6 ms·

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 r

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?
- throwaway2331 5y ago
  Ironically, erowid and other "drug" related forums contain the best "practical" knowledge and nuances of actually having to take the medication. They're not scientific or robust, but they are empirical. That's why most pharmacists and prescription-writing physicians will look at you funny (or get combative) if you tell them generic brand X isn't as effective/good as generic brand Z for you. 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.
  - jason0597 5y ago
    I remember reading a very big thread about MDMA on Bluelight [1]. They were trying to figure out why the MDMA manufactured today is very different empirically compared to the MDMA manufactured in the 80s. Lots of very interesting chemistry discussion One thing I particularly remember is somebody bringing up the example of their cat. Their cat had some digestive issue and couldn't poop so it was prescribed medicine. One brand of medicine worked wonders for the cat, while a generic brand didn't work at all. Both were supposed to be the same exact molecule! [1]: https://www.bluelight.org/xf/threads/what-is-wrong-with-the-mdma-available-today.791073/ https://www.bluelight.org/xf/threads/what-is-wrong-with-the-...
soylentcola 5y ago
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.
- throwaway2331 5y ago
  I had the same experience with vyvanse. Insomnia and ADHD medication are a dangerous combo -- one that's hardly recognizable until it's too late. 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.
  - dr_dshiv 5y ago
    > slavic nootropics and neuro-regenerative peptides (e.g. semax/NASA, BPC-500, more info?
    - throwaway2331 5y ago
      Apologies; I confused BPC-157 with TB-500, and made a horrible amalgamation. 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.
cwkoss 5y ago
> 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/2007/021977lbl.pdf 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.
- throwaway2331 5y ago
  Old FDA data. Here's the latest: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021977s046,208510s003lbl.pdf 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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257105/
- jkhdigital 5y ago
  ~30 year old article on how red blood cells metabolize many classes of drugs: https://onlinelibrary.wiley.com/doi/pdf/10.1002/bod.2510090402 https://onlinelibrary.wiley.com/doi/pdf/10.1002/bod.25100904... 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.
  - cwkoss 5y ago
    Very interesting, thanks!
jkhdigital 5y ago
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.

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?

throwaway2331 5y ago
Ironically, erowid and other "drug" related forums contain the best "practical" knowledge and nuances of actually having to take the medication. They're not scientific or robust, but they are empirical. That's why most pharmacists and prescription-writing physicians will look at you funny (or get combative) if you tell them generic brand X isn't as effective/good as generic brand Z for you. 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.
- jason0597 5y ago
  I remember reading a very big thread about MDMA on Bluelight [1]. They were trying to figure out why the MDMA manufactured today is very different empirically compared to the MDMA manufactured in the 80s. Lots of very interesting chemistry discussion One thing I particularly remember is somebody bringing up the example of their cat. Their cat had some digestive issue and couldn't poop so it was prescribed medicine. One brand of medicine worked wonders for the cat, while a generic brand didn't work at all. Both were supposed to be the same exact molecule! [1]: https://www.bluelight.org/xf/threads/what-is-wrong-with-the-mdma-available-today.791073/ https://www.bluelight.org/xf/threads/what-is-wrong-with-the-...

soylentcola 5y ago

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.

throwaway2331 5y ago
I had the same experience with vyvanse. Insomnia and ADHD medication are a dangerous combo -- one that's hardly recognizable until it's too late. 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.
- dr_dshiv 5y ago
  > slavic nootropics and neuro-regenerative peptides (e.g. semax/NASA, BPC-500, more info?
  - throwaway2331 5y ago
    Apologies; I confused BPC-157 with TB-500, and made a horrible amalgamation. 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.

cwkoss 5y ago

> 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/2007/021977lbl.pdf 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.

throwaway2331 5y ago
Old FDA data. Here's the latest: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021977s046,208510s003lbl.pdf 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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257105/
jkhdigital 5y ago
~30 year old article on how red blood cells metabolize many classes of drugs: https://onlinelibrary.wiley.com/doi/pdf/10.1002/bod.2510090402 https://onlinelibrary.wiley.com/doi/pdf/10.1002/bod.25100904... 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.
- cwkoss 5y ago
  Very interesting, thanks!

jkhdigital 5y ago

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.