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.

[1]: https://www.bluelight.org/xf/threads/what-is-wrong-with-the-...

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.

A few months ago I started taking 15mg diphenhydramine every night just to make damn sure I always get enough sleep. I had taken it occasionally in the past, but didn't like the lingering effect it had the next morning. Then I had a conversation with my sister, who said that she takes it every night for the antihistamine effects after a doctor told her it's fine. The morning after effects seemed to fade (or I got used to them) pretty quickly once I started regular dosing.

Of course I have mixed feelings about ratcheting up the number of medications I'm taking daily, but to be fair OTC allergy medicine is a far cry from using something like Ambien or benzos to manage insomnia.

more info?

What do you want to know? Do you have some specific goal you want achieved or curiosity that you would like satisfied?

It's been a bit since I've been involved with these things. Most of it is underground, but I can give you a quick rundown.

BPC-157 and TB-500 are regenerative peptides. BPC-157 seems to be more "global" and neuro-involved throughout the body, while TB-500 is more local and structural (joints, tendons, etc.). BPC-157 also has a (prolonged) effect in some that negates the effects of amphetamines. Subcutaneous injections of BPC-157 have helped get rid of my recurring ganglion cysts and golfer's elbow.

Semax would fall under "slavic nootropics," along with Selank, and if I remember correctly Epithalon. All have "sub-versions" of varying efficacy. F.e. all have "N-Acetyl" and "N-Acetyl Amidate" versions. NASA would be the shortened version of "N-Acetyl Semax Amidate" -- which in my experience is the "strongest." With NASA, while I was injecting it subcutaneously it brought a sort of structure to my mind I hadn't had since I was a child. It's like feeling everything is falling into place, and a loss of the feeling of helplessness.

If you've ever used noopept, it's like that except with more real and long-lasting effects. I would liken it to bromantane, too.

If not, it's difficult to explain what they are, because they're such a different class of drugs that there's no reference point to base their effects off of. Imagine that you have a drug, but instead of giving you a few hours of a noticeable "high" or "low," instead you get a small, but perceptible shift in how you view the world, and how you filter all the information coming in. Like a micro-micro-micro dose of LSD. No high, no impairment, just a beneficial "shift" in your perception that lasts for an indeterminate, but long time.

A few of my friends were career-researchers and likened these effects to be genomic (subtly altering the expression of genes all around the body) rather than physical (that is, simple physical reactions like consuming more electrolytes would cause you to hold more water, and become bloated, because electrolytes attract and "hold" water; or how drunkenness is simply a temporary shift in the delicate GABA/glutamate balance in your brain). The purely "physical" drugs require constant re-dosing to be effective, while the more genomic ones (such as peptides) can have long-lasting effects even after they've been ceased.

Intranasal is more cerebral, "in your head" type of effects.

Subq is more bodily, "all around your body" type of effects.

If you're looking at it as a nootropic, I would recommend the spray. It feels similar to prozac and wellbutrin, if they weren't so terrible.

If you're looking at is as an anodyne or body-anxiolytic, I would recommend subq. If feels like baclofen.

For example, with eating weed, you get bodily sensations, and so its effects are more on your body, i.e. physical; while with smoking weed, the "sensations" are more in your head, and mental.

Likewise, with injecting NASA, the effects seem to be spread around your body and more "physical"; while administering NASA intranasaly, the effects are more mental, and focused "in your head."

The route of administration changes the expression of the drug on your body and mind. Dependent on that, it can either be a nootropic (nasal route) or akin to a mild and sensationless (compared to painkillers like opiates) muscle relaxant (subcutaneous).

It's difficult to explain, because the effects are so mild and without the normal "Oh, I'm on drugs. I can feel it" sensations, that you can only see them in hindsight (in my case, by perusing old journal entries).

Only thing in the vein has been a better ability to plan, reason about in my head, and make use of visualization to reason about problems (and their solutions).

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