The main thing about Phenylacetone meth is that there's so much of it
dynomight.net
dynomight.net
https://www.improbable.com/airchives/paperair/volume19/v19i3...
Author and journalist Sam Quinones talks about his book, The Least of Us, with EconTalk host Russ Roberts. Quinones focuses on the devastation caused by methamphetamine and fentanyl, the latest evolution of innovation in the supply of mind-altering drugs in the United States. The latest versions of meth, he argues, are more emotionally damaging than before and have played a central role in the expansion of the homeless in tent encampments in American cities. The conversation includes an exploration of the rising number of overdose deaths in the United States and what role community and other institutions might play in reducing the death toll.
https://www.econtalk.org/sam-quinones-on-meth-fentanyl-and-t...
https://www.theatlantic.com/magazine/archive/2021/11/the-new...
Once you establish the facility and pipeline, you can crank out industrial amounts of crank. The precursors are cheap and used in huge quantities by legitimate labs.
We could get our real cold symptom treatments back as true OTCs and stop wasting so much time chasing petty criminals.
It would also help identify drug addicts and get them help before problems become bad.
Of course, one might argue that it’s fine, because it’s the drug users themselves who would suffer from this. But, considering the current push to get people vaccinated against their will, for their own good, I don’t expect this argument to work for drugs either… who am I kidding, of course people should have a right to use as much drugs as they want, but should have no right to get a job if they are not vaccinated, it’s 2021 after all.
...Do you have sources on this? My awareness of Portugal's situation is basically the opposite of that, ascertained via [1][2][3] et al. I'm interested in dissenting information if it's available. I also wonder why it is that the assumption is "more drug use" == "bad" when the range of things that constitute 'drugs' is so wide - from alcohol to cannabis to lsd to cocaine, there's a ton of delta between the effects (sociological and personal) of use.
[1] https://transformdrugs.org/blog/drug-decriminalisation-in-po... [2] https://substanceabusepolicy.biomedcentral.com/articles/10.1... [3] https://www.cato.org/sites/cato.org/files/pubs/pdf/greenwald...
> In the first five years after drug policy reform, use of illegal drugs rose slightly among the general population but fell again in the following five years.
I remember looking at the actual figures, and what happened was that use of heroin in Portugal went down significantly, and use of all other drugs went up significantly, giving slight rise in total drug use on net.
> Use among 15-24 year olds fell throughout the decade,
This implies that use among other groups than 15-24 year old had not fell throughout the decade.
> and among the general population was lower in 2012 than in 2001.
The reason they pick year 2012 is because it's convenient to their argument, and they give out the game later:
> However, consumption trends in Portugal have been keenly disputed and often misrepresented. While drug use during individual lifetimes among the general population appeared to increase in the decade following reform, use within the past 12 months fell between 2001 and 2012. Both the World Health Organization and the United Nations Office on Drugs and Crime consider use in the past 12 months (recent drug use) or within the past month (current drug use) as better indicators of trends among the general population.18
> Since 2012, past-year use appears to have risen, particularly among those over the age of 25.20 This is, however, based on relatively limited data from SICAD (the Portuguese drug dependence agency) and only one further dataset — in 2016.
The lesson here is that there has been a lot of very dishonest reporting about the results of drug decriminalization in Portugal. You are just another victim of it. Omission of critical facts, cherry-picking groups and dates, and flip-flopping between different ways to measure as needed, are all very common techniques in crafting narratives, misleading people into believing falsehoods, without actually stating them outright, so that they can't easily be caught with blatant lying -- the blatant falsehoods then are repeated by people who were tricked into believing false narratives, which facilitates spreading it, while allowing the authors to wash their hands.
Of course, you don't need to trust some random guy on the internet who's too lazy to dig up relevant statistics, you can keep believing the non-profit industrial complex. You might spend some time looking up these figures yourself, but why bother, after all these non-profits would never lie to you, would they?
I'm not sure it's all that cut-and-dry. The story seems to be a general increase in the consumption statistics, but a decrease in criminal statistics. Maybe not a silver bullet for ending drug abuse, but a net benefit for Portugese society.
Alas, I don't live in Portugal... maybe someone who does can chime in?
>This implies that use among other groups than 15-24 year old had not fell throughout the decade.
Within the context of logic, that is not an implication.
If a pull quote or headline shows a good statistic for one cohort, it's a fair bet that other cohorts didn't show such a positive result, or else the touting would have been something like "overall" rather than "15–24".
Does the article have anything to say about general population?
> "While drug use during individual lifetimes among the general population appeared to increase in the decade following reform,"
Perhaps it was unchanged meaningfully / statistically significant enough to comment?
Like angry people, the vast majority of folks don't turn to violent crime, especially if other avenues exist. Society can provide this if necessary and we already have laws concerning violent crime that we can use.
I'll note that most of us pass addicted people every day when we leave the house. Most of them, you simply won't know they are addicted and if you are normal, you'll probably assume a person or two is addicted, yet they are not.
Yeah, people high on meth do crimes. But at least if the stuff is legal they won't do crimes to buy meth.
https://www.inverse.com/article/39899-recreational-weed-cali...
Basically the whole legal drug movement is targeted at non-addicts to let them pay a premium for a sanitary, legal, controlled experience. The political justifications for the movement are all about harm reduction. But the reality is that if you are an apothecary in SF, you don't really want junkies hanging out in your lobby, for the same reason that communities don't want junkies in their streets. Mental problems, theft, possible violence, behavioral issues -- it would chase away paying customers, and impose security and liability costs on them.
Those unwilling to pay for that more civilized experience go to the street. One important thing to remember is that legalization did not destroy the illegal market. They are different markets, although there is certainly overlap.
https://www.nytimes.com/2019/04/27/us/marijuana-california-l...
I agree there shouldn't be a blanket decriminalization of drug use because it does alter judgement/motivation and make a theft or even violent crime more likely.
I've personally had 3 full doses, and I can't be sure of my own protection. I'm on medicine that moderately suppresses my immune system, and it is likely that I am not protected.
And I'm one of the lucky ones: Some folks simply can't be vaccinated or simply won't get any protection.
And this isn't even getting into the fact that the folks not getting vaccinated means there are more chances for the virus to change in ways that make the vaccine worthless.
Me - and others - depend on everyone that can get vaccinated to, well, get the freaking vaccine. Not getting the vaccine is putting others at risk. And this is with vaccines working as designed.
Since around early Summer Delta has been the dominant variant, which is extremely more transmissible.
Even if vaccinated, Delta still retains effective transmutability, though (maybe?) to a reduced degree even for fully vaccinated individuals.
Since we still don't have sufficient tests to do blanket systematic tests of the entire population on a regular basis, it's extremely difficult to find asymptomatic cases. I've never been notified of an exposure, and have not had symptoms that I could attribute to COVID, thus haven't ever been tested during the entire pandemic.
For all I know, the vaccines could be effective and I might have had an asymptomatic case from someone who's not using WA notify (Washington state's notification app system) and would never know it.
I worry about the risk of spreading the disease to those who are not yet able to be vaccinated, which will soon thankfully include ages 5+ in the US; but that still doesn't allow for providing strong resistance and immune system training to the youngest children.
If vaccine works to protect people who are vaccinated, but does not significantly reduce transmissibility, why force it on people who don't care about being protected? Do they not have a right to make their own choices when it comes to their own bodies? If not, why do we want to give people right to choose taking drugs, given their highly detrimental effects on their bodies and on their lives, in addition to high risk of overdose and death? This all seems completely incoherent to me.
Take this to its logical conclusion, please. It's the big bang's fault!
Return to gravitational singularity, and all that.
I believe the former. People like taking drugs after all.
But what makes you think the latter is likely?
(Anecdotally, from what I can tell American teenagers seems more likely to bing drink hard spirits than German teenagers who can legally enjoy a pint at the local pub.)
Was that an intentional cultural mixup? My brain just stopped working after reading it, because of how little sense it made.
Pub is just the best English translation for 'Kneipe', and whether you drink a UK pint or half a litre of beer doesn't make too much of a difference.
When in Canada a doctor told me to buy some pseudoephedrine pills to treat a clotted ear and I found the experience so nice, that when back in Germany I walked into a pharmacy to get some.
The looks...
https://www.fda.gov/drugs/information-drug-class/legal-requi...
Behind the counter just means there is less chance of folks stealing it and more control over who buys it and the amounts they buy.
There is generally a good amount of things you can get at the pharmacy that are like this: Most of the time, they are simply ordered if someone wants them because there isn't enough demand to keep it on the shelf. Most require no ID either: Sweet almond oil (for ears) is the example I can think of.
Related: In some states, they require a prescription for it because their laws are stricter than the federal guidelines.
Problem: taking massive amounts of loperamide to get an opiate effect is a myth
Of course, the manufacturers were all happy to fall in line anyway and dramatically raise per-tablet prices (and packaging!)
Except one manufacturer.
Several years ago, I bought a 200-ct bottle for US$9 shipped to Canada. Now it's US$36.
In extremely large doses it has a distinctly weird feeling. I wouldn’t call it getting high, so I’d suppose that is indeed a myth, but gosh it feels hard on your heart at those doses.
Typically it’s addicts trying to avoid withdrawals (and who felt they did not have access to other opioid replacement therapies for various reasons) that tried that. Some died.
A decade or so ago I was reading a drug forum where an addict-chemist reported that acylating loperamide extracted from OTC pills allowed it to pass the blood brain barrier and deliver a true opiate high. His only reported test subject was himself, so I don't know if it was a genuine effect or not. And I haven't kept up with drug forums in recent years to see if this idea/technique spread. If so, it could explain the pill quantity restrictions; pseudoephedrine went through many years of changes in packaging/formulation as manufacturers tried to keep their products OTC while placating governments that didn't want those pills used as illicit drug precursors.
I ended up just buying it on Postmates, delivered, no ID check.
I was in Vegas some years back and got some under the laxer US rules, and have enjoyed a few years of having it available, but alas my supply has run dry.
Or know someone here who can ship some over to you?
They ID you in Oz, but it's fairly easy to get. Pharmacists know the PE stuff is junk!
I've also found Ritalin works as a decongestant too! (for which I have an ADHD prescription)
First time was in 2019: I went to Walmart for something for my ears on flights, after some back and forth the pharmacist recommended me pseudoephedrine.
Second time was in Sobeys last month (can fly again, yaaay) and I asked for it directly. The pharmacist had some trouble finding it, but sold it to me with no further issue.
Sudafed PE is phenylephrine. It is not a pain killer, and it does not have the same safety profile as acetaminophen (Paracetamol for some of you). Not saying either is actually unsafe, but the drug interactions will most definitely differ and you might find yourself suffering.
I totally agree that it doesn't work very well.
Sad thing is many products were reformulated with phenylephrine, an uncontrolled similarly structured molecule that's completely junk as a decongestant.
https://news.ycombinator.com/item?id=28938888
The theory is that new meth is based on a synthesis using a chemical called P2P rather than the old synthesis that used ephedrine. There are claims that this new form of meth is chemically different in some what that started creating schizophrenia around 2017.
However, when I looked into it, there doesn't seem to be much support for this idea. Current meth is more pure than ever before. Some people suggest that the use of lead could be responsible, but not all P2P syntheses use that, and it wasn't common in 2017. Instead, it seems like the explanation is just the obvious one: P2P synthesis has resulted in people doing much, much more meth than ever before.
You can start with two chemically identical intoxicants, and either by marketing or random path dependencies one gains a reputation in the subculture for making people go crazy. You can bet that large number of people are going to act wild on it.
This is no different than the reputation different types of alcohol have garnered. Gin makes people mean. Whisky makes people emotional. Tequila makes people party like crazy. It’s all ethanol, but those cultural preconceptions become self-fulfilling prophecies.
In many ways that makes these rumor filled, science light, unsubstantiated media stories about “this is the most dangerous drug ever” incredibly irresponsible. The stories themselves create the cultural preconditions around encouraging more self-destructive behavior among users. This isn’t even just drugs. Look at the moral panic over Four Loko. The same cocktail of ethanol and caffeine has been consumed as amaro and coffee by rich women since time immemorial. Yet it never caused moral panic until the “wrong type of people” started consuming it.
Like, a drunk person might misinterpret someone accidentally bumping into them as aggression. And would be less likely to suppress the urge to respond in kind.
For sure, alcohol reduces inhibitions. If you're a naturally chip-on-the-shoulder kind of person, alcohol will turn you into a certified jerk. Alcohol can turn other kinds of people into lovable fools as well though.
But I'd overall turn the 'cultural' aspect a little further even. I think I have observed a couple of times people to consume alcohol in order to be able to transgress cultural norms because the cultural norms themselves are 'parametrised' for the sober-drunk states.
I.e. get into a fight sober? Could be unacceptable even to someone who wants to get into a fight. After 4 beers? May be perfectly fine for your peer group. Same goes to other things, like dancing, approaching strangers, etc.
What I really found interesting for example is, in my abroad term in Canada. The sober Canadian society was overall friendly and polite, definitely friendlier than in my German home. People held up doors for me (a 20 something man, felt really weird and unexpected), you got compliments for what you wore (never happened to me in Germany), etc. pp. But this radically changed in the 'drunken space' where people were a lot more aggressive and fights were much more the norm.
So... the normal definition that everyone already uses?
I mean overall increased opportunity for violence. Less inhibition might mean I'm more likely to say "fuck off" to someone rather than just think it. Which could lead somewhere.
Granted, I’ve been diagnosed with various mental health disorders related to emotional regulation, so perhaps this is dependent on individual brain function.
Responding to perceived aggression with your own aggression is not a given. It's a culturally decided response, not an instinctive one.
A good christian is supposed to respond to aggression by "turning the other cheek" and not responding at all. A strict, honor based society might say the only way to respond to aggression is by killing that person.
Western culture falls in between these two. Reduced inhibition simply makes your judgement of the consequences worse so people usually make the choice they want to make (shaped by their culture) and just don't think though what it could mean.
I understand the sociological theories you are referring to, but I'm not sure how useful they are.
The same goes for strains of marijuana, beyond THC and CBD other psychoactive compounds are inconsistently present with uncertain psychoactive effects (if any). Further there may be complex nonlinear interactions (e.g. two compounds produce no effect but adding a third can change the experience, particularly if you consider reaction products from combustion).
In any case the uncertainty is good for marketing.
These are the theories mentioned in the article referenced in the comment you replied to. It might be the meth itself. Gin, whiskey, and tequila are different colors, and it's not because they are compositionally identical.
You’re not entirely wrong, but a splash of liqueur into a small cup of coffee is pretty different from dissolving caffeine pills in tall boys of malt liquor.
Malt liquor drink, 30mg caffeine. Tastes like Yoo-hoo.
What about krokodile?
Desomorphine is not any more inherently dangerous than other opioids (so, still quite dangerous of course).
The synthesis pathway that Krokodil producers used are quite bad and unrefined, but quite surprisingly do work and does appear to produce desomorphine.
The problem was the producers were usually addicts who then injected the reactions solvent mixture, rather than extracting their product.
https://www.bbc.co.uk/news/world-asia-58838834
https://www.nytimes.com/2019/02/12/world/asia/north-korea-cr...
Alcohol effects some subgroups (like Asians) differently so why not have more complex behaviors as genetic as well?
I used to believe that. It seemed obvious to me and a phd chemist friend of mine that - as you say - the different reputations were a cultural/social creation. The drink itself was just different amounts of ethanol.
Then one day that chemist friend of mine decided to get a bottle of Hornitos Reposado. We usually preferred a good bourbon or weird herbal stuff[1]. We drank most of the bottle, but that wasn't unusual for us at the time[2]. We were intending on a normal evening of video games. MTG, and/or VtES. Instead... we ended up spending the evening having the stupidest, most aggressive, pointless, childish, "macho" argument of our lives. It was shockingly out of character for us. The amount of ethanol consumption wasn't large, and we drank it at a normal rate. Both of us had been a LOT drunker in the past. The only significant difference was our unusual choice of tequila.
While I agree that the cultural preconceptions are probably responsible for most of the effect, there is at least some truth behind the reputations of different types of alcoholic beverages, because the actual drink isn't just ethanol. The different brewing/distilling/aging processes produce different amounts congeners[3][4]; their psychological effects might be small, but small effects amplified through social mechanisms are how "culture" is created.
> In many ways that makes these rumor filled, science light, unsubstantiated media stories about “this is the most dangerous drug ever” incredibly irresponsible.
Hear, hear!
> moral panic over Four Loko ... amaro and coffee
Yah, people have probably started putting whisky (Irish or otherwise) in their coffee the morning after they invented the whisky. Also, you probably have to drink the entire giant can of Four Loko to get the same caffeine in a typical cup of coffee.
> Yet it never caused moral panic until the “wrong type of people” started consuming it.
It's disturbing how often this kind of bs ends up just being a fancy form of racism/sexism/${targeted_group}ism
[1] e.g. Pernod, Herbsaint, Chartreuse
[2] Yes, we were regularly drinking WAY too much. 375ml/day/person minimum. WAY WAY WAY too much...
[3] https://en.wikipedia.org/wiki/Congener_%28beverages%29 "These substances include small amounts of chemicals such as methanol and other alcohols (known as fusel alcohols), acetone, acetaldehyde, esters, tannins, and aldehydes (e.g. furfural)."
[4] Also, the different amounts of sugars means different effects on bloodsugar/insulin/etc. The resulting effects are probably complicated and difficult to explain, but their contribution to the different reputations might be larger than we expect.
The infamous "meth mouth"? That's caused by not sleeping and by just overall letting one's life go to shit. Amphetamines do suppress saliva production, so they aren't great for teeth, but it's 95% the lack of sleep and other associated behavior patterns.
I've taken pharmaceutical adderall (which is 75% d-amp and 25% l-amp btw), and pharmaceutical dextroamphetamine (100% d-amp), and illicit, presumably cartel-sourced, and presumably very pure d-methamphetamine. When taken orally, d-meth is, in my opinion, simply a superior ADHD drug (it is much more dopaminergic than amphetamine, yet causes less peripheral stimulation, so you get a much more favorable ratio of positive cognitive effects to negative peripheral effects).
However, the moment someone starts taking (especially smoking, since the RoA of any drug makes a massive difference in addiction, doubly so for meth) hundreds of milligrams, it becomes a completely different drug. It becomes super deleterious to health through the sleep deprivation and risky behaviors alone. Furthermore meth has a unique property that amphetamine apparently doesn't, which is that it can become directly neurotoxic in large doses (meth has some serotonin release, like a much, much weaker form of MDMA, whereas amphetamine has virtually none, so it's possible that that's the mechanism). This is why in the research literature there's a lot about methamphetamine "neurotoxicity", but the papers conveniently omit that if taking oral doses comparable to what's given for ADHD, it's not neurotoxic whatsoever (and frankly may be neuroprotective, especially against traumatic brain injury).
So yeah, your analogy to Adderall is spot on. I've often seen people derisively refer to Adderall or other amphetamines by saying "we're basically giving kids meth!". Which is true in a sense, except it's really the other way around: meth is really not very different from Adderall. If someone were to smoke 100mg+ of amphetamine, their body would break down the same way it does in a meth user, except possibly for the direct neurotoxicity effect I mentioned.
Just adding on: Other key differentiator between recreational and therapeutic amphetamine usage is the pharmacokinetics: Vyvanse is the best in this regard - it’s actually an amphetamine prodrug that gets converted to amphetamine in the bloodstream over the course of ~2 hours, giving a very smooth release. Adderall achieves a similar end (to a lesser degree) by combining equal ratios of four different amphetamine salts with various absorption rates to smooth out the serum concentration curve. Dexedrine and Desoxyn I believe are both single salt compounds, and thus have a slightly higher risk of dependency due to their sharper peaks. Of course, other RoAs like smoking or injecting amphetamines recreationally take the effect to a whole new level with even sharper curves, dramatically raising the chances of addiction and negative side effects.
Vyvanse hits C_max around 3 to 3.5 hours. But you'll hit the maximum "acceleration" (as opposed to "velocity") around 1-2 hours like you said.
Fun fact: Vyvanse was basically designed to have more meth-like pharmacokinetics, since meth also takes about 3-3.5 hours to peak in the blood. Having done both lisdexamfetamine and d-methamphetamine orally, the C_max numbers in the literature are definitely correct because those numbers line up perfectly with when I subjectively peak.
> Adderall achieves a similar end (to a lesser degree) by combining equal ratios of four different amphetamine salts with various absorption rates to smooth out the serum concentration curve.
Yup, and I forget the exact mechanism but I have seen a paper arguing that the 75:25 ratio actually does improve the efficacy. Although I can't remember what the mechanism actually was...
> Dexedrine and Desoxyn I believe are both single salt compounds, and thus have a slightly higher risk of dependency due to their sharper peaks
Correct, both are 100% d-enantiomer, and both due have somewhat sharper peaks as a result. Although to elaborate AFAIK Vyvanse is really the only super unique one. Adderral does/should have a slightly smoother peak but largely the levoamphetamine seems to serve to up the norepinephrine-y effects (that is to say, the "I need to be doing something right now" effects, whereas dopamine is moreso the "once I start something I can keep doing it" effects).
Also methamphetamine in particular when taken orally is very vyvanse-like, as I mentioned above. So it's really exclusively with the fast RoAs like smoking or injecting it where you get the really crazy instant spike. (That last sentence is just from my general understanding, I've never taken meth in a non-oral RoA so I can't speak from experience)
It's like a more strict version of extended release (EX) and timed release formulations (there's a difference!).
Vyvanse is metabolized to d-amphetamine in your blood cells (the specific mechanism escapes me right now), unlike the regular non-prodrug versions which get "metabolized" first in your stomach and intestinal tract, and then your liver.
However, there is a set speed that vyvanse gets converted into free-circulating d-amphetamine, determined by how quickly (or slowly) your blood cells metabolize it. Unlike regular d-amphetamine, where the speed, and effect, can be "messed" with (or rather "tuned") on a variety of factors, such as:
0. Carbohydrate intake (regular, non-fructan and non-galactin, carbs get released into the bloodstream and trigger an insulin release response, which also happens to dull the effect of excitory neurotransmitters)
1. Stomach pH (acidicity == lesser effect, basicity == higher effect. E.g. drinking orange juice with d-amphetamine will lessen its effect, while taking tums will increase its effect, many times TOO much)
2. Certain liver enzyme inhibitors (mainly those in black pepper and grapefruit/pomegranate) will decrease the rate of amphetamine clearance, thereby intensify its effects
3. Caffeine (will potentiate amphetamine)
4. Personal physiology (not much you can do except play around with dosage and the aforementioned 4 factors)
Now, with the regular IR version, you can take more or less (1-5mg here and there) depending on your specific circumstances to get into the "right" spot where you're not overly or under stimulated, but just enough to be in that Goldilocks zone of flow.
However, with the ER version you lose the ability to get your "Goldilocks Dosage." You can still play around with the aforementioned factors, but this time you're restricted to a specific dosage now (say 5mg) and a specific dosage in some set amount of time later (say another 5mg, about 4-6 hours later).
Yet, with vyvanse you get even less of an ability to play around with the dosage. Take 60mg, and your body will slowly metabolize it to a set amount per hour, regardless of almost anything you can control. If that amount/hour rate doesn't coincide with your Goldilocks zone, you're shit out of luck -- and Vyvanse will not "work" for you.
There's so much more that goes into this, but I've frankly written way too much of an essay at this point.
On paper, each generic must pass some bio-equivalency test with the FDA. Most of the time all that means is "we at generic brand X ran our own experiments and concluded that we show similar blood concentrations of drug A, to Brand-Name Z." And then every professional involved in that supply chain writes it off as "basically the same," excluding all the little implementation/manufacturing details that go into each specific producer, much less factory (quality control is frankly disturbing in many of these plants).
You won't find a lot of practical information written within scientific literature, aside from basic chemistry/biology (the low-level details). Most of the time the researchers running these experiments have done less research and have less hands on experience than the people who have to use this medication on a daily basis. Many times reading the scientific literature is just a rabbit hole that leads to nowhere, except feeling like "you're on to something."
Apologies for the rant.
Certainly need to read some of the research literature and places like /r/DrugNerds (that community is super legit). The public health/doctor-y type websites are the worst for actually getting info since they never go into details and often give bad advice, so I’d stay away from the “traditional” resources if you’re trying to go deep
Any unwanted effects (insomnia if I take it too late, etc) are almost entirely due to the l-amp, but the slow release of Vyvanse made it essentially impossible to titrate and my options were either to take a dose so low it wasn't effective or deal with regular insomnia due to lingering amphetamine effects into the evening.
I guess ideally I'd have IR d-amp but I assume it's considered too "abusable" so it's rarely prescribed. Meanwhile, my whole goal is to get useful effects without taking enough to feel like I'm tweaked out or high.
In my experience, I've had to run the gamut on all the "other" ADHD drugs (ritalin, adderall, d-amphetamine ER, etc.) and then prove they weren't effective, for my insurance to finally approve it. I've heard of some people even going so far as to get prescription meth (desoxyn) because nothing else would work! Strange world.
I've stopped taking meds entirely. I don't know if it's because I'm getting old, and even a "low" dosage (5-10mg) makes me feel very uncomfortable, or if it's because I've used a lot of different slavic nootropics and neuro-regenerative peptides (e.g. semax/NASA, BPC-500, etc.), but I just do not have any tolerance for it anymore.
Fortunately, this loss of tolerance coincided with the ability for me to function very well on simple caffeine alone.
Do you have any more information about this? Can't find it on google - would be very interesting if its true but I'm a bit skeptical - I've never heard about blood cells being a primary site of drug metabolism.
A search turned up:
> "Lisdexamfetamine dimesylate is converted to dextoamphetamine and L- lysine, which is believed to occur by first-pass intestinal and/or hepatic metabolism."
(https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/02...)
According to this, sounds like its mostly intestines and liver, which is much more typical for drug metabolisms.
Here's the latest: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/02...
> 12.3 Pharmacokinetics
> Metabolism Lisdexamfetamine is converted to dextroamphetamine and l-lysine primarily in blood due to the hydrolytic activity of red blood cells after oral administration of lisdexamfetamine dimesylate. In vitro data demonstrated that red blood cells have a high capacity for metabolism of lisdexamfetamine; substantial hydrolysis occurred even at low hematocrit levels (33% of normal). Lisdexamfetamine is not metabolized by cytochrome P450 enzymes.
EDIT: A better one: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257105/
Basically, RBCs have lots of enzyme systems that serve (in part) to protect the important parts (e.g. haemoglobin) from oxidation. Put a bunch of lisdexamfetamine in the blood, and the RBCs will gradually hydrolyze it to cleave off the l-lysine and leave d-amph.
Combine that with also constricting the blood vessels of your gums, and you get a great mix of infection of dying tissue.
Whatever the pharmacological impact of meth usage on oral health, it's pretty clear to me that it's a much smaller factor than the general gone-to-hell life of a full time addict.
"Meth mouth" is mostly caused by neglect, not the biological effects of amphetamines. Long-term heroin & crack users suffer the same kind of severe tooth decay as meth addicts. If you smoke meth every day, but still somehow manage to brush & floss your teeth every day, your oral health won't be any worse than the average American.
https://www.cdc.gov/tobacco/campaign/tips/diseases/periodont...
I'm not 100% sold on it yet, but my city has always been "welcoming" to homeless folks and it has never been a huge problem. Now it looks like an actual zombie apocalypse out there in some parts, and there are periodically meth busts of hundreds of pounds in just random apartments, not even kingpin types.
Combined with the anecdotal evidence from social workers, there's a whole lot of smoke out there that the "new meth" theory might explain.
The random apartments are probably stash houses used for storage of bulk quantities that would be broken down and distributed to dealers.
I’m not sure I follow? I know drug fear-mongering is a favorite tactic of politicians but I’m not sure I understand what government contractors have to do with it. Are you alluding to private prisons? Or perhaps some other piggy-back industry that I’m unaware of?
Background: I'm prescribed 20mg/day of extended release Adderall, via a legitimate ADHD diagnosis. If we take the article's "meth is 2x as potent as Adderall" statement at face value, that would mean I'm taking 10mg equivalent of meth per day.
Now, since part of the reason I take this medication is to remember to take my medication (a joke, yes, but not without its kernel of truth!), I've accidentally double dosed myself before. I've also done the same previously when I was prescribed instant release Adderall. In either case, I've never experienced anything like a euphoric high, but I have experienced the kind of "uselessly driven"/tweaker sort of side of it. And, let me tell you, I do not like it when that happens. Although I'm in no hurry to find out, I honestly find it hard to imagine what the high must actually be like in order for people to voluntarily subject themselves to the negative effects of this drug. And, I don't even exceed the therapeutic range when this happens!
I wish there was some way to actually understand why people abuse meth without actually smoking meth myself, which I'm unwilling to do, for obvious reasons.
Your 20mg of XR addy is equivalent to 10mg IR and another 10mg taken roughly 4 hours after, but let's forget the XR part and just assume it's a 20 IR for convenience (it doesn't change the math anyway, just the pharmacokinetics).
20mg IR Adderall is 15mg dextroamphetamine and 5mg amphetamine. That's about 17mg dextroamphetamine equivalent. Given my estimate of d-meth being 30% more potent than amphetamine, you're taking an equivalent of about 13mg of d-methamphetamine a day.
> In either case, I've never experienced anything like a euphoric high, but I have experienced the kind of "uselessly driven"/tweaker sort of side of it. And, let me tell you, I do not like it when that happens.
See you're amphetamine tolerant. Give your 20mg dose to an amphetamine naive individual, and they will get the euphoria for the first couple days at least of taking it. The euphoria quickly fades, though.
You are correct that when you overdose and aren't stimulant naive, you often end up with mostly the downsides with little upside. There's not too much value in pushing the body past its "equilibrium" level of stimulation (in your case 20mg XR).
> Although I'm in no hurry to find out, I honestly find it hard to imagine what the high must actually be like in order for people to voluntarily subject themselves to the negative effects of this drug. And, I don't even exceed the therapeutic range when this happens!
> I wish there was some way to actually understand why people abuse meth without actually smoking meth myself, which I'm unwilling to do, for obvious reasons.
Have you ever done MDMA? That makes it easy if you have, because MDMA is like a way gnarlier version of methamphetamine: it's shorter lasting and releases WAY more serotonin while still being very dopaminergic. Methamphetamine, taken in oral doses enough to get you slightly tweaking but not at a crazy level, is kind of like 10% of the sensation of "rolling" (rolling means being quite high on mdma) while feeling like a smoother, less physically tweaky version of Vyvanse, which itself is a smoother, less physically tweaky version of adderall.
(For context, when comparing adderall to dexedrine to vyvanse, adderall is by far the tweakiest due to the l-amp. Personally, I'm a dextrorotatory supremacist so I won't touch the l enantiomer with a 10-foot pole)
If you've never done methylynedioxy-methamphetamine, and you clearly haven't done regular methamphetamine, you likely don't "know" what serotonin feels like, unfortunately. But the TLDR is methamphetamine is a smoother and somewhat more dopaminergic version of amphetamine, with the added bonus of some minor (significant when you're smoking it though) serotonin release as well, whereas amphetamine has almost no interaction with serotonin to the best of my knowledge.
I hadn't expected anyone would answer my comment, much less that anyone would provide a concrete reference point that was actually within my experience. I have used MDMA and experienced the high you're describing. For reference, I was high enough that I felt it certainly would not have been a good idea to try driving my car anywhere, but not so high that I felt taking my dog for a walk around the block would have been at all risky.
I found it pleasant, and wished it would last longer, but I don't think it's anything I'd go for if i were only 10% as intense and came with all the twitchy/tweaker effects. The jaw clenching I got from MDMA was more than enough of that.
But, as far as this:
> See you're amphetamine tolerant. Give your 20mg dose to an amphetamine naive individual, and they will get the euphoria for the first couple days at least of taking it. The euphoria quickly fades, though.
When I said "never," I meant "never." I didn't experience it the first time I took amphetamine, the second time, or this morning.
I have experienced some mild euphoria from prescribed dosages of opioids in the past, and, as I mentioned, I've experienced the high of MDMA, so, I think I have some sort of reference point here, although I'm sure they're very different highs.
Maybe it's because the starting dosages my doctors had me trying out initially were very small. Maybe it's because that initial dosage was 10-15 years ago, and I don't really remember it well (which would imply it wasn't very memorable). Or, maybe I did experience some euphoria, but just couldn't classify it as such because of my limited drug experience thus far.
In any case, as you said, I am not amphetamine-naive anymore and certainly don't get high off my medication at prescribed dosages, or even somewhat higher than prescribed dosages.
Again, thank you for helping me understand a bit of the appeal of smoking meth, without actually smoking meth. :-)
While we don't know the exact MoA of the jaw clenching, it's likely a form of excitoxicity, presumably a result of excess glutamate firing. This is why high-bioavailability magnesium, such as a chelated magnesium glycinate, helps a lot with the jaw clenching while rolling.
In other words, it's not the serotonin itself that causes the jaw clenching, AFAIK. The "10% of rolling" was me describing just the serotonin dimension of the mdma vs meth experience, not that it would be 10% of the rolly feeling with 100% of the clenching etc :P
> When I said "never," I meant "never." I didn't experience it the first time I took amphetamine, the second time, or this morning.
Very interesting! I definitely have experienced the euphoric high before, but only when starting prescription amphetamines. Yeah, it may have been that you started with a low enough dose, or just that your neurochemistry is pretty resistant to it.
The reason I mentioned the tolerance thing is because there's a common ADHD myth that if someone has ADHD that amps won't get them a euphoric high, and rather will just "calm them down". But in truth anyone can get the euphoria, and most of the "difference in how ADHD people respond to stims" is just an artifact of them having tolerance. It is of course true that ADHD medication can and often does make ADHD people feel more "calm" due to the greater cognitive control etc, but it's not necessarily true that they/we can't actually get "high" off it.
> Again, thank you for helping me understand a bit of the appeal of smoking meth, without actually smoking meth. :-)
Any time :P I've never smoked it myself but having taken it orally for years, as well as having vaporized DMT many a time, I think I have a pretty good imagination for what it would feel like :P
When it comes to studying this, you have to separate out:
* The high rates of drug abuse by people with mental illness.
* The correlation drug use with other sources of stress. Drug use may not be the source, but a result of the source. (But I think we can all agree drugs probably aren't happening matters.)
* Misdiagnosis of temporary drug-induced psychosis as a permanent, incurable mental health illness.
* Race, sex, age, and location, since this all affect the normal rates of schizophrenia for each population group.
OR:
* Show a significant increases in rates that can't be explained by the above. (If this rate tripled, it's pretty clear something bad is happening.)
Very few studies do this, because it is very difficult and there is little incentive to do high quality research.
1: I'm bipolar which is sometimes considered to be on the same spectrum
It doesn't seem to be common in the legal markets, and especially not at the kind of doses addicts would be exposed to.
From Wikipedia on Levomethamphetamine:
> In larger doses (more than 20 mg/day), it loses its specificity for MAO-B and also inhibits MAO-A, which increases serotonin and norepinephrine levels in the brain.
So there is a difference in response at higher doses. I would expect that addicts could be exposed to much more than 20mg/day, which begs the question of whether we even know what several hundred milligrams a day could do.
That's without getting into method of consumption. I'm not a chemist, but would we expect both isomers to break down under heat the same way? Or is the l-meth potentially being converted to something different than d-meth when smoked?
If the issue is the quantity, I would have expected schizophrenia to be constantly present. There's a fixed upper limit on how much people can do in a day, and overdoses have always existed, so there have always been people teetering on the edge. The amount heavy users use hasn't changed, there's just more heavy users and more users in general.
There doesn't seem to be debate that P2P processes create l-meth and d-meth, and that l-meth was less common in earlier versions.
I also don't think there's a debate that l-meth and d-meth have different effects. They're both used in prescription drugs, and those drugs are not interchangeable. You can't treat ADHD with l-meth, and you can't use d-meth in segiline.
None of that is conclusive. It could still be the quantity, or even something we haven't though of like an interaction between meth and fentanyl (which started its rise around 2015). I just don't think the evidence is so weak that we can discard the potential that l-meth is involved.
Methamphetamine is very, very stable. It stays as methamphetamine when it's vaporized, regardless of whether we're talking d-meth or l-meth.
> There doesn't seem to be debate that P2P processes create l-meth and d-meth, and that l-meth was less common in earlier versions.
Not quite. p2p done naively creates racemic meth, yes, but the modern methods, which have been used for years, purify that to enantiopure d-methamphetamine. They do this by bubbling d-tartaric acid through the racemic mixture, which separates the two enantiomers thus yielding the desired pure d-meth.
Furthermore, historically racemic meth was much more common. AFAIK the infamous "shake and bake" technique creates racemic meth. I do know that there is a pseudofed route that yields d-meth, but I think it's different than shake and bake. So don't quote me on this paragraph, but at a minimum we know that in the last several years, almost all meth seized in the US is highly pure/potent d-methamphetamine. There is less l-meth than ever.
> I just don't think the evidence is so weak that we can discard the potential that l-meth is involved.
On the contrary, the evidence is so weak that we literally can discard that l-meth is involved. First of all l-meth is better studied than you say. I would bet to approve the l-methamphetamine-based vics vapo inhaler they had to at least do animal models with large amounts of pure l-meth.
Second of all, and this is what blows the giant hole in your argument, there is no surge of l-meth. There is less l-meth than there has ever been in the history of methamphetamine.
Thirdly - this ties into the second point - you seem to thikn that getting racemic methamphetamine is something particular to the p2p method. It's not. As a general rule, synthesis of any compound yields the racemic version (if we're talking a compound with two enantiomers). This is definitely true for meth, where almost every method yields racemic meth. AFAIK there's a pseudoephedrine route that yields straight d-meth, but like I mentioned above the current state of the art is just to do a big p2p synth route and then separate out the d enantiomer specifically.
the shake and bake method uses "sudafed"/pseudoephedrine. therefore, it will produce d meth
> This is definitely true for meth, where almost every method yields racemic meth
not quite true, because the main precursor pseudoephedrine already had the correct stereochemistry in place. you would actually have to do effort to racemize that asymmetric carbon. But it is true that if your precursors are racemates or not asymmetric and you are not using some fancy asymmetric catalysis or tedious resoltuion your product will be racemic. An example of a racemic meth synthesis that does not involve P2P is direct amination of allylbenzene.
Do you know if these are well understood and tracked over time?
I think it's actually the opposite of impurities. The tech and supply chains have gotten so good, the purity had gone way up and the cost down, that people are just using way more of it.
You are off by 8+ years ... P2P made meth became mainstream after 2008 because that is when Ephedrine was banned in Mexico [1].
[1.]https://www.justice.gov/archive/ndic/pubs31/31379/meth.htm#:....
It used to be "meth" users would say..."At least I am not a dope junky using H." Heroin users would say... "At least I am not a tweaker." Now they are one in the same when I see them, which is generally cyanotic, apneic, and have been down for a while. We don't have enough Narcan to counter a bad batch of "M30" pills. Talk to your kids and tell them not to use any pills, not even once.
Education, not fear is what allows people to decide for themselves if they want to try/use something and it seems more likely that if/when they try these substances they'll at least be prepared for the consequences and be more likely to be responsible with their use.
Anecdotally I have many friends who were taught abstinence. Once they got into weed they realized just how much of a lie abstinence teaching was, they then graduated to trying other drugs, but not responsibly, because they had no idea how these other drugs worked. They had no idea what an OD might look like or what the risk of getting poor quality drugs might do. e.g. look at cocaine - how many people have any clue what that is cut with? I'd imagine almost every single one of my friends couldn't tell you what north american cocaine is predominantly cut with and they couldn't tell you what to do in the event of an OD, or what the exact symptoms of a cocaine OD even are! The lack of education is terrifying, really.
Not all abstinence is the same. Just because one is free to try anything, it doesn't mean people have to try everything.
Once they got into weed they realized just how much of a lie abstinence teaching was, they then graduated to trying other drugs
The problem isn't abstinence. The problem is the lie. Give people the proper, accurate information, and many will simply decide to abstain themselves. I think you and I would agree on this point about information.
The lack of education is terrifying, really.
That's ultimately the result of lies, deliberate obscurity, and attempts at thought control. It's far better to trust people with accurate information and let them decide for themselves.
I was growing up in a neighborhood where most part of people above 14 were using something. Most adults were using something heavy and awful, like heroin or desomorphine or whatever. I grew up watching them every day, and I grew up with insane fear of what chemicals do to human body and brain.
I am 35 today, I have never in my life tried anything, even a cigarette. For me fear works perfectly as a reason to stay away from drugs.
But to be fair, it is self-induced fear, from life lessons and not from school lessons.
I guess what I’m asking is, is taking meth + fentanyl marginally safer than taking just fentanyl? I know neither is safe. I’m just curious how the two interact and what you mean by counterbalance.
I’m also curious if, somewhat counter-intuitively, fentanyl addicts could be “treated“ with adderall to make their drug use safer? At the very least adderall has to be safer than street meth?
The entirety of my knowledge of street drugs came from D.A.R.E. and Breaking Bad so apologies if these are ridiculous questions.
Correct. M30's are opiates pressed to look like percocet - when from the street, typically fentanyl or another potent opioid.
Why wouldn't you only want to take one? Or do you usually only take the other, recreationally, when you get too stimulated or depressed?
Certainly not something to make a habit of, you’ll be dead in the long run (but I suppose no one gets out alive in this life anyway). Cheers.
I honestly can’t tell what’s worse, a speedball or using Alcohol to blackout after 18 hours of being on speed.
Oh I know what’s worse, Meth + Fentanyl. How the wicked live.
Because kids do what their parents say? I mean, it might be the cynic in me from the years of DARE lies, but I don't think this is enough. Most parents won't have an honest conversation about it: You know, talk about the effects and the good parts alongside the risks you take when you get it.
They won't drive you to safer things.
And an amount of them are going to try it nonetheless: An amount aren't going to be kids, either.
And this is the real reason I support full legalisation and controlled production - even of a lot of drugs that I wouldn't do. We can more reasonably assure there aren't bad batches of pills. We can more easily realize when folks are using regularly and offer (free) help. We can more easily try to sway folks to things that harm less. And we can research ways to do this more easily. It isn't perfect, but the war on drugs definitely isn't either.
Can you elaborate? I have no idea what this is about. I thought meth was smoked.
The pills they're referring to, 30 M (https://www.drugs.com/imprints/30-m-8232.html), are oxycodone pills (a powerful opioid), but he's likely actually specifically referring to pressed fent (or fent analogue) pills that are made to look like real oxycodone pills. Or perhaps a mixture of meth and fentanyl, such as what George Floyd was taking the day he died (see https://interactive.kare11.com/pdfs/Autopsy_2020-3700_Floyd.... as well as the other evidence around the case)
There's a big problem where, now that the government has really cracked down on so-called "pill mills" - which like all of the war on drugs was the worst thing they could have done, because now the demand is being filled by fentanyl and fentanyl analogues that are pressed to look like oxy pills, but aren't. Oxy alone can be dangerous, but fent is another beast (particularly illicit).
As one anecdote I just had a friend-of-a-friend (I didn't know them personally) die of an overdose earlier this year. They took "oxys" orally which were actually pure fent analogue, and now they're dead. They are yet another fatality of the war on drugs (and also the war on COVID since the lockdowns were the proximate cause of them picking up their opioid habit again)
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Oh, and to elaborate on the GP's point about overdoses being the result of running out of meth, methamphetamine increases respiration rate, which will theoretically counteract the respiratory depression induced by opioids (which are how opioids always kill, with the one exception that fent and related analogues can possibly kill by an addition mechanism of action known as wooden chest syndrome)
That sounds like a really, really bad idea. Wow.
Could this explain the falling prices described in the article? Fentanyl is the money maker. Meth is being priced to encourage more opioid use?
I’m approaching 40. (Ugh, I hate to admit that.) I grew up during the D.A.R.E. era. Just Say No. Cartoon All-Stars to the Rescue. “Drugs” were this boogeyman, and whatever they were, they would turn you into a junkie instantly.
I have no idea how you’d study this, as I think this was a pretty much cross-cultural message, but I wonder what would have happened if we could have educated teenagers that, well, “we know you’re going to do drugs, they all have side effects, but some are not that bad, and some will absolutely ruin you.”
Because: I have done a lot drugs in my 30s. Pretty much the full club drug buffet, with the exception of meth and opiates. (Also never smoked a cigarette yet.) And you know what? There are varying degrees of bad. There’s this jaded sense that you build up, that you’re a bit bitter that you wasted quite a lot of your childhood education in D.A.R.E. I wonder if we could have possibly successfully pulled off harm reduction education in drugs, and given people a better set of mental tools to understand what drugs are truly bad, namely meth and opiates, and which drugs are quite honestly far less deleterious than vodka. (You cannot tell me, with a straight face, that weed is physically and socially more harmful than drinking.)
I don't think it did this. I'm in my early 40's and grew up with DARE. When we were younger, they really leaned into the danger factor and pretty much said you'll hurt everyone you know.
And then, you realize they are liars. I didn't have to actually do drugs to see that. Why would you learn that is a moral failure from lies? I didn't even worry about those sorts of things when I was a preteen/young teen, honestly.
That's like saying "I did a lot of drugs, except the ones that _really_ fuck you up". 100K people will die in the US this year from hard drug overdoses. 93K died last year. This also ignores the fact that several times the number are circling down the societal shitter due to their addiction.
That's not to disagree that e.g. MJ is less dangerous than alcohol when consumed in moderation (although it doesn't have the same effect, so realistically people will just consume both, hopefully not simultaneously).
But don't forget the audience: there's a number of folks on this site who think that heroin and meth should be legal, and freely available, and they will read your comment with that bias in mind. I'd much rather have the old DARE bullshit than allow this to happen.
Why? Do you think somehow things would be worse with legal, controlled drugs?
Meth is already legal, in actuality. It's just controlled in production and distribution and only available by prescription. There are millions in America taking legal meth right now.
Can’t fool serious drug users, takes one to know one.
> He suggests that new meth might be chemically different in a way that caused people to go crazy, starting around 2017
2017 is not a significant year, it's just the year of one of his anecdotes. A small town in West Virginia didn't have a meth problem and then in 2017 it had a meth problem and a mental health problem.
"Southwest Virginia hadn’t seen much meth for almost a decade when suddenly, in about 2017, “we started to see people go into the state mental-hospital system who were just grossly psychotic” [1]
He has other anecdotes from much earlier. "Susan Partovi has been a physician for homeless people in Los Angeles since 2003. She noticed increasing mental illness—schizophrenia, bipolar disorder—at her clinics around the city starting in about 2012" [1]
[1] https://www.theatlantic.com/magazine/archive/2021/11/the-new...In 2016 the Centers for Medicare and Medicaid finally started to crack down with their investigations and enforcement and issued compliance guidance and toolkits to help states fully implement the required coverage.
Is it possible the upticks don’t represent a new group of addicts so much as they represent a new group of people who are eligible for affordable treatment? It doesn’t seem terribly far-fetched to me that CA would have implemented the required coverage in their Medicare & Medicaid plans fairly quickly while West Virginia’s plans would have waited as long as possible to comply.
> only $1k per pound now.
Wow that's crazy. An equivalent quantity of generic adderall would cost ~$20k. Meth is effectively at commodity-level prices, if true - the drug war premium seems gone.
I'm skeptical about overdose rates being attributed to meth. Meth is fairly hard to OD on - it'll ruin your life and brain, but rarely kills acutely. I suspect meth being used as an adulterant mixed with other drugs (esp opioids), or novel non-meth psychostimulants, play a significant role in the increase of psychostimulant ODs by ~9x over the last 10 years.
I think a lot of this data is getting mixed up with the (at the time quasi-legal) pyrovalerones and cathinones that were widely available through the clearnet over the past 5 years. Those have much greater acute risks and were highly accessible to people without drug connections.
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However, I'm skeptical of the initial premise of the article:
> Ephedrine meth was like a party drug. […] You could normally kind of more or less hang onto your life. You had a house, you had a job. […] P2P meth was nothing like that. It was a very sinister drug.
Tweakers have been around for decades, I suspect this is just misleading anecdata.
Steve Mould has a great video [1] on homochirality in nature and says, "Why are all the sugar molecules that you buy from the shops right-handed? ... If you were to make some sugar for yourself in a chemistry lab by mixing some chemicals together, you would get a 50/50 mix of left-handed sugar and right-handed sugar." He goes on to describe how enzymes in nature exclusively make homochiral molecules, and since all our sugar is made by enzymes, all our sugar is homochiral.
Later in the video he describes how you can filter enantiomers by finding an enzyme in nature that 'eats' the undesired enantiomer, finding the DNA for it, and coercing bacteria into producing that enzyme. This seems quite complicated and potentially out of reach for a clandestine drug-making operation. Is there another way?
It is possible to do asymmetric reductive amination using enzymes but this is out of the scope of clandestine producers. Likewise a chemical and not enzymatic asymmetric reductive amination would be easy in a bench lab, probably to expensive and impractical in a clandestine setting.
[0] Joseph S. Bozenko, "Clandestine Enantiomeric Enrichment of d–Methamphetamine via Tartaric Acid Resolution", JCLIC, 2008, vol.3 (not publicly accessible but you can find this if you know where to look)
I will back the Tartaric Acid hypothesis. If it's being done, this is the only way it makes sense. It requires nearly nothing but the D-Tartaric Acid and Ethanol/Methanol + basic glassware.
Disclaimer: Am not a chemist.
Phenylacetone synthesis yields racemic methamphetamine.
You can actually use a laptop screen, and polarized sunglass lenses to check the optical rotation at home, cheap polarimeter.
As far as purifying enantiomer with amphetamine and methamphetamine goes:
It can be done relatively easily with just D-tartaric Acid.
Look up "Procedures for the Resolution of Racemic Amphetamines"
https://erowid.org/archive/rhodium/chemistry/amphetamine.res...
I do not believe this practice is in use in illicit drug manufacture. There's no economic incentive and it requires some braincells.
From "Selective Crystallization of Methamphetamine with d-Tartaric Acid:"
Phenylisopropylmethylamine was resolved by treatment with 0.4-6 moles of dextro tartaric acid in water or aqueous ethanol containing 0.4-6 moles hydrogen chloride.
A mixture of phenylisopropylmethylamine 150, d-tartaric acid 82.5, and H2O 330 g was treated with HCl to pH 4 to deposit 120 g L-phenylisopropylmethylamine-d-tartrate salt, which gave 88 g L-phenylisopropylmethylamine. The D-enantiomer (58 g as the HCl salt) was isolated from the filtrate.If you're curious, read up on some of the synthesis methods for P2P. Chemists are continually honing their craft to provide superior purity and price:
https://erowid.org/archive/rhodium/chemistry/phenylacetone.h...
Aside from the often amateurish reduction of (pseudo)ephedrine to methamphetamine, the most popular precursor to amphetamine and methamphetamine is phenyl-2-propanone (also called P2P, BMK, Benzyl Methyl Ketone or Phenylacetone). There is an astounding array of synthetic routes to this compound, both due to the relative simple structure of the compound, and also because of its popularity. [...] Here is a collection of some of the possible methods of synthesizing phenyl-2-propanone, ranging from simple one-step methods to elaborate multi-step variants, and from the very easy to the very complicated. Welcome to the world of P2P.
Once you've got P2P, the end product isn't too far behind:
https://www.erowid.org/archive/rhodium/chemistry/p2p-meth.ht...
Also, a nitpick: the author refers to the condensation product of benzaldehyde and nitroethane, which is phenyl-2-nitropropene, abbreviated P2NP, incorrectly. He calls it "nitrostyrene (NTS)", which is the one-carbon-shorter homolog.
The other thing to keep in mind is that higher production volumes mean longer supply chains, and with illegal drugs longer supply chains mean more cuts (usually sugars, rarely toxic per se), and more cuts means an increased variance in the potency of the retail product, and variance in potency leads to users accidentally taking more than they intended to. The toxic effects of most drugs have a supralinear dose-response relationship, so these unexpectedly high doses can lead to problems that don't "average out". Often we over-focus on toxic fillers, but forget the risks created even by nontoxic fillers.
Can you give a bit more detail about what's wrong here, and how it might be fixed? Are all mentions to nitrostyrene/NTS incorrect? This is used repeatedly in the cited papers, so I'm confused if they are also wrong, or the post has mangled usage, or what.
I also recall the show depicting meth users having all those problems - Jesse is paranoid the missionaries are bikers, there's that guy digging a hole in his front yard, Spooe and his head, etc
Seems like the drug was fucking people up way prior to the last few years in fiction.
> Seems like the drug was fucking people up way prior to the last few years in fiction.
Meth has always, always, always been known to cause those behaviors/effects since it first became widespread. Breaking bad shows those behaviors because they're classic tweaker behaviors. The scene where Jesse distracts the guy by digging is super spot on. Brilliant scene.
So yep, the paranoia, hallucinations etc have nothing to do with "new meth", they're just what happens when someone abuses sufficient amounts of meth. And the more potent the meth, the easier it is to get to that threshold. But note that you still need to be smoking or injecting quite a bit. The people exhibiting psychosis and the like are using hundreds of milligrams per session.
Then imagine my surprise when I open the article and it literally covers every one of those points, section by section. Brilliant.
I guess the only minor thing I'd add is that the way the cartels (and others) are getting pure d-meth is by bubbling through d-tartaric acid or the like at the end of the process, which separates the racemic meth into its l and d enantiomers respectively.
I'm glad this article debunked the fallacious "new meth" article that cropped up here the other day.
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EDIT:
Oh and one more thing. There's a common myth among tweakers about "n-iso", which is structurally very similar to methamphetamine - similar enough that it will join the crystal lattice - but it is at best inert, but might actually cause undesirable side effects. The fact that n-iso exists is real, but if you look online you'll see tons of tweakers convinced that they've been smoking n-iso and that it's why they smoke meth and just get a headache and other bad physical side effects but don't get the stimulation or the pleasurable rush. What's actually happening is that they've spiked their tolerance so high that they're getting almost exclusively the bad effects. It's analogous to how if someone takes MDMA for 4 days straight, by the end of it they're not going to "roll" at all because they've acutely downregulated their serotonin (and dopamine) receptors, and furthermore that they've literally (almost) exhausted their current pool of neurotransmitters, which need to be re-synthesized by the body.
When looking at the DEA seizure data it's clear that meth is one of the most pure and potent (wrt methamphetamine, the dea defines purity as what % of the compound is meth, meaning either levo or dextro methamphetamine, whereas potency only factors in the d-meth content, since d-meth is the enantiomer that actually gets you cerebrally high) street drugs out there. By comparison, cocaine is one of the most disgusting, cut at the source level with stuff like levamisole (which is thought to be disastrous to health, ie it's not just inert), and then further cut every step down the chain, albeit usually with inert cuts (baby powder, baking soda, glucose, creatine, that kinda stuff) the lower down the chain you get. Seriously kids, don't do cocaine. It's overhyped and a waste of money.
So anyway, as I said two paragraphs above, n-iso is real but the idea that there's tons of n-iso crystal floating around is just an urban legend promulgated by tweakers who spiked their tolerance the moon and refuse to see that fact.
What does this mean?
In general when taking amphetamines for ADHD-type symptoms, you want to maximize the cerebral stimulation while minimizing the peripheral stimulation, because the latter causes [most of] the unpleasant side effects like inability to eat/sleep. Note that some degree of peripheral stimulation is unavoidable regardless of whether one is taking pure d-methamphetamine or not, and also probably some amount of peripheral stimulation is desirable because ADHD is not just difficulty in maintaining focus/attention but also getting the kick in the ass to start tasks in the first place. But in my experience relying on the peripheral stimulation (which, for example, Adderall produces more of than Vyvanse) simply doesn't work long-term, and just makes appetite regulation and the like get totally out of whack.
As this article shows, there's any number of ways of making MA but separating out it's racemic mixtures has always been considered hard for backyard-ers.
If this is now commonplace then it does seem to represent a somewhat of a seismic shift in the illicit drugs business model.
The overwhelming majority of US meth is cartel-sourced. They have massive superlabs and then transport kilos upon kilos across the border. That's how they have the sophistication to synthesize their own p2p, separate out the enantiomer, etc.
It's the inevitable result of the war on drugs. You make it near impossible to be a small time cook - due to the difficulty in acquiring precursors, acquiring space to work in where you won't get asked questions, etc - and soon the whole market is ran by mega cartels that operate as de-facto states.
Downregulation is a natural homeostatic mechanism that happens with almost everything. Any time a certain receptor gets stimulated above baseline, over the long-term it's going to get downregulated. The actual neurobiology of how this works is enormously complicated and beyond my (and probably almost anyone's) understanding. I do recall that NMDA receptors have a critical role to play, given that NMDA receptor antagonists can attenuate some (presumably not all) of the down or up regulation
"P2P is old school," he said. "Hell, I used to cook by that route circa 1980."
The fight has come full circle. In the 1980s, the U.S. government severely restricted access to P2P seeking to curtail methamphetamine production. Meth makers shifted to ephedrine, which could be found in common cold remedies. When authorities cracked down on ephedrine, they switched to pseudoephedrine, the active ingredient in Sudafed and other decongestants." https://www.cleveland.com/world/2009/12/old_school_meth_meth...
https://wikileaks.org/gifiles/attach/130/130179_Secrets_of_M...
That said, I suppose in reality it's just a more in-your-face presentation of what's already in many organic chemistry textbook in any number of libraries.
Frankly, I reckon there's little that can be done to stop the illicit manufacture of these drugs for the logical reason that they're such simple molecules. Many are just minor variations on the basic d-enantiomer (dexamphetamine) which essentially is only a benzene ring with a single branch containing a CH3 methyl and a NH2 amine group. So it stands to reason that there are many comparatively simple ways to synthesize them and that more are likely to be found. Moreover, the more precursors there are, the harder it becomes to ban them all, as eventually we'll hit the point where certain precursors are too ubiquitous and or important to ban.
It seems to me that if we're to take harm minimization seriously then we need to take a more sophisticated approach. For staters, we need much more efficient public health measures to detect and separate out genuine self-medicatiors from the partygoers who take illicit drugs.
As we know, these sympathomimetic amines have been prescribed by the medical profession for decades for certain depressive illnesses, ADHD, etc., but because of their their potential for abuse - not to mention certain moralistic attitudes among many politicians - these drugs have a horrible stigma attached to them and that has stopped many undiagnosed people from being prescribed them legally. The consequence is that many of them self-medicate with illegal drugs and the outcomes are often dire.
I think that taking a serious approach to medicalizing the problem would help very significantly. This would also include distinguishing the amines from the opiates. Whilst the medical profession understands fundamental difference between these two classes of drugs, public policy often doesn't and the drug problem ends up as an amorphous mess that becomes even harder to sort out than it otherwise would have been.
Therefore, there needs to be a more nuanced and sophisticated understanding amongst the general community to the effect that someone who turns to illicit amines is likely doing so for fundamentally different reasons to another who has turned to opiates. A more sophisticated approach to the drug problem would lead to better outcomes for not only those addicted to drugs but also for society in general.
Despite its controversial title, the book is pretty boring unless you’re actually following/putting into action his various ‘recipes’. I suppose having read certain information therein that concerns me I’m obliged to say something about it if it might save someone from coming to harm.
Anyone who’s read various other posts of mine would know that I neither hold conservative establishment views nor am I an anarchist—except in the sense that I believe democracy needs urgent reform but not through violence. Thus, essentially, I’m against censorship, and usually it’s not my style to criticize anyone who puts an alternative view. So why am I acting as if I want to censor parts of Priesler’s book? It’s simply because some of the actions he advises are outright irresponsible.
First, my position is that [as stated] it doesn’t make sense to try to censor any of the chemical processes for any of the sympathomimetic amines whether they be legal-OTC, legal-on script or illegal, but it’s my opinion that they should be confined to a chemistry text or an adjunct to one—one which describes the chemistry at a commensurate level to the actual processes involved and that appropriate chemical nomenclature is used to do so.
Priesler’s cookbook approach is irresponsible for these reasons:
1. Whilst he states in very fine print on the ISBN/copyright page “Neither the author nor the publisher intends for any of the information in this book to be used for criminal purposes...”, as an attempt to cover himself legally, he does not emphatically state that the drug manufacturing processes he describes are covered by international treaty—in that the production of such drugs and possession of many of their precursors are illegal in almost every jurisdiction worldwide—that is, unless one is in some way ‘licensed’ to possess or manufacture them. Yes, those tempted to undertake such manufacture will almost certainly know this already, but the exact ramifications ought to spelt out in considerably more detail. More about this in a moment.
2. Priesler’s cookbook approach means that he’s written the text down to a level where he expects those who’ve either no theoretical or practical knowledge of chemistry or who have only novice-level chemistry skills to undertake what is essentially sophisticated chemical engineering/synthesis. In a practical sense, there’s much here that can go wrong for both the manufacturer and the drug consumer. Normally, such manufacturing processes would be undertaken by experienced chemists in a pharmaceutical company or research institutes, etc. where much of chemical engineering involved is specifically aimed at QA—ensuring that the manufacturing process proceeds safely and that the end product complies with proper purity and quantitative tolerances/standards, etc. Backyard manufacturing is usually not conducive to high standards or being highly consistent.
3. Despite Priesler’s warning that the "book is sold for informational purposes only, etc." it’s very difficult to conclude that he actually means it, for if he had done so, then he’d have written up the information in the manner that I've suggested above. Clearly, Priesler is deliberately goading authority to provoke a response and all indications are that he’s been very successful in doing so, especially given that he’s suggesting that chemistry neophytes take up the dangerous challenge.
4. One doesn’t have to look any further than Chapter One—Chemicals and Equipment to illustrate the issues. First, anyone experienced in organic synthesis of this caliber doesn’t need lessons in how to handle their glassware (thus my assertion he’s deliberately pitching at neophytes); second, the purchasing of almost any quantity of just about every one of the 32 precursor chemicals listed on pages 6 and 7 will draw the attention of the powers that be; and so will most of the Listed Essential Chemicals on page 7.
5. Moreover, the quantities of chemicals that Priesler is suggesting that one obtains are quite staggering. For example, under Imports and Exports we find 500 gal or 1 ,500 kg of acetone; 500 gal or 1 ,364 kg of ethyl ether; 500 kg of potassium permanganate; 500 gal or 1 ,591 kg of toluene just to mention a few of the more dangerous ones.
I understand his logic by suggesting that one’s likely to be less ‘exposed’ if one makes one large batch instead of lots of little ones but my mind simply boggles beyond belief that any neophyte drugmaker/chemist would be handling the mentioned quantities of those dangerous chemicals in ‘backyard’, less-than-ideal conditions—as three of those I’ve mentioned are highly volatile and their vapors dangerously explosive. Playing with such quantities in suboptimal conditions is living dangerously in the extreme not to mention that by purchasing such huge quantities one would be waving red flags to the world.
Any reasonable person would never recommend such a risky and dangerous undertaking.
How is meth "industrially" produced? Is it Walter White-esque clandestine factories? Is it clever people in their garages? Is it done over the border?
> The chemist, a burly man with a master’s degree in biochemical engineering described the industry’s transformation, as the pair worked at an outside table.
https://www.theguardian.com/world/2020/dec/08/mexico-cartel-...
Where it's made is one matter but I'd imagine its only significant precursor would be ergotamine tartrate (a la Hoffman), as ergotamine is a commonly available drug for migraine (although somewhat less so than some years back, as it's been largely superceded by sumatriptan).
The next alternative I'd imagine would be to get 'raw' ergot and process it: https://en.m.wikipedia.org/wiki/Ergot although I'd guess that gathering and refining the fungus would be no mean feat for any backyard manufacturer.
It's hard to imagine there being any other major human-manufactured precursor due to the complexity of the molecule. Moreover, refined ergotamine for medical use is a mixture of various ergot alkaloids. Presumably, this would complicate the synthesis but I've never bothered to think about how it would or to what extent.
It turns out there are more than a couple LSD labs, some having a bigger internet presence than others.
Suppliers will not sell directly to random people, but as it turns out their approved resellers are happy to offer spoonfuls of LSD in powder form to anyone who asks!
https://imgur.com/a/r2FkJOD (not my picture)
I've never produced it and as you'd be aware it'd be stupid of me to offer advice based on chemical knowledge as it's manufacture is illegal - despite the fact that the various methods are widely known.
From time to time, I've seen busts of clandestine labs on TV and it's easily doable in a garage or shed. Seems the smell of volatiles often gives them away (e.g.: propan-2-one or similar reagents), or they catch fire (seeming a common occurrence) which burns the place down thus attracts attention.
As an expert, you'd know that a racemic mixture results. As backyard-ers don't have the means to separate the enantiomers, law enforcement uses the fact to determine whether stuff they've collected originated in a backyard lab of from a pharmaceutical complex. Nevertheless, I gather from the article that's narrowed. It seems, that when one's made enough money manufacturing gets reasonably sophisticated.
https://www.theatlantic.com/magazine/archive/2021/11/the-new...
P.S.: If you live in the US, then it's readily available from Canada.
In my opinion, this is a plausible hypothesis.
1.) Even in cases of extreme poverty, people will put in significant effort and sacrifice to secure some degree of privacy, because it's a basic human desire (a desire I've seen in nearly every person I've ever met.)
2.) ULTRA-METH PSYCHOSIS
I'm strongly inclined to favor 1 over 2 until I see some very, very compelling evidence otherwise.
It doesn't make sense to 'outsource' production of narcotics to antagonistic nations or criminal enterprises.
https://www.reddit.com/r/askscience/comments/94rk1a/how_is_m...
No, it's not. Please stop spreading this age-old myth*. You can literally buy prescription meth in a bottle, and it's called Desoxyn.
Adderall is extremely similar, because amphetamine is quite similar to meth (just an inferior version IME). D-meth is probably 20-30% more potent than d-amp dose for dose, but with somewhat reduced unwanted peripheral (body) side effects. The other main differences are meth releases some serotonin (not nearly as much as MDMA) while amp releases almost none, and that for whatever reason methamphetamine takes 3-3.5 hours to reach peak blood concentration when taken orally, whereas amphetamine peaks much sooner.
* I get it, the point isn't literally that it's meth, just that it's similar. But it's silly thing to say rhetorically when you can literally get prescription d-methamphetamine in the US under the brand name Desoxyn.
In any case, high dosage of Adderral (or consistent use) has very similar effects to Meth use (obviously not methhead no-teeth level stuff, but definitely euphoria, delusions of grandeur, paranoia, insomnia, drastic appetite suppression, irritability). Psychosis can also occur on Adderral.
A nicer version of Adderral without all the anti-abuse stuff is Dexedrine, you get a more pure amphetamine and is generally smoother since it doesn’t have the Levoamphetamine that creates the characteristic ‘lethargic’ feeling after the initially speedy-rush.
The funny thing about all of this is that it’s legal, and I shit you not, me and my doctor would speak about finding ‘smoother’ meds (imagine two crackheads discussing what would be a nicer high), all totally legal and not frowned upon.
One hell of a PR job by team ‘legal speed’ :) Glad I’m off that shit because I really did feel and act like a Meth-head by the end of it.
I know, comparing uppers and downers, not the same effects, etc.
Definitely cognitive tasks would be considered more impaired by weed than beer, at "roughly equivalent to a pint" level. Likely neither would be a big deal.
Weed is neither upper, nor downer really, it an hallucinogen.
That means less ordered thinking. Quite possibly an increase in creativity and lateral concept matching (say, making or appreciating witty comments) but also an impairment to short term memory and direct logical reasoning.
For motor skills and reaction times, beer definitely hits harder.
FWIW, here's my definition of a "hard" drug: https://news.ycombinator.com/item?id=29028924
They've been devastating for good reason, which is that with oxycodone the long proven, well established administration and monitoring protocols for narcotic opioids were not observed.
Essentially, every narcotic opioid ever discovered or used has addictive properties and thus they all have the potential to addict users. Opiate addition takes a very pernicious form because withdrawal makes the addict feel so absolutely rotten which is instantly fixed by restoring the level of drug to its normal 'maintenance' levels.
Opiates come in a huge range of types and strengths. Some are considered sufficienty mild or innocuous to sell OTC without a script, others are considered too powerful and dangerous to ever sell legally even though they do have legitimate medical uses, heroin (diacetyl morphine) falls into this category in most countries as it's considered too 'hot' to handle/administer - although the UK is one exception where it's used for intractable pain (as in terminal cancer).
(The UK struck out/did not sign the section that covered the complete prohibition of heroin in the international treaty on banned narcotic drugs because its doctors used the rationale that heroin is actually a more effective painkiller in terminal cancer cases over morphine (which in fact it is by a reasonable margin) - thus addiction was a secondary consideration in such dire circumstances. Whilst the UK, didn't ban heroin for medical use, it agreed to the other provisions of the treaty - those concerning its illegal trade, and possession, etc.)
As I said, ALL opioids that induce narcotic and pain-reducing effects have the potential to be addictive - even mild OTC ones. I'll use myself as an example here. Years ago, I used to take OTC painkillers for the occasional headache of the type that included both codeine and paracetamol (acetaminophen) and whilst they cured the pain I found the headaches becoming more frequent which then led me to take more tablets. Eventually, it dawned on me that the codeine was the reason for the increase in frequency of the headaches - not what caused them in the first instance. I then switched to the paracetamol-only tablets and the frequency of my headaches subsided to the frequency that they were originally.
Of course, in my case, withdrawing from the codeine was was trivial - just a simple matter of switching to codeine-free tablets, but it's anything but simple for a heroin addict - in most cases it's a fucking painful 'nightmare' of the worst kind.
Right, I've taken a long time to get to the point which is this: simply introducing a new opioid drug, especially so a powerful one such oxycodone, without keeping in place all the existing protocols that cover the medical administration of opoids which have existed for well over 100 years is a recipe for an unmitigated disaster - and that's exactly what happened.
We know that Purdue Pharmaceuticals and its owners - that ragbag mob the Sacklers - were the irresponsible pushers of oxycodone, but in many ways it's how we'd gotten to the point where oxycodone was so widespread that it's had such a devastating impact on the population that is so damning and it still must be explained in detail.
What's never been explained to me or, for that matter any other member of the public, why the FDA didn't nip this potential problem in the bud at the outset when it originally approved oxycodone. Moreover, why did the second line of defense fail so catastrophically - that is, why didn't the medical profession - all those doctors prescribing oxycodone - use their knowledge of opiate addiction (which is basic 101 pharmacy knowledge required for them to pass their medial exams), stop the opioid crisis before it took hold?
The opioid/oxycondone crisis is one of the greatest failings in public health administration in modern times. Purdue and the Sacklers started the crisis but why public health administration failed so catastrophically has never been answered.
But to answer, I think the term is used colloquially all of the time and of course is open to interpretation.
I would suggest it has nothing to do with a drug's pharmacology or chemical structure but rather the degree to which a drug when taken in easily-consumed quantities can shape our perceptions of the world, the likelihood of negative externalities due to consumer behavior and the probability of becoming addicted to the drug.
A mixture of those things makes a drug "hard" in conversational language e.g. something that dramatically changes a persons perceptions, frequently has negative externalities and can cause addiction with short-term sustained use is a "hard drug". Like alcohol.
When addicted to such a drug, the negative externalities typically expand in scope and severity and if the use scales to a significant portion of the population would generally be regarded as an undesirable state for society to be in.
There's actually a US company doing this as well: https://biobot.io/
An "acquaintance" of mine who is a well seasoned meth user did ~1.5g and didn't die.
She certainly wasn't better off for it.
meth-ee (μέθη) means being high (by alcohol or weed).