeah hurts so bad. Going to take some aspirin now.

Comments like this make me wish I could down vote things.

In our first aid course, the instructor told us to give aspirin in case of a suspected heart attack (while rushing the victim to hospital, of course).

Which is exactly why I take it before a long haul flight. A friend of a friend died due to a blood clot likely caused sitting cramped in economy class 14 hours

Unless you're sunburned, dehydrated, have been drinking... Fighting cancer, etc

I think those numbers are suicide attempts.

Aspirin causes blood to thin and could exacerbate ulcers and such, not good to take for cuts and bruises etc

The judgement from my pharmacology instructor was that paracetamol, when used within the recommended doses and durations, is a very safe drug with very little side effects.

Whereas acetylsalicylic acid ("Aspirin") was the example of heirloom drugs still in prescription free use only for historical reasons. 'If you came requesting approval for ASA today they'd laugh in your face. "With that side effect profile!"'

The other big issue with Tylenol is that the active dose is very close to its lethal dose -- far closer than other common over-the-counter drugs. People assume that since it's available without approval it must be pretty safe, so people take more than recommended.

The maximum safe dose for Tylenol is 4g per day. The low end of the toxicity range is a daily dose of 7.5g-10g for an adult, ~2.5X the maximum recommended dose - or just 12 grams spread over 2 days. The effects are exacerbated by alcohol use. And worst of all, people take it for hangovers. [1]

So, the toxic dose of Tylenol is only 2.5X the active dose, whereas for ASA it's 8X, for ibuprofen it's roughly 10X, and naproxen is about the same. Tylenol is much more dangerous than Aspirin.

Tylenol leads to 50,000 ER visits per year and 25,000 hospitalizations. It would lead to way more deaths if left untreated.

[1] https://www.uspharmacist.com/article/acetaminophen-toxicity-...

> So, the toxic dose of Tylenol is only 2.5X the active dose

The effective dose starts at 500mg. Most people are likely going to be taking 1 or 2x 500mg tablets for acute issues - and I'd argue that's often enough for most cases where you want short-term analgesia. Both 500mg and 1000mg will improve SPRID6 scores (dental; https://www.cadth.ca/sites/default/files/pdf/htis/june-2016/...).

Where I've complained of medium term pain (expected duration: weeks to months) my GP has suggested NSAIDs instead. They're not without their own problems but I think I'd personally prefer their safety profile to long-term Paracetamol.

All Tylenol figures are in daily totals, and Tylenol lasts 4 hours. 500-1000mg taken 4x daily is 2-4g. That makes the therapeutic index 1.875-2.5 as I mentioned. 12g over 2 days is 1.5X. Again that’s without alcohol which folks do not seem to appreciate.

People can and do exceed these numbers hence the 50,000 ER visits per year. It is the leading cause of acute liver failure in the United States.

The bar shouldn’t be “often enough for most cases” when 1.5X the dose for 2 days can kill you. Either the safety margin is too low or the warnings aren’t nearly big enough, but the numbers don’t lie, the status quo is bad. Especially when the alternatives require way less diligence on your part and are sold as equivalent adjacent products.

That's exactly why I take NSAIDs over Tylenol if I can.

The safe dose I believe is around 4g in 24hrs (2g/24hrs if you have known liver dysfunction). That’s like 8 extra strength Tylenol.

Another commenter alluded to why it is the number 1 cause of acute liver failure in the US: that’s because we can buy bottles of a couple hundred pills and thus the majority arise from suicide attempts.

The British used to have a big problem with paracetamol (what Tylenol/acetaminophen is called there) and acute liver failure, so they mandated only blister packs for the medication, no ability to buy large bottles. Suicide rates due to paracetamol and acute liver failure decreased as a result. In fact, aspirin is also an issue in the UK, and this mandate also helped with that.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31616/

It's often mixed with opiates that people abuse. I'm thinking of percocet (oxycodone + paracetamol). While interaction with alcohol is best avoided, the reality is that people aren't ending up in ER's because they took two 500mg's and had half a bottle of wine with dinner.

I just understood why I had one terrible day a few years ago.

In the UK, the NHS advice for anything mildly painful is "take paracetamol or ibuprofen" (e.g. https://www.nhs.uk/conditions/common-cold/), so they must judge the risk at typical doses as very low.

It’s ignorance. I legitimately had no idea until I looked into it. Others I’ve talked with have said they had no idea. Ibuprofen makes me feel like I’ve been poisoned if I take too much or on an empty stomach. So acetaminophen was just what I took. (And when I had significant sleeping problems and was working three jobs so it really mattered if I slept or not, I took a PM version which was also not great.) Now I generally don’t take pain medication even if I’m pretty severely hurting, but if I do I stuff my face and take ibuprofen.

> Ibuprofen makes me feel like I’ve been poisoned if I take too much or on an empty stomach.

Yes well, it will. Do not take it on an empty stomach. IANA doctor, but if one prescribed you ibuprofen it would say 'with a meal'.

"nearly 25 percent of the population in the U.S. [takes] acetaminophen each week"

That's crazy. I take it maybe once or twice a year. And I will generally take ibuprofen in preference to acetaminophen.

The idea of taking an OTC drug that often is bizarre to me.

It might not seem that bizarre if you frequently experienced chronic pain.

So your theory is that a quarter of the US population experiences chronic pain?

Would it be that shocking? Considerable proportion of population are old people and those have all kinds of chronic pain. In women, anemia is frequent and can manifest through head pain. So you end up taking innocent looking pills to make it better. The periods can hurt too, so.

Plus, I have rather small social circles and I know about at least three people who have chronic pain ever since they were kids. Nothing life destroying, but constant annoyance or mood killer.

And those are frequent pains I know about without googling. It is not unusual.

Unfortunately with so many overweight, joint pain may be frequent

Not a theory, fact: https://www.cdc.gov/nchs/products/databriefs/db390.htm#:~:te....

I do that, believing it’s acceptable risk, but I’m probably very poorly informed. My mental model is that it’s technically dangerous if I take an order of magnitude too much, while drinking heavily. Since this goes for most things in life I dismissed any qualms long ago.

Always preferred acetaminophen to ibuprofen; it feels more like “the real thing”. Maybe it’s the de-stressing effects alluded to in TFA.

The thing they tell me (when I buy in bulk) to worry about is my liver as well as developing a dependency (headaches caused by not taking paracetamol). I don't know at what dosage+frequency either of those occur, though. If you do take it (or any other non-prescribed medicine) weekly or more often, I think it would be wise to do a cursory check on that or ask an apothecary or doctor next time you see one.

(To be clear, I don't even buy it for myself and I know that the person whom I do buy it for doesn't take it weekly, hence my not knowing these details despite buying decent quantities of it. We buy in bulk only because it lasts a long time and we always put off going to the apothecary because why go more than necessary especially in a pandemic)

>"nearly 25 percent of the population in the U.S. [takes] acetaminophen each week"

my guess: half of half the population takes them 4 days every month, eg menstruation pains.

My mother always pushed ibuprofen for menstrual issues, though I suspect that will still be a portion of this 25%. Chronic pain of some type is an issue for most anyone over 40.

Another somewhat-related rabbit hole:

> A Scottish woman with a previously unreported genetic mutation (dubbed FAAH-OUT) in her FAAH gene with resultant elevated anandamide levels was reported in 2019 to be immune to anxiety, unable to experience fear, and insensitive to pain. The frequent burns and cuts she suffered due to her hypoalgesia healed quicker than average [1]

Acetaminophen can elevate anandamide levels [2]. It would be interesting to know if the altered perception of risk could be related to the "immune to anxiety" effect experienced above.

[1] https://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase#Fun...

[2] https://en.wikipedia.org/wiki/Anandamide#Synthesis_and_degra...

My wife is like this in BOTH regards and I have been baffled by her for over a decade! I tell everyone, I have never met ANYONE like her, I honestly thought she was completely unique.

By all accounts she seems to be utterly immune to both physical pain and does not experience fear.

(1) She was a glass blower in college and would regularly get large burns that did not seem to bother her at all. She has multiple tattoos that she says caused no discomfort, gave birth to both our children without any drugs and to this day says it caused her no pain. She is aware of things happening but they do not bother her. Not in a bad way, I have often told people, she does not feel anything.

(2) She can say anything to anyone, anywhere and feel nothing like anxiety. This has also baffled me but I NEVER would have thought the two were somehow connected. I've asked many times if she ever gets nervous or anxious talking to people and says she does not and it is clearly true. In ten years I've never seen her cry or so much as tear up. When we lived on a farm she was our go to for any slaughtering, she sliced our goats throat without even wincing and I saw her once stand up to a 1,000+ pound charging heifer without thinking twice and made nothing of it.

It blows my mind but makes so much sense that this could be a single DNA mutation! Hopefully it is one 23 And Me can check for!

As some who is diagnosed with both hyperesthesia [1] and anxiety disorder, it's really funny how your wife is the opposite of my experience. It reminds me of Murakami's Wind-Up Bird Chronicles we experience the same things and lead similar lives yet our senses can be so different to a point where something fatally painful can be so pleasurable to others.

[1] My skin is hypersensitive to pain, to the point sometimes it's very painful to put on clothes. Usually it's manageable with wearing large clothes, but it's worse if I haven't had enough sleep or some allergies (or salty food etc) are causing inflammation.

> things and lead similar lives yet our senses can be so different to a point where something fatally painful can be so pleasurable to others.

If you ever try even a small amount of psychedelics you'll be amazed how different the world can feel just by modifying your senses a little bit.

My wife is for all intents and purposes the opposite of yours and always complains about me and our kids being afraid of nothing.

Her life, and so in some respects also mine, revolves around overcoming her own fears, so it's really interesting to read your opposite experience, thanks for sharing!

honestly, it kinda sounds like a textbook psychopath.... at least from what you are describing here...

Real world psychopaths has no problem understanding the concept of pain, if you punch them in the face they’ll get mad and punch you back.

The way “lack of theory of mind” works is when they decide in their free will to hit you and you hit them back, they don’t quite understand how that happened despite them not intending to hit themselves.

I watched a hitman on death row get interviewed by a psychiatrist who wanted to know why he was the way he was. The psychiatrist explained to him that he had this trait (felt no pain, felt no anxiety, etc). He explained it's common in people with dangerous careers. He explained that people with this trait who grow up in nurturing homes tend to come out ok and usually work dangerous roles. This hitman grew up in an abusive home and that coupled with this trait was what shaped him into what he became.

As if you've read those textbooks?

I would point out that it is pretty normal not to cry for 10 years. Like most women cry at funerals, not randomly.

No, this is not at all normal.

Are there any downsides to this mutation?

You can misread the risk of any situation and die a horrible death.

More seriously, pain is a warning signal that tells you something is wrong. I'm not sure how accurate the reading is without the pain signal. It may cause you to misjudge any number of things (muscular fatigue when you swim, frostbite when you hike in cold weather, burns when you blow glass...) that may have severe complications immediately or later.

Apart from that, not much.

> and die a horrible death

which you wouldn't experience as such ;)

You can still feel really stupid through the whole experience.

I used to take two Tylenol before large presentations and I would feel a lot less anxious.

I've heard this is a common trait for stunt devils, special forces and contract killers.

Wow, do you know if this sort of selection criteria is confirmed through genomic testing or reliant on hear-say?

This was from a psychiatrist interviewing a hitman on death row, explaining to him his condition after the hitman had been curious to know. It's a well known but rare psychological phenomenon, I think the genomic link is only a relatively recent find.

It's a fascinating article.

Even more fascinating: nobody here in the comments on the most skeptical site I know has pointed out that the article fails to provide even a hint of the degree to which it alters those perceptions. Is it 1%? 10%? 30%? 80%?

Kind of an important detail.

How to measure the degree? You've wrote percentages as an example, how they should be understood? The frequency of altered behavior? But there are tons of different factors altering behavior, as personal so situational factors. They somehow also should be measured.

I would be much more skeptical, if they provided measurements outside of ordinal scale of measurement[1]. One can compare two setups on basis less/greater, but not to measure them in absolute scale.

[1] https://en.wikipedia.org/wiki/Level_of_measurement

Using standard-deviations would be good, assuming risk-assessment is a normal distribution.

It would be standard deviations in some specific situation. Maybe in 2-3 situations. Like answering questions of a psychologist and inflating a balloon in a kind of a computer game.

Does it influence a driving style of a person? People could overcome biases, and possibly driving as a habit would be more strong than acetaminophen.

The only reason to go numeric with this study is to measure statistical significance of their findings. I'm sure they did it, but their numbers have no meaning outside of their study.

Numeric is also a good sanity check. If they claim e.g. 3 standard deviations of risk-taking increase on typical doses of paracetamol, then there's something wrong with the study, because we would have noticed that already.

I'm sure they did all the math. It is just journalists do not report it, because it's too boring. And in this case this math would be meaningless if you didn't dig into methods, experimental plan, number of participants, how they where split into groups, and so on. With this numbers one would need to report all the science article. If you interested in such details, you should go to the original article.

Speaking of skepticism, I personally just believe, that article is good enough. Mostly they are. In this case I see no methodological troubles, the experiment seems straightforward, I would have no troubles designing it, based on this journalist's article and I'm not a professional scientist (though I have a psychology degree).

> If they claim e.g. 3 standard deviations of risk-taking increase on typical doses of paracetamol, then there's something wrong with the study, because we would have noticed that already.

If they claimed 3 std-devs of increase, it would be 3 std-devs of increase in a specific model situation of risk taking from the experiment. It would be great news, it would mean that researchers found a good model situation with high sensitivity to a paracetamol. Would be nice to see how some other factors influencing risk taking show themselves in this setup.

I've been reading a bunch of medical studies recently and I've found the same thing painfully often. Wow, this study is p<0.01, that's amazing! How much did the substance alter the measurement, though? Never mentioned.

There is evidence to suggest that it suppresses empathy as well https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015806/

I wonder if people with a high tolerance for pain are also less empathetic.

I can confirm this anecdotally.

I've always had near zero empathy for anyone who isn't a close friend or family member, and I have very high pain tolerance, to the point of outright ignoring minor wounds on a regular basis and then finding them later (sounds edgy, actually majorly annoying finding unexpected blood stains on clothing or furniture, or realizing I have an eyesore of a bruise somewhere).

Don't know why you're being downvoted. Of course this is all anecdotal and armchair psychology/psychiatry/neuroscience/neuropharmacology, but there could plausibly be some kind of correlation, here, and every anecdote adds to the discussion, even if of course they shouldn't be taken as empirical support for the hypothesis.

I've seen research about how opiates seem to reduce perception of both physical and emotional pain, which may partly explain why some people in unfortunate situations may become addicted. Emotional pain isn't adjacent to empathy but isn't necessarily orthogonal, either. If there's anything to this, it makes me wonder if there could also be some correlation between opioid receptors and empathy, or even some sort of correlation between pain and emotions in general.

While we're talking anecdata, for the first ~30 years of my life I found absolutely no relief from acetaminophen for anything from illness to injury to random headaches.

A couple years ago my wife cajoled me to try taking it again, and I went from bed ridden to feeling poorly but able to function. Not a miracle cure but really helpful a few times a year. Is there any known association of age and acetaminophen effectiveness?

Would someone inclined to downvote the parent comment explain why?

My first instinct is it's people who have a high threshold for pain who don't appreciate being called out for a lack of empathy. But perhaps didn't have a rational defense to jump in and comment.

It would be interesting to hear a response from a downvoter contradicting this instinct.

More likely, the people doing the downvoting have low thresholds for pain and do not want to see people with low empathy become normalized, as it would make their pains feel even worse.

> ignoring minor wounds on a regular basis and then finding them later

In my experience that's pretty common, especially among guys. It's a running joke with my wife that I'll be leaking blood without even knowing I cut myself. Or I know, and just don't really care. Several of my friends are similar. It does lead to awkward explanations sometimes. My wife still doesn't really understand how I can have a great big scabbed over wound or a nice big purple bruise with not the faintest idea when/where I did it.

I wouldn't say I'm low on empathy, either. But I hide it pretty well, bury it quite deep.

Anecdotally I used to be less empathetic but I took some steps to change that long ago.

But, high pain tolerance would still describe me even after that point... I've had broken ribs, broken fingers and toes, broken hand and wrist, chipped teeth, broken nose, seriously infected abrasions, large boils (now these fucking hurt), torn labrum on left shoulder, surgery on right shoulder with a really uncomfortable elastomeric pump, a few minor head injuries, minor fracture in one foot, cigarette tattoos, high-speed bike crashes with no protective gear, a perplexing squishy fluid sac under the sole of my foot from sprinting, etc.

I still feel pain but I would have to imagine that a pain-sensitive person might not get up to the same stuff that I do. It really depends on the type of pain.

The two most excruciating were dengue fever and a couple bouts with moderately-sized kidney stones. Dengue was worse, definitely earning its local name here of "bone-break fever" due to the intense and constant aching. Near the end there is a characteristic rash, which is mercy compared to the first 3-4 days. The whole experience left me physically destroyed for months! I returned to lifting weights after I thought I had recovered, but my one-rep max lifts were halved on every single movement and it took another month to return to the level I was at before.

Strangely true in my experience. But it makes sense..

Yes, I have low empathy and a high pain threshold even when I broke a collarbone. I only have harsh words for those with low thresholds for pain.

From Wikipedia:

Paracetamol apparently might modulate the endogenous cannabinoid system in the brain through its metabolite, AM404, which appears to inhibit the reuptake of the endogenous cannabinoid/vanilloid anandamide by neurons, making it more available to reduce pain. AM404 also appears to be able to directly activate the TRPV1 (older name: vanilloid receptor), which also inhibits pain signals in the brain.[24]

Exogenous cannabinoids are also associated with greater risk taking:

https://www.researchgate.net/publication/7958920_Acute_Marij...

I would love to permanently down-regulate my anxiety. I do not find it a useful emotion. Standard anxiolytics have helped a fair amount, but I’d love to just kill it off as an emotion.

Isn't this is what meditation is for?

I ask myself: Could any pf these findings be conflated with psychopathy? And or are any of the anecdotal evidence provided here by commenters actually not due do acetaminophem/paracetamol, but rather psycopathic personality distortions? I am genuinely curious. We will never know of course, at least not about my second point. The first can be tested with more rigprous science.

It's usually prescribed specifically for fever, not just for any pain.

Could this be why so many people (myself included) report feeling a sense of wanting to live a more proactive life when sick with a fever?

You'd think it would just be because you're feeling a sense of contrast from your usual more energized state and want to avoid wasting energy on unproductive things once you get it back, but could it actually be because the Acetominophen reduces our overall sense of anxiety?

The article talks about how there have been studies that show it dampens all emotions, but to feel more sure about long-term efforts, you don't strictly need to be emotionally charged or inspired, you just need to be less anxious about the potential failure of such efforts.

> It's usually prescribed specifically for fever, not just for any pain.

It is regularly prescribed (alone or as part of a compounded drug with opioids) for post surgical pain; as I understand it's the most effective common non-narcotic painkiller for traumatic injury, but not as effective as NSAIDs (or steroids) for inflammatory pain, because it doesn't specifically target inflammation.

> report feeling a sense of wanting to live a more proactive life when sick with a fever?

There is (very weak) theory that, given that viruses want to spread to more hosts, and given that certain infections like toxoplasma or rabies can change the hosts behaviours, that a virus wants us to get out more and be more socialable. The urge to live a life when we feel when sick with fever could be part of the infection changing our behaviour to make it spread!

Viruses and other things exploit our behaviours of sneezing and coughing to spread after all, so why not increase the chances some more.

There was one study done that showed that those who were just injected with the flu vaccine (as a safer way than actually infecting people with the flu) that they became more gregarious and went out socialising more.

The science is pretty weak and can be explained that those who had the vaccine felt more protected and invulnerable, so it does not prove anything.

The researchers theorised that sexually transmitted diseases may also want to spread. Its possible that being infected by STDs could make you more promiscuous therfore.

There's no studies done on covid infections and change of host behaviour. Suggesting that people might not be fully free in their decisions when pre-symptomatic and infectious would mainly be not helpful, useful and also dangerous.

To me, the idea that viruses could affect our mental state is so out there its similar to the idea that the bacteria in our guts could affect our mental state 20 years ago.

Does anyone know if ibuprofen is risky with sustained, long-term usage of the recommended dose? I have a relative who uses it habitually, and I can’t help but worry.

It seems safer than Tylenol, but I don’t understand why it would be safer.

They recently had a toothache, and they took 4 right away and more several hours later. When I expressed concern, they said the doctor told them to go ahead and take 4 immediately when in severe pain. But it feels like more and more studies and anecdata are casting suspicions on Tylenol, so I wanted to ask if anyone knew the central reason why ibuprofen might be safe in comparison.

Yes. Google “ibuprofen kidneys”.

All of the nsaid drugs have risks if chronically overused. End of the day, if you’re taking otc pain relievers for more than a week, you should look at treating root cause.

Thanks!

Naproxen, ibuprofen, acetaminophen, aspirin are all ototoxic (damaging to hearing), so that is one concern.

I almost never use pain killers, but if I have to reach for one, it will be naproxen. Naproxen is longer-lasting. It has a metabolic half life of as much as 17 hours in the body, compared to just around two hours for those others. This has advantages, one of which is simple economics. One naproxen pill works like 4 consecutive ibuprofens or acetaminophens.

I was prescribed naproxen in the early 1990's, at the University of British Columbia sports medicine clinic for some wrist tendinitis. Stuff worked, so I remembered the name well. I didn't know that just a few years after that, it had become over-the-counter. One day I googled it by name and so it goes.

One down side of naproxen, sort of, is that it's not recommended for children. You will not find a children's naproxen.

Naproxen isn't a direct replacement for ibuprofen, acetaminophen or aspirin.

It much stronger and has different interactions. For example you shouldn't use when taking cipro.

I've used it and found it works really well but uses a different method for reducing pain compared to the others.

> uses a different method for reducing pain compared to the others

This is not true; all the over-the-counter painkillers are COX enzyme inhibitors. Of course, they are different molecules with different additional properties and metabolic products. For instance, aspirin is a blood thinner whereas naproxen isn't. The remarks about the different interactions are absolutely true.

With regard to mechanism of action, one oddball is paracetamol (acetaminophen, Tylenol).

Wikipedia: "Despite its common use, the mechanism of action of paracetamol is not completely understood. Unlike NSAIDs such as aspirin, paracetamol does not appear to inhibit the function of any cyclooxygenase (COX) enzyme outside the central nervous system, and this appears to be the reason why it is not useful as an anti-inflammatory.[24] It does appear to selectively inhibit COX activities in the brain, which may contribute to its ability to treat fever and pain."

What makes naproxen "stronger" is how it endures in the body.

> I almost never use pain killers, but if I have to reach for one, it will be naproxen.

Same. I also find naproxen to be the most effective on the rare occasions I need a pain killer.

I believe Dr. Rhonda Patrick says that it can increase risk of stroke and heart issues after prolonged use. I would look her up and see because I might be wrong.

NSAIDs can reduce blood flow to the kidneys so they don't recommend it long term because it can cause kidney problems. Tylenol is metabolized into harmful byproducts (I think just like alcohol) but if you stay below some maximum amount per time period, your liver can neutralize it.

I occasionally take some paracetamol if I've suffered some upsetting emotional event, like a bad argument at work. It's most likely just a placebo effect, but I do feel like it numbs my emotions a bit and helps me stop fixating on the memory.

I'm well aware it's not the healthiest behaviour, but I consider it better than the other ways I know I would likely respond, by either sinking into a mild depression, or using alcohol and/or other intoxicants.

So the anxiety and really all parts of our psyches serve important purposes. But sleep, for instance, is possibly the most important physiological thing we do in a day. It’s also common for anxiety and the like stress responses to disrupt or even negate the possibility of sleep. So in those cases, it’s definitely worth dialing the anxiety and stress processes “back” with external aide.

Any estimate of how many deaths result for increased risk taking due to acetaminophen? I guess that would be extremely hard to quantify and might require running a RCT. Or finding a natural RCT - e.g. two similar regions or countries - one where acetaminophen is widely used and another where it is not.

Interesting. How did they think to test this hypothesis in the first place?

This is very interesting - I had recently read about the empathy lowering effect of Paracetamol and the cynic in me could not help but wonder if any corporate folks may have (ab)used it to become more sociopathic (which is a requirement for success in many of the more dysfunctional corporate contexts)

I don't for a second believe the implications of this article for acetaminophen/paracetamol/Tylenol.

But I do want a drug that does this. I haven't seen anything like it mentioned on HN.

Wouldn't this be exactly what startups want?

Another discovery brought to you by big aspirin.

Edit: It was a joke. Aspirin isn't trying to take down Tylenol, but to not compare this result with a wider selection of painkillers reads to me like a PR play.

If it's a question with food, why not every product we ingest?

https://news.ycombinator.com/item?id=25551877

Reply on news.ycombinator.com