The restrictions on purchasing pseudeophedrine should be repealed. Their imposition led methamphetamine manufacturers to switch to a more efficient process based on different ingredients. Purity and production volume increased substantially.

A repeal won't turn back the clock on that of course, but it will make life easier for people with congestion.

https://dynomight.net/p2p-meth/

The need to show an ID to purchase real pseudoephedrine (feels like an oxymoron to write that) can be a legitimate PITA. I am American who lives abroad but is frequently back in the U.S. for family reasons. I suffer from sinus problems, so I periodically need to purchase pseudoephedrine-based products. Because I have no state ID, the show-ID-based workflow essentially fails. For whatever reason, the pharmacies won't take a U.S. passport (or foreign ID card), so they end up spending 15 minutes futzing with the data entry software, only to resign to entering garbage into the system.

And as OP points out: Phenylephrine is 100% useless.

So at least here in Germany, we pretty much all use nasal spray with xylometazoline, and it's very effective as it also binds to adrenergic receptors. It does not seem to be available in the US, and at least from a cursory search I cannot find out why...?

EDIT: After looking a bit more, the simple answer seems to be that it's not FDA approved for nasal congestion, and since there's not much money to be made, there's simply no incentive to go through the costly approval process..

Additional context on why phenylephrine was ever approved to begin with—apparently it is effective if you use it as a spray, but apparently nobody bothered to check what happens when consumed orally, and it turns out your digestive system degrades it quickly and it doesn’t even make it into the bloodstream.

It is little known that it is super easy to make

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

from PE in mild conditions and aqueous solution. It has a hell of a kick and I’ve heard anecdotal accounts of people becoming seriously addicted but stimulant users as a class greatly prefer methamphetamine.

This is a perennial topic on HN, which is generally inhospitable to drug prohibition to begin with; it's possible to lay out the schematics of the counterargument:

* While there can't be any defense for the marketing of phenylephrine as a pseudoephedrine replacement, restrictions on pseudoephedrine are not irrational (that doesn't make them right, though I think they are).

* Pseudoephedrine by itself practically is methamphetamine, just in an unproductive chemical configuration. It is extraordinarily simple (though: not safe) to convert pseudoephedrine into meth.

* Pseudoephedrine is widely, practically universally available in the US without a prescription. It's a "behind the counter" drug, and, because of rampant abuse, access requires ID, like alcohol. Further, because the point of restricting pseudoephedrine is effectively a "rate limit" (to prevent people from acquiring enough Sudafed to make meth production practicable), Sudafed purchases are tracked.

* We've hashed out on HN the argument about whether that tracking results in spurious prosecutions. The one case I've seen us come up with, the arrest and prosecution of William Fousse, concerned someone who had a pseudoephedrine addiction (he was using it to come up from habitual alcohol benders).

* Restriction of pseudoephedrine does basically zero to staunch the flow of high-quality methamphetamine, which is produced at industrial scale with more sophisticated chemistry in Mexico and Asia.

* But restriction of pseudoephedrine might reduce the incidence of garage meth labs, which pose their own distinctive dangers to communities.

The argument in favor of continued pseudoephedrine restriction would be that the cost of the policy is relatively low (it inconveniences allergy sufferers, but most of those sufferers only marginally) vs. the public safety benefit (which is also probably low, but also probably nonzero).

Only thing I'd quibble with is the reason most consumers switched off of pseudoephedrine. The manufacturers knew that the inconvenience of having to go to the counter would reduce sales so they just replaced it in the aisle with an identically branded product with a different active ingredient. Most people made no affirmative choice at all; they're just buying "Sudafed", but now it's a placebo.

I’ve had two doctors and two NPs tell me to stop using sudafed. It dries out the mucus membranes and allows infections to start. If you’ve had sinus infections before, they suck and you don’t want them again. Give the Sudafed away.

(It also gives me horrible insomnia if I take it at night so it wasn’t a huge hardship).

Guaifenesin thins the mucus instead, makes it more watery so it drains down the throat with no further complications like sore throat and coughing. And the extra volume helps flush bacteria out of the sinuses.

An interesting tidbit to add, for working in the industry:

The restricted process around buying pseudoephedrine is imposed by state governments and not the federal government. A number of the states coordinate their policies, so it looks like nation-wide action but really isn't (in a legal sense).

FDA doesn't have the legal authority to put medications "behind the counter" like you would see in Europe or Canada. So untangled this is a weird mess of overlapping jurisdictions.

Good summary. To add to what you've said, Sudafed (as an example brand name) opens your eustachian tubes which are passages from your inner ear to your throat. If you think you might be getting an ear infection, Sudafed increases draining and potentially helps prevent a worse infection. As mentioned, it helps air equalize to the atmosphere via these tubes. If you make a yawning motion now and hear your ears crackle, that's the air moving through your eustachian tubes. You'll notice that crackling decrease when an ear infection may be imminent. I tried the useless alternative and discovered on my own that it was, indeed, useless. And it was quite expensive, with great marketing on the box.

In my experience phenylephrine is worse than useless. Not only does it do nothing for congestion, but it makes me feel wired in a bad way and unable to sleep for at least 24 hours. I hate phenylephrine.

I read this and was puzzled, until I realized that you are talking about the pills. The nasal spray is effective, although probably not more effective than a saline solution.

Why not just use xylometazoline (aka Otrivin) at least as a nasal (spray) decongestant — or isn't it available in the U.S?

Xylometazoline is very effective. Sure that doesn't solve the oral/body-wide absorption of a decongestant but it's a good start.

From my personal experience phenylephrine (as a nasal spray) does work but it's one step off being useless. I've occasionally had to use it as a fallback when I haven't been able to get xylometazoline (where I am xylometazoline is only available in pharmacies whereas phenylephrine is also available in supermarkets and elsewhere).

It's interesting to note that the bans and restrictions on pseudoephedrine have had large negative consequences. Not only have ordinary users missed out on a good decongestant but it seems drug cartels have largely overcome the shortage of pseudoephedrine by substituting the precursor phenylacetone (P2P). Not only that but they've even managed to separate the chiral components of the final drugs which makes them indistinguishable from medical pharmaceuticals.

Incidentally, I prefer not to use pseudoephedrine as a decongestant, whilst I receive no mental stimulation from it, it nevertheless has stimulating properties that make me feel queasy. It's why my first choice is xylometazoline. There's also the related decongestant oxymetazoline, which I've found effective but it's not as good as xylometazoline (for me at least) but it's still vastly superior to the near-useless phenylephrine.

Well, phenylephrine is ineffective when used incorrectly. You're supposed to grind the pill and snort it. Works much better ;-D

It's not the only drug treated this way. You can go to any pharmacy and see a ton of things on the shelves that are just cards you have to take to the counter, and then see what's actually behind the counter. Insulin needles, for instance, even though you can also just buy those in bulk on Amazon. I'm not sure what does and does not get tracked in a statewide database, but at minimum, regular Ephedrine, typically sold under the brand name Bronkaid, is tracked this way, because it can also be used to manufacture meth. I don't even think in this case there is an alternative formulation like there is with Sudafed and generic equivalents.

The monthly purchase limits on these tend to be ludicrously high, though. I think they're state by state, but in Texas, you can purchase up to 9 grams a month.

But think about all the jobs the government by created running that registry, prompting the drug makers to formulate and manufacture bogus decongestants and then eventually studying that those bogus decongestants were in fact bogus.

(in case it wasn't obvious, this is broken windows fallacy)

I went to the doctor recently. I usually take what I am taking so they can see it. I was taking Sudafed and had just purchased it. She took it out of my hand and told me basically all that and threw it in the trash.

Great summary. It's a classic case of government action ending up a net negative for society. Everything would've been great if they'd just minded their own business.

It is darkly amusing to me that it took the FDA well over a decade to conclude what was immediately obvious to anyone who has ever tried phenylephrine: that it is not worth taking

This reminds me when EU banned some eye drops with the product name Proculin which have been very effective. The replacement Berberil is useless, literally no effect.

Proculin made your eyes white white constricting the blood vessels for hours. All the stoners had it in their pockets.

Since it constricted blood vessels one could use it also to reduce the local inflammation on pimples, which was a neat off label usage.

yes, well, the other part of the story you would not know it maybe unless you frequent among addicts or psych wards where the practice is done indeed there is a third such nasal decongestion / meth class drug known as BENZEDREX it is a OTC decongestant .. an inhaler.. okay, fine. but what drug addicts, and in my experience for whatever reason, people with hard psych illnesses like to do is pop the inhaler open. inside is a benzedrex-laden ball of cotton which is then chewed upon for the high

FWIW phenylephrine wasn't a new drug; it was and still is used all the time in IV form to increase blood pressure in anesthesia and critical care.

But it's useless as an oral decongestant.

pseudoephedrine have serious side effects, they are rare but could be fatal

I swear phenylephrine works... so I'm just falling for placebo?

Only the second to last paragraph was necessary.

It comes full circle if you go back far enough.

Before Sudafed was common in pills, they had the small disposable inhalers where the pseudoephedrine was not in crystal form but was dissolved in vaporous liquids like menthol. Inside the inhaler there is a cotton piece soaked with the pleasant-smelling liquid. The aroma vapors are drawn right up into the sinuses along with the active ingredient.

The inhaler itself was first marketed during World War II by the well-established 19th century Vicks company, already very successful for decades with it's earlier VapoRub aromatic topical OTC formulations. People are probably aware that this is one of the companies that is older than the US FDA. Older than the Fed & income taxes too, for those who are keeping score ;)

Natural products like ephedrine have long been the inspiration for medicinal chemists to synthesize similar compounds for potential screening as new drugs, so a number of new experimental relatives such as pseudoephedrine were produced eventually.

As the name implies, people did not always know what the real difference was between ephedrine and pseudoephedrine, since both molecules have the same molecular weight, naturally because both have the same number of carbons, hydrogens, oxygen, and nitrogen content.

Only a slight difference in chemical structure between the two, which got figured out soon enough.

Some of the less-similar new drug candidates were ordinary amphetamines. They are the ones that really got popular fast, especially in wartime :\

Now when the unique inhalers were born, it was a bit of the new synthetic ingredient along with the traditional aromatic mixture that Vicks was famous for, and the Vicks Inhaler was deemed safe & effective as recommended for OTC use. People loved it. Nobody had ever had anything as effective as that.

IIRC it was 50 milligrams per inhaler soaked into a few hundred milligrams of aromatic essential oil mixture. As expected they were a lot stronger when you first started smelling one.

That's because it was 50 mg of meth-amphetamine in the Vicks inhalers.

Parents would buy them for their kids, because they were so "safe", for self medication naturally, even at times when they would not consider dosing them up with cough syrup.

There was never any FDA-approved prescription for methamphetamine in any other form, only this one OTC product.

I would think the inhalers themselves were patent encumbered until the 1960's (remind you of an Epipen?) and by the 1970's other companies like Sudafed offered their own version, only not containing meth, give me a break.

The meth version of amphetamine became recognized as a dangerous drug in the after-war years when the negative effects became apparent with soldiers who had been given it in pill form habitually as stimulants, often when facing the most serious combat.

No other company ever was able to put meth in their inhalers, but Vicks slipped in under the wire and couldn't even be stopped for decades until some time after the DEA came into being. Everybody else was using pseudoephedrine from the start. By this time crystal meth was just beginning to emerge, which people were trying to avoid when they saw what it was like, at the same time different people started seeking meth more intently. Orders of magnitude more out-of-hand now.

The way Vicks stayed under the radar the whole time with meth in it, was hiding in plain sight.

Right there on the inhaler in fine print where it always was, active ingredient desoxyephedrine 50 mg.

Simply a less-common alternative chemical name for meth, and desoxyephedrine had become a very uncommon rapidly deprecated name quite early. Way before any amphetamines were commercialized, they were instead marketed using the well-known convention based on the Alpha-MethylPHenylEThylAMINE type nomenclature.

Anyway, back in the 1970's when it was first becoming known that shady operators were cooking meth by starting with inhalers, I looked at one of them and sure enough, 50 mg meth per Vicks inhaler. Who knew?

For a while there I figured they must be starting with way over 20 inhalers and probably would not extract nearly a gram of meth but it sounded feasible. I wasn't going to be the one to do it, my first job out of college was working for a company that was a real pharmaceutical manufacturer. So I wasn't going to tell anybody either. There was already talk among law enforcement about cracking down on this kind of thing. Suspicion of inhalers was beginning to barely arise, it was thin but widespread among anybody who had heard anything about this.

Eventually I figured out that the clandestine cookers were synthesizing their meth by using the pseudoephedrine in non-Vicks inhalers as starting material for their reactions ! Well, what do you know? Was I wrong the whole time?

I "guessed" so.

With not-so-blurry 20/20 hindsight, I would estimate that before I got around to figuring this out, a clandestine chemist had come along way before I knew a thing and had started out extracting grams of meth directly from Vicks inhalers. And the meth heads loved it, found out it was coming from inhalers and the word got around among them.

Some other chemist picks up the inexact word-of-mouth and by this time Vicks inhalers are outnumbered, sharing shelf space with numerous alternative brands, all of them containing pseudoephedrine as expected, and cheaper too. If they look at Vicks, it's the odd ball out, that doesn't look like the same kind of "ephedrine" as everything else. So they figured out how to do some home made reactions starting with Sudafed. And this is what was just starting to go through the roof.

This was before the Sudafed pills really took over, once they showed up they flew off the shelf way faster than the inhalers because there were more milligrams.

One day in the '70's I was in Walgreens and there was somebody buying over a dozen Sudafed inhalers so I knew what they were up to.

I went over to the aisle and looked at the then-current Vicks Inhaler, which I hadn't checked in a while, sure enough 50 mg of desoxyephedrine, active ingredient, same as ever.

The poor Sudafed buyer wasn't the least bit aware that real meth was right there on the shelf next to it.

And I wasn't going to say a thing :)

Most doctors and pharmacists didn't even have a clue.

Within a few years Vicks stated putting in pseudoephedrine themselves instead of meth.

Until it got way too far out of hand and the pseudoephedrine became tightly controlled, much more tightly than the meth was, as can be seen.

Edit:

"And now you know the rest of the story" - Paul Harvey

PSA: Kroger and Kroger-owned supermarkets require ID to purchase any "cold medication" including those only containing phenylephrine. It's a stupid policy.

Buy your cold medication at Walgreens. Good luck finding a non-Kroger grocer.

> Their preliminary review of studies suggested that it is probably, in fact, useless. This proceeding is now proposing to ban it on the grounds that it's ineffective

Is ineffectiveness really a good reason to ban a substance? Why not just ban labeling it as a medicine instead?

No worries, "Meth" was largely unknown in my area, until you guys exported "Breaking Bad". Roughly a year or two later, it started to be available here as well. Thanks for that, media industry, that was a wonderful move! /s