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Scientists often talk about the "therapeutic index" or "safety ratio" of a drug. It's the LD50 (dose at which 50% of recipients die) divided by the effective dose. Common hard drugs like heroin or methamphetamine have a safety ratio of about 6-10 [1]. "Soft" drugs like marijuana or LSD often have safety ratios of about 1000.
The safety ratio of acetaminophen is under 4. A typical dosing schedule for an adult is 4-6 500mg tablets within a 24 hour period [2], for a total of no more than 3g. 7g of acetaminophen can kill you, and 12g is likely to [3]. Acetaminophen is the leading cause of liver failure in the U.S, causing 50% of cases and 20% of transplants.
When they tell you "don't exceed 6 doses daily", they really mean it, and it's across all acetaminophen-containing products. The margin for error is narrower than heroin.
[1] http://politicsofsin.50megs.com/risk/Toxicity.Comparison_Add...
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC3585765/
[3] https://www.ncbi.nlm.nih.gov/books/NBK441917/
Saying this to encourage label reading and to refute those who might try to characterize your wife's experience as anecdotal. And for those who stop reading a page like this one, after the first paragraph that touts "no evidence": https://www.tylenolprofessional.com/safety-and-efficacy/safe... when at the bottom it reveals the Liver Warning.
This is why you have to be very, very careful. If you're doing 8 500mg Tylenol pills and then you also do 6 doses of DayQuil or Mucinex without realizing it's also acetaminophen, you can end up needing a liver transplant.
There are other studies where Dextromethorphan improves both objective and subjective measures of coughing: https://pubmed.ncbi.nlm.nih.gov/37232330/
They also picked a study that shows honey outperforming Dextromethorphan but ignored all the studies that show honey performing similarly or slightly worse than Dextromethorphan, or studies where honey showed no measurable effect.
There are so many studies and papers published now that you can find both positive and negative results for just about anything. When someone starts pulling up singular random links to papers you should be suspicious. Be even more suspicious when someone is calling for bans or regulations based on those individually selected papers
One of my favorite slides is when we compiled dozens of trials on something that’s basically a nitrogen fertilizer, which as much of a guaranteed positive effect as you can get in agriculture. When compared in a graph most of the trials show an overwhelming effect on increasing yield over an untreated check, however there’s always a portion of the trials where the yield decreases compared to the (untreated) check.
Real life is extremely noisy for a multitude of circumstantial reasons that are either not practical or possible to control for, so a single trial is generally worth fuckall. It takes a lot of testing to see a consistent trend across them.
Auvelity is interesting, but the exact mechanism of action is not very clear.
Auvelity is a combination of two drugs: Dextromethorphan and Bupropion. Bupropion, aka Wellbutrin, is an antidepressant by itself. In Auvelity it helps alter how Dextromethorphan is processed by the body, but we can't rule out that it contributes to the antidpressant effect. I mean it's literally an antidepressant.
Dextromethorphan has a lot of interactions and gets a lot of comparisons to ketamine because it has NMDA affinity, but if you look at the table of receptors it interacts with the serotonin receptor is one of the strongest interactions. It is a potent serotonin reuptake inhibitor, which is also known to have antidepressant effects. It also has some sigma receptor interactions which might be doing something significant.
The NMDA interactions get all of the attention because if you put "ketamine" in the headline you get a lot more attention, but NMDA may be much lower on the list or even negligible for this combo.
Should read “NMDA receptor antagonists _may_ give rise to treatments that _may help prevent or ameliorate the symptoms_ of Alzheimer’s.
Nobody even knows how Alzheimer’s works at all — like most diseases it’s a description of some detectable symptoms, some of which could even turn out to be the body defending itself.
Thus compounds that may have a mechanism of action that affects some concomitant, visible symptoms might potentially be useful.
The use of definitive sentences about unknown results is how we end up with wellness and some “biohacking” nonsense.
N=1, I've had very positive experiences with DIY Auvelity, using 150mg Buproprion XR that I'm RX'ed with 60mg OTC DXM-only tablets.
Doesn’t that suggest that the effect overall is neutral?
If that implies the effect is neutral, then by extension that means nothing works at all.
The only cold and cough medicine that really truly works is the over-the-counter stuff, pseudoephedrine, works amazing for me. I usually pick up a box of the stuff when school starts in the fall and I go through half a box of it by the following summer.
To be fair, you're doing pretty much the same by claiming these studies exist without proof.
I think it's perfectly reasonable to contest the research summary this article is providing. All science-based articles on interesting topics are going to be like that. But you're writing your comment as if they took a flyer on DXM, and the research consensus is in fact that DXM is not effective. It's not as bad as phenylephrine (it has detectable, if immaterial, impact in adults), but it's pretty bad.
The point of the article, of course, isn't that Dayquil should be illegal because it's dangerous; it's that it doesn't work. Having spent an unreasonable amount of time in HN pseudoephedrine threads, I think the broad consensus of this site is that phenylephrine should be taken off the shelves.
From what I remember it was actually quite effective topically but not through pill form. Could be wrong.
Also makes me wonder if there's an alternative function to DXM for people with colds (maybe it makes them feel better in other ways). Or it's just good marketing and associated with NyQuil having other drugs and people assuming DayQuil works
The case against DXM is nowhere nearly as good as the case against phenylephrine; phenylephrine is a scam, and DXM is a drug everyone thought was the gold standard cough suppressant, but then serious studies knocked down its effectiveness.
You used to be able to get Nyquil with real sudafed in it. That was the gold standard. It's not even available behind the counter anymore, presumably because they can make more money from morons buying the placebos.
As an aside:
> In January 2011, the FDA set a maximum amount of acetaminophen that could be packaged in combination opioids like Vicodin or Percocet. The odds of hospitalization due to opioid-related acetaminophen toxicity plummeted.
Yeah, the acetaminophen was there to PREVENT abuse of the Vics and Percs 'cause you'd overdose on the acetaminophen first. Sure, there was an easy workaround, but that was it's intent.
which is a much, much worse way to go, apparently
What do you mean "morons"? Say I'm a normal person who doesn't habitually read magazine articles about drug effectiveness. How am I supposed to know that phenylephrine doesn't work? It's in the drug store and they're selling it as a decongestant; I have good reason to believe it will decongest my nose.
But then drug makers realize they can get more sales by selling a placebo that won’t have the friction.
It's much better at clearing congestion than at making crystal meth. And, as the joke goes, it's easier to make an effective decongestant from meth than it is to buy it from a store.
When I want to get irrationally angry about something in a department store, I'll walk over to the shampoos, which for some reason always have a whole entire aisle dedicated to a single product, when they all do literally the same exact thing, just with different scents and advertising budgets baked into the sticker price.
That ignores over a century of law regarding drug safety and efficacy, and false advertising.
Somewhere on a shampoo forum people are complaining that all computers do the same damn thing. I guess they probably just don't know what they're talking about.
They're all Turing machines
But I don't have time to do that. I would rather have a retailer do that curation for me and provide me with effective high value products, and stand behind returns when they miss the mark. Then as a customer I can reward them for that value added work.
That's why Costco is great most of the time. Although they sometimes miss the mark with certain products they stock.
i don't need to smell like grandma
I think the phenylephrine stuff is absolutely messed up. I personally had no idea it was ineffective, and I've bought medicine with that included, believing it would do what it says it does in the active ingredients list. To me, this is criminal, and these companies should be taken to court for outright lying about their products. (And the FDA should be slapped, hard, for not having done something about this by now.)
But when it comes to the CVS brand of acetaminophen costing $5 and the NyQuil brand costing $10, that's just... the result of normal market forces. I'm not a big "free markets" guy (because we don't, and can't, have truly free markets, and if we could and did, it would be a disaster), but it's pretty normal and common for people to pay more for something just because some company did a better job advertising it than their competitor did. That's just life.
It's funny, because when I go to a pharmacy, the store brand is usually shelved right next to the big-name brand, and there's even often a little card next to the store brand (or even printing directly on its packaging) that says "Compare ingredients to $BIG_NAME_BRAND!" And yet, people still buy the big name brand. ::shrug::, that's life.
It's similar to the shampoo example (a huge selection of borderline useless products that make money purely because of marketing) but with a minor safety consideration, too.
You ask what is new about this, and the answer is, in 2026 context: nothing, but compared to the year 2000: plenty. Regulators used to issue fines for this behavior, and for worst offenders, regulators used to shut them down. Lying to customers is illegal in most jurisdiction, it used to have consequences, and it should do so again.
I wish the industry, our health organizations, and most people in general acted as though this were true.
The environment we live in in general is increasingly hostile to people who ask those questions, do their own research, and take responsibility for their health in this way. I have first hand experience having reversed chronic health conditions myself by doing my own research. What have and do others say about it? Everything: every person on the sidelines watching who have formed opinions about how things are supposed to be, and how doctors and nurses and pharmacists are supposed to know better, attack and ridicule me and others like me and when we "look at what is effective and what the active ingredients are" we are gaslit and told we can't possible understand and know that and to leave it to the experts. Of course the definition of expert is only ever tribal and is a moving trojan horse for whatever best allows the agenda of an industry to establish its control over you.
What, to me, should be illegal, is building expensive branding around a group of very basic analgesics - well and other groups like antihistamines.
In the UK I can buy an own-brand 16-pack (8 g) of paracetamol in a supermarket for £0.35 / $0.45. At the same time, I can buy a packet of Panadol (GSK), same substance, same content, same amount, for £2.35, nearly 7 times the price of generics.
How is THAT legal, and how are people so unaware as to actually buy it? "Unaware" may be the key here.
There can be some arguments made (maybe you think the generic cuts corners and it is only 4.5% vinegar instead of 5%), and the same arguments can be made for the drugs. But IMHO they come nowhere near to justifying the price gap.
The thing that is particularly frustrating in the case of the drugs is how the brand-name is (for many people) the vernacular name. I grew up in a family that called many drugs by their actual name (eg ibuprofen & acetaminophen), but when I go to the doctor, many of them insist on calling them Advil & Tylenol. Sometimes it seems to take them a second to recognize the generic name.
> How is THAT legal
Why shouldn't it be? Companies are free to set prices to whatever the market will bear. In this case it's based on customer ignorance, which makes it feel icky, but I don't think that's a reason to legislate this sort of thing.
> and how are people so unaware as to actually buy it?
Yeah, I don't know. I do remember that, many many years ago, I didn't know about this, and would always go for the big-name-brand version. At some point I learned to look at the active ingredients and just buy the cheapest one that had the same ingredients in the same dose, but I don't recall when or why I learned that, or why I didn't know that before.
I think there's also an implicit quality judgement sometimes, even if it's unfair. When it comes to groceries, say, canned tomatoes, and I see some fancy-looking Italian brand that I've heard of, my brain will automatically rate it much higher than the grocery store's own branded version of it. Maybe that's an effect of marketing/advertising, maybe it's something else, I don't know. And sometimes it's actually true: tomatoes are not all created equal. I think something similar happens with drugs, even if it's an entirely different kind of product.
People also often assume that something that costs more is automatically higher quality. For some types of things, that can be true (because yes, there is such a thing as a better tomato, and sometimes it costs more to cultivate said better tomato), but for drugs in a regulated environment, that doesn't really make sense. But people pattern match on what they know and what they feel.
this argument makes very little sense. Plenty of very potent drugs are in the single digit mg range in a tablet that weights hundreds of mg.
More importantly, as always, it is a problem of incentives. There is no strong, commercial entity focused on removing ineffective drugs from the market, but plenty of commercial pressure to keep them. The FDA has zero incentive to clean house. The magic hand of the market is supposed to be consumers choosing not to buy these drugs because they are ineffective, but for many reasons (choice, placebo effect, basic scientific literacy) this does not happen.
I don't know what the most effective entity is. I cannot personally imagine a commercial structure to support this, but perhaps one could be built.
I am convinced that many people ask LLM's "give me a citation URL" and don't bother to read it.
> The results of this review have to be interpreted with caution because the number of studies in each category of cough preparations was small. [...] There is no good evidence for or against the effectiveness of OTC medicines in acute cough.
For anti aging stuff, the workhorse ingredient is retinol (with a few formulation variations).
However, it is very difficult to buy _just_ retinol - most beauty brands bundle up retinol with a bunch of other ingredients. This has a couple of issues:
1. You won't know your retinol dosage. These creams almost never tell you the retinol proportion and concentration.
2. You're overpaying by _a lot_. The luxury name brand cream will cost maybe 10x more than the similarly sized $9 bottle of retinol from the ordinary, but it will only contain some fraction of retinol.
Tbf this has been slowly changing and I see even La Roche Posay sells retinol bottles for $50. Insane markup, but smaller than what was the case 5 years ago.
This is all compounded with the fact that it's very difficult to tell if your anti aging cream is actually working from your own experience:
- its effect is slow acting
- it's difficult to compare the result with the counterfactual, unless e.g. you only use it on half your face
Completely unrelated, I noticed recently that tire detailing spray that makes your tires look black, and the recommended lubricant for my garage door weather stripping, which both cost $15 or more for a little bottle, are just silicon oil that costs pennies for that amount. I have no moral problem with charging higher prices for convenience plus clarity of what the use is. I do think it’s amoral, obviously, to be involved in snake oil sales and unbelievable that the government allows it.
Edit: this is the first result from a Canadian pharmacy searching for cough medicine. Worse it’s for kids: https://well.ca/products/homeocan-kids-0-9-cough-cold-day_88...
It's really worth talking to your pharmacist even if you know what you're buying. There's so many more options behind the counter and they're really knowledgable.
The tire stuff might be the cheap shit that's not so safe just because tires are so thick and robust. Or maybe it's actually designed for tires.
The very "medicine" you linked to in fact displays it right on the cover.
[0] https://en.wikipedia.org/wiki/Metamizole
[1] https://en.wikipedia.org/wiki/Agranulocytosis
DXM is fine but oral phenylephrine should be banned. The only reason it's in any of these drugs is because they don't want to lose sales when the real version that works is locked behind the pharmacy counter after hours. It's a scam to keep sales up.
DXM is also not a placebo, although it might be specifically for cough.
I don't especially want the FDA to ban them, but requiring separating out the acetaminophen might not be the worst idea.
...
> So the only ingredient that’s doing anything in that bottle of DayQuil makes up just 2% of the bottle: the roughly 8 grams of acetaminophen, which separately would run you about 16 cents at Costco.
Why are they comparing the price of CVS DayQuil to Costco acetaminophen? Either compare CVS DayQuil to CVS acetaminophen or compare Costco DayQuil to Costco acetaminophen.
Funny amphetamine used to be an over the counter cold medicine, which the article doesn't mention despite talking about the meth precursor?
Fine article but these two details stuck out to me while reading it.
It definitely works for me. It'd be wild if for all 44 years of my life, it's only worked because of the placebo effect.
The article mentions phenylephrine, and that shit definitely doesn't work. Not even a placebo.
Ketamine is neurotoxic itself and can cause permanent brain damage. I can't find the info but there was someone in the tech industry who accidentally overdosed and suffered a two year bout of severe debilitating depression culminating in suicide.
i believe you are referring to Felix Hill.
https://docs.google.com/document/d/1-jBoSEVlryiX1IaSzV4vKuih...
"On mental health, psychedelics and life
This is a story about mental health, psychedelics, psychology and the mind. It is a story about the joy of family, the joy of friends, the joy of being in love, and the joy of doing scientific research. It is a story about life, the world, and how amazing they both are.
After 18 months of intolerable torture, and after many months of consideration I have decided to end my life."
If you want to do it the smart way, just consult erowid.org and use a little common sense.
https://erowid.org/chemicals/ketamine/ketamine_faq.shtml
>You’ll also find lots of cough medication with guaifenesin, which has similarly thin scientific backing.
He links ( https://pubmed.ncbi.nlm.nih.gov/24003241/ ) which shows that guaifenisin had no measurable effect on sputum volume or consistency (p = 0.12 for volume). But there are other studies with broader outcome measures which show positive effects:
https://link.springer.com/article/10.1186/1465-9921-13-118
>The pilot study was a randomized, double-blind study where patients were dosed with either 1200 mg extended-release guaifenesin (n = 188) or placebo (n = 190), every 12 hours for 7 days [...]
>Subjective measures of efficacy at Day 4 showed the most prominent difference between treatment groups, in favor of guaifenesin.
>The DCPD assessment of symptoms also indicated advantages for ER guaifenesin over placebo for the between-day changes from baseline in response to the questions “Over the last 24 hours how often did your phlegm prevent you from going to public places?” (Day 2; p = 0.0016) and “Over the last 24 hours, how difficult was it for you to bring up phlegm?” (Day 5; p = 0.0070).
G tends to do well in subjective (symptomatic) assessments, even when subjects are blinded, but poorly in objective assessments. However, this isn't enough to condemn it.
It's so utterly ridiculous how much space the Cold and Flu section of the medicine aisle takes for no reason at all.
And the whole thing about combining so many medications is just silly, especially the marketing for it. "Why take 3 medications for your cold symptoms when you can take just this one?" then gets countered with "Why take a cold medication that has ingredients for symptoms you don't have?"
IMO, DayQuil should never have existed simply for the reasons the article mentions: It leads to people being unaware of what they're taking. Yeah, the label is right there, but you gotta consider the lowest common denominator when selling things to the general public.
If they sold these chemicals as singular treatments then the abuse would go through the roof. The "accidental OD" scenario where an innocent patient quadruple-doses is realistic, and anticipated, and the shrewd consumer will avoid this.
I injured my legs, then on top of it, had a minor cold recently, and finally grabbed a bottle of Coricidin HBP out of desperation. I have also been stocking up on 0.0% beers. Between doses of the former and bottles of the latter, I managed to get some great-quality sleep and rest.
The other thing to notice about the Cold and Flu section of your pharmacy is that most all the treatments are supposed to relieve congestion, clear phlegm, and serve as an expectorant, such as all the cough drops with lemon, or menthol. If you are a lifelong smoker with a productive cough, this is great. That includes habitual pharmacy patrons who've always purchased their cigarettes and cigarilloes right there at CVS, next to the candy aisle and the booze aisle.
If you live in a desert and/or suffer from chronic E-N-T dryness and dry coughs, then these treatments will make your life a living hell and must be avoided at all costs. Think about it.
I think we need to do more around accidental overdoses than suggest that everyone should be a "shrewd consumer".
All these overdoses are happening because people do not read the warnings and they do not follow the instructions; and if they cannot understand the warnings and if they cannot follow the instructions, nor even consult a professional, then perhaps they deserve an overdose?
It would also fix the homeopathic snake oil as well, which has started showing up as options in previously-reputable medicine aisles. So at any rate, be on guard if you don't want to end up accidentally buying a bottle of water plus flavoring in your cold-addled state.
They should probably have to split up large words with dashes or even spaces "phenyl-ephrine" "psuedo-ephedrine". Maybe even "phenyl-eph-rine" "psuedo-eph-edrine". One authoritative list published by the FDA (they already keep a list of what's allowed to be sold OTC in the first place, right?) of how the active ingredient names have to be distinctly stylized to best inform.
In America? No idea. In the UK it's because they sell codeine+tylenol OTC, and they want it to poison you if you try and get a codeine buzz from it. Incredibly this is true.
In fact, it’s so effective against pain and fever, it keeps doctors from having to resort to prescribing opioids. Countries that haven’t restricted its use do not have nearly the same problem with opioid abuse.
It makes me wonder if its continued restriction is motivated by profits off the opioid crisis, rather than patient safety.
And then there's OTC drugs which are sort of in a weird middle area - and where some of these I feel personally might work best. Make them easily accessible to anyone without a prescription but at least a pharmacist has to hand it to you. They are the experts at dosing and what combinations of drugs are safe after all !
Drug prohibition has caused magnitudes more harm than decriminalization and legalization.
And part of this article is about claims from what is likely inert or mild effect at best. Remember, we used to have amphetamines, pseudoephedrine, and much more potent drugs to alleviate colds and such. But because of the forever-drug-war , we're stuck with substandard crap, and everything good gatekept by doctors.
I honestly do not trust somebody with a doctor license who I talked to for 7 minutes out of 259200 minutes (6 months).
For example, when I went on a camping trip, I got bit by 15 ticks. After I got back, went to doc for 15 day doxycyclene, gold standard. And its cheap, like $15. NOPE, fucker wanted the ticks in a bag to grind up and waste a $400 Lyme test. And that test is only 60% accurate, tons of false negatives.
If I could have, I would have bought doxy, scaled it to my weight, and did the 15 day run.
But nope. I ended up getting the second recommended, amoxicilian as "fish antibiotics".
I got another staph infection previously in the united states. Needed to go to a doc in the box who misdiagnosed it. A few days went by and i needed to go to another doc in the box who gave me topical and trued to give me a steroid shot. Needless to say it progressed and turned into fullblown MRSA which required admitance and a IV antibiotic. Extremely painful. I don't have the ability to add the costs but north of $10k easily.
That's why drugs should be legalized.
I think your maximalist conclusion of "drugs should be legalized" might have some second-order effects that might be net worse for society, though. Addiction, misuse, MRSA, overdoses, etc.
Also do you see any ironic connection between your two examples: easily accessible antibiotics and a medically resistant infection?
- Alcohol, tobacco & weed are already legal... why them and no other drugs? Check how many deaths do alcohol & tobacco provoke.
- Taxes, lots of taxes, literal mountains of money... a small percentage of which can be redirected to treating addicts.
Legal status (along with stigma associated with it) does prevent them from getting help before completely crashing out. It has the additional side effect of whatever portion of their lives they come out of it with being completely destroyed by the legal process. You know, because chronic illness obviously deserves punishment.
So I guess the real question is: what is the goal? Help chronic illness, or punish people that do things we don't like?
Also, don't we already have laws for literally all the bad things someone can do while addicted? If not, then why is it bad just because they are suffering from a chronic illness?
https://www.health.harvard.edu/newsletter_article/the-power-...