5 ms·

Great writeup! Just adding on: Other key differentiator between recreational and therapeutic amphetamine usage is the pharmacokinetics: Vyvanse is the best in

by wswope 5y ago

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.

__blockcipher__ 5y ago
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)
throwaway2331 5y ago
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.
- coolspot 5y ago
  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?

by wswope 5y ago

__blockcipher__ 5y ago

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)

throwaway2331 5y ago

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.

coolspot 5y ago
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?