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As a soon-to-be PhD graduate, I'm perversely curious as to how much these clandestine chemistry jobs actually pay . . .
the pay can be quite good; but don't go bringing any other concerns to the HR department.
I believe the severance packages also tend to be pretty bad
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"Take whatever you want, I-I have money, I have a lot of money. I have... um... Please, don't do this. You don't- You... Y-You don't have to do this..."
Plus issues with what to put on your resume, and getting references.
I’m guessing the hells angels do not have a diversity policy or a policy on harassment?
I’m pretty sure the Hells Angels have a policy on harassment, you could say it’s almost a job requirement.
They have a two letter diversity policy: "No".
A start-up offer from a loose acquaintance came my way 2006-ish and it was quite lucrative. But seeing what happened to the dude long-term proved to me the power and importance of "No"
Many years ago in college I was offered a job doing IT and infosec/opsec for an interesting group of people. Turned it down for many reasons including not wanting to live in constant paranoia, but it was suggested that the pay would be excellent.
Reminds me of the bit on Clerks about contractors passing on dangerous jobs with the second Death Star as an example.
Pay is great but the non-compete is a little aggressive. Don't bring up the NDA as it's even worse.
I suspect that once you start working in the field, there's no walking away. You will be a slave scientist. The cartls won't let you walk away from it.
Making opiates for the Sackler family with the blessing of the US government for distribution to addicts via 'pain clinics' probably pays about the same as making opiates for the Guzman cartel down in Mexico for transport over the border into the US for distribution to addicts on street corners.

In both cases you probably want to keep paying your taxes, however. In the latter case you'll need some cover story to explain where you got the money from.

Really the drug situation in the USA is pretty farcical. You can manufacture amphetamines and opiates at scale for the ADHD/chronic pain market, with relatively few restrictions, but the prisons are full of people involved in the clandestine trade in the very same substances.

Well before you earn your PhD I would expect you to be able to make other types of chemicals which are not illegal, even though they may be equally as toxic and only about 10X less profitable.

But you could sell more than 10X as many kilos of legitimate materials and not be limited to only a clandestine supply chain, so the financial upside alone is way better by comparison.

Criminal organizations are limited to the clandestine activities and prefer them anyway, you've got to figure they're making lots more money per kilo, but sometimes I would think they might only be coming out ahead by not paying any taxes. I do think they spend a lot of money on "insurance" but it's not going to legitimate insurance companies either.

As a professional you'll never need to stoop that low, and they'll never be able to reach as high as your actual baseline.

Great. Now I'm on a list.

(Honestly, I find it interesting that things mentioned in the article seem like plot points in the Vince Gilligan universe of Netflix shows.)

Gilligan and crew did research. The economics of production are important parts of the plot.
There is a point in breaking bad where walt rants something like "since our synthesis isn't stereospecific, explain how our product is enantiomerically pure?"
It's interesting to note that as methamphetamine and amphetamine were more regulated in the 50s and 60s, it became more prevalent. Then in order to stamp out illegal production, the precursor chemicals were monitored. So what happens? Production becomes more dangerous.

Solution: Just make every kind of drug legal to produce, but regulate the purity. Be very explicit about the dangers. The only thing prohibition does is make drug consumption and production dangerous and needlessly expensive.

Adderall anyone? There's a panoply of legal ways to obtain amphetamines, but the US medical system is far less competent at customer service than the black market due to regulatory capture.

I think it's critical to appreciate that Physician Regulations, the AMA, etc. are the main culprits here. How they avoid getting properly blamed for things like the opioid epidemic, I have no idea.

I suspect that most people who understand the role AMA plays in prohibition and drug abuse also aren’t super interested in focusing on blame. The whole thing is a complicated system of perverse incentives and counterproductive policies. It doesn’t really matter if the AMA is 20% or 60% to blame.
Blame is a poor choice of words. Ideally we could stop letting physicians write their own regulations, and instead have at least one mechanism with incentive to promote national health, rather than the medical industry complex.
Traditionally, doctors, as men of science, have been given wide latitude to prescribe, since there is no one treatment that is good for everyone. Unfortunately, that seems to be changing, as doctors are expected to adhere to a standard regimen of treatment options. It is the dangers of institutionalization of our healthcare.
Calling doctors men of science is extraordinarily generous. Scientists do things like collect data to test hypotheses.

The ama lobbies aggressively against national medical record standardization etc.

At the end of the day, it's about whether the person making decisions has good incentives. And that's not the case in the present system.

I was being a bit facetious in using the term, but that was the image given to doctors once upon a time. Nevertheless, my point is that doctors are not mere technicians applying handbook remedies. They are generally given wide latitude to try novel ideas when appropriate. Unfortunately, that appears to be changing.
I think that if we legalize dangerous addictive drugs then we might as well legalize all medications/drugs by which point the medical establishment loses a big chunk of the income that it gets from being a monopoly supplier.

I wish society was mature enough for full legalization, but often those pushing for legalization underplay the negative problems associated with drug use. Particularly for that 'harmless plant' marijuana. A university acquaintance went acute schizophrenic shortly after developing a pot habit, that could be a coincidence but the timing is suspicious. A second cousin became mentally retarded immediately after smoking a joint. He's now a 30 year old who can't tie his own shoes.

Big businesses already have enough power to shape politics, we're still in the process of stamping out cigarettes. I've noticed a lot of smoking on Netflix so clearly they're still working on a comeback. How long until they put coke back into Coca-Cola and funding scientific studies about how a bump a day is actually good for you.

Then there is the seriousness of surreptitiously giving someone an addictive substance, to put the hook into them, which I consider to be interfering to the working of the brain and akin to murder. At the moment the focus is around the drug being illegal as opposed to the deleterious effect it can have. Criminal gangs use this tactic fairly frequently as an alternative to killing someone but I believe it should solicit the same punishment.

A lot of people who are against legalization make this argument that those who are for it ignore the negative consequences, but for large swathes of pro-legalization people, that's just not true. I know there are negative consequences, and I know that in a very small number of people marijuana can cause serious consequences (and in larger numbers of people, harder drugs like cocaine and heroin can cause more serious consequences).

But the fact that things can cause negative consequences is not sufficient reason to ban them. The obvious example here is alcohol - it is beyond clear from data that alcohol is incredibly harmful. It is beyond clear that it is more harmful than at least some banned substances (marijuana, LSD, MDMA). It is likely that it is more harmful than harder substances like cocaine, but with less data on those we can't say for sure.

So yes, there are negative consequences, but as a society we have decided that we allow people to do things that cause negative consequences (as evidenced by the legality of alcohol). There are limits on that, but with alcohol as a line by which to judge those limits, it's clear that to have any kind of coherent public policy, marijuana should be legal. Or, of course, alcohol could be made illegal. The point is that if you think that alcohol should be legal but other drugs should not, you're just engaging in hypocrisy.

* I did use the qualifier 'often' which is not 'all' and to my opinion it's not enough. People readily forget the downsides and need constant reminders.

Edit: please note that the following includes the qualifier “most” and please understand that this does not mean “all”.

I think alcohol is a bad example as alcohol for most people has a way of punishing abuse on its own and quickly thereby maintaining a tight association between the high and the hangover. The aversion to the hangover means that for most people it's a self correcting problem. Most other drugs don't come with this and the association between the high and negative consequences are more remote and infrequent.

I think alcohol, despite the obvious and extensive damage it causes, is a great training drug that teaches most people moderation through first hand experience and encourages caution with other drugs.

Using alcohol as an example kinda makes the case for prohibiting alcohol as opposed to legalizing other drugs.

I encourage you to actually do some research on alcoholism - both the number of people it affects as well as the way it prevents itself. You're dangerously uninformed on the topic to be presenting these kinds of opinions.
oh, come on! I think you're right on this issue, but since when are opinions dangerous? He's giving his honest opinion of the issue according to his experience.

You will be much more effective if you simply try to enjoy the conversation than trying to call out people for having "dangerous opinions".

You put quotes around "dangerous opinions" - you're wrong to do that, because I never used that phrase. I said he was dangerously uninformed.

There are times when people can have valid, personal opinions and times when there's just objective reality. Some people these days say that their opinion is that the 2020 election was stolen. That's not a valid opinion - it's just wrong. Saying that hangovers make alcohol self-regulating when >10M people in the US are alcoholics (for whom it is, as a point of fact, untrue that alcohol is a self-regulating substance) is not a valid opinion - it's a misunderstanding of reality.

As someone who knows people who have been very severely negatively affected by alcoholism, I do not enjoy conversations with people who make points about alcohol that are totally uninformed and suggest that we should base policy around those uninformed thoughts.

I just think you would enjoy the conversation more if your experience was not dependent on someone else's opinion. You are also assuming something about another person that is more than likely untrue. Sounds like a horrible way to live.

No offense to you, but who named you the arbitrator of "valid opinions"? I doubt you are that arrogant in person, but you sure are coming off that way.

Most =/ all. For some it doesn’t work this way and that is very costly to us all. Hence the great deal of damage that it causes. I’m not sure what point you’re trying to make, is alcohol too dangerous therefore we must legalize more drugs?
The point is that we should have a coherent policy in the US around how we treat drugs.

Either we should accept a certain threshold of danger around drug use and allow all drugs under that threshold to be used (with appropriate regulation), or we should not accept the use of dangerous drugs and should outlaw them.

Right now, US drug policy is that a fairly dangerous drug (alcohol) is not legal, while other clearly less dangerous drugs (marijuana, most hallucinogens, MDMA, etc.) are not legal. It should be changed to be a rational policy in which everything less dangerous than alcohol is legal or a policy in which alcohol is not legal.

If anything I think perhaps reducing the legal age for drinking in the US. Where I’m from getting black out drunk is considered immature and people are expected to grow out of it, but then we start a lot earlier. Plus we learn how to handle alcohol * before we learn how to drive so it’s not considered matcho to drink and drive. I think cigarette companies like the 3 year gap of being able to buy cigarettes but not alcohol.

I’m pretty pro legalization, I think it’s probably best handled at the cultural level, but until society matures there is going to a fair bit of collateral damage and I think we should be honest about that.

* it’s a generalization… obviously it doesn’t work out this way for everyone.

>The point is that we should have a coherent policy in the US around how we treat drugs.

But we have had a coherent policy around drugs in the US:

1. Identify a potential issue with a particular drug;

2. Investigate the issues and examine the evidence;

3. Create a set of policy solutions to address the issues;

4. Pick the least effective, most harmful policy solution and implement that.

5. Profit!

All you have to do is look at all the major drug legislation over the past 130 years or so to see that such is, in fact, the case.

I'm not so sure about that. If you've ever talked with a full-blown alcoholic, the allure of drinking is almost a reflex with no consideration for its effects. I don't think they even remember having to lie in their own vomit or the severe hangover they will have to endure. The hangover is enough of a deterrent for myself, but they don't even think twice about it. Its amazing, really.

I'm convinced the only reason alcohol is legal is because it is culturally embedded. If it were being introduced anew, it would be prohibited. Its far worse than most illegal drugs.

I didn’t think I’d have to follow up a post on using a qualifier “often” with another post about using a different qualifier “most” which obviously doesn’t encompass “all”. Counter examples are clearly presumed necessary given the aforementioned damage.
I understand your point that most people who drink alcohol do not become alcoholics. But that is true for all drugs, really. I think the thing that separates alcohol is the long cultural acceptance.
Alcohol is incredibly easy to produce from almost any available organic matter makes it difficult to ban.
And the US tried that, and it was a complete failure. Yet we as a society somehow failed to learn that lesson and here we are.
At no point did I advocate prohibition of alcohol, I am suggesting that others pointing out the incredible harm alcohol does doesn’t do a great job in making the case that more drugs should be legal.
I disagree entirely with this viewpoint - alcohol is one of the most dangerous and addictive substances available, with serious long-term health consequences. While the opiate epidemic has made a lot of headlines, CDC data IIRC points to the alcohol resulting in the premature deaths of about five times as many people (not by direct overdose as with opiates, but via associated medical conditions like liver failure).

Alcohol has a complex set of biochemical effects, but note that part of the issue is that it's similar to opiates, i.e. it triggers the release of an endorphin-like molecule that people get addicted to in the same way as with morphine or heroin.

I still don't think alcohol should be made illegal, but in terms of long-term medical effects, it's certainly more dangerous than cannabis/THC and psychedelic drugs like mushrooms/psilocybine. It really belongs in the same class with amphetamines, cocaine, benzos, and opiates.

If alcohol is one of the most addictive substances around I do not think we need to worry too much. Alcohol is actually not very addictive. Most people can drink regularly drink large amounts of alcohol without feeling the least bit of addiction.

Alcohol is very bad for your health and it is a horrible thing to be addicted to but it is not very addictive.

The mechanism of alcohol addiction is well known and studied, and alcohol is certainly in the same addictive potential class as cocaine, heroin, nicotine and amphetamines.
That's why it should be mostly about protecting the youth who are more likely to be uninformed about dangers. It is true that outright prohibition is pointless, but it can introduce a bit of friction that forces users to have to put in a little effort in order to try it. Because of the effort, it is more of a deliberate decision.
Absolutely - education and regulation are much more effective strategies than prohibition along pretty much every dimension. We've drawn the very reasonable line that young people whose brains are still developing don't get alcohol, and of course we should extend that standard to other drugs.
> A university acquaintance went acute schizophrenic shortly after developing a pot habit, that could be a coincidence but the timing is suspicious.

Early adulthood is when mental illness often sets in, especially illness like Schizophrenia. You're implying cause one way without considering the other likely alternatives:

1) Your acquaintance started smoking a lot of pot because of the onset of early schizophrenia symptoms as a coping mechanism.

2) They are unrelated and early adulthood is just when people experiment more with drugs, and also when conditions like Schizophrenia start to manifest.

> A second cousin became mentally retarded immediately after smoking a joint. He's now a 30 year old who can't tie his own shoes.

I don't know what to say to this other than nobody's ever established an even remotely plausible link between these two things, assuming you aren't being hyperbolic.

"that could be a coincidence" is a qualifier that includes the points you brought up.

A friend of my 2nd cousin smoked a joint from the same stash and no such effect so it's clearly a combination of marijuana and the individual. Unfortunately such experiments are hardly repeatable in a clinical setting, he's not the only one, it's happened to number of people. One of the other mothers was collecting stories to try to turn into a book, give me a minute and I'll try to find it.

Edit: it may take me a while to find it, I think it ended up getting published but it wasn’t something I paid much attention to. I’ve only met my second cousin and his family once and a very long time ago.

A plant allergy gone wrong?
If I'm not mistaken, I believe there is a strong causal link between marijuana and schizoid type effects. I don't think this is even disputed. Maybe he was predisposed to it anyway, but the marijuana certainly did not help.
> I don't know what to say to this other than nobody's ever established an even remotely plausible link between these two things, assuming you aren't being hyperbolic.

This one’s simple: unless they, or someone they know, grew the plant themselves, there is no practical way to know what really went into the joint. I’ve witnessed people having hallucinations after a joint, which seems unlikely with cannabis.

I’ve had hallucinations from pot that I’ve grown from seeds myself. As have others from the same pot. It was extremely strong hydro grown under stress, the bud glistened.
> I think that if we legalize dangerous addictive drugs then we might as well legalize all medications/drugs by which point the medical establishment loses a big chunk of the income that it gets from being a monopoly supplier.

Yes, absolutely.

> those pushing for legalization underplay the negative problems associated with drug use

But those problems already exist and are amplified by the prohibition.

I don’t understand how prohibitionists still believe that the ban on drugs would make drug use disappear when the last 80 years of prohibition completely failed at that.

It’s clear that prohibition does not work. But if we just try long enough it might? That’s not science, that’s ideology.

Prohibition on supply just increases the prices which encourages more people to jump into the market. For prohibition to be effective there needs to be strong punishments on consumption.

As someone who consumes quite a large amount of gray and black market medicine I'm actually pro-legalization of all drugs. I hate the medical monopoly and the overbearing government. But I also think people need to be very honest and frank about the consequences of legalization.

My concern, beyond what happens to other people, is that I'll have to check the ingredient label for a longer list of substances I don't want in my body. We have enough food fraud as it is with suppliers lying about the content, I want it to be an extremely serious crime to add drugs to food.

IMO I think legal prohibition is not the way to reduce consumption of a bad thing in a society, but to do what was done for smoking. You have to treat them as a public health issue, make it culturally distasteful and more and more annoying & expensive, but legal, to do so. That is what effectively reduces usage vs. straight out police prohibition.

And when people talk about legalization, they are not saying get rid of the entire doctor supervision & prescribing system, which creates a legal outlet.

The only problem I see with legalizing all prescription drugs is that a lot of people would use them off label or in inappropriate context (ie taking antibiotics when you have a viral infection).

I think this could be managed with an appropriate regularity framework that I think should probably apply to psychoactive drugs as well. This would be some sort of licensing system. Anyone can get a license to buy antibiotics but it requires taking class and passing a test that demonstrates you understand the risks and agreeing to follow certain rules and procedures. A procedure for antibiotics might be that you agree you'll only purchase them if you have tested positive for a bacterial infection. All drugs should only be purchased for yourself (unless you have a distribution license which should be more difficult to get). If you get caught breaking any of those rules, you lose your license for some period of time and are subject to other penalties.

I think for something like antibiotics, no one would bother getting licenses as it's not worth the time of getting and keeping your license up to date (licenses would likely require annual renewal and continuing education). You'd just go through your doctor the couple times a decade you need them. But this could be hugely beneficial for a diabetic person that doesn't want to go to a doctor once a month to get their insulin prescription renewed. Or women that want birth control without paying doctor fees. Yes, it would result in less revenue going to our medical system but that seems like a plus side in those cases.

I don't deny that some drugs are incredibly dangerous but our society allows a lot of dangerous activities. If I want to buy a BASE jumping rig, I could do that and then start legally jumping off of cliffs with it as soon as it arrived. My chances of dying doing that are far higher than my chances of dying while taking most drugs (maybe some like fentanyl are exceptions). Would you consider whoever sold me the rig a murderer? Or do you think I'm an adult and should be allowed to make my own decisions as long as they're well informed?

surreptitiously - adverb in a way that attempts to avoid notice or attention; secretively. "Mary surreptitiously slipped from the room"

i.e. it was something done to you without informing you. To use your analogy it would be like blind folding someone and pushing them off a cliff (with base jumping gear on) if they lived I'd consider that at least attempted murder. But with secretly giving drugs to someone there is no way to avoid interference with the workings of a sound mind so that I think is on par with murder.

I thought you were implying companies adding addictive substance to their products in attempt to get people hooked which I thought a regulatory framework would fix. If coke puts cocaine back in their drink, it would require a license to buy so they wouldn't be able to do it without informing people.

Are you actually talking about something more akin to date rape? I'm really not sure if I understand how that might work. You slip someone opioids without them knowing until they're addicted and then you stop but reveal to them they're addicted to opioids hoping they continue that addiction? Or do you stop once they're addicted and just hope they figure it out? Or you just keep feeding their addiction without them knowing until you feed them a dose they OD on?

> Criminal gangs use this tactic fairly frequently as an alternative to killing someone but I believe it should solicit the same punishment.

Criminal gangs tend to take the more active holding people down and injecting people with drugs approach than the slow sneaky process. But once addicted the addict is now reliant on the gang for their continued supply and can be controlled. The real life instances I’m aware of was done on people who were preparing to testify against their family members in a gang. It was a speedball injection. But is has been depicted in fiction such as in the move ‘the town’.

My relatives were involved in sheltering them to get them clean, but as soon as they went home the gang found them and got them addicted again.

Gotcha. I guess I don't understand why you'd expect that behavior to become more common as a result of drug legalization.

All that would still be very illegal (I imagine injecting someone with even a completely safe saline solution without their consent would be considered assault in most jurisdictions). The type of people that are comfortable doing that clearly don't care about the law. I just don't see drugs being illegal as a limiting factor on crimes of that nature in today's society.

I'd also like to mention that a major source of funding for many criminal gangs is the black market sale of drugs. If we legalized and regulated drugs, they'd lose that source of money and I'd personally expect to see a decline in organized crime.

Safe saline is the least of the victims worries, water quality isn’t that important to the extent that many safe injection packs no longer include it. Tap water is usually fine, puddle water is usually fine. In medical settings the law of large numbers mean that usually isn’t good enough but for one offs it’s ‘usually’ ok.

It’s the action of adding chemicals to your brain that can and likely do have harmful long term effects, not limited to addiction, and many still unknown. If such an act was done to me I would consider it within my rights to kill that person in retribution.

I’m less confident on the expected drop in organized crime as taxes on the drugs usually means there is now money in tax evasion. Without tax it may become so cheap that other problems start to dominate.

The whole point of bringing up saline solutions was to point out that what you're describing is already illegal even for much less serious offenses. I'm not a lawyer so don't know what all crimes would be involved with injecting drugs into someone against their will but I'm willing to bet money it is breaking several.

As for illegal drug sales persisting despite legalization, how many people are still buying illegal moonshine? It does exist, I've seen it, but it's not nearly the problem it was during prohibition.

Despite being illegal forcibly getting someone addicted isn’t treated seriously at all. Unlike murder where there is a missing person or a body to show that a crime has taken place you with forced addiction you now have the addicts word which is considered inherently unreliable.

I’m more worried about organized crime/political corruption than I am about freely available drugs, but organized crime has all sorts of ways to make money so I don’t think we’ll be rid of it that easily. I think people underestimate the prevalence of how much corruption still exists. I even think it’ll get worse as fewer non-compromised people want to take police jobs.

Also prohibition ended 1933 but the major crackdown on gangsters was in 1970 due to a long period of federal government inaction.

Antibiotics would be far worse to deregulate than even the hardest recreational drugs, because widespread flawed use would harm other people at scale by promoting drug resistent strains.

I think legalisation ought to be driven largely evidence of harm, not just by abuse of the drugs, but systemic harm both of legalisation vs. criminalization, but with a reasonably high level of ability to take personal risk.

E.g. for drugs where we know addiction drives crime, even fairly substantial harm from the drug itself might still mean legalisation is a net gain. Heroin might fit in that bucket (a small UK trial with prescribing it saw offending rates for those in the trial drop dramatically, and so reducing net harm to society).

At the same time high risk may justify a high degree of regulation of specific drugs to ensure people are at least aware of the dangers, and aim to reduce recruitment.

>Antibiotics would be far worse to deregulate than even the hardest recreational drugs, because widespread flawed use would harm other people at scale by promoting drug resistent strains.

That particular cat is well out of the bag as, according to the WHO[0], a full 1/3 of antibiotics users obtained their last doses without a prescription. In fact, many countries (unlike the US) don't require prescriptions for antibiotics.

Which really sucks, as antibiotic resistance will (barring some serious scientific breakthrough(s)) likely be a huge problem over the next century or so.

I don't have a good answer WRT that, but agree with much of what you wrote.

[0] https://www.who.int/europe/news/item/21-11-2022-1-in-3-use-a...

And that's just humans using antibiotics. Roughly 2/3rds of antibiotics are used for veterinary purposes.

But yes, we need to be much more careful with how we use antibiotics than we currently are and I also don't have a good answer for how that happens.

> I think that if we legalize dangerous addictive drugs then we might as well legalize all medications/drugs by which point the medical establishment loses a big chunk of the income that it gets from being a monopoly supplier.

Do you seriously think this is why medication is regulated?

In most developed countries prescribing and dispensing are separated (doctor/pharmacy) in part to prevent this. Japan is a notable exception and guess what: more drugs are prescribed per capita there than the rest of the OECD.

I would include pharmacy in the medical establishment, and yes I expect them to place significant lobby pressure to maintain their monopoly.
> A university acquaintance went acute schizophrenic shortly after developing a pot habit,

That's the age most people find out they're schizophrenic

This implies that the dangerous production is the fault of the government. It is the fault of those who want to produce it. They are making bad choices. A responsible government should not make it easy to make bad choices.
You are implying there is anything inherently bad about amphetamines.
Sure, and prohibition also didn't cause any harm to people who didn't drink, mandating the addition of poison to rubbing alcohol using legislation doesn't cause anyone to be poisoned, etc.
"They are making bad choices."

This sort of reductionist, simplistic "reasoning" is going to be the death of us all.

Trying to find a moral failing in every human weakness, every human ignorance, every human desperation? It's just disgusting.

> It's interesting to note that as methamphetamine and amphetamine were more regulated in the 50s and 60s, it became more prevalent

This is an extreme example of “correlation does not equal causation”

The regulation came from the expanding popularity of these drugs. It didn’t cause it.

Likewise, regulating precursor chemicals wasn’t some causative factor in further drug use. It was the next level of regulations added in response to the increasing drug use.

Regulations and limited availability don’t cause more people to use drugs. That’s not only an illogical conclusion, it ignores the order of how things happened.

The increased availability of fentanyl has been a driving force in more people using opioids in general. Note that most people aren’t seeking out fentanyl (though many are), they believe themselves to be purchasing more traditional opioids. The increased availability of fake pills has definitely increased opioid use. The idea that opening the floodgates to more access will somehow decrease usage is inconsistent with evidence and inconsistent with reality. It also just doesn’t make sense.

To steel-man OP's argument,

> Regulations and limited availability don’t cause more people to use drugs.

All else held equal, all this does is increase the price of doing drugs.

There are arguments to be made about the history of the demand for drugs. I think we can safely say, though, that it stays at a stable 'Some people really want to do them'. Whether or not that means growing a plant or potentially getting shot depends on the regulations.

I'm generally in favor of drug legalization and/or decriminalization, but I'd draw a line at meth. There is a reason for the "Meth, not even once" PSAs and memes. The drug is really just that addictive that it can ruin people's lives by getting them hooked after just one session.

Even if you disagree with my stance, I think it would be a grave mistake to not acknowledge that different drugs have different capacities for harm, and the fact is that the addictive nature of meth makes its harm potential astronomical.

Libertarians tend to take potential solutions to the extreme, but seldom is anything so ideologically pure. Still, the idea that government can protect people from themselves is a noxious one. Drug legalization is an attractive one for that reason alone, but there are limits. Drug addicts are by definition not rational actors.
Presumably they were at one time a “rational actor”. Before the drugs.
Yes as libertarian who was offended by the idea of regulating what adults can put in their bodies at home, I have changed my mind after seeing real world consequences. As a young college student its easy to believe some kind of naive model of humans as basically well-intentioned or rational or at least a blank slate. Experience tells me that most illegal drug (and heavy alcohol) use has negative externalities and tends to harm the character of the user over time. An assertion younger me would have probably found offensively moralistic (what is “character” anyway?) but here we are.
You just described my history on the subject. I once believed that too.
So you've decided to support an ideology that restricts the freedom of all people to do as they please because you think it's harmful for them. I've decided >20g per day of carbs is harmful for people that choose to do it. Watch out buddy I'm going for bread pasta etc... I don't think people should be able to eat it. I'm coming for your rights.
I think that as a policy matter it is better for society to create an exception to the rule of complete bodily autonomy, mostly because of harm to people around the user. I don’t think users should get jail time but some penalties are ok. This is partly based on personal experience and partially on stats like increasing DUI rates post cannabis legalization. I don’t see much of a slippery slope argument to be made from psychoactive drugs to carbs, which are a basic nutrient anyone can find anywhere.
the question isn't whether or not a substance should be in use in a society, but whether its users/producers should be caged
The amphetamines are all similarly addictive, it's just that methamphetamine is more active at smaller doses. This general class of drugs is widely prescribed to children and adults to treat ADHD in the United States (many argue over-prescribed).

People who use amphetamines 'recreationally' seem to mix it with alcohol, with very bad long-term effects on health. It also seems to drive people towards reckless and poorly-considered behavior, which is similar to the effect cocaine has on many people.

It's a wise life decision to not associate with cocaine and amphetamine addicts, certainly. However it is also curious that people in treatment for ADHD also develop a dependency on the drug, although perhaps in a more controlled manner due to it being prescribed, yet few people in the medical-pharmacological world seem to be that concerned about it.

> However it is also curious that people in treatment for ADHD also develop a dependency on the drug, although perhaps in a more controlled manner due to it being prescribed, yet few people in the medical-pharmacological world seem to be that concerned about it.

Dose makes the difference. The kind of dependency people with ADHD develop on their meds is closer to the kind a person with mobility issues develops on their wheelchair after spending some time using it.

"The amphetamines are all similarly addictive" oh, you mean like pseudoephedrine (sold as sudafed) and crystal meth? Blatantly they are not.
I think the comparison you want to look at is Adderall vs. methamphetamine. Incidentally, addicts can't tell the difference between the two drugs if ingested in pill form at the same relative dosage. This is comparable to how opiate addiction works; an addict can't tell the difference between morphine and heroin, it just takes twice as much morphine to get the same effect.
I suspect you don't know what you're talking about. Have you any actual experience with drugs? Because I can tell the difference between MDMA and various somethings sold as MDMA but aren't, and I'm hardly a drug expert.

Again, have you any decent experience with drugs?

There are a lot of nerdy people with ADHD on this website, ADHD procrastinating time away. I would actually trust them on this specific drug class actually, you can get prescribed meth with an ADHD diagnosis, just most don't.
Which fails to answer the question, or acknowledge I have some experience with this type of drug. Neat.
People with ADHD don’t get “high” on Adderall taking therapeutic dosages in the Milligrams. They take it to turn the noise down in their head so they can focus and be productive.

The comparison to meth “addicts” is absurd. People with ADHD are not taking Grams of prescribed amphetamine pills to get high like some one blasting their brain with a bag of street meth with the intent of feeling euphoria.

Do you actually feel "euphoria" taking more than the prescribed dose of Adderall? I've been encouraged to try increasing the dosage by psychs before and I just can't. It feels more like a panic attack than anything.
I’ve accidentally taken double doses and had a massive migraine. As for euphoria, your brain gets used to meds so you will only feel normal taking doses, even higher might feel more energy but never high
The dose and the purity is what makes all the difference here. When someone takes Adderall orally, they are taking racemic amphetamine and dextroamphetamine at a dose typically around 10-20mg per day. When someone smokes pure d-methamphetamine, they are typically smoking 50-70mg in one or two large hits. Now, I do not condone or suggest this, but imagine taking 50-60mg of instant Adderall in the morning.
I have on accident it just gives you a massive headache
I think when most people say they're taking Adderall, they actually mean Dexedrine or Vyvanse, which are both D-amphetamine.
IMO I think addictiveness is a matter of dosage. A lot of ADHD people who have these medications can forget to take them, stop taking them for days in a row, don't want to take them because of side effects and stop taking them for years after years of usage or only take them during school & work days, which all doesn't sound like addictive behavior to me. In practice junky addiction comes from junky usage patterns and behaviors.
You don't become addicted to therapeutic doses of amphetamines. There is some degree of physical dependency, but it's safe to stop taking them cold turkey and would only take ~a week-a month to return to "baseline" after that.

This is actually not true of the non-stimulant ADHD drugs like Intuniv; you have to taper that one off over a few weeks or unpleasant things happen to your heart rate.

And, of course, ADHD patients constantly forget to take their drugs, and the system where you have to get a new prescription every month isn't even something they can reliably do, being ADHD patients.

> There is a reason for the "Meth, not even once" PSAs and memes. The drug is really just that addictive that it can ruin people's lives by getting them hooked after just one session.

If you believe the propaganda - memes are not a quality source of information. You need to be less willing to repeat what you've heard sand more willing to dig out the facts. The same is said of crack ("one hit and you're hooked") but it's a lie. I've spent several full evenings smoking it and I am not going back to it. To some people, maybe one shot and then doom, but to most it's an incremental downward slope depending on many factors. Not denying crack is a bastard and I would probably not support legalising it either, but please don't parrot back rubbish you've been told.

If this is still the level of HN debate ion drugs, to repeat soundbite anti-drug propaganda, I feel we're getting nowhere and burning a lot of fuel doing it.

To be clear, my stance against meth comes not from "anti-drug propaganda", but from knowing people whose lives were ruined by it. I'm pretty open about drug use, and after hearing their experiences with it, it is absolutely a drug I would refuse to touch.

I'm not arguing these anecdotes are data, but for me personally they are enough to highlight the unequal danger of meth.

Are you saying those peoples' lives were totally fine, and then when they tried drugs they were ruined?

My understanding is that most people whose lives are in ruin and use drugs, use drugs because their lives were already ruined in some way or other.

> Are you saying those peoples' lives were totally fine, and then when they tried drugs they were ruined?

Yes, I am. They weren't ruined immediately, but the addiction quickly ruined them.

> My understanding is that most people whose lives are in ruin and use drugs, use drugs because their lives were already ruined in some way or other.

I think your understanding is woefully incorrect, almost to fall into the caricature of what "bad drug users" look like. Many people (myself included) like to use drugs because they make you feel good. Just look at, for example, the popularity of pubs in England - do you really think that all alcoholics only became alcoholics after their lives were already shitty?

Yes, I am. They weren't ruined immediately, but the addiction quickly ruined them.

Questionasble. There's a good asrticle in the spectator asbout this I can't find now, am at work. It suggests a very different interpretation.

Can't quite find it, try this instead, covers the same ground.

https://www.walesonline.co.uk/news/wales-news/doctor-heroin-...

> I think your understanding is woefully incorrect, almost to fall into the caricature of what "bad drug users" look like

Well, my experience.

Used to buy a bottle (700 CC) of spirits and it would last about 2 weeks. Became seriously mentally ill a few years ago, started drinking equivalent of 450 to 500 CC of spirits per evening (~1/2 litre), every evening, for a long time until the cash fortunately ran out. At least I could feel something, anything, when I drank.

When I got better the drinking subsided, almost back to my baseline again.

QV also soldiers on heroin in the vietnam war, when out of the stress of war they typically just gave it up iirc.

Tens of millions of people in the US are prescribed amphetamines. They don’t spiral into a cycle of addiction and loss of self control.
>It's interesting to note that as methamphetamine and amphetamine were more regulated in the 50s and 60s, it became more prevalent. Then in order to stamp out illegal production, the precursor chemicals were monitored. So what happens? Production becomes more dangerous.

http://en.wikipedia.org/wiki/Giffen_good

Methamphetamine wasn't the only drug being regulated in the '50s and '60s. The other stimulants, like cocaine, were restricted at the same time. But methamphetamine is by far the hardest drug to regulate, so its relative prevalence increases.

>Solution: Just make every kind of drug legal to produce, but regulate the purity.

This is suboptimal. Recreational stimulants are not all the same level of dangerous. (Which would be an incredible coincidence.) The better solution is to find the safer stimulants (possibly variants of methylphenidate) and allow those to be used recreationally, hopefully cutting into the demand for the really bad stuff.

There have been countries like China in the Opium Wars period that had limited restrictions on drug consumption. It ended up with a substantial fraction of their population being addicted to opium and basically non-productive.

HN is full of smart people who (wrongly I think) assume that because they have the self-control and discipline to either avoid drugs or to use them relatively safely that the rest of the population does too. This does not seem true in my experience. I forget the exact stats but roughly 1 in 20 Americans is an alcoholic, and that's with a drug that humans have been consuming for thousands of years and that has established social rituals around consumption. It seems likely to me that increasing access to and decreasing stigma of highly addictive drugs like opioids or amphetamines will lead to substantial increases in addiction rates.

> It ended up with a substantial fraction of their population being addicted to opium and basically non-productive.

Do you have any evidence of this? I don't believe this to be true from general reading, but can't back it up. My rcollection is that the workers would work hard during the day then smoke opium in the evenings.

This article claims 27% of the adult male population were addicts in 1906 (5% of total population): https://sci-hub.se/10.1007/s10571-007-9225-2.

They don't specifically mention work output but I find it hard to believe that opium addicts were particularly productive in most jobs. I don't think China was very industrialized at the time so I doubt what we would today conceptualize as a "worker" was a substantial fraction of the population at that time.

Thankls. I'm a little cautious if this as it relentlessly uses he word 'abuse' instead of 'use', as if it has made up it's mind already.

I also found this, which may disagree: https://academic.oup.com/book/32900/chapter-abstract/2766221...

The ‘Problem’ of Opium Smoking in Canton Virgil K.Y. Ho

Abstract

Both the causes of opium consumption, and the allegedly calamitous social, political, economic, and cultural impact of opium smoking on Cantonese society were greatly exaggerated in official propaganda and scholarly writings. Opium served Canton and its urban inhabitants many positive social, cultural, economic, and political purposes, making it difficult to over-simplify the phenomenon of opium smoking as nothing but pernicious.

"but I find it hard to believe that opium addicts were particularly productive in most jobs"

well maybe, but do you have any experience with this other than feeling? Same has been said of dope smokers, but many are productive. Also in china a few centuries ago there was no welfare state and for most, no work = no food = beg or starve. So as a non-productive person, you didn't live too long (edit: to be fair, this is just my assumption. I may be wrong).

Abit more, from https://en.wikipedia.org/wiki/Opium#Recreational_use_in_Chin... that suggests something very different:

It is important to note that "recreational use" of opium was part of a civilized and mannered ritual, akin to an East Asian tea ceremony, prior to the extensive prohibitions that came later.[50] In places of gathering, often tea shops, or a person's home servings of opium were offered as a form of greeting and politeness. [...] The image of seedy underground, destitute smokers were often generated by anti-opium narratives and became a more accurate image of opium use following the effects of large scale opium prohibition in the 1880s.[50][51]

> well maybe, but do you have any experience with this other than feeling? Same has been said of dope smokers, but many are productive. Also in china a few centuries ago there was no welfare state and for most, no work = no food = beg or starve. So as a non-productive person, you didn't live too long

Not with opium smokers but I have some familiarity with opioid users and they are generally not good workers. Of course maybe there are tons of opioid users who pass as totally functional people and so I don't recognize them, but I doubt that. Marijuana is also clearly not addictive in the same way as opioids are (perhaps it is slightly addictive and maybe more so now that it has become stronger). It seems to be more like caffeine where its use is ritualized but people don't have a very hard time with cessation if forced to. I would bet daily users of cannabis are significantly less productive than the average population, but I know a couple in high performance jobs, so it's certainly not guaranteed.

I imagine in the China of the early 1900s many of the opium users did die just as many heroin/fentanyl users today do. I have talked to addicts who expect to die of their drug addiction and openly say so.

Edit: I thought about it a bit more and I am aware of some functional addicts addicted to (legally proscribed) pain meds. So I suppose it is possible opium users/addicts were more like this group. I doubt it though because China went to extreme lengths to eradicate opium from the country after the communists came to power.

A fair and measured answer, thanks.
> and that's with a drug [...] that has established social rituals around consumption

You're missing something vital, that those social rituals are often supportive of alcohol consumption. In the UK "beer or queer" (= drink up or there's summat wrong with you"). Alcohol abuse is as much an embedded social problem as a personal one. Who hasn't tried to force another drink on someone who's clearly had too much? To my regret even I have.

On top of that, just look at alcohol advertising everywhere. It should be banned.

>HN is full of smart people who (wrongly I think) assume that because they have the self-control and discipline to either avoid drugs or to use them relatively safely that the rest of the population does too. This does not seem true in my experience. I forget the exact stats but roughly 1 in 20 Americans is an alcoholic, and that's with a drug that humans have been consuming for thousands of years and that has established social rituals around consumption. It seems likely to me that increasing access to and decreasing stigma of highly addictive drugs like opioids or amphetamines will lead to substantial increases in addiction rates.

IMHO, that's a little reductive. The primary issue isn't use/abuse of such substances. Rather, it's the criminalization of use/abuse that's the biggest problem.

I say that because putting someone in jail because they have a problem with substance abuse doesn't make any sense. I'd add that providing comprehensive treatment for those who have such issues would be less than half the cost of interdiction, enforcement and incarceration.

What's more, both the substance abuse and legal issues/incarceration limits the economic potential of those who have resolved their issues due to stigmatization of those with criminal records.

I'll go even farther and say that drug prohibition (as we saw with the 18th Amendment[0]) creates black markets, and since there are no legal avenues to address disputes, and begets violence on a wide scale, further depressing economic output and social cohesion.

I don't disagree that substance abuse brings misery to many -- but penalizing those who use such substances without them negatively impacting their lives with legal issues and potential violence seems way too extreme.

If we invested USD$10-15 billion a year (as compared with ~USD$50 billion on "drug enforcement") into the resources required to provide treatment for anyone who wants/needs it, and legalize/regulate all "drugs", will save money, increase economic output and improve social cohesion.

It's a win/win/win if you ask me.

> If we invested USD$10-15 billion a year (as compared with ~USD$50 billion on "drug enforcement") into the resources required to provide treatment for anyone who wants/needs it, and legalize/regulate all "drugs", will save money, increase economic output and improve social cohesion.

I don't think there is much evidence for that (nor against it). One country that has tried something like that is Portugal and from what I can tell it has worked moderately but not spectacularly well. The problem with assuming that the US would have the same outcome is that the US shares a porous border with a part of the world heavily involved in drug trafficking and the US is a much larger country and larger consumer of narcotics, so the demand effects are hard to compare with Portugal.

> It's interesting to note that as methamphetamine and amphetamine were more regulated in the 50s and 60s, it became more prevalent.

~0.2% of Americans had ever used marijuana when it was first made illegal, whereas ~90% of American adults have used it now.

Preach!

Tax it, regulate it, educate on it.

Society is okay with harmful recreational drugs (i.e., alcohol and tobacco), so let's start having grown up conversations about the other ones too.

Yes, they can and will be abused but that is a health issue, not a criminal one.

>It's interesting to note that as methamphetamine and amphetamine were more regulated in the 50s and 60s, it became more prevalent.

My step-mother noted that she was prescribed amphetamines during all three of her pregnancies (late 50s, early 60s) for "weight control."

Which, these days, seems crazy.

That said, I'd note that none of my step-brothers seem to have been negatively affected by in-utero exposure to amphetamines.

I'm surprised to read that there are recent innovations in illicit techniques of making methamphetamine that mirror legitimate pharmaceutical methods, but only because I thought methamphetamine was already a legitimate pharmaceutical to some extent.

https://www.goodrx.com/methamphetamine

Other amphetamines are quite well represented at the average pharmacy at least.

I think it’s more that Eli Lilly and co don’t need to deal with the same supply issues/challenges that warrant the innovation. If they want to make Meth, they can probably just get a bunch of pseudoephedrine delivered.
I don't know chemistry but my reading of the article makes me think the pharmaceutical meth is just the decongestant (L) isomer
You can buy the L isomer OTC as a decongestant, but desoxyn is the D isomer, a stimulant, perscribed for ADHD and narcolepsy.
There used to be a very active forum on clandestine chemistry (The Hive) that eventually got shut down when Strike (who ran the forum) got busted. I cant remember the details (it’s been almost 20 years) but I think 60 Minutes did a report on it and he was anonymously interviewed? He also wrote a couple books on it.

The Rhodium archives were also a nice collection of scientific papers on synthesis routes combined with first hand reports on success/failure. It was a pretty comprehensive site.

I believe the archives are still hosted somewhere.

There were a great number of successor forums to the Hive. Some are still active, some even are clearnet sites you can find when searching for archives of the Hive.
The optical resolution of racemic amphetamine/methamphetamine has been known for years.

https://erowid.org/archive/rhodium/chemistry/amphetamine.res...

What has surprised me is how infrequently it seems to be carried out, given the materials required for it.

This is all you need:

- D-Tartaric Acid (You can buy it from import sites in bulk for $30-60/kg)

- Lye/Sodrium Hydroxide

- Ethanol/Everclear (if you're converting meth, you'll also need Methanol)

- Glassware

- Distilled Water

The process is stupid-simple and takes a matter of hours, any idiot could do it, and the difference it makes in effects (racemic vs optically-pure D-Amphetamine vs D-Methamphetamine) is obscene.

It seems like many of the clandestine chemists are behind the curve in the same way that LAMP-stack shops are in terms of the HN crowd in tech.

Source: Originally was an organic chemistry major with an intent to pursue psychopharmacology

> The process is stupid-simple and takes a matter of hours, any idiot could do it, and the difference it makes in effects (racemic vs optically-pure D-Amphetamine vs D-Methamphetamine) is obscene

(My organic chemistry is very rusty, and my knowledge of amphetamines is non-existant.)

I'm assuming from what you wrote that the D- enantiomer is one you want. What does the L- enantiomer do, if anything?

The L-enantiomer is actually readily available for purchase over-the-counter.

Vicks Vapor rub/inhalers and other decongestants use L-methamphetamine. The D-enantiomer causes CNS stimulation. The L-enantiomer causes only PNS (Peripheral Nervous System) stimulation, so it produces no euphoria or enjoyable effects.

Only unpleasant side effects, like tachycardia and anxiety, etc.

This is why racemic amphetamine/methamphetamine is so (comparatively) unpleasant, and the pure D-enantiomer is superior and "cleaner" feeling.

Racemic amphetamines have a much higher chance of inducing psychosis.

FWIW I find the Vicks Vapor rub fumes enjoyable and euphoria inducing. Edit: I think it's the eucalyptus oil that I am reacting to.
It's also well known as a miracle cure to various demographics of grandmas.
The active ingredients in Vicks Vapo Rub are just:

Camphor

Eucalyptus oil

Menthol

Perhaps you're thinking of a different Vicks product?

Ah it's just the inhalers then, my mistake

Another interesting one found in inhalers is Propylhexedrine, from Benzedrex inhalers

Is this the difference between Adderall and Dexedrine?
Yeah, Adderall is "Mixed-isomer amphetamine salt", it's a "proprietary" blend of 80/20 dextro/levo.
Agreed the process is very simple. The innovation that makes the resolution worth it is (as Derek also mentioned in the blog post) an efficient way to re-racemize the L-meth to DL-meth, which can then be resolved again. With steady state production and pooling this means it can be done using just one batch size (and not ever smaller "brsm" style bathces). If these steps are efficient enough you definitely get much more bang for your buck. Here is one such method[0] which probably inspired these drug manufacturers (as they use thioglycol and AIBN, which has been found in clandestine lab seizures).

[0] https://sci-hub.se/10.1021/jo061033l (published in JOC in 2006 - so only a mere 2 decades behind the curve)

Oh wow, now this is interesting.

To ELI5 this, what the commenter is saying is that you can take the "useless" L-Meth, and convert it to racemic, mixed D/L Meth.

Which you can then perform a second resolution step on, to convert/purify further, to the opposite chirality and get D-Meth.

The very interesting thing about this (if I were a clandestine chemist, or someone who wanted to get high at home), is that:

- AIBN is a readily available reagent, it's not difficult to acquire or would put you on any lists. This is in comparison to much of what you need for other synthesis techniques

- You can buy L-Meth legally over the counter. The extraction process would be a bit of a mess (quite literally) but should be doable, some basic recrystallization and/or conversion to freebase.

(comment deleted)
To further ELI5, racemic means a mixture of left handed (Dextrorotatory) and right handed (Laevorotatory) versions of the same compound. Some molecules can have two different shapes that are mirror images of each other, and these different shapes can interact differently with our biology.

In this case, the right handed version is available in stores with no prescription, while the left handed version is a very controlled substance.

I have a friend who, fortunately, escaped the drug world and is happily recovered now. One of the many interesting things I learned through talking to him and his friends is the pervasive idea among addicted that street drugs were always better in the past. Everyone vividly remembers their drug being much better when they first got into drugs, with steadily declining effects over the years.

Many of them had elaborate theories about changing synthesis or chirality or cutting agents or active impurities. They would even have theories about modern prescription Adderall or prescription opioids being 1/4 as powerful as in the past due to conspiracies by manufacturers.

The drugs may have changed slightly over the years, but the sad reality is that the real change was their accumulated tolerance and long term damage from drug abuse had blunted their response so much that they could barely feel the drugs any more. For some, this blunted reward response carried over to daily life, with depression and a hedonic being pervasive among the long term users.

A sobering reminder that the negative effects of recreational drugs last long after the hangover. I’m seeing an alarming trend of young people reading “harm reduction” material online and assuming they know the full picture of the risks of drug use. Seeing addicts (most of whom assumed they were using intelligently and practicing “harm reduction”) discuss their long term effects is a sad look into the realities of drug use. There is no free lunch.

> A sobering reminder that the negative effects of recreational drugs last long after the hangover. I’m seeing an alarming trend of young people reading “harm reduction” material online and assuming they know the full picture of the risks of drug use.

I don't think that's ever been in question. Harm reduction isn't some utopian ideal that safe drug use == nobody ever suffers long-term negative effects.

Conquering those demons takes a lot of time, introspection, and often outside help. Harm reduction is about making sure you live long enough to hopefully get there.

True, but you are saying that with more awareness than many young people have when they are first looking into it. The brain tends to assume "risk reduction" means "risk approaches zero" and thus negligeable risk.
Harm reduction itself isn't a bad thing, the problem is if it displaces other forms of help for drug users, or ends up encouraging more drug use.

e.x. skip to 2:00 in this video https://twitter.com/sav_says_/status/1603512522509668352

I think your comment is an example of an important discussion we need to have around what are the consequences to our drug policies, whether they are tough-lovish or harm-reductionist. I can see value in both, in different circumstances.

However, the video you link to is from a notorious far right propaganda outlet. I don't think people will get an honest perspective from TPUSA, who clearly have an axe to grind (and bills to pay, which they accomplish by manufacturing outrage).

Ricci Wynne posts most of his videos like this independently (https://twitter.com/RawRicci415). In most of them he lets the video speak for itself. I don't have any reason to believe he's lying and I think he'd strongly dispute being characterized as "far right".
Do you react similarly to left wing propaganda, or is your “partisan sources do not provide honest perspectives” limited to right wing sources?
Yes, I do. I despise the far left.
> I don't think that's ever been in question. Harm reduction isn't some utopian ideal that safe drug use == nobody ever suffers long-term negative effects.

To you, maybe, but it only takes a cursory glance at drug-related subreddits to see numerous people suggesting that you just need to follow harm reduction websites, stick to some arbitrary rules (e.g. only do MDMA every N weeks and take X, Y, and Z supplements), and you can avoid the negative consequences. You may know that’s untrue, but it’s common to see among drug users.

It’s also common to blame drug users who experience problems on failure to follow harm reduction guides, as if the guides are a perfect guide for avoiding the harms.

> Harm reduction is about making sure you live long enough to hopefully get there.

Modern harm reduction websites are about education in general, not just helping addicts survive. You will find things like dosing guidelines for first time users, expectations for what to expect, how to prepare, and so on.

These things are targeted at beginner drug users or the drug curious.

What negative consequences are there to doing MDMA or LSD a couple times a year?

Especially when comparing with the negative consequences of doing alcohol.

The argument that any drug use is bad is pretty blown out of proportion.

> Especially when comparing with the negative consequences of doing alcohol.

This sentiment is confusing to me. I get that alcohol is bad. But how is that relevant to whether or not MDMA or LSD are bad?

I see it come up in these conversations pretty regularly, so there's probably a point there I'm missing. But I can't help but read it as "this thing I like to do isn't bad because other people do a different bad thing".

I think the point is people disproportionately tsk tsk about the harms of drug use compared to the harms of alcohol.

Personally I think most substances in moderate quantities taken only occasionally are no big deal. Yes there is probably some minute health impact visible in long term longitudinal studies but it's probably dwarfed by other lifestyle factors. I would rather be someone who exercises regularly, eats a healthy diet and uses MDMA or cocaine a few times a year than a sedentary obese teetolar who's never touched drugs.

The worst part is that keeping them all illegal drives people towards whatever is available, and some of those choices are far worse than others.

A more flexible approach would see drugs regulated purely based on actual harm coupled with availability of a less harmful analogue (will fentanyl users pick heroin if it's more easily available than fentanyl? If so regulate one much more strictly than the other)

Incidentally that approach might well see tighter regulations on alcohol than several currently illegal drugs.

Smart, well adjusted drug people will frequently point out that most common drugs they use (LSD, MDMA, MDAA, psilocybin, etc) have an orders of magnitude better risk profile than smoking or drinking. The latter is essentially socially ubiquitous.

That community has an ongoing bitterness about this double standard.

Usually though, people making this point are not advocating for heroin or meth (although there's a reasonable argument there that the drug is not what does most of the damage in those situations - krokodil is just heroin manufactured with an extremely dirty process. It's perceived as being much worse, but what's "much worse" are the impurities from using gasoline as a solvent.

MDMA and LSD in particular have the advantage of no fast, cheap ways to synthesize at the expense of safety or purity.

I think the reality with LSD in particular is the normal way of making it is fast & cheap anyways. I'm sure you _could_ cut some corners. But why? We're talking about a drug used in microgram doses. Synthesis several kilograms and you have basically created an annual supply for an entire continent.
The majority of the population accepts the risk associated with alcohol. So touting risks of other drugs as if they where somehow greater than that already by most accepted risk feels dishonest.

Now you can say, well I don’t drink alcohol either, but that’s not the reality of most people.

There is another approach though. You can imbibe in any of these things and also acknowledge that they are probably a negative thing.

I'll have a drink occasionally, and (more rarely these days anyway) I'll occasionally have too many drinks. But I won't look at either of those as "well, I didnt do heroin, so that was a good choice".

I tend to look at it just as if I had eaten mcdonalds or taco bell or a tub of ice cream. It's something that I wouldn't do if I really wanted the best for myself (for some definition of best. Obviously everyone will have their own. Maybe your best is exploring your psyche, and damn whatever consequences may or may not come).

You don't need to justify it. Just recognize that you're probably trading off something else in your life for it, and in some cases that tradeoff may be sizable.

In any case, I think the comparative view isn't a great one. It implies that you have to have some kinda vice, and at least you kinda picked a lesser one. My own ideal would be to do very little of any of it, maybe even none. But if I miss that ideal, I don't have to rationalize it away.

LSD can mess you up big time even with a single intake in your life.
If you have a family history of psychosis, it can trigger schizophrenia or bipolar.

If you're not predisposed to psychosis, can it really do anything besides give you a bad trip? Bad trips are traumatizing and may take a while to work through, psychologically, but it's not permanent damage.

Personally, I had a very bad trip that led me to stop doing drugs and, ultimately, to a lot of very positive changes in my life.

The problem with advice like this is, how do you know you're not predisposed to psychosis if you haven't tried it yet? It needs to be more actionable.
Also "harm reduction" is patronising to users.

People use drugs for there benefits

Addiction is a symptom, generally, of alienation. To the addict the drug is helping. As the addicts loved ones that can be hard to belive, and demonstrably untrue. But still.

A much better paradigm is "benefit maximisation"

Ask ourselves what social policies will help maximize the benefits of drug use.

Leads to the same place with the harm, but without patronising users, and allows us as a society to explore the upsides of these drugs

"harm reduction" doesn't mean "good addiction" or even "risk reduction" . It means dying more slowly with less collateral damage. It means what the name says.
Unfortunately it doesn’t mean just one thing. People use a slogan like “harm reduction” to describe a wide array of beliefs and practices ranging from the very practical (don’t make sobriety a condition of care) to the very dogmatic (it’s not ok to discourage drug use of any kind, anyone who suggests otherwise is part of the problem). Most people will be somewhere in between those extremes. Once a slogan has been in use for some time, you can’t take the words at face value anymore. The mean whatever people use them for, not what they would mean in plain English.

As an aside this is true about language more generally. There is no true meaning of any given string of words. Language is a communication tool (and a lossy one at that). History of use gives words and phrases additional contextual meaning beyond any dictionary definition. Feedback is often necessary to avoid misunderstanding.

> this is true about language more generally. There is no true meaning of any given string of words. Language is a communication tool (and a lossy one at that). History of use gives words and phrases additional contextual meaning beyond any dictionary definition. Feedback is often necessary to avoid misunderstanding.

Very insightful. It would be great if we all were a bit more aware of this.

"accumulated tolerance and long term damage from drug abuse had blunted their response"

The succinct term for this phenomenon is "chasing the dragon".

First heard that term in the movie "Killing Zoe." Takes me back.
> an alarming trend of young people reading “harm reduction” material online and assuming they know the full picture of the risks of drug use

Is anyone attempting to harm-reductively try meth?

Yes.

The “harm reduction” websites are full of information about things like: Dose ranges for beginners, what effects to expect at different dose levels, routes of administration, and so on.

This information is targeted at beginners or drug curious people.

Methamphetamine has a bad rep, but taken orally in small quantities it is not much more dangerous than adderall, and has pretty much the same side effects. It can be legally prescribed for ADHD (brand name Desoxyn).
Meth is significantly different than regular amphetamine. Consider that simple changes in isomers can elicit radically different effects. A great example is levmetamfetamine (or l-meth), which is sold over the counter as a decongestant (as opposed to d-meth, the “fun” kind).

Now, if the difference between a “left-handed” and “right-handed” meth molecule can be so great, it shouldn’t come as a surprise that adding a methyl group to regular amphetamine will change its effects considerably.

This can be seen in the different receptor binding profiles (which receptors, where in the brain, and how strong or long the modulation is).

Meth’s increased addictive and neurotoxic effects are owed to this difference in receptor binding.

Probably not, but this is an artifact of the audience of "harm reduction" material. If there were things aimed at students and professionals who take prescription stimulants informing them that there's an alternative prescription stimulant that is comparably very highly reviewed by patients[0] for boring reasons like "it helps me live my life and has fewer annoying side effects" then that probably wouldn't be "harm reduction" material.

[0]: https://astralcodexten.substack.com/p/know-your-amphetamines

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The sad thing is many overdoses are due to people who quit, lose their tolerance, but take the same amount of their drug as when they were still actively using.
> The drugs may have changed slightly over the years, but the sad reality is that the real change was their accumulated tolerance and long term damage from drug abuse had blunted their response so much that they could barely feel the drugs any more.

This varies with the drug. MDMA is notorious for losing its "magic" after six or so trips. There's a special empathic, soul-opening quality to it - the kind of thing that makes it such a good candidate for treating PTSD. But after a few times, it becomes more like a regular psychedelic amphetamine.. fun, but not life-changing.

On the other hand, pure psychedelics don't really lose their magic. Tolerance develops, but goes away after a week. Psychedelics aren't associated with brain damage, while MDMA mildly is.

Then there's opioids, of course, which are ruinously addictive and fickle with tolerance.

When you're on the outside of the community, it's easy to lump "drugs" together and make generalizations. But every class of drug is different.

The champion of pointless addiction is tobacco
Nicotine is a very effective nootropic, better than almost all the well known ones, and it's also a remarkably good schizophrenia treatment. It gets a bad rap because of the delivery mechanism, but there's a reason people like smoking.
I don't have any personal experience with amphetamines, or any of the stimulants other than caffeine. But plenty of my passengers were struggling with substance addictions. I had a passenger who was whacked out on something. He disappeared real quick - I couldn't figure out how he got over that wall...

One of my passengers, whom I helped get off alcohol, said her downward spiral started with stimulants. Her husband had brought cocaine home from 'work' in California. He had emotional problems related to childhood. When cocaine got expensive they switched to meth amphetamine. She realized it was causing problems for her when she realized she'd been short with her youngest child.

At one point her other boy was prescribed Adderall (amphetamine) for ADD. That experiment only lasted for two weeks. She kept these Adderall pills on reserve, and used them to wean herself off the methamphetamine. That's when her anxiety started. After a few months of medical treatment, she found the 'anxiety' was perfectly relieved with alcohol. Whoops. [She ran back to the bottle every time she got a little stressed. I eventually encouraged her to use cannabis to mellow out: https://news.ycombinator.com/item?id=21889546 ]

Our dear leaders should come out of their ivory towers and figure out what actually happens on the streets. The War on Drugs has been ongoing for over a hundred years. People cycle in and out of jail/prison, but they don't get better from being mickeyed up (incarcerated).

From my perspective as a simple former taxi driver, the drug war is just a make-work program for public defenders: the bad chemicals get confiscated and the bad people get locked up, but people still have the same amount of unaddressed distress. People are usually worse off after getting corrected than they were before.

Two of my passengers informed me that cocaine is a much more pleasant drug than meth amphetamine. I don't have any reports about heroin vs. fentanyl. [Someone on twitter pointed out the drug cartels transitioned to Fentanyl when it became apparent that Afghanistan's heroin production was going to go offline.]

Bringing back cheap plant-based drugs (cocaine, heroin, etc) is an important step of harm reduction while society figures out how to effectively address the reasons behind our suffering.

Nixon declared the War on Drugs in 1971.

https://www.britannica.com/topic/war-on-drugs

Humanity has a long history of self-medicating distress. At first this was mostly with alcohol. America's prohibition efforts started in the early 1900's: prohibition, Harrison Narcotic Tax Act, etc.

https://en.wikipedia.org/wiki/Chasing_the_Scream#Background_...

https://en.wikipedia.org/wiki/War_on_drugs#20th_century

Is any regulation considered an act of 'war'?

I pay taxes, do you call that a War on Income? If so, when did it start?

Federal income taxes in the US started around the beginning of the 20th century.
Taxation is built right into the Constitution. Article I, Section 8, Clause 1 of the United States Constitution (the "Taxing and Spending Clause"), specifies Congress's power to impose "Taxes, Duties, Imposts and Excises".

No one ever called this a War on Income. My point is to the OP that claims the War on Drugs has been going on for a hundred years by pointing to any regulation of drugs. Lots of things are regulated and we do not generally call regulation a 'War on' something. It is okay to tone down the hyperbole.

The parent comment can hardly be credited with the phrase. When Nixon announced his new policies he called it a war on drugs. A catchy phrase that stuck. Far too late now to try to rename it for some sort of pedantic consistency.
Legislating morality is like casting pearls before swine, best to focus on helping those who want to live decent lives voluntarily. Part of that can be accomplished with designated methamphetamine or whatever dens where adults can get high and then sober up before being allowed into family neighborhoods. Without legal fears, it should be easier for addicts to get in touch with those who offer rehab services or harm reduction replacement therapies such as methadone. But mostly we want to enable parents who don't want their kids to be offered drugs keep it this way, and same for other deranged excesses of our days.
> But a human-designed synthetic process can always be human-redesigned. It happens constantly in the drug industry - the production of such a common drug as ibuprofen changed completely in the early 1990s, for example (a story for another time). For an illegal drug, that means that law enforcement will always be a step or two behind as new methods come on line. And it means that stopping the supply of such a drug will be difficult-to-impossible as well.

1) I wish he would have provided a link for the ibuprofen story.

2) With regards to the very last bit, You'll never stop the production. Ironically, "the war on drugs" has meant more and higher quality drugs.

What might be possible is mitigating the financial incentives.

It might also be a good time (read: long over due) to ask: why so many people have so much pain (i.e., physical or emotional) that they require a persistent altered state of mind (to defuse the pain)?

I'm not talking about prevention. I'm talking about a society / culture that is as good at generating customers for these substances as the producer are good at meeting those needs.

Loved the author’s writing style. He strikes a nearly perfect balance of casual and humorous with precise domain jargon.
Read his other pieces... he's been writing for 20 years now...

https://www.science.org/blogs/pipeline?AfterYear=2003&AfterM...

His 'Things I won't work with' posts are classics.

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

Whenever chemistry posts pop up on the front page, if they’re from science.org they’re probably by Derek Lowe and I know that I’m in for a great read, even if I understand nothing in the article.
The teaser line about ibuprofen synthesis is interesting because he didn't put enough "tease" into it for non-chemists to understand the kind of funny analogy. Superficially, one would not expect that a "green" synthesis would start with HF acid, but here it is anyway and it works. A "you gotta be kidding me" moment that makes sense after thinking about it.

I think that's the analogy he was trying to make in the article that only chemists would "get" about the innovation of chiral resolution, I have to admit the first time I read about that I was like "you gotta be kidding" but after thinking, it makes sense.

I'm trying to think of a similar "you gotta be kidding" in CS/IT, but its too early in the morning.

"Green synthesis" in chemistry should probably be renamed. "Closed-loop synthesis" is closer to what it's about. The fundamental concept is that you're not producing any waste products or unwanted side reactions, and all the reagents and catalysts are recycled back to their original state at the end of the reaction.

This typically involves synthetic routes that start with small molecules and build larger molecules from them in a specific manner (rather than say, cleaving a large molecule and then having to throw away part of it as waste). With something highly reactive like HF acid, it might mean generating the HF from a fluoride salt, using it in the reaction, then converting any leftover HF back to the salt at then end of the process.

I agree with you completely in a technical sense although greenwashing has become enough of a cultural icon that its hilarious to contemplate "watch me do something green" start with cracking open a container of HF, LOL.
That layout has more of an impact on perf than -O3 to -O1?
What if instead of all the money poured into law enforcement and prosecution we instead make treatment for addiction completely frictionless, effortless and guilt-less.

Like walking into a supermarket easy.

Of course progressives have been begging for that to happen with mental health in the USA for decades, so all this is a fantasy to try to help people in society.

We do not have the technology to make mental health care supermarket easy. Psychiatric drugs have NNTs in the dozens, terrible side effects, or both.

It's a fantasy because it has no chance of working even before you consider the enormous amount of resources it would require.

I strongly suspect the same about just letting people do copious amounts of legal drugs and then trying to fix addictions they develop.

Stepping in after the damage is done is usually both much more expensive and way less effective. Ounce of prevention and all that.

The ounce of prevention doesn't work. Prohibition has been a huge failure.
That might work if drugs were as easy to stop than start. Addiction treatment has a very low success rate with high relapse rate, and its incredibly expensive per user. The best treatment remains not starting in the first place.
Prohibition doesn't work at all at stopping people from starting in the first place. It has over a hundred years of failure.

Switzerland hugely reduced an endemic heroin problem in part by making it a health issue instead of a criminal issue.

And Portugal has shown a lot of success in decriminalization of most drugs.

Illegal drugs are perhaps the 2nd largest business globally, after petroleum. Prohibition is an abject failure at "not starting in the first place".

Yes. I was not claiming prohibition did anything.
So how do you suggest "not starting in the first place"? How would you implement that if not prohibition? Keeping in mind that the parent comment made a concrete suggestion on what could replace prohibition.

If prohibition didn't do anything then we should surely drop it. And then?

Well, policies that introduce a little bit of friction into the choice to do drugs would be a good start. Mostly, education that warns against the harms.

But, your comment seems to indicate you are more interested in legal ways you can use them than recognizing the lives that have been damaged.

Then you've completely misread my comments. Where did you get the idea that I'm interested in anything other than what actually works in reducing harm? Can you quote me?

Pumping money into education about the pros and cons of recreational drug use would likely do a lot to reduce abuse and addiction. However only talking about the harms was already tried and was a failure. Most kids will at least try alcohol or marijuana or vaping nicotine and if you've already lied by omission about the pros they won't trust you anymore. But if you can manage to educate in an unbiased and scientific way that would likely lead to fewer lives damaged. Worth a try at least.

Yes, more education that is honest about the effects, good and bad, would be the best approach. But that involves a cultural shift where celebrities, teachers and parents all recognize the dangers and preach/remind young people how bad it is. I was not saying you were more interested in doing drugs, but your language just seemed to weight users' interests equally with harm reduction. That is just my instinct though. Sorry, if I am mistaken.
> The best treatment remains not starting in the first place.

This is not shown. Many many people try drugs like speed, marijuana, cocaine and do not become addicted, many only do them a handful of times.

Absolutist policies are the ones that encourage draconian laws and responses because by the very nature of your statement, the first time is the worst time.

How about a recreational drug driver's license? It is how we respond to a situation that matters, not getting into the situation in the first place, esp when that situation is so easy to get into.

That does indeed seem to be working in Portugal.

One unpredicted side effect of making it a health issue instead of a criminal issue is that it's no longer so cool to young kids. Breaking the law is a bit of a rebellious thrill. Getting an addiction like Uncle Bob and having to visit the doctor a lot, not so cool.

Chirality is an interesting topic, and controlled chiral synthesis is pretty cutting-edge chemistry. The real masters of this art are biological enzymes, i.e. the proteins that catalyze all chemical reactions. A lot of the modern catalysts used in chiral synthesis are themselves chiral, which is essentially mimicing the biochemical approach.

For this to work, however, the starting molecule needs to be what called pro-chiral. For illustration, imagine a flat triangular sheet of paper with three different elements at the points. How could you only label one side of that sheet? Well, if you take a copy of that triangle and glue one side to a table, then there's only one orientation in which all three points of the other triangle will make a one-to-one correspondence. This corresponds to the enzyme (glued to the table) specifically binding the pro-chiral molecule (i.e. a carbon atom with three different substituents) and then the free surface of the triangle is where the reaction takes place.

I suppose someone could develop such a system for amphetamine synthesis and it would qualify as 'green chemistry' (which really just means producing the desired product without generating a waste stream via a closed-loop process), and this might even be how it's done in the legal pharmaceutical world today (methamphetamine is sold as Desoxyn for ADHD treatment). There are better things for chemists to put their time and energy towards, in my opinion.

As far as the legality and safety of drugs, it seems pretty clear that criminalization just fills prisons while generating large profits for organized crime cartels, with many associated problems (i.e. violent crime), while not reducing the population of drug addicts. A public health approach based on educating people about the very negative health and social effects of drug and alcohol addiction seems like the more reasonable approach. Bans on advertising and promotion of drugs might be wise as well, as has happened with tobacco and alcohol to some extent.

> ... Methamphetamine has a chiral center, so you can produce the pure (D) isomer, the pure (L), the exact 50/50 racemic mixture, or anything in between. (L) methamphetamine is a pretty good decongestant, but it is otherwise unenjoyable and has no market as a drug of abuse. The classic P2P reductive amination will of course give you the racemate; there’s nothing chiral about the synthesis at all. At the other end of the scale, reduction of pseudoephedrine starts with a pure chiral material, and you get only (D) methamphetamine as a product.

What he's talking about is molecular mirror images. Our bodies can tell the difference between the (L) and the (D) form. The former drains your sinuses and the latter gets you high.

This is a tangential plot point in Breaking Bad. In the episode "Boxcutter," Walter White asks: "If our reduction is not stereospecific, then how can our product be enantiomerically pure?"

There's a lot to unpack there, but it implies that Walt is isolating (D) methamphetamine exclusively. It also implies that this is occurring through a selective reductive procedure.

The first few seasons established that the synthesis relies on methylamine through a reductive procedure called P2P. But that procedure produces (D) and (L) forms in equal quantities.

What Walt is revealing in that one sentence is that he's developed a way to do the reductive amination step in the P2P cook such that just the (D) form is isolated. His use of the term "stereospecific," implies that the selectivity is close to 100% in the bond-forming step itself. The process therefore doesn't just produce highly pure product, but does so very efficiently.

At the time period of the show, such a reaction would have been very close to cutting edge research.

I'm sure they used real chemists to help with the screenplays, but it's more akin to Michael Crichton levels of sophistry.

I also recall reading that they had someone at the DEA to vet each episode to make sure they never gave out a workable recipe, but I can't find a source for that, that isn't SEO clickbait.

I don't know about where street drug trafficking were heading these last 8 years since I didn't met a real life drug dealer since 2014, I only heard from (ex)-drug users, social workers, ex-dealer, and of course, the press. That in northern europe...

The current thing on the rise here seems to be ketamine, according to a social workers.

There was in local news papers article about gangs shooting (and launching grenades?) at each other after confiscated cocaine shipment... And Stephen Colbert joked about Belgium asking for help to distroy cocaine seizure. I met people who did jail time for various substances trafficking. I met people who were in recovery for cocaine addiction. I even met with someone advocating for drug legalization... And I know for sure some ex-neihbours set up a phony business to launder years of pot trafficking benefices.

But I never met, heard or read or whatever or whoever having encountered methamphetamine in any way (or someone having met someone else having encoutered methamphetamine)...

And I live 30 minutes away in train from the closest dutch city. I also live in the city with the (reportedly) highest number of drug users (and dealers?) per capita in the country.

So I don't know what to think about d-tartric acid seizure in holland and belgium, and where the corresponding drug is sold, but methamphetamine is definitively not a thing here.

Meth is super common in Northern California, I live on the outskirts of silicon valley and the local paper's police blotter is always "meth, drunk, meth, drunk, stolen property from car".
Remember: without chemistry, life itself would be unprofitable.
Methamphetamine is a troubling drug. As difficult as vodka socially, and much easier to consume. As a example of "better living through chemistry" it is really a counter example. (I think that was the point)

But there are so many better examples:

* MDMA

LSD

Viagra

* Methylphenidate

MDMA in particular revolutionizes social interaction in the same way as alcohol, with fewer health consequences, albethey not zero.

For some people Methylphenidate is a wonderful brain tonic. (Ritalin)

Better living through chemistry is possible. Professional labs, quality control et etcetera are required, not prohibition and sketchy underground chemists

Really? You can't take a higher does of ritalin to get a similar abuser profile as meth at lower doses?
There's an amusing hyperlink ("drastically wrong") in his post -- the replies from the chemist who runs the blog at that link are hilarious.

I won't post it here because it goes to a page describing exactly how to cook meth, but it's amusing enough to be worth following the bread crumb left by Derek.

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> In fact, the quest to learn more about these [consciousness-altering] substances has been one of the things driving progress in organic chemistry over the centuries.

Wow, didn't know this.