The Uselessness of Phenylephrine (2022) | Hacker News Reader

The Uselessness of Phenylephrine (2022)

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The fact that phenylepherine is ineffective is quite old and has been common knowledge for many years. What is news is that the FDA is finally acknowledging it. I've maintained my own reserve of pseudoephedrine for years.

https://gizmodo.com/report-many-over-the-counter-decongestan...

https://www.forbes.com/sites/daviddisalvo/2015/10/26/the-pop...

https://www.newscientist.com/article/2089555-breaking-bad-sn...

> I've maintained my own reserve of pseudoephedrine for years.

Synthesizing it from widely-available and affordable street drugs, I assume.

https://improbable.com/airchives/paperair/volume19/v19i3/Pse...

Easily the best example of why the stupid federal law limiting access to a useful decongestant backfired.

In what way did it backfire? It's a useful decongestant. But it also basically is methamphetamine, with just a couple easily-reversible Rubik's turns to make it a decongestant instead of an ultra-powerful stimulant.

Didn’t prevent people from getting meth, but did allow drug companies to make millions selling a useless compound. I doubt that was the intent of the legislation.

The same company sells both compounds. I don't think this was a huge moneymaker. I think the PE thing was just there to retain the sales that moving Sudafed behind the counter sacrificed. That doesn't make it OK, but it does sort of argue against the idea that the regulation was just a moneymaking scheme.

Agree with that. Just more failed war on drugs stuff.

Only if you judge the outcome strictly by how many people are consuming meth, but there are other important endpoints to this policy, like "reducing the number of backyard meth labs", which are problems in their own right.

Water, consisting of hydrogen "basically is" and explosive, as is table salt, consisting of Sodium, which explodes when coming into contact with water. How can we let these two dangerous substances go unregulated! Think of the children! who will get to have interesting high school chemistry labs, that is.

That Sudafed "basically is" meth misunderstands chemistry, and the resourcefulness of the real life Walter Whites of the world. Hells Angels and the Cartels operate under the nose of the DEA so there's no way meth or drugs are going away. It's time for the government to admit they lost the current battle of the war on drugs to drugs. Current tactics aren't working and it's time to take the war to the demand side of the equation. Cut down the demand for drugs by getting addicts off opiates and stimulants with an army of therapists and councilors and rehab programs. With a large helping of harm reduction and government assistance. Wishful thinking, I know, but making all forms of basic chemistry illegal is like trying to make water not wet.

No, this analogy isn't plausible.

Hmm. Say more?

table salt, consisting of Sodium

The difference between a Sodium ion and a Sodium atom is one of the profoundest in chemistry and a fundamental topic of its high school version.

You realize your "best example" is a joke, right?

Yes, the punchline of the joke is that synthesizing pseudoephedrine from meth is more convenient than buying Sudafed after the law on restricting sales ostensibly to reduce meth production.

i.e., the law didn't do much to halt meth production but did put a bunch of barriers around a useful drug _and_ promoted the use of phenylephrine instead, a useless drug in pill form. A huge net negative.

At least if I followed that path, I would not be required to have my purchase recorded in an insecure government database.

Why are you worried about the government recording your usage of Sudafed? What is anybody going to do with that information? Serious question! I understand the principle involved; I just want to know if there's some practical concern.

Every database that contains your PII increases your exposure to a breach and likelihood of having to deal with it. It's not the sudafed use that makes it a target: it's the driver's license.

Right, but this particular database presumably doesn't have anything especially sensitive in it, apart from your Sudafed consumption.

I don't mean to dismiss that point, it's a valid point, I'm just considering it closely.

Anything a government uses to uniquely identify and track individuals (i.e. driver's license) is the target.

Until very recently, drivers license numbers were effectively public in a lot of states (they're deterministically generated from public information).

Hey, that's pretty cool. I suppose I now know Ron DeSantis's drivers license number up to the last digit. And the soundex algorithm is cool (using fuzzy lookup in a list that way to get close/vague matches is novel to me and might be useful). I had heard of soundex but didn't know how it worked until now. Thanks for the TILs!

https://stevemorse.org/dl/dl.html

http://www.highprogrammer.com/alan/numbers/index.html

It's none of their business. Simple as that.

Sudafed usage, probably a copy of the drivers license, your address, any phone number you give them, and how often you buy a drug the DEA considers a precursor to something really terrible.

Usually no one even looks at it (so why have it even?!?), but when they do it’s a potential intro to a full on Brazil situation.

Luckily the whole thing is generally considered a waste of time, so usually nothing comes of it. But why make yourself a target if you can avoid it?

Well, it seems pretty obvious why they have it: so they can match purchases of Sudafed at different retail outlets at different points in time. And it's obvious why they want to do that: because there really was a huge epidemic of people making straw purchases of Sudafed to feed large numbers of low-volume amateur meth labs.

In the years after this policy was put into place, there were news stories about how effective it had been in eliminating backyard meth production. You don't see those stories anymore. I suggest, with weak confidence, that the reason you don't isn't that backyard meth has roared back, but rather that it's so decisively not a part of the equation anymore that stats about it don't really matter. Meth comes from overseas now, not from backyards.

That doesn't solve the meth consumption problem, but it does eliminate one significant meth externality.

I love how we're still stuck not being able to buy Sudafed normally though. :(

You mean, by walking into the drug store and asking for it?

By literally going to the aisle with the decongestants, taking a pack, and paying for it like every other thing I would be buying. Like every other OTC drug.

Without having to give ID, find a pharmacist, etc. I remember those days. They're long gone, obviously.

"Find a pharmacist"? I can tell you where the pharmacist is! They have their own checkout aisle!

And bankers hours, and their own waiting line! Perfect!

What they're going to do with it is prevent me from making a purchase if I've crossed some arbitrary limit as if exceeding that limit automatically makes me a drug trafficker.

From there, it's not too far of a stretch to imagine the government assigning someone to review the list and to expend additional investigative resources into merely "suspicious" cases. Plenty of good tragedies start this way.

If the government has an interest in preventing drug manufacture then this is the absolute worst way to go about prosecuting that agenda. It harms the wrong people and it offers no impediment to actual producers.

The information cannot possibly be useful, it may become a liability, and I didn't ask to be protected from myself.

They're just going to say "no", right? They're not going to "automatically make you a drug trafficker". They're just trying to enforce a rate limit.

So, if the concern isn't that I'm trafficking, then why am I being told no? Isn't this the logic the government used to assert this right for itself in the first place?

Otherwise, what right is it of the government to enact this rate limit? What interest are they protecting? How is the rate limit decided? What can I do if I disagree with the rate limit? Why is a private business being burdened with the governments agenda here?

I get where you're coming from, it _is_ a /small/ thing, but the implications immediately become onerous if you think about their meaning inside of a "free" country.

You're not being told "no". You can just go buy some Sudafed right now if you want to. It's not like there's an application process. There is a rate limit; that's it.

In order for a rate limit to be effective, at some point it has to apply, and at that point, I'm told "no." More concretely, in order to implement a rate limit, you have to sign an electronic log book, and the government can view that log book whenever it likes, without any sort of review or auditing, of course.

This isn't the primary concern anyways, the point was, in order to implement this seemingly simple action, many liberties have to be sacrificed and the boundary between innocent and criminal and government and private business become significantly marred.

Perhaps those sacrifices are immaterial to most lives and could be ignored without consequence, but the originalist in me says this is folly, and as I've shown it's easy to think of the dangers that some innocent people might endure as a result. Worse, comparing these dangers to the outcomes of the system itself, the whole endeavor seems to have negative value.

Finally, as we've seen in history many times, now that this electronic logbook exists, it's use will naturally continue to expand until the government has secured for itself the right to view nearly every single "questionable" purchase you make at a pharmacy.

It's an entirely unaccountable act from the government. I'm not sure why anyone would expend effort minimizing it.

The only liberty being sacrificed here is showing an ID at a pharmacy counter to get Sudafed. I'll stipulate that's a liberty being sacrificed, but it isn't "many".

This particular "logbook" has existed for almost 2 decades now, and its scope hasn't creeped from there, so your second argument is pretty easy to shoot down.

I think the evidence pretty strongly suggests that this policy, which was put in place to create a rate limit on the purchase of a chemical that isn't so much a precursor to methamphetamine as it is a slightly tweaked version of methamphetamine, is in fact simply used to create a rate limit.

> The only liberty being sacrificed here is showing an ID at a pharmacy counter to get Sudafed.

It would be interesting to know if the people concerned about the need to show an ID to vote share that concern about the need to show an ID for access to medicine.

> This particular "logbook" has existed for almost 2 decades now, and its scope hasn't creeped from there, so your second argument is pretty easy to shoot down.

The policy has proved ineffective at curtailing the availability of methamphetamine while inconveniencing honest people. That's not something the public is clamoring for more of.

But it never really was. It came about to begin with as part of the Patriot Act. The lack of expansion is unsurprising given the lack of any 9/11-style crisis to use as an excuse in the intervening two decades. The test is when the next one comes.

One of the failings of the existing style of government is that the "passage by both houses of Congress and signed by the President" system used to pass legislation is the same system required to repeal it, which rightfully makes it harder to pass bad laws, but wrongfully makes it harder to repeal them. And then they get passed during a crisis and inconveniently stick.

You already need to show ID for most medicine! This is such a weird discussion.

Name an over the counter medicine you need to show ID for.

Sudafed isn't an OTC medicine; it's a BTC medicine. Most medicines aren't OTC. But there are, obviously, OTC products that require ID; for instance, every alcoholic beverage.

Purchases of alcohol at the grocery store are not individually logged and tracked by personal ID. I’m certain that is not what happens when I show my birth date to a cashier.

Most large retailers (e.g. Target, Walmart) now scan the barcode on your ID at the POS when buying spirits.

Because it's required by law, or because they want to track you for their own purposes and if you don't like it you can patronize someone who doesn't do that?

That's just begging the question. The only reason it's BTC is that you have to show your ID to get it.

It's weird to me that we've completely normalized having to present ID to buy any medicine at all, especially one that has an excellent safety and efficacy record that I was buying without an ID for a decade. Why should I have to ask the government's permission to cure a runny nose?

The problem with Sudafed isn't that it's ineffective or unsafe for its users; it's that it has the same or higher abuse potential as codeine cough drops did. We took codeine completely off the market, but you can just go buy Sudafed whenever you want.

Significant numbers of people are not going to the pharmacy and buying Sudafed because they have a cold and consequently getting addicted to Sudafed, which is what had been happening with codeine.

It's clearly because you can make methamphetamine out of it. But you can also make methamphetamine out of other things which limiting access to cold medicine demonstrably hasn't prevented.

When Sudafed was put behind the counter, it was likely that a plurality of all Sudafed purchases in California were abusive.

More than likely, I would think, since plurality just means more than one.

But the justification is not the same. People were going to the drug store for cough drops and unintentionally ending up addicted to opioids. Nobody was going to the drug store for a decongestant and accidentally making meth out of it, and the number of people getting addicted to pseudoephedrine itself was neither large enough to justify the change, nor its explicitly stated rationale. Nor an effective means to bring it about if the claim that showing an ID isn't a burden is to be believed because it would have no effect on the small minority of people who might go to the pharmacy for a stuffy nose and thereby become dependent on pseudoephedrine, since they would still get it.

Meanwhile the stated rational of limiting availability of methamphetamine hasn't gone well either.

This before we even mention that the OTC replacement, phenylephrine, is not only ineffective, it's a more dangerous drug than pseudoephedrine from a cardiovascular perspective and the switch has plausibly killed some people.

> You already need to show ID for most medicine!

Do you? You have to show an insurance card to file a claim, but I imagine there is a lot of overlap between the people without ID and the people without insurance. And there appear to be free clinics that don't require ID, implying that it isn't required by law.

> In order for a rate limit to be effective, at some point it has to apply, and at that point, I'm told "no."

The alternative is you don't buy any Sudafed in the first place. So you've basically told yourself "no" anyway.

I realize you dislike the government logging your purchases, but you haven't answered GP's question about why you dislike it.

> You're not being told "no". You can just go buy some Sudafed right now if you want to.

You effectively are in many cases, just as predicted by most when these laws were put into place.

First, it became far less of a relatively benign "after the fact" logbook as it was when first implemented. It is now networked and real-time. Many chain stores implement their own interpretation of what they feel a rate limit should be. This tends to err drastically on the side of conservative, and might look back much further than you assume.

Second, it's added risk - many independents simply don't want to bother with such a risk, and thus don't bother stocking it. It also adds handling costs.

And third and most importantly - it completely and irrevocably ruined the supply chain. It is now legitimately difficult to find it in stock reliably - and if you run out of it at 2am, it's no longer just a minor inconvenience to run to literally any convenience store.

Most stores simply no longer carry it, and only a handful of 24 hour pharmacy options exist compared to 20 years ago. Those pharmacies also have consistent supply issues, so you better not have strong brand or dosing preference.

Prices went up, and availability plummeted. It's out of stock roughly a third of the time I've needed to go run out to get some, and is no longer just an afterthought item to stock up on at Costco. Typically you're settling on buying the smallest boxes they make since all other sizes are out of stock, and paying even more per dose.

And it absolutely is a slippery slope. Loperamide has now met the same fate in many states, and has become multiples of the expense it used to be and a very much pain in the butt to get. No more qty 120 bottles from Costco at 2 cents a pill - entire market killed because people got used to this new norm.

It's just one more chip away at the American quality of life. Not a huge one, but one that adds expense and friction for what amounts to a questionable amount of gain.

Edit: That is all to say - it's far more than "just a rate limit". Ruining the OTC market for cold medication might be worth it, but that's more or less what happened here. It wasn't like the top 5% of buyers got scraped off the top and sent to jail and everyone else carried on per usual. The cold aisle of your local supermarket took a giant step backwards from 20 years ago in price, availability, convenience, and effectiveness. That was the cost of these creeping regulations. Some may even say the chilling effect was the entire point.

For me, it’s a matter of it’s none of their business. No one’s accused me of making meth, but here’s all my PII in a database “just in case”.

It’s literally harder for me to buy cold medicine than a gun. I hate everything about that situation.

I mean, the reason they keep the database is especially clear here, right? They're just trying to enforce a rate limit. It's the most obvious public policy response you can have to "a drug that in small quantities is a useful decongestant, but in moderate quantities or above is an ultra powerful stimulant whose abuse is ravaging parts of the country".

I get it. I just find it frustrating, and I'd like to know that my PII was removed after the rate limit period.

I agree with this!

The primary question to me is whether the risk of data breech outweighs the harm from not keeping the data, and while 20 years ago this tradeoff may have made sense, I'm not so sure it makes sense now.

If the data is breached, an attacker learns... that sometimes you have a cough?

...and your SSN, and your driver's license info, and all the other personally identifying information they collect and store in the DB.

Generally not your SSN - I've never had to give it for Sudafed - but at least full legal name, birthday, gender, home address, driver's license number, telephone number, location(s) you've been to buy medication, and possibly email address.

Much of which would be covered as PII and PPI, and, in combination with info from other other data breaches can tell someone a lot about you.

In addition to at least your full legal name, birthday, gender, home address, driver's license number, telephone number, location(s) you've been to buy medication, and possibly email address.

You do not in fact provide an email address to buy Sudafed. The rest of that information is for most people already a public record.

I'm not saying that makes it OK to assemble into a database, and I think the point about amassing PII is well taken, but I think people are probably overestimating the value/hazardousness of this particular data set.

It’s an attractive nuisance which seems to provide zero practical value overall, let alone for it’s stated reason to exist.

It decreases the number of backyard meth labs, which are a danger to their surroundings. Despite the availability of overseas industrial meth, meth labs would make a comeback if you could simply buy pseudo-meth at the drug store to shake-and-bake in your garage.

A more robust fix compared to keeping a list of cold medicine buyers would be to decriminalize or legalize hard drugs, ensuring that a clean, inexpensive supply is available for those addicted under medical supervision, providing a safe place for those who choose to use, providing judgement free addiction treatment, increasing invest in addiction prevention, and addressing the systemic issues that drive people toward drugs due to a lack of opportunity, lack of support, or lack of understanding the negative impacts of drug use.

Oh, so I guess we just draw the rest of the owl. Good to know that if we fundamentally alter society and sidestep the challenges in doing so, we can avoid the burden of occasionally having to show our ID for one more drug than before.

We can and should do the things you're suggesting, but I can't get behind the logic that we should wait til we can accomplish those things, when we can take any other more straightforward measures to mitigate "people making meth at home next door to people who don't like meth labs".

> I can't get behind the logic that we should wait til we can accomplish those things

Where in my post did I say we should stop taking IDs and then wait until all of those are 100% fully accomplished before trying something else? Re-read the post - it's not there.

I'm arguing a more robust fix would be to do all of those things. That's not incompatible with keeping the current system of checking IDs until we hit some critical mass where the fixes for the more systemic issues reduce the need for checking IDs.

I don't know where you live but I cannot buy a guy by just showing up. They take ID, they require a license and still run a check. The only exception is when you get your CCW which removes the license per handgun (not long gun/shotgun) but requires a background check.

It's legal defense in depth, similar to not talking to police without an attorney present. All it takes is an overzealous prosecutor or social worker to ruin someone's life by misrepresenting some random circumstantial facts. This happens all the time in drug cases, for example, where the possession of innocuous items like small baggies allows prosecutors to take charges from regular possession to intent to distribute or trafficking.

Even if someone isn't doing anything illegal, since >90% of cases end in plea deals it's good legal hygiene.

https://www.zdnet.com/article/buy-too-much-sudafed-and-you-m...

But if cops will choke someone to death about selling a cigarette, do you really want them to know about you buying Sudafed?

It’s funny that there is no outrage about a national psuedophredrine database. But people go nuts about a national gun database

It's almost like people generally understand why pharmacies are regulated to rate limit the purchase of Sudafed, and that the political consensus generally isn't an ideological opposition to any kind of regulation, the way you mind find it on a message board.

Sudafed PE is a much more salient and annoying topic than the behind-the-counter real Sudafed. I think it really does piss people off to get tricked into buying fake decongestant. But that's a separable issue from having to ask (and to show ID) to buy the real stuff.

I know of families who struggle to keep enough psuedophredrine in the house when their minor kids get sick and they need some for themselves.

These people are just very paranoid. This is my field of work for the last 15 years.. people think way too highly of the govt capabilities and negatively on their goals. If we actually did 1/10th of what people accused us of our lives would probably be much easier.

Something tells me there is more than just a government owned database involved. Likely at least one third party vendor system... Not to mention every pharmacy chain probably stores or at least transmits it through one their own systems.

But what if it were a secure government database?

Lol, that article is really brilliantly hilarious. SNL should do a "Bizarro-World Breaking Bad" where Walter and Jesse go around buying up crystal meth so they can cook Sudafed.

Indeed. I've known that phenylepherine is worthless for a long while, and just make it a point to buy a pack of the real stuff every 6 months or so, so that I always have it on hand when I need it. In my state, it's controlled - you have to get it from a pharmacist (though you can do so without a prescription) - they take your driver's license and don't allow you to purchase it too often.

That is a US federal law (the Combat Methamphetamine Epidemic Act of 2005)

And now we've got a fentanyl epidemic filling the void and even more power handed to Mexican cartels since meth got harder to produce domestically. Drugs continue to win the war on drugs.

You can't fight a war against inanimate objects. You can fight a war against drug addicts. You cannot possibly win a war against drug addicts without addressing the fundamental problem.

Most of us cannot make these drugs ourselves. To restrict them effectively would certainly curtail their abuse?

The presumption here is that an addict, unable to get their "favorite" drug, will now just stop doing drugs entirely. This is not the case.

Drugs can also be stolen, from homes, and from pharmacies, and from ambulances.

There are way more vectors than people care to ponder. If you've ever had an addict in your life, you're forced to.

In other news, the bureau of labor reports that the number of unemployed chemists have skyrocketed, and lab equipment manufacturers are reporting a surprise bump in sales.

If the mountain will not go to...

Shake-n-bake meth was relatively easy to do for the average methhead.

Also, do not underestimate the capabilities of a meth user when they get fixated on something.

Bonus - meth causes among other things incredible focus.

I’ve noticed the comments on hn become more meth curious over the last couple of years… I know the state of CO has been pressuring doctors not to prescribe aderall. Mine got taken away because i only took it when i needed to force myself to really work (a few times a month). Now i use pseudoephedrine.

Doctors handed out oxy like candy and when people couldn’t get scripts they turned to H on the street

Teachers push any kid that can’t sit still while being bored for hours to be taken to the doctor for adhd, where they are quickly prescribed amphetamine salts. What do you think they will hit the streets for if their addy script ever gets cut off, or, there’s a shortage of supply? (happened recently). Methamphetamine.

Many people use small doses of meth the same way they would take a daily dose of adderall.

You can actually be prescribed literally methamphetamine. Not amphetamine, methamphetamine. It’s rare, but it exists.

Hard drugs have been illegal in America for generations, and yet every city has had a junkie community all this time. How much more failure must we entertain?

Vice or someone reports that you can make the new formulation, in a backpack, in a Walmart bathroom, with supplies you haven't even bought yet. Given that, and, well, the Internet, I'm sure making it isn't hard for an addict to learn how to make these drugs, even though it's not common knowledge and you and I can't do it.

"We just need to wage the war on drugs harder, then it will surely work."

It turns out it's not possible to do that. We've been trying since the 1960's.

Longer than that if you count one of the OG drugs - Alcohol

The "fundamental problem" is the breakdown of community (drug abuse being primarily being a function of the existence or lack of interpersonal involvement and responsibilities that would preclude spending time and money on them). People who are comfortable huddling in their cars, homes, and exclusive social clubs, and who would rather spend money on cops rather than social programs, aren't going to like the fix for that.

Do you have a source for this?

> drug abuse being primarily being a function of the existence or lack of interpersonal involvement and responsibilities that would preclude spending time and money on them

AFAIK there have always been addicts in every culture. Alcohol, various drugs, and strongly self destructive behaviors are not recent additions to the human experience. But I don't know any if the numbers or the research on this root cause you mention.

I suspect they're referring to experiments like the famous "Rat Park". There is clearly a strong social and environmental component to addiction susceptibility, at least in rats.

I don't know if I'd go as far as to say it's the fundamental problem, but definitely a major factor.

"AFAIK there have always been addicts in every culture."

Surely you would agree that there the proportion of addicts varies by culture and society, that the US for example has a much higher proportion than many poorer nations? I don't know about the first comment's claim that lack of interpersonal relationship is the root cause, but a strong social component looks obvious to me.

Cite? Every nation has an underbelly.

Poorer nations, those folks tend to die pretty fast though.

There was this article about Iceland combatting teen drug abuse by providing alternative activities and social outlets:

https://www.naturalhigh.org/icelands-radical-transformation-...

Iceland isn’t really a poor country though, even if it doesn’t have a high GDP. It’s more like New Zealand.

cite for what? my comment is basically asking for a citation for the OP's (and your) claim that substance abuse isn't culturally dependent?

I didn't claim that it wasn't culturally-dependent. Both people turning to drugs to self-medicate, and people not supporting and funding effective interventions - people on both sides rejecting or not seeing the opportunity to engage in community-building - is absolutely a culture issue.

No, it's merely a personal observation. In that vein, I'd think it more correct to say that there are always addicts on the margin of every culture.

Not the OP, but bring back real jobs and real way of spending your time (like real family and friends) and much of the meth problem will get solved by itself.

> AFAIK there have always been addicts in every culture

Alcohol addicts are a totally different thing compared to drug addicts. You can die as a result of alcohol, but there's nothing like fentanyl in the alcohol world (I'm talking about the scale of the disaster, I know about the few alcohol intoxications here and there).

There is in countries where alcohol is illegal, like in the Middle East. There, wet have similar problems as we have in the western world with poisoned supply - people buying liquor, but it turns out to be bleach. So I'd say bleach in your liquor is the fentanyl of the alcohol world. We don't see that in countries where alcohol is legal though, hmm.

> social programs

Do you have any links to social programs that have successfully dealt with meth addiction?

Can't say I have seen any locally (New Zealand) and we are a country more likely to see such programs?

I don't, but I'll ask you to consider the following:

1) The implication of my statement wasn't that social programs would solve the problem single-handedly, but that they're more effective than enhanced law enforcement spending.

2) This would seem to be, at the very least, supported by the people who advocated for treating the (mostly white and middle-class) victims of the opioid epidemic in the US as suffering from a medical rather than criminal affliction.

> I don't, but I'll ask you to consider the following: 1) The implication of my statement wasn't that social programs would solve the problem single-handedly, but that they're more effective than enhanced law enforcement spending.

What do police have to do with the effectiveness of social programs? A fundamentally ineffective social program will be just about as ineffective no matter how much funding it gets - because the problem they are approaching isn't one that they can solve.

>A fundamentally ineffective social program will be just about as ineffective no matter how much funding it gets - because the problem they are approaching isn't one that they can solve.

Correct - ironically, as you're describing most law enforcement agencies. The money spent on police - particularly their generous overtime and pension pay, equipment outlays, and hilariously ineffectual training - could be used to fund social interventions that actually work.

Until the past few years, I held a similar view. I.e., if we could just dry up the demand for the product, the rest of the system would crumble.

Then the whole Sackler / Oxycontin thing came to light. And I saw (well, second hand) a normal person get hooked on pain meds after back surgery, thanks to those assholes. And they're not in prison.

That's when I concluded that we lack the collective will to take the necessary steps to fully stop the trade of addictive drugs.

The problem with decriminalization/legalization is that those are the most abused drugs.

However, our drug war is causing Mexico to descend in to anarchy and people are dying by the thousands, or living in total fear of cartels that we trained in the School of the Americas.

Thus, I conclude we have to decriminalize and treat our addicts. Enforcement is not working. If we had a sane drug policy 30-40 years ago, Mexico might be a healthy vibrant trading partner.

Meth is not harder to produce. It's now mass-produced from P2P, with chiral purification using various methods (like pulling one enantiomer with tartaric acid).

Yes. But now it's produced in para-industrial labs, mostly in other countries, rather than in apartments and back yards, where those ad hoc labs were actually real public safety problems.

Isn't increased financing of major drug cartels a serious public safety problem?

Weren't most pseudoephedrine-to-meth operations in rural areas or otherwise situated away from the general public to avoid detection?

Was Al Capone a public menace, or a businessman saving countless thousands from methanol poisoning and distilling accidents?

Plenty of these stories documented either way: https://www.cbsnews.com/amp/pittsburgh/news/police-erie-boy-...

Por que no los dos?

But any "benefit" of the likes of Al Capone ended with prohibition, i.e. the thing forcing the alternatives to be methanol poisoning or mob hits.

And you wouldn't need to check ID to rate limit cold medicine if you would just check ID to rate limit what people make out of it.

I wonder if the users are sad to miss out on the artisanal small-batch experience.

https://slate.com/news-and-politics/2021/03/montana-steve-da...

Adding chili powder was his trademark.

> mostly in other countries

Another case of needless regulation driving outsourcing, and putting our small manufacturing business out of work.

I'm curious about the chemistry here (though I have very little chemistry background), so, bearing in mind that I have zero interest in producing methamphetamine, perhaps you can elaborate a little:

– I can't see how Phenylacetone can have chirality

– I don't understand how any enantiomer of P2P (if one exists, see above) can be selected for specifically via a chemical reaction, especially here with tartaric acid, which is a chiral molecule itself, so surely you would need a specific enantiomer of tartaric acid to start with?

I'm sure these are basic questions, I'm just a dabbler. Any links welcome, no problem if this is out of place for HN.TIA

P2P doesn't have chirality, but methamphetamine does. Any carbon atom with 4 different groups attached to it will always be chiral, in meth it's the carbon next to the nitrogen. It has: methyl group, phenol group, hydrogen, and the amino group.

> – I don't understand how any enantiomer of P2P (if one exists, see above) can be selected for specifically via a chemical reaction

You just react P2P and get a racemic mix of L- and D- enantiomers of meth. Then you react it with tartaric acid, which will preferentially react with the "right" meth.

> tartaric acid, which is a chiral molecule itself

Ah, I see the confusion. Tartaric acid derived from biological sources consists of just one enantiomer, that's why you can use it to do chiral resolution.

Thanks, very informative!

I would like to see “taxes” be the winner of the war on drugs

It's worse than that, because it's not actually a void that's being filled - meth production simply switched to a different pathway that's even more effective and potent. There's actually more meth than there was before the ban.

https://dynomight.net/p2p-meth/ "The main thing about P2P meth is that there's so much of it"

Really, I'd read somewhere (might have been browsing the subreddit out of curiosity a while ago) that the meth was much worse now that they had to switch to a process that results in more chiral junk. Interesting.

It was, briefly, and then they figured out how to purify it I guess?

Drugs winning the “war on drugs” would be a problem for the “war on drugs” only if reducing drug use had actually been a priority of the “war on drugs” at any time in its half century of existence.

The majority of fentanyl is produced by a handful of labs in China. If the USA were serious about stopping the fentanyl overdose problem, it could be done with political pressure.

Ask yourself why that isn't happening?

You can buy 6 boxes of sudafed per month (24 doses each). Isn’t that more than the recommended (and probably safe) daily limit? I dont doubt your intentions but I don’t think you actually need 6 boxes per month + a stash.

They mention one box every six months, which is entirely reasonable.

For an individual, perhaps. But if your house has a lot of people in it who get sick at the same time because they live in close quarters, then maybe not.

Not sure how widespread it is or if there's a federal limit, but my state (Washington) even makes it illegal to possess more than 15 grams of it.

If my math is correct, 15 grams would mean more than 20 normal boxes of Sudafed, if each box is 24x 30mg.

I usually buy boxes of 48x 30mg, but even then I'd have to stash 10 boxes for it to be illegal.

Which is 2 boxes * n years + 6 boxes available at any given time.

Im not saying it’s unreasonable, just that the monthly limit is probably higher than he realized and he doesnt need to stockpile them.

The point is more to not be in a position to have to go out and buy some when I'm feeling cruddy. Since it's controlled, I can't just have some shipped to my door when I'm laying in bed sick. I just got in the habit of picking it up periodically to ensure that it's on hand when I need it.

Yup, nothing says fun times (and mass spreader) like sitting in line and doing paperwork while sick.

So why buy 1 every 6 months? Just go buy 6. This sounded like you were trying to avoid the limits:

> Indeed. I've known that phenylepherine is worthless for a long while, and just make it a point to buy a pack of the real stuff every 6 months or so, so that I always have it on hand when I need it. In my state, it's controlled - you have to get it from a pharmacist (though you can do so without a prescription) - they take your driver's license and don't allow you to purchase it too often.

I think you're reading something into it that isn't there. It's just not on the shelf, I'm not likely to notice it and incidentally purchase it when I'm buying ibuprofen or whatever, and I have to go out of my way to get it. I can't just have Amazon overnight some to me. As a result I've just gotten in the habit of buying it periodically without waiting for "I'm sick" to be the reason for the purchase. The 6 month period isn't "trying to not get noticed", it's "that period comfortably covers my household's needs with some breathing room".

Sure, I could buy 6 boxes at a time. I just don't. There's not really any good reason to min-max my pseuodephedrine acquisition.

When your kid gets sick late and the pharmacist leaves at 6, why not have a packs of pills wherever you are.

Or god forbid, you run out at work and forgot the CVS takes a siesta nationwide at 1:30.

Absolutely. But it sounded like he was afraid he wouldn’t be able to buy enough at once, hence the accumulation.

At least here in Switzerland, it's available over the counter, you get quizzed by the pharmacist to check if your symptoms are worth it or not, but no id or any registration required.

Actually, coming from the UK I was surprised I had to go through this, but now I realise I was previously buying the ineffective stuff, I was also surprised by the very, very mild buzz the swiss stuff gave me.

I just came here to say that I actually find phenylephrine nasal spray quite effective - but I use it for a different use case: stopping nosebleeds quickly. It's quite effective at that and came recommended by an ENT, so I do believe it's an effective vasoconstrictor when applied locally and I'm glad it's available.

That's legitimate. The FDA's issue with oral phenylephrine is that it's metabolized in the gut before it gets to the sites where you want it to work.

I wonder if it will work as a suppository.

It’s worth a try. I’d recommend buying a separate spray for your nose though.

“This medicine smells like crap.”

Reminds me of the old joke: what's the difference between an oral thermometer and a rectal thermometer?

Answer: the taste

"Oh, Dad..."

Seriously, my late father _loved_ that joke, as do I.

I heard that for the first time from my dad. It's a certified dad joke.

As a certified dad, I have to agree.

This reminds me of the funniest scene in the movie Idiocracy, where he loses track of which cable goes in the mouth vs ear vs butt. A laugh a day keeps the doctor away, enjoy :-)

https://youtu.be/zop3VG_K9HU?si=k8LDptGhvQDxtsTB

For the future, please remove the ?si= parameter from your YouTube share links. It uniquely identifies you and allows Google to track your social circle with certainty. (Not that they couldn't do it already)

what if he wants google to know his love for idiocracy?

Yup!

https://my.clevelandclinic.org/health/drugs/20786-phenylephr...

Phenylephrine is a popular topical and suppository treatment for hemorrhoids.

As per the article, you would likely be correct

You are correct.

This. Phenylephrine works great as a decongestant nasal spray, and it's not as addictive as oxymetazoline. (It doesn't last as long either, but that doesn't bother me.)

I wonder if it could be applied to the under-eye area to reduce dark circles caused by thin skin. People use caffeine topically for this reason.

EDIT: Looks like it does work for this! Nice!

It helps me a lot with post-nasal drip.

I haven't tried lately (moved on to aother anti-histimines) but with a Driver's license, I could pretty readily get ahold of it.

Then had to disengage based on what it was doing to my blood pressure.

Were you using a ‘D’ version? Like Claritin-D? I got that by accident once and my heart pounded like I was on speed. I’m highly sensitive to that stuff, same at the dentist the local anesthesia makes my heart race.

Third generation antihistamines are amazing.

Zyrtec changed my life.

I used to majorly struggle with ‘hayfever’ as we called it, to the point it ruined my summer.

I was miserable as a child, only winter gave relief as I was allergic to both tree and grass pollen.

Then zirtec came out. Originally as a prescription and that coupled with Flonase completely got rid of my symptoms without fatigue!

The old antihistamines I’d have to take so many to get help that I could barely keep my eyes open.

Then I moved to Texas from UK and the flora was completely different thus I didn’t react at all!

It was heavenly.

Then I moved to Oregon and many, many, trees and plants are the same as in the UK and my allergies came back.

Much weaker this time as a lot of people age out of these types of allergies, as my mother did.

OTC zirtec sorts it out.

Anecdotal really but I thought I’d share.

Yeah, I cycle between kirkland nasal spray and eyedrops.

And now going back on-site, the headcolds you pick up with proximity to people, Sudafed was AWESOME, it's just a pita to get and I shouldn't use it a lot.

> my heart pounded like I was on speed.

Pseudoephedrine literally is an amphetamine, and famously the precursor to meth(amphetamine). I don't have a similar reaction but I'm not surprised some people are more sensitive.

Note that Zyrtec's patent expired in 2007, so it's now available as generic Cetirizine.

Surprised this is the only comment mentioning the amazing Zyrtec (with Cetirizine) (probably misspelled, even with the bottle in front of me), in poem form.

But yeah it does work, smashingly. Also I found changing my AC air filter helped.

The fact that drug companies' "tests" indicated that it worked shows how corrupt the system is. There is in fact no way it could have worked, yet the data they provided decades ago showed that it did. This is why we should never, ever trust drug companies, it's just kind of funny that somehow in the last few years some people decided that Pfizer was a hero instead of a psychopathic (in the purest clinical definition) money machine.

You can still get pseudoephedrine, for example Claritin D, the D for decongestant. It's not by prescription but you have to sign for it at the pharmacy desk, present ID, and I believe it's reported to FDA/DEA and there are limits to how much you can buy per month.

That's mostly right, but it's not reported to anyone. It came from the "The Combat Methamphetamine Epidemic Act of 2005".

If you want to sell pseudoephedrine, your org has to "self certify", keep a logbook purchasers have to sign, require ID, enforce the purchase limits, train employees, etc. But, the logbook doesn't go anywhere unless some investigation or audit prompts that. So, if you're a really determined cooker, you can still go to a bunch of different stores...though you're leaving a paper trail. And some big brands might cross-check and have an org-wide electronic log book.

https://www.deadiversion.usdoj.gov/meth/index.html

I was under the impression that there are state-level databases in some states that actually track sales. I am likely incorrect, since a quick google doesn't find anything.

https://help.eaglesoa.com/29/en-n-eagle/Pharmacy/Pseudoephed...

Doesn't it take a ton of the stuff though? I thought people stealing pallets of it was the only viable way to source enough of it. Seems like just having some inventory control is a sufficient deterrent.

Depends on how much you're wanting to make. Sending smurfs to buy/steal from several locations was a thing for a while. But these cooks were never going to be cartel level secret lab under the commercial laundry location. These were the cook a batch in the trailer out back type of cooks. Jesse before teaming up with Mr White

Googling around a bit, a typical 20-count box of pseudoephedrine (2.4 grams of "active ingredient") yields roughly 2 grams of "high quality" meth with the shake-and-bake/one-pot method. Not the only ingredient, of course, but close to 1:1 of in/out.

> So, if you're a really determined cooker, you can still go to a bunch of different stores...though you're leaving a paper trail.

Isn't meth a lot easier to come by these days? I have to imagine it's more convenient to cook street meth back into Sudafed to fix your stuffy nose than it is to cook Sudafed into meth to get your fix.

see "A Simple and Convenient Synthesis of Pseudoephedrine From N-Methylamphetamine"

https://improbable.com/airchives/paperair/volume19/v19i3/Pse...

A "cook house" burned down from me a couple months ago, so there's clearly still domestic cooking going on here (Cali hi-desert around JTNP).

> I have to imagine it's more convenient to cook street meth back into Sudafed to fix your stuffy nose than it is to cook Sudafed into meth to get your fix.

Maybe, but more people are willing to do felonies to get/sell meth than to do the same thing for pseudoephedrine, and its just as illegal to by meth to cook pseudoephedrine as to cook meth from pseudoephedrine.

> That's mostly right, but it's not reported to anyone.

IIRC, its reported to a centralized state database in (near) realtime in some states, but in any case it is definitely the case that chain pharmacies generally have their own electronic tracking and flagging to avoid getting nailed the way CVS did [0], which may be shared systems like MethCheck [1], which can also be used by independent pharmacies.

So, you’ve got to choose your targets carefully for your “shop at lots of different pharmacies” plan.

[0] https://www.justice.gov/archive/usao/cac/Pressroom/pr2010/14...

[1] https://totalverify.equifax.com/solutions/methcheck

Can confirm. Snag a copy of the NCPDP Telecom spec, (pricey doc, but is basically the Bible for PBM's) for the gorey details.

>but it's not reported to anyone

I'm apparently wrong about that. Seems NPLEX/MethCheck was made a requirement US state by US state over a number of years. So there's no national monitoring, but many (most?) US states require it and give law enforcement access. And like most things set up that way, enforcement and monitoring varies by state/county/etc.

It very much is reported in a national database.

https://help.eaglesoa.com/29/en-n-eagle/Pharmacy/Pseudoephed...

Anecdotally, I usually by psuedophredrine at CVS. I bought some in Orlando and tried to buy more at a completely unrelated store in Puerto Rico and was denied.

There's probably straight pseudoephedrine available anywhere you can get something with it added.

Based on a few comments here, having it behind the counter is apparently pretty much just a waste of time, with meth production having moved to some other synthesis.

I mean, I get the reason behind it and I honestly don't know if it's a good or a bad thing, but the idea of pseudoephedrene sales being monitored like that is so foreign to me. I bought cold medication in pharmacies in 3 different countries always asking specifically for pseudoephedrine and it never occured to me that was a meth cook thing.

In NZ, pseudoephedrine products were banned, and now no-one smokes methamphetamine at all! Totally worth removing an effective medicine from the market.

Haha, I am of course kidding, the meth trade is fuelling gang violence harder than ever, and it now really sucks if you get heavily congested sinuses.

When I'm travelling via Australia I try to buy as much pseudoephedrine containing medicines as I think I can bring back to NZ without looking like a smuggler, and then ration them out to family members very begrudgingly.

Meanwhile, methamphetamine is coming into the country in large quantities in shipping containers (along with illegal firearms). Banning pseudoephedrine was totally worth it...

And now something similar is occurring with cough suppressants, the ones that contained dextromethorphan, i.e., the ones that worked, turns out some people were abusing them recreationally, (DXM is a disassociative in high enough doses), so now that's gone, and we're left with pholcodine, which I find far less effective, but that too is looking likely to be banned, because apparently that's abusable too.

I'm not sure our regulators have the balance right.

You really can't get it at all? Wow! I'm in Australia, they just have an ID check and I think they just record how many times you've bought it over whatever time period in a shared database.

It works so well (and the PE version of everything is so useless), it must be really crap not to be able to get any!

Might be available by prescription, but no chemist stocks it, to be fair, they were getting ramraided a bunch back in the heyday.

I laughed out loud when I read about the lobbyists who are trying to keep phenylephrine from being taken off store shelves.

In one article about the FDA panel vote, a lobbyist said that most consumers hate the alternatives -- nasal sprays because of the discomfort and pseudoephedrine because it's stored behind the pharmacy counter -- and so depriving them of a hassle-free option is anti-consumer.

The fact that the hassle-free option has been shown to be ineffective was, as you might guess, never mentioned.

My understanding is the nasal spray version works, but the oral just gets metabolized ineffectively?

Correct

Oh wow, didn’t realize this

Thank you for sharing, if this is true it will win me a really good arguement. I know someone who hates Phenylephrine, so I will buy some nasal spray just to surprise them.

Unfortunately, this is the actual logic which will be used to justify it staying on shelves.

> The decongestant is in at least 250 products that were worth nearly $1.8 billion in sales last year, according to an agency presentation.

Look those yachts aren't gonna buy themselves.

"Ok fine, you can still sell it over the counter... except a X by Y sign stating 'This product is completely ineffective if taken in pill form' needs displayed on the shelf where the product is sold"

I could actually go along with that so long as other ineffective things like homeopathic water get labeled the same way.

The same stores sell completely ineffective homeopathic "medicines" alongside real medicines already. There are no signs. Its already up to the consumer to determine what may or may not actually work at the pharmacy.

A few years back, I came down with the flu and went to CVS for medicine. I purchased what I thought was a non-prescription alternative to Tamiflu. It was a bad case, and I dutifully followed the dosing instructions and took the medication throughout the whole illness. It turns out the product and the supposed function is complete homeopathic nonsense. It was sold in a medicine isle along with known "functional" cold medicine, and had some "Active Ingredient" listed on the back (similar to any other drug label.)

I spent my money on a product sold by a pharmacy that is quite literally a scam. I'm naturally a skeptical person, but I didn't think I needed to independently check whether what's on a pharmacy store's shelves is medicine or a scam. That's not my lane, I trusted that the pharmacy would only sell medicine that works.

Just wait until you start reading drug trial data!

If you bought it at a for profit pharmacy, then it did work precisely as they expected it to.

I always assumed that was the whole point. A placater. This probably isn’t even news to them.

I believe the official word is "placebo" :)

If only there was a simple physical maneuver that could transform the location of something from behind a pharmacy counter to the customer-facing shelves!

Mah liberties!

I recently went to the grocery store for ear drops. The real ones were sold out but two fake ones were still on sale. Just magic water, might have even made my ear ache worse. Nobody cared that meds are on sale in the pharmacy were fake. The pharmacist didn't care, the manager didn't care. I ended up making a simple alcohol vinegar mix at home on the recommendation of the pharmacist.

Context: On Sept 12th 2023, an FDA panel (the NDAC) definitively voted to find phenylephrine ineffective: https://www.medscape.com/viewarticle/996369 Next will be re-assessing its GRASE status and potentially removing it from stores.

I always thought it was pretty brazen of them to openly label their cold medicine as 'placebo effect' (pretty sure that's what the 'PE' stands for).

I always thought it was for Phenyl-Ephrine, but this is so funny/perfect I will use this when explaining to people to not buy Sudafed unless it's behind the counter.

I always assumed it was there to subtly confuse people into thinking they were getting Pseudo-Ephedrine.

I thought the E is silent in the latter, but I'm a much better speller than pronunciator. Maybe!

This strikes me as an example of a larger phenomenon. Take for example the counter-insurgency wars that have become normalized since 9/11. In these conflicts, there is enormous pressure to minimize casualties because these directly undermine the political will to conduct military operations. As such, the strategic objectives eventually degenerate to mere "presence", and commanders are effectively unable to pursue the kinds of operations that might actually translate into military success.

Similarly, we've collectively decided that selling an OTC drug that is effectively inert is somehow preferable to selling a useful-but-abusable substance, at which point one might argue that it's even safer to sell nothing at all.

(1) I think there's pretty wide agreement that selling Sudafed PE is worse than selling nothing at all, and I'd sort of expect it to be off the shelves sometime soon (it should have been much earlier than this).

(2) "Selling nothing at all" is actually not the policy. Real Sudafed is simply a behind-the-pharmacy-counter drug. You don't need a script to get it (plenty of non-abusable drugs do require scripts, a much higher bar). Real Sudafed is to a first approximation available to everybody.

> Real Sudafed is to a first approximation available to everybody.

I didn't actually know this, and it's good to know. That said, I'm not certain that most people are aware that it is available without a script. Maybe I'm wrong.

If you walk up to the pharmacy counter at any Walgreens or CVS, literally the first thing you're going to see is a shelf of decongestants.

I can’t speak for your Walgreens or CVS, but at mine you’ll see a shelf full of phenylephrine-based decongestants only, because the pseudoephedrine-based ones are behind the counter and out of sight.

Lots of pharmacies display cards in the regular decongestant section that you can take up to the counter to get the ID-required OTC pills. It adds an annoying step, but they are hardly out of sight.

Not trying to be condescending, but are you sure you're referring to "behind the pharmacy counter (i.e. where the pharmacist stands)" rather than on the regular shelves? That's where it's prominent—although as someone else noted there are often "see the pharmacist for the real stuff" cards on regular shelves too.

Yes.

you need to provide a government ID. so probably not an option available to illegal aliens (in many states).

Not sure if it’s still the case, but a few years ago I was traveling and staying overnight near St Louis, and was shocked to find that it actually required a prescription there, but only in the county that St Louis was in.

The Dutch take this to the extreme, where the actually effective anti-cough medication dextromethorphan is completely unavailable, but complete bullshit herbal mixes which claim to help are a dime a dozen on every store shelf. I can't even imagine the amount of needless suffering people with chronic cough go through in the Netherlands.

The effectiveness of dextrometorphan is... underwhelming in most people. But you are correct that no effective cough suppressant is available OTC in Europe.

Dextromethorphan is one of the other “scientifically proven ineffective” OTC products mentioned by the authors.

Once when I had a quite severe cough I did some (highly motivated) research and my conclusion was that there is no such thing as an effective cough suppressant. At least, none that isn’t also a consciousness suppressant.

Low dose codeine is notoriously efficient.

High dose codeine too. Permanently cures coughing!

Indeed. Codeine was even available over the counter in the US until the mid 1960s. But of course it was also addictive, so now it's prescription-only.

Funnily enough I found codeine is available OTC in the Netherlands.

Codeine is what I ended up using in that one (thank goodness) case. It does work to suppress coughs, as well as other functions, like breathing! Watch the dosage.

As a consciousness suppressant I wonder if DXM is safer than diphenhydramine. When I'm sick, being able to essentially sedate myself is honestly pretty valuable.

DXM is crappy as a consciousness suppressant. At low doses it doesn't do much. At higher doses it's likely to do the opposite: make you dissociate and hallucinate. It doesn't help you sleep.

I bought some Chinese medicine in China for the reason that pseudoephedrine is not available and it was actually too effective, dried my nose up so much I kept having nosebleeds. But of course, I prefer the actual effect of pseudoephedrine that doesn't have this side effect.

I have yet to figure out how Europeans treat minor ailments. Those green-crossed "pharmacies" (only open weekdays during business hours) have 4 or 5 OTC drugs and the rest of the store is just pseudoscience.

Most of the time: You rest. Most folks have sick days that they can use to stay home and recover. If you need more than a couple of days, go to the doctor.

And honestly, that takes care of a large portion of the medication. I bought it in the US to have the ability to survive a workday: IF I'm staying home and resting and sleeping, I tend to need less of the stuff for a minor ailment.

They do sell a few things in the pharmacies here (Norway) that help, mostly with pain and to do things like dry your nose (nose spray, not as many pills) and loosen up phlem. You can get allergy medicine. And so on.

And honestly, I worked at a pharmacy for 8 or 10 years in the US and there is only a handful of drugs OTC there, too - but there are more brands and more products that have multiple drugs in the same dose. The drugs just differ at times. US stores sell the pseudoscience as well (It angers me, but it isn't just one place doing it, which is the point).

Many of the pharmacies here are open longer than business hours, but it also doesn't always matter. The doctor offices tend to close at 3pm, before the pharmacies. If you are expected to stay home from work, you can get to the pharmacy.

Paracetamol, Ibuprofen, Aspirin, Xylometazoline and sleep. Or go to a doctor and get told to get the same stuff, with some prescription-only cough syrup.

The rest of the pharmacy is for old people looking for miracle cures to being old.

"Phenethylamines I Have Known and Felt Kind of Meh About"

cant wait for TIKFKMA

I laughed out loud.

For those unaware, "Phenethylamines I Have Known and Loved" (aka PiHKAL) is Sasha and Ann Shulgin's book that is half semi-fictional autobiography and half detailed synthesis and in-vivo effects observed in the enormous family of psychoactive phenethylamines. The autobiography part is only available in print, but the chemistry section is freely available[0].

There is a sequel, a similar book for tryptamines called TiHKAL[1].

They are stunningly bold in their chemistry, administration and discovery of novel drugs, and in making good science available under dubiously legal circumstances.

[0] https://erowid.org/library/books_online/pihkal/pihkal.shtml [1] https://erowid.org/library/books_online/tihkal/tihkal.shtml

Psychoactive phenethylamines??? I've never heard of that, I'm just really into nasal decongestants.

Discussed at the time:

The Uselessness of Phenylephrine - https://news.ycombinator.com/item?id=30858202 - March 2022 (592 comments)

The risk:reward ratio is infinite — it has adverse reactions but essentially no benefit. It’s about as much “medicine” as was drinking radium.

Good riddance.

https://www.nbcnews.com/health/health-news/fda-panel-says-co... -- "Phenylephrine — found in drugs including Sudafed PE, Vicks Nyquil Sinex Nighttime Sinus Relief and Benadryl Allergy Plus Congestion — is the most popular oral decongestant in the United States, generating almost $1.8 billion in sales last year, according to data presented Monday by FDA officials."

* Wasting peoples time and money while consuming their $.

* key part is consuming their $.

If you like the author Derek Lowe's writing like I do you might like his "Things I won't Work with". Here's one of my favorites:

https://www.science.org/content/blog-post/things-i-won-t-wor...

> If the paper weren't laid out in complete grammatical sentences and published in JACS, you'd swear it was the work of a violent lunatic. I ran out of vulgar expletives after the second page.

I love his work.

Phenylephrine is ineffective when taken orally. It is super effective topically or iv. I can definitely tell, because it's the most commonly used vasopressor used under anaesthesia (iv). Also used topically to avoid nosebleeds during nasal intubation.

Curious about how this aligns with the bioavailability point discussed in the article. Presumably if the gut lining is where the bulk of metabolism occurs then IV sidesteps this and increase the bioavail drug, leading to improved efficacy.

The gut metabolism makes it less available, which is why if you put it in your stomach not much shows up in your nasal lining. If you spray it or inject it directly where it needs to go, no problem.

I was indeed surprised to see it go by in the mix during one of my wife's c-sections. I'd always thought it was a completely useless thing, but there it was keeping her blood pressure stable under the anesthetics.

Probably will get downvoted for this, but a bunch of my family members are pharmacists. Their quiet opinion is that most pharmaceuticals don’t work. Even the ones that are thought effective. The data is anecdotal, but is over 15 years of watching people come in for prescriptions. The other aspect, is they say it’s mind boggling to see what kind of drugs people are on.

I’d like to think you’ve heard them grousing about specific things like this and misinterpreting that as a general mistrust. Every medicine I’ve ever taken had an objective, quantifiable effect on me.

Except for phenylephrine, of course, which only served to teach me how to ask the pharmacist for the good stuff.

I think that people are hoping for larger effects. I have been a lifelong allergy sufferer. Many years ago, my doctor gave me an intranasal antihistamine. It came with a piece of paper about the studies done on it. Patients rated their symptoms on a 1-5 scale, and the study observed the ratings with and without. The placebo group rated their symptoms, say, 4.0. The people on the drug rated them 3.5. I would say that's exactly the effect I got from the medication, an improvement, but not a complete elimination of symptoms. Certainly some people are going to go to their pharmacist and say "this does nothing", and that might lead them to believe it's all a scam. It's not really a scam, it's just that expectations were not set correctly. People want "this will cure you and you'll get a gold metal in the Olympics!" but all we have is "this will make life slightly less miserable".

It's probably the same for many conditions and medications. Antidepressants don't turn you into someone who is always happy. Painkillers don't make recovering from surgery a joy. I think that people even had the same feelings about COVID vaccines; they wanted "one shot and you'll never be sick again", but all we got was being 90% less likely to get COVID or whatever. None of this makes these things a scam. Rather, they are imperfect technologies that we work to improve. Silver bullets are rare, but they do exist. Just not all the time. (Have you died from strep throat or polio recently? People used to all the time!)

Huh, that’s an interesting point and I bet there’s something to it. I’m taking OTC allergy meds right now but still have some symptoms; it’s not an instant and complete cure. Anyone who expects an instant improvement from most kinds of medicines is going to be sorely disappointed, and doctors need to diligently explain that such-and-such will help a problem, not immediately fix it altogether.

Yup, exactly. OTC allergy meds are often an improvement; I certainly notice if I forget to take them. But it's not like my nose turns into the air-intake equivalent of one of those helicopters that sucks up water for fighting forest fires. Such a technology may not exist ;) (That said, pseudoephedrine is pretty good for me on the worst days.)

We now know that most published medical research findings are false. That likely includes many of the studies that the FDA relied upon to approve certain drugs.

https://doi.org/10.1371/journal.pmed.0020124

My impression is that the situation has been improving in recent years. Between study pre-registration, larger subject groups, and greater statistical rigor I have a lot more confidence that drugs getting approved now actually do what they say on the label. Of course, this is also part of the reason why it now costs >$1B to bring a new drug to market.

It’s been known for years that Phenylephrine is useless and was just kept on the market because of lobbying.

Pharmacist here. Most pharmaceuticals do actually work but finding the right one for a patient can sometimes be harder than you would think. I suspect your family members are quiet about their opinions for a very good reason.

It’s really difficult to untangle the placebo and nocebo effects. I was recently surprised to learn there are studies showing placebos can be effective even when people are told they are taking a placebo. Ie literally telling people, “take this pill every day, but please understand it’s a placebo and has no active ingredients whatsoever”. And yet, their symptoms improve. The theory is that the subconscious mind acts on some information (white-coated professional giving me a medicine) without being fully affected by the conscious mind’s knowledge that the pill ought to do nothing.

It’s even possible that the negative attitudes of your pharmacist family members toward the medications their patients are taking are affecting their efficacy!

You're missing the part where they told participants what the placebo effect was, and that taking the placebo would make them feel better in spite of it having no active ingredients, and it did indeed do so.

"Suggestible You" by Erik Vance explores this phenomenon, and really turned me around on placebos. I'm, generally speaking, not particularly susceptible to placebo effects, and always kind of (arrogantly) chalked placebo effects up to people just being gullible and wanting to see something that wasn't there. It turns out there are actually genes that might be responsible for the physical impact of the placebo effect in the brain.

There's an enzyme - catechol-O-methyltransferase - which is coded for by the COMT gene. This enzyme catalyzes the metabolism of dopamine in the brain. COMT has three common variations - AA/AG/GG - which substantially alters how effective the enzyme is at metabolizing dopamine. AA results in significantly reduced enzyme activity, which can result in dopamine built-up in the brain, which results in increased sensitivity to stress, anxiety, and pain, but comes with the bonus of enhanced cognition, motor skills, and memory.

AA genotypes also tend to be "placebo responders", while GG genotypes tend to be non-responders. This tends to imply that placebo responsiveness isn't purely psychological, but physical - and indeed, it turns out that in AA "responders" you can turn off the placebo effect by administrating naloxone (which works by binding to opioid receptors)!

This has really interesting implications for pharmacological research, too - if there are people who are genotypically predisposed towards or against placebo effects, then a drug trial that stacks responders in the trial group and non-responders in the placebo group which would produce a drug efficacy signal that could be just the placebo effect.

Is the COMT gene stuff discussed in "Suggestible You"? I recently learned I have the AA variation and from what I understand so far, it seems like it might be an explanation (or at least part of one) for why I am so sensitive to a number of vitamins and medications. I hadn't heard about the placebo related thing. But anyway, I am interested in continuing to learn more about it (it has been somewhat difficult for me to find digestible information about it online) so might look into that book if it discusses it much at all.

Yup, it's discussed extensively, predominantly as "val/val" (GG) and "met/met" (AA).

Anecdotally the most useful drugs are antibiotics and corticosteroids. Other remedies I found truly impactful are neti pot usage everyday if needed and zone 2 daily exercise.

Placebo effect is strong.

"Medicine" never wandered that far from religion, after all.

Of course you are going to get downvoted and you should.

I know my blood pressure medicine works for instance because every time I talk to my doctor about reducing it or getting off it, I monitor my blood pressure and it spikes.

I know psuedophredrine works.

And your data is just that, “anecdotal”, it’s no better than the people doing “research” by watching YouTube on the toilet.

Ehh. Your experience is similarly anecdotal. You ignore that there is a placebo effect, blood pressure is a surrogate marker for cardiac events, and drugs can have adverse effects.

It’s best to look at all cause mortality in your example. Many studies have looked at that endpoint if you are curious.

It’s “anecdotal” that I can measure with a machine that gives a number and that I track over a period time?

It’s not like I said “I feel better” when taking it. So my blood pressure just magically comes down after I’m taking it?

What did you think "anecdote" means? Why wouldn't your individual report of your meter measurements count? You haven't shown us the data, shown that you've controlled for confounding factors, or anything.

You posted an anecdote.

https://www.ahajournals.org/doi/full/10.1161/01.HYP.00001036...

I mean it is technically anecdotal evidence; it is just a story about you and wasn’t collected in any systemic way, we have no way to abstract it.

But there’s also lots of clinically collected evidence behind blood pressure medicine, right? I don’t see why anyone would have reason to doubt you.

GP didn't say your blood pressure meds or pseudoephedrine don't work, they said "most drugs don't work." I would have preferred some specifics, but we didn't get them so you shouldn't argue as though they were given.

Do you think that 80% of prescribed drugs don’t work? Even 50%? I’m limiting it to prescribed drugs because those are the ones that a pharmacists would be most concerned about.

And a “pharmacist” isn’t exactly the best trained person when it comes to knowing how to do a drug research or to know its efficacy for patients compared to even a GP who is monitoring patients and keeping records of blood work and other stats

They didn’t say prescription drugs. OTC drugs are also drugs. (In fact, they’re the drugs the article is about!) And the majority of drugs are OTC drugs. I would fully believe that the majority of OTC drugs do basically nothing.

(Consider: how many problems are there with your body that you’re actually likely to be able to solve with a drug that can be taken safely and correctly at basically any dose, basically any schedule, quitting whenever you like, and without checking for cross-drug interactions? Because those are the requirements for a drug to be OTC. There exist far more OTC drugs than there should, given the number of OTC-able problems, is what I’m saying.)

This is a really bad take. I hope you or your family members reconsider. Also maybe they shouldn't hold negative judgemental views on the customers that make their job possible?

This is also a bad take.

GP specifically mentioned prescriptions, so the customer/patient is not at fault here, if there is a judgment here, it is toward the doctors. And just because something earns you money doesn't mean it is above criticism.

I still don't share GP's opinion in that most medicine don't work. I think some don't work, and some is misused or used preemptively, therefore showing no effect. And I am also dubious about a lot of comfort medicine, but for most people I know who are under proper prescription, it is obvious that it works, it includes psychatric medicine.

I think american medicine just chooses prescribing medication first.

Patients are definitely more likely to take a medication than change their behavior. Patients also ask for medication. And then there's the whole pharmaceutical system.

My personal experience is that many older people I've known have a startling number of bottles of medication they take every day.

I also know some older people that have exercise and eating right as part of their regimen and rarely take any medication.

>I also know some older people that have exercise and eating right as part of their regimen and rarely take any medication.

Not to be pedantic, well actually let's be. But this is pretty poor medical thinking. Are patient's not on meds at advanced age because they exercise? Or are they able to exercise because they're otherwise healthy and feel good? This kind of simplifying causes a lot of harm in medicine and a lot of patient blaming.

My observation seems to be two broad groups. Maybe the fit ones eventually become the bottle ones? Maybe the no-bottle ones are resisting medicine?

One thing is for certain - it makes me uncomfortable how many different medications some people take every day.

I don't take many medicines and then only ones that I have found to work for me. Pseudoephedrine absolutely does work, phenylephrine does not.

As a pharmacist, I can't help but laugh. I'm guessing they're quiet because their peers see them as quacks. Most don't work huh? Cancer death and morbidity rates are falling like a rock. Antibiotics? Antifungals? Hep C cured? HIV/AIDs guaranteed death turned to decades of symptom free life? Hell, we wouldn't have an opioid crisis if the damn things didn't work. The premise is just laughably silly.

It seems some people see that placebo's can have effects in a select few paradigms of care and extrapolate that to "all drugs must be placebos." Which is just smooth brain conspiracy talk.

It seems like a wild breach of professional ethics to sell medical treatments that they don’t believe will help their patients. Did they mistake themselves for cashiers or something?

yesterday:

Phenylephrine for colds and allergies don’t work, FDA panel says

https://news.ycombinator.com/item?id=37485940

Public service announcement: sinus rinse (e.g. NeilMed) works. Available in every drug store with no prescription or pharmacist involvement necessary.

It's gross, though. Do it in private.

It doesn't reduce the sinus inflammation. At least for me all I end up with is a still congested, but now watery nose.

Noted. At least you've tried it.

The water dripping out of your nose: that's a feature, not a bug /s

It's useful to rinse out the sinuses so that nasties don't grow there.

If you already are pretty bad off, yeah it usually doesn’t help. It really helps prevent it from getting that bad though, by washing out pollen, gunk, etc. and hydrating things.

I have swollen nasal polyps (or something) which causes every single cold I get to eventually transform into a 2 week sinus infection + cough ordeal.

Netty pot with salty water and a pinch of baking soda, and an even saltier water gargle clears things up nicely. And is very budget friendly.

It was when I had the mother of all sinus infections that someone told me about this. Never had the problem again. YMMV.

People imagine it must burn, because getting water up your nose when swimming burns. But the salt & baking soda neutralizes that.

Ask your ENT to look into adding Budesonide [0] to your saline rinse. It is intended to keep polyps from growing (and has worked wonders for me).

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374675/

It's been superseded by Mometasone. It's more lipophilic.

Since I have seen a number of recommendations for sinus rinse in this thread but haven't (yet) noticed this specifically mentioned: It is important to use sterile water if you are using water for the rinse. Water directly from the tap apparently may not be safe for that purpose (there was a case earlier this year where a person died from a brain eating bacteria - they were apparently infected from using unboiled tap water for a sinus rinse.)

https://www.healthywa.wa.gov.au/Articles/N_R/Nasal-irrigatio... https://www.everydayhealth.com/lung-respiratory/too-many-peo...

it's been discussed before here.

Brain Eating Ameoba! https://www.bbc.com/news/world-us-canada-53302773 Yes, it was in Florida.

From the referenced paper:

“Other examples of scientifically proven ineffective OTC medications include guaifenesin as an expectorant, dextromethorphan as a cough suppressant, and chlorpheniramine for cold symptoms.”

> dextromethorphan

Wow, seriously? I abused plenty of this to get high back in my day. And I can say that smoking while on it was definitely way easier, I barely coughed at all.

My read of the headline was "bullshit! It's a great alpha-1-adrenergic vasopressor in anesthesiology and critical care(1). Funny how ones training and past experiences affect this. Similarly I read unionized as the chemistry un-ionized every time.

(1) https://www.ncbi.nlm.nih.gov/books/NBK534801/#:~:text=In%20t...

My kids seem to derive benefit from chewable tablets which I tell them to suck on. Curious if anyone has found different research on metabolization in the mouth versus gut?

Oral and rectal blood goes directly to the greater circulation without going through the liver (that metabolizes most toxins) first.

Phenylephrine did its job of convincing people to accept restricting access to pseudoephedrine, since there was a substitute that could still be freely available. Now it'll be taken off the market, but pseudoephedrine that actually works will still be restricted.

At least the homeopathics consumers will buy instead have fewer side effects

I, like many others I suspect, bought phenylephrine when Sudafed first disappeared from store shelves. It was 100% ineffective for me from the first dose.

In the meantime, Sudafed has become one of the most difficult to acquire substances for my daily life (I need it every day as directed by my doc). So many times when I go to a pharmacy to get it, they're out of 96-count or 48-count or any count, meaning my one allowed purchase/month nets me less than a month's worth. Or the state's tracking system is down (this happens frequently) and they won't sell me anything. IOW, buying Sudafed is difficult and often infuriating.

Meanwhile, meth problems haven't gone away—-in fact meth use is WAY up since these restrictions were put in place in the aughts. Sure, hiding and tracking it got some of the meth production moved south, but it didn't negatively affect meth availability. Supply is plentiful, prices are down, purity is up. Even Oregon, who restricted Sudafed to prescription only, has seen a 3x increase in meth deaths. [1]

Sadly, the restrictions on Sudafed are unlikely to ever change as lawmakers rarely care that their laws hurt a ton of law-abiding people as long as they can claim something about being tough on crime.

[1] https://www.nytimes.com/2018/02/13/us/meth-crystal-drug.html

I've been in this boat too, and it's infuriating. I once had a doctor that wrote me a script for it though and the pharmacy let me get a whole 90 day supply with no problems. I ended up moving and couldn't see this doc anymore, sadly. This was in the late 00s though, I don't doubt that they closed this "loophole" and don't allow docs to write for that anymore.

I find it interesting to see this. I use it as a nasal decongestant (pill form), and it works like magic. Completely dried up in like an hour or so. Granted, my nose leaks 24/7 like a leaky faucet, so it doesn't last, but that's just bad genetics.

In my sample size of 1 I concluded this substitute didn't work years ago. And why can't I find an actual good antihistamine Doxylamine succinate sold separately anymore. New crap that doesn't work replaced old working products....

Question: why does anyone want to use stimulant decongestants anyway, when corticosteroid nasal sprays (the -metazolines) are equally effective at treating a runny nose, and much more effective at unplugging a stuffy nose?

How long do they last, and how easily is a tolerance developed for steroids? I’m asking this as a chronically congested person who doesn’t like the side effects of extended release pseudoephedrine, but it works.

Metazolines are not steroids. They are vasoconstrictors and immediate decongestants. You may be thinking of fluticasone, which is used to desensitize the nose to allergens over time but which has very little immediate decongestant effect.

Nasal sprays like Afrin (oxymetazoline) give me major rebound congestion, even if I only use it for a couple days. I.e. even if I just use it for one night to make it easier to sleep, I always feel like I'm more stuffed up the next day.

The only thing I'll use these days is a neti pot/sinus rinse. It obviously doesn't open up my sinuses as much as something like Afrin but there are no negative side effects for me.

Hoping this adds to the pressure to get pseudoephedrine back on the shelf.

Anyone who has ever taken phenylepherine knows that it is completely ineffective.

But, like most moral panics, the fantasy of kids stealing pseudoephedrine pills and becoming Meth Lab Moguls, was too much.

I wish they would give similar treatment to homeopathic "remedies." It's appalling to find them sold at drug stores when they've never even been proven effective in any way. You can literally give the opposite "medicine" to someone and they wouldn't be able to tell the difference.

I will go to my grave swearing nyquil used to be some sedative mixed with psuedoephedrine, but modern pharmacy people seem to have no memory of it.

Here you go - don’t say I never gave you nothing!

https://www.drugs.com/mtm/nyquil-d.html

I assume the original documents/testing that got it approved stated how effective and safe it was.

It's never worked for me and I didn't understand why people bought these products.

They were marketed as working and have similar side effects as pseudoephedrine-based products. I’d think those would be pretty strong contributors to a placebo effect.

This is no different from “cough syrup”, that doesn’t work

Knowledge. Availability. Marketing. FDA.

But honestly, I would direct my anger at the lack of transparency and oversight in the supplement market, rather than this. Glad the FDA has finally corrected course.

If the pharmacy counter is closed, something that maybe might work is better than nothing.

I recommend oxymetazoline.

phenylepherine is the otc version of pseudoephedrine, what Sudafed was originally created with.

If you need Sudafed that works, go to the phamacist and ask for "real sudafed". You might have to scan your ID if you live in certain states and you actually need a Rx if you're in Oregon (lol), but for most free states you're good to just purchase it at the counter.

They changed that last year: https://www.statesmanjournal.com/story/news/politics/2022/01...

Oregon no longer requires a prescription since 2022.

> phenylepherine is the otc version of pseudoephedrine

That’s mostly incorrect, both are “otc” (over-the-counter) wherever you can buy them without a prescription. That’s what that means.

Psuedophedrine requires an ID to purchase and must be kept behind the counter in any state in the US. It's a federal requirement. Stores are also required to keep a record of purchases for 2 years.

If you were able to purchase Sudafed without having someone get it from the back or out of some locked cabinet, and also hand over your ID, it wasn't psuedophedrine.

He said “at the counter”.

It's ambiguous. GP said "some states" require an ID. I'm clarifying it's all 50 states require an ID to purchase psuedophedrine and the other associated federal restrictions.

He said “you might have to scan your ID in certain states”; the ID and logbook requirements for a purchase of anything but a “single sales package” (basically, 2 Sudafed) of pseudoephedrine is a federal requirement applying to every US state and territory.

It's a different substance. Not version.

> You might have to scan your ID if you live in certain states

The “certain states” involved being “the United States” since 2006, unless you are buying a “single sales package” with less than 60mg of pseudoephedrine [0] (which is the dose in two Sudafed caplets [1].)

[0] https://www.fda.gov/drugs/information-drug-class/legal-requi...

[1] https://www.sudafed.com/products/sudafed-sinus-congestion

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