Comment by __blockcipher__
5 years ago
Yeah it's all very straightforward when you look at usage patterns. Often meth abusers will smoke multiple points across a day (a point = 100mg). As a result they stay awake for days straight, don't eat, and often will engage in enormously risky sexual behavior (this is the dirty secret of AIDS btw...it arose in the context of the "party and play" gay subculture where people would smoke meth or other drugs and have sex for hours and hours and hours straight with many, many different partners...but I digress)
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.
Great writeup!
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.
Totally agreed. Expanding a bit on some of the stuff you mentioned:
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)
Adding on: the problem with vyvanse is that there's no way to mess around with the dosage to get it "just right."
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.
Thank you for in-depth explanation. Is there a book or some website where all this knowledge of ADHD medication usage nuances is collected in one place? Like a missing ADHD manual?
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Yep. It's why I switched from Vyvanse (lisdexamfetamine - basically just d-amp bound to lysine which is then metabolized into d-amp during digestion) to IR generic Adderall (a mix of d-amp and l-amp).
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.
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I’ve been on Vyvanse for a couple years now, and while I was titrating up the dosage I got into the habit of “spreading out” the capsule by opening it up and taking half about three hours apart. The idea was to make sure that the peak effect occurred at the right time. I recently discovered that this probably served no purpose whatsoever, and taking the entire pill at once produces pretty much the exact same overall effect profile.
> Vyvanse is metabolized to d-amphetamine in your blood cells
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.
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Meth causes your mouth to produce to less saliva which removes the bacteria moderating ability of your mouth.
Combine that with also constricting the blood vessels of your gums, and you get a great mix of infection of dying tissue.
It's a myth. I have met hundreds, maybe thousands of long term addicts of meth, crack, and heroin... Lifestyle addicts suffer from massive tooth decay & dental problems, in similar proportions, regardless of which drug they were using.
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.
The 'dirty secret' you refer to (1) is mostly wrong because partying with LSD was popular in the early 80s, not meth, and (2) the gay community is and always has been very up front about risky behaviors and how to minimize the risks. Just because you're unaware of something doesn't make it a secret.
In the American urban gay community, neither LSD nor meth were nearly as popular as prescription amphetamines (pills) until the 1990s, when bathtub meth (crank) manufacturing really took off. They were all always available, but the pills were so cheap & easily obtainable that they were a natural favorite.
MDMA/"Ecstasy" was quite popular in the 80s ("mollie" today), as well as Amyl Nitrite/"poppers"/"rush". The club drugs.
All other literature have told me exactly the contrary in terms of attitudes concerning risk. So, do you have a non politicized source for your statements?
My somewhat large reading about this and some real life knowledge says this is a very true POV.
Amphetamines also cause capillary vasoconstriction which eventually kills off your gums
Pharmacologically, amphetamines are no worse on your mouth than regular nicotine or caffeine usage. And while cigs & coffee aren't necessarily good for your oral health, they also don't generally cause major gum disease and tooth loss.
"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.
That's incorrect, at least in the case of cigarettes. According to the CDC, you have twice the risk of gum disease if you smoke versus nonsmokers. They also state that the more you smoke and the longer you smoke, the greater your risk. That doesn't directly imply a causal link, but it sure winks really obviously in the direction of one.
https://www.cdc.gov/tobacco/campaign/tips/diseases/periodont...
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