Thanks. I'm glad to know it's not what it appeared at first glance. And apologies if I drew any unwanted attention to your account.
2,266 karma · joined November 6, 2017
Pretty much everything about this guy rubs me the wrong way. The usual cheesy testimonials / vague promises of content which never really gets previewed, the obvious astroturfing, which he continues to respond to as if they're organic genuine comments, etc. Just leaves a really bad taste in my mouth.
https://news.ycombinator.com/threads?id=vich (hasn't commented since aug 2020)
https://news.ycombinator.com/threads?id=matthieuchabert (hasn't commented for 10 months)
https://news.ycombinator.com/threads?id=vivty is slightly sketchy as well but not super cut and dry
Wait, what? This seems completely at odds with the literal definition of viral load per https://en.wikipedia.org/wiki/Viral_load:
> Viral load, also known as viral burden, is a numerical expression of the quantity of virus in a given volume of fluid, including biological and environmental specimens.
Okay, now imagine that I have a baby. I offer you a .0001% ownership in the baby, and you have to get (potentially, but often actually) woken up for 1 week out of every 6.
Does that sound like an arrangement that a rational, healthy, self actualized person would agree to? Of course not. You're getting all of the downside and none of the upside. In fact in many cases the "leadership" team themselves aren't even on call!
My previous job I was on-call 1 week out of every 6. My first on-call week I got paged 100+ times (obv many of these alerts were firing within a minute of each other, but even accounting for that I was still being woken up multiple times per night). That week was particularly bad but I was still woken up an average of >= once per week on my on-call weeks. My team - the sole SRE team - was on-call for everything, including of course the 6 other dev teams' services.
Even worse, when I would fight to get bullshit alerts removed (the alerts that don't actually indicate a problem), I would get incredible pushback from, of all people, my own manager! (who was the manager of the SRE team since like I mentioned we were the only SRE team)
So not only were half the alerts bullshit, but I was counter incentivized to actually fix the problems causing the alerts. One great indicator of how bad things were was that everyone else on the SRE team (except the manager but he somehow always had unusually light on-call weeks) had a 5 minute delay set for pages, because the vast majority of pages would resolve within 1-3 minutes.
Oh, and by the way we weren't given any extra compensation whatsoever. Indeed I was told it was "part of the job description", which effectively meant that SRE skills were less valuable than the devs, because the devs were making identical salaries with no on-call requirement whatsoever! So a more specialized and, at least at this organization, difficult skillset, was worth less.
Anyway, I quit that job, and never looked back. I still have a friend on that exact team who is still putting up with being on-call, despite the incredible impact it has on his ability to go out and do stuff (mid 20's guy). I hear him complain about it all the time. But, like most people, he doesn't have the balls to either (a) push for internal change (which in fairness I tried and failed, although half the reason I failed was because nobody else on my team was willing to stick their neck out and push for the change with me), or (b) quit and find a new job.
So...yeah. Kind of rambling but we have a huge problem in our industry with people who either "don't have lives", or kind of do yet have so little self esteem or whatnot that they can't actually say no and protect their personal lives. In most cases on-call is simply a case of someone getting a raw deal and being too afraid to admit it to themselves.
Speak for yourself, but I would never accept a $150k a year gig that expected me to be on-call, say, 1 week out of every 6. $150k is absolutely a "9-5 and stop thinking about work when you get home" kind of salary, if we're talking California standards
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
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.
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
Take this to its logical conclusion, please. It's the big bang's fault!
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.
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
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)
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.
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.
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)
Only Vyvanse is anti-abuse, because the dextroamphatamine is bound to a lysine molecule. The body must cleave the lysine before it becomes active so snorting it doesn't give the instant rush.
Adderall has no such countermeasures. You're probably getting confused by the fact that it comes in both IR and XR formulations (instant release vs extended release). So if someone has XR adderall, it's not as snortable as IR. But it's still more snortable than Vyvanse is, and you can just get IR adderall which is totally abusable. (BTW X milligrams of XR is really just X/2 mg instant release and X/2 mg delayed release beads that take on average 4 hours to activate. So it's roughly equivalent to two X/2 mg IR doses split 4 hours apart) And finally the XR can be countered by crushing the beads up, although it's a bit laborious.
Amphetamine obviously has its risks, and particularly when prescribing to children doctors seem to write some ridiculously high dosage prescriptions without fully understanding what the drug is like. But you can just say that rather than doing the juvenile "it's really just meth in a bottle" shtick when there is literally already actual meth in a bottle that you can (with great difficulty) get prescribed. And that fact - that methamphetamine exists as a drug that can be prescribed - is much more interesting and surprising to people, given that the lay public is completely unaware that methamphetamine has any pharmaceutical uses.
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.
> 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.
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.
But some of it is certainly true. Vaccination makes a very significant difference in hospitalization among the very at-risk subset of the population. But in the healthier demographics, vaccination status is irrelevant to "net hospitalization" because in those demographics COVID itself is irrelevant to hospitalization when compared to other causes of hospitalization.
Since I didn't mention it explicitly, I mentioned all-cause mortality because that's going to be very correlated to all-cause hospitalization as well (and the fact that mortality itself is something we should care about).
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.
The at-risk populations can be vaccinated. Let's get them (voluntarily) vaccinated and be done with it. Enough of these mandates which serve more to enrich giant pharmaceutical companies than they do to improve public health.
BTW, while mortality isn't the only outcome of concern, I'd be remiss if I didn't mention that Pfizer's 6 month RCT - the highest quality data we have of this kind, period - showed no improvement in all-cause mortality in the 20,000+ people they vaccinated compared to the control: https://www.medrxiv.org/content/10.1101/2021.07.28.21261159v...
> During the blinded, controlled period, 15 BNT162b2 and 14 placebo recipients died; during the open-label period, 3 BNT162b2 and 2 original placebo recipients who received BNT162b2 after unblinding died. None of these deaths were considered related to BNT162b2 by investigators.
So the highest quality evidence indicates that vaccinating a similar population will make no difference in net deaths. (One possible counterargument would be to argue that transmission was unusually low during the study period, but AFAICT that's simply not the case)
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Back to your comment:
> People tend to argue "but what about $arbitrary_unhealthy_habit, we don't regulate that!" when someone mentions this, but $arbitrary_unhealthy_habit has been accounted for in terms of resources required to treat people (assuming a working healthcare system), whereas a once-in-a-century-level pandemic hasn't, so it's not a valid comparison.
I won't make that argument, but I did want to mention that - while unrelated to mandates per se - we basically scaled down our healthcare capacity across 2020, at least in the US, due to all the furloughs and the like from the missed medical appointments, as well as (in many places) suspension of "elective" surgeries. And more relevant to the vaccines, a small but real number of healthcare workers have been or are in the process of being fired for non-compliance with the mandate, regardless of their prior infection history etc
Furthermore while protection against infection/transmission wanes incredibly quickly compared to natural immunity, the protection against severe disease/hospitalization does much less so. Therefore it is quite silly for a vaccinated person with a functioning immune system to be afraid of catching COVID. (This is usually the point in the discussion where people start saying "what about this one super rare immunocompromised person who the vaccine doesn't work well for"...)
So the whole idea of population-level vaccination to stop the spread is absurd on its face. And the real world data only further underscores that (mass vaccination did not stop the 2021 waves, and if anything it seems like vaccination helped briefly prevent some people from acquiring natural immunity due to briefly protection them against infection, which just made the vaccinated population even better substrate when Delta came roaring).
If someone's concerned about COVID, they need to get vaccinated and stop trying to control everyone around them. It's really quite simple. The collectivist benefit of vaccination is poor at best, and has a lot of theoretical concerns associated with it such as https://journals.plos.org/plosbiology/article?id=10.1371/jou.... Whereas the individual benefit wrt mortality&morbidity is a much stronger argument.
Is your implication that there is something wrong about AWS running OSI-licensed open source software as a service?
In general your comment doesn't make much sense to me. First of all it assumes a highly biased position in the AWS vs Elasticsearch war, but furthermore it's not even clear that the two situations aren't comparable. In both cases something that was free is having something built on top of it.
BTW the whole idea of Wikimedia Enterprise is providing higher levels of service availability. It's not really about the "content" itself. It's analogous to when you have a user of some service of yours that is flooding the service with requests and causing performance issues. A common pattern is to convert them into a paying customer and give them some guarantees about availability, while using that revenue to make sure there's enough hardware / engineering time to keep things running smoothly.
Finally, the "middleman vs author" distinction you introduce is entirely irrelevant. To use the Elastic example, it doesn't matter who wrote the software, what matters is it was written under a permissive license, and therefore the author of a given code doesn't have any "ownership". Similarly, someone who contributes to Wikipedia doesn't own that content either. In both cases the actor is contributing to the commons and has no expectation to put any restrictions on their contribution.