Comment by throwaway2331

5 years 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.

20 comments

throwaway2331

Reply
coolspot  5 years 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  5 years 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  5 years 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-...

  • __blockcipher__  5 years ago

    Not that I know of. One of the side effects of amphetamine usage is compulsively researching details about amphetamine, so that’s where my knowledge comes from :)

    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

soylentcola  5 years 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  5 years 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.

    • jkhdigital  5 years ago

      > Insomnia and ADHD medication are a dangerous combo

      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.

jkhdigital  5 years 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.

cwkoss  5 years 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/2007/02...)

According to this, sounds like its mostly intestines and liver, which is much more typical for drug metabolisms.