Re: Vyvanse (and I'm sorry, but the name still sounds to me like an up-market vibrator), you say that it's attached to lysine. I know that lysine is an amino acid, and looking up what secondary effects might be magically at work here, there's some talk that it acts as anti-anxiety:


"2. May Reduce Anxiety by Blocking Stress Response Receptors

Lysine may play a role in reducing anxiety.

One study found that it blocked receptors involved in stress response. Researchers observed that rats given lysine had reduced rates of stress-induced loose bowel movements.

A one-week study in 50 healthy people noticed that supplementing with 2.64 grams of lysine and arginine lowered stress-induced anxiety and reduced levels of the stress hormone cortisol.

Similarly, adding 4.2 grams of lysine per kilogram (2.2 pounds) of wheat flour in deprived villages in Syria helped reduce anxiety scores in males with very high stress levels.

After three months, consuming the lysine-enriched flour also helped reduce cortisol levels in women.

Lysine may also be able to help people with schizophrenia, a mental disorder that disrupts an individual’s perception of the outside world, often resulting in an inability to understand reality.

Though research is still in its early stages, lysine may have the potential to improve schizophrenia symptoms in combination with prescribed medication."

Given that all this is off pop-science websites, I'm dubious, but IF lysine isn't simply sitting there inactively but contributing to anti-anxiety, it MAY be that people feel Vyvanse is helping them more because they're less anxious/twitchy on top of the amphetamine helping with focus effect.

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this sounds like a shitty situation for anyone who’d be best helped by Desoxyn.

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Read with interest. My 10 year old started meds this fall. Have been through Focalin (sad, eye twitch), Vyvanse (“empty hollow feeling” - who doesn’t want to hear this from their 10yo!), now Concerta (seems ok but appetite issues across all three and intense nightmares, unclear if nightmares are drug-related). Just to be clear, I hate this. I feel like it’s the worst case scenario – it’s not obvious to me that it’s actually helping with focus or impulsivity, and it’s definitely not helping with emotional regulation. And at the same time, I’m worried that it’s impacting his height, and it’s definitely impacting his weight. I’m waiting for that “light switch” that I keep reading other people have had, but it’s not happening for him.

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"A rat model also finds some modest superiority for d-amphetamine, showing that both isomers improve attention, but d-amphetamine additionally improves hyperactivity and impulsivity."

How do they measure rats' attention/hyperactivity/impulsivity ? Is the "Spontaneously Hypertensive Rat" as mentioned in the linked study basically rat-ADHD ?

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Are the non-adderal sample sizes too small (in addition to the other potential biases)?

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My first thought as to a mechanism for the higher ratings is that Desoxyn is so scary to prescribe that a prescription is only ever written for especially low-risk, well-behaved patients, and people drawn from this population are just much more likely to have good outcomes.

Are there analogous cases for other conditions (drugs A and B seem like they’d be pretty similar, but drug B has a reputation of addictiveness so is rarely prescribed) where one could test this hypothesis?

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A lot of doctors prescribe Ritalin first. Do you know what their reasoning might be?

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as someone who has had a long "it's-complicated" relationship w/ adhd diagnosis and the various medications (almost always ritalin variants) that came with it, i've long thought about writing a post on how I see the issue, mostly relating how i feel society is overdiagnosed but undertreated. But i dont want to do the research required to make sure I don't wind up promulgating a bunch of bullshit. So i'm just going to dump a bit here.

I've long felt some underappreciated connection between how we deal with something-something-adhd and how we deal with vision impairment. We have a pretty precise science for diagnosing vision issues, and accordingly we can treat them very effectively and precisely. Psychological issues are naturally a lot more difficult and complicated and we know fairly little about how the treatment actually works (as opposed to lenses, which have been a nearly exact science for like 300 years). Other than that big difference, i feel there are some big similarities - vision is much more of a spectrum than a binary, a fact which is universally acknowledged, and treated appropriately. Also, it seems that most people have some form of vision correction - to wit, modern society's demands for visual acuity are substantially greater than the innate level of a typical human, due to the wordy and high-tech nature of the modern economy. Most people address this issue by self-medicating with caffeine, but if caffeine isn't strong enough, or if they're too dependent to get more benefit from it, the priveleged and savvy among them go to their therapist and complain about back pain i mean my corporate job is boring so i can't focus anymore and then they get an adhd diagnosis and an adderal prescription for the first time in their life at age 23.

I don't think the problem is that they shouldn't be getting adderal or that their adhd isn't "real" - rather, they have some degree of adhd, at least relative to the expectations of modern society, and so i feel they should get some degree of stimulants, if they feel the stimulants are helping them. I really more feel like stimulants should be available over-the-counter, tho i can't comment on the potential this would create for abuse. But coffee is over the counter, and self-medication seems to me the ideal means to handle a problem that is very spectrumy and subjective and relative to expectations rather than binary and something that only trained psychologists can really wrap their heads around (I have very little idea of what borderline PD actually means, but if i'm haveing trouble focusing at my boring job one day i can easily make the ad-hoc decision to have an extra cup of coffee).

tl;dr - i'm not sure that over-the-counter stimulants is a good idea on the whole, but I think thinking about it at least illustrates some of the problems society is having with the very binary, therapist-centric approach to "diagnosing" and treating adhd/adhd-esque symptoms.

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What makes you afraid of prescribing 20mg Desoxyn? Not a NYT hit piece, right? Regulators?

P.S. big pharma, perhaps you'd like to attach lysine to desoxyn and slap a patent on that sucker?

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This seems weird, because most of the essay is like "here are all the reasons why dexedrine-based things are better and patients like them more" and then at the very end you say "but I usually start with Adderall". Why are you choosing the thing that you evaluated to be worse?

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A mixture of drugs having fewer side effects than a single drug makes sense to me if the side effect profiles vary and their magnitude is proportional to dosage. Instead of 100% of side effect A you could mix four drugs and get side effects A, B, C, and D but each of them at one-quarter the magnitude so much less noticeable/severe and possibly below reporting threshold. Not to mention interference effects - Effect A might somewhat counteract Effect B.

Indeed, if you had *50* drugs to choose from you might want to use ALL of them in your formulation to minimize drug-specific side effects. Think of it as a balanced portfolio, like buying an index fund rather than individual stocks to minimize variance. Does nobody make drugs like that? If not, why not?

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Here we can see just how potentially dangerous the very profession of psychiatry is.

I am straight edge for everybody but alcohol and it has never occurred to me to try hard drugs, but having read but one article on the subject I now kind of want to try some meth and see if it helps me remember my house keys and the street sweeping schedule more readily.

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Dexedrine has worked wonders for me over the past ~20 years I have been on it. I generally describe its effectiveness to other people as without it I would have a GED rather than a PHD. I have been on all the other standard options at other times, but Dexedrine has hands down been the best. However it has also been noticeably more difficult to obtain than the other medications I have been put on over time.

A couple of examples:

Scott uses the name "Dexderine" in his post for the simple reason that this is what _everyone_ knows this drug as. However, if one takes a written prescription for "Dexedrine IR" to a pharmacy, some will say that no such drug exists and will refuse to fill it unless the pad of paper that you already spent 30 minutes driving to your doctor's to get says dextroamphetamine, because the brand name IR no longer officially exists. Never had this happen for Adderall (of any release) or Ritalin.

Unlike (to my knowledge) adderall, several years ago there was a year long nationwide shortage of dexedrine and the 100 year old medication was going for $1 per mg, _if you could find it at all_.

Finally, due to insurance issues several times in the past few years I have had to find a new prescriber for my medication. Each time the prescriber has reacted with confusion and slight disgust that I would be on dexedrine rather than adderall - each time insisting that dexedrine was far more dangerous than adderall before reluctantly giving it to me after seeing I had been on the same dosage with no problems for 10+ years.

As for Desoxyn, to be honest it sounds too good to be true. Dexedrine works so well for me that I am hard pressed to think that there might be something even better. I would also be worried about tolerence build up. Admittedly (based on Scott's last paper on the topic) there seems to be no agreement on whether Dexedrine has tolerance issues, but as I haven't experienced any with dexedrine, and have with (the admittedly mostly unrelated) Straterra and modafinil, I would be fearful (perhaps irrationally) of anything more potent that might take away the effectiveness of what I have now.

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The Sci-Hub links don't work for me, I think because they point to .se rather than, say, .st. Cheers.

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boy do i have thoughts, this post was tailor-made for me

1. now i'm real sad that i live in a country where desoxyn is extremely illegal. i didn't even know it existed, and i thought i knew about all the stimulants.

2. at least i still have vyvanse which i'm on right now

3. a quick google tells me that i now live in a country (i recently moved) where i have access to dexedrine! can be an interesting option because...

4. i do crash from vyvanse and i crash bad (or more like: i'm just not very functional once vyvanse is gone from my body). this led my psychiatrist to an unorthodox solution...

5. which is that right now i take 30+15mg of vyvanse. how, you may ask? easy. every day i wake myself up at 8am, take a 30mg pill, go back to sleep for an hour or two (on good days) so it kicks in, then at noon, i take another 30mg pill, open it up, mix it in 32 fl oz of water, and drink half of it (and reserve the other half for the next day). with this combination, i'm on vyvanse basically until i go to sleep (midnight-1amish). i don't know how sustainable this is on the long run (my blood pressure is unhappy sometimes), i've been on it for about a year and change now.

6. vyvanse has powerful anti-anxiety and anti-depressant effects on me. it's magic.

7. ironically, my adhd symptoms are much worse on vyvanse than, say ritalin, but...

8. i took ritalin for like 6 years as an adult (IR for like 5 years and then XR for like another year) but by the end it made me extremely miserable and made me anxious and it was... bad

so i don't know. vyvanse was the best i've had until now but i might be able to give dexedrine a shot (i'm having my first session with my hopefully new psychiatrist next week) and maybe i can have a combo of vyvanse + dexedrine (the latter so i don't crash and i don't have to "hack" vyvanse).

god i have so many more thoughts but this is already a long comment.

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One reason for the higher rating of Desoxyn might be _because_ it's the risky prescription. It's the option that is taken when all else has failed.

So either the patient is not helped by Desoxyn, in which case it joins the long list of other drugs that didn't do nothing. At that point you're not going to rate attempt one million.

Or _finally_ it's the solution to the problem. You've tried everything including that nasty tea the aunt of a colleague suggested, so of course you're going to be over the top when you find something that works. You're going to tell everyone how great Desoxyn is.

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As someone diagnosed with ADHD, I used to try to self-medicate by ordering things off of the dark web. I tried 10 - 20mg of Dexedrine and Adderall on different occasions, and found Dexedrine less anxiety-inducing, better for productivity, and "cleaner". However, as some reports/scaremongers claim, I also found that even 10mg of Dexedrine was indeed more mood-lifting and euphoric than 15mg of Adderall (so I think it may not be simply a matter of d-amphetamine being slightly more potent than a mixture).

Based on my totally uninformed armchair neuropharmacology knowledge, l-amphetamine tends to be more NEergic and d-amphetamine tends to be more DAergic, and I think I read somewhere that NE may temper some of the subjective pleasurable effects of DA (though can't find where I read this). Subjectively, this kind of feels true to me. If it is true, it may partly explain why Adderall is considered less recreational or addiction-forming than Dexedrine.

I'm currently prescribed Adderall, and it works okay for me, but I've always wished I could ask my psychiatrist if I could try Dexedrine. I've refrained due to not wanting to be seen as drug-seeking (and in this case, I guess I actually kind of am drug-seeking?). I'm considering maybe linking this article to him, though he might see this comment and suspect it's me.

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I've taken Vyvanse and Ritalin, and I switched from Vyvanse to Ritalin because although Vyvanse worked for ADHD, it also gave me anxiety as a side effect. Ritalin worked less effectively than Vyvanse, and so I'm back to self-medicating with Caffeine. Interested to know whether people think it's worth trying to get back on the actual-medication train.

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I agree Vyvanse is “smoother” once I’m used to it, even compared to Adderall XR. While acclimating it still causes tension and trouble sleeping. But after that It almost feels like being normal and in a good mood, able to get things done. Adderall feels more like a stimulant, if that makes sense. Equivalent doses are hard to figure out because adderall has a shorter but stronger peak.

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Welcome back Scott, I’ve missed Slate Star Codex.

I have some questions that are broader than the minutiae of the chemistry and pharmaceuticals. This has been bugging me for a while because my best friend from childhood was never diagnosed with ADHD ( it wasn’t really recognized in girls in the 1970s) but as a grown woman continues to have marked behavioral issues like inability to be organized, utilize a single calendar, focus in anything except a video game (which she can get lost in for up to 20 hours), get into any kind of routine, etc. She believes she has ADHD, and not being qualified in any way to issue a verdict, I’m inclined to agree-ish. Which brings me to my questions:

Are there any clear research findings about

1) How the differential for diagnosing ADHD differs in girls from boys (if it does, although my own necessarily limited reading suggests it does);

2) Assuming ADHD persists into adulthood in women as well as men, is Adderol the typical medication or something else?

3) What are the adult diagnostic criteria as opposed to the childhood criteria?

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Hello! An interesting read! :-)

I thought the lysine in lisdexamphetamine was removed upon contact with erythrocytes all over your blood stream, but the remaining amphetamine molecule is being broken down in the liver.

When you compare the doses of a drug abusers of 800mg to the therapeutic 20 mg, is tha solely the users report or was the batch analyzed? Cause i read "speed" usually is around 5-15% pure. So a 5% would equal a dose of 40mg. I wonder how much of the damage we see in the "common speedabuser drugfiend" that is actually from the amphetamine it self, or it just being impurities, bad nutrition and sleep hygiene that are destroying them.

My impression was always that amphetamine, given you dont have cvd or hypertension are well tolerated medicines by and large.

Olav :-)

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I've been on meds for ADD since 1999, but have very limited experience with any of these. I started on IR Ritalin (no idea why that over Adderal) and learned to read that day. (Yes, it was that sharp.) A couple years later, Concerta came out, and I stayed on that until 2016. At that point, I was interested in trying new things, and the psychiatrist I was seeing at the time suggested Vyvanse (I also asked about Modafinil, which he said no to). I got a week's worth, and couldn't see any difference between that and the 54 mg Concerta I was on at the time. I didn't try anything numerical, but I was watching my behavior pretty closely (and it was really obvious internally if I forgot the Concerta) so I'm pretty sure the effect or lack thereof was really. So I stuck with the Concerta, because there wasn't really any reason to change

Two years later, I switched to Modafinil due to issues with Oklahoma rules on Schedule II stuff. It works pretty well (although the couple of weeks I was detoxing were interesting) and it's a lot easier to deal with, so I'm going to be on it for the foreseeable future.

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I’ve been through most drugs commonly prescribed for ADHD, and once when I lost my insurance, I bought crystalline methamphetamine off the dark web, administering it orally by dissolving it etoh/h2o and dosing with a graduated dropper. I will say that it certainly worked better for me than Adderall, and I even went from 60mg/day Adderall to 5mg/day methamphetamine, though 10mg/day worked best. The only reason I stopped it when I regained insurance coverage was that the effects lasted a very, very long time, which made sleep difficult, to say the least, though I’m glad if this isn’t the case with most Desoxyn users (it doesn’t seem to be a huge problem from patient reports, I gather).

The subjective difference between these two amphetamine preparations was that meth-, at the appropriate (read: low) dose, was significantly “clearer,” which I attributed to the main noticeable difference: low/no “body load” with meth-, as defined by tachycardia, muscle tension, and food tolerance/GI upset.

Trying to rationalize this difference, I noted that methamphetamine is apparently less peripherally active, perhaps because its less polar and so a greater percentage of the serum concentration is taken up by the CNS? I’m skeptical of the idea that a significant portion of Adderall’s effects are due to activity in the periphery, but it seems consistent with the data, at least.

The following is pure speculation, but I’m relatively comfortable with the idea that the addictive potential of any drug is in direct proportion to how well a patient/subject *tolerates* it. The high doses (200-300mg/day) that recreational users take sound pretty insane to me, but for sure 200mg of Adderall sounds absolutely terrifying, while I’m sure 200mg of methamphetamine would be much gentler on my body and general well-being, which satisfies me as an explanation for how methamphetamine tends to ruin lives while Adderall tends to improve them, by and large.

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what is the least speed-like ADD medication? does anyone know if strattera actually works or is it basically a placebo?

the reason I ask is that I briefly took ritalin for ADD, but it had a bad effect on my personality and thought process. made me more talkative, impulsive, and made things seem profound and interesting that weren't. this is certainly what you'd expect amphetamines or other stimulants to do, but it wasn't good and I eventually stopped taking them.

on the other hand, they did treat the ADD, i was actually able to be organized, stick to a schedule, and efficiently manage the logistics of daily life. but the quasi-manic mental state outweighed these benefits.

so if there are options that won't do this, I want to know about them! especially if someone had a similar experience and switched to some other medication.

I assume if such a thing exists, going to a doctor and saying "hey doc, can you specifically not give me the liable-for-abuse schedule II drugs?" wouldn't get pinged as drug-seeking behavior.

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I'm confused. If the lion's share of difference between "methamphetamine abuse" and "responsible Adderall use" is attributed to administration route and dose, wouldn't we see a large black market for Adderall with similar use cases to meth (ie to get really really high)? As we don't see that, surely the chemical differences can't be ignored?

If meth can induce euphoria, and (I assume) Adderall can't, couldn't that and its impact on the brain translate to addictiveness and explain the differences in high user ratings?

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Genetic profile can predict response to amphetamines. It's all about the dopamine for me.

I take amphetamines for post-concussion effects, complex PTSD from childhood trauma, and pain. I've got genetic dopamine issues and have used my 23andme profile to figure out what is going on and how to move forward.

I've got the Warrior version of the rs4680 gene (Worrier/Warrior gene, COMT Val158 Met ) - meaning that I process neurotransmitters very quickly and they are quickly reabsorbed. This results in perpetually low dopamine levels and novelty-seeking to up those levels.

Warriors handle stress well, have a higher pain tolerance, better emotional resilience, get less pleasure out of life...


That Warrior version has all sorts of manifestations. It protects kids from PTSD as children (lower intensity emotional response to trauma, which I had a lot of), but a concussion make us more susceptible to PTSD as adults.

Another gene (can't think of it off the top of my head) results in fewer dopamine receptors in my frontal cortex. Meaning I don't get as big a bang from my dopamine hits.

Lastly, a concussion messed up my dopamine transport system, severing many connections. This means I have less dopamine delivered.

Ritalin, and Adderall later, were the only medications that helped me.

Then pain blew everything out again.

I hit a quadfecta. Fast dopamine reabsorbtion, fewer dopamine receptors, a damaged dopamine transport system, and chronic pain challenging the system.

20+ years after the concussion, I had a vertebrae dislocate (L4 spondylolysthesis) due to an undiagnosed whiplash from the concussion.

That pain, which didn't go away after surgery, combined with a narcissistic wife drove me over the edge.

Adderall, kratom, a divorce, and working on trauma issues have me functioning again.

The reluctance of physicians to prescribe amphetamines has caused many problems through the years.

I hope to use this post to figure out some better ways forward.

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If what your saying about desoxyn is true then the fact that it is not prescribed is absolutely criminal. I have adhd and drugs do not help. I mean they do but the side effects are overwhelming compared to their effects. And I only have mild adhd. The amount of people suffering from adhd are huge and if we have a easy cure right near us its something that we have to test.

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I have tried Adderall, Vyvanse, and Desoxyn. Desoxyn had the largest impact on my mood, bringing great euphoria. This is purely anecdotal, but that could be one reason why Desoxyn ranks so highly among user reports.

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Why do you not try prescribing Desoxyn? What are you afraid of?

Also, in general, do you think going to your psych and saying "I heard of this Desoxyn thing and would like to give it a shot in case it works better for me than Adderall." is likely to have a bad outcome? (Like, ending up on a list of drug abusers or something?)

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I'm surprised that we prescribe non-XR Adderall to anyone, but maybe I'm more prone to addiction than most.

About 20yrs ago I was prescribed Ritalin (worked, but made me feel bad), Concerta (ditto) and then Adderall. The Adderall worked great, until I started saving it up and taking lots of it at once. This led to 48 hour programming binges (I learned a lot of programming!) but was pretty bad for me and unsustainable so I stopped taking anything.

More recently I tried Vyvance and it was great, and had none of the desire to re-dose, but had to stop because of blood pressure concerns. Now I'm on Wellbutrin which isn't as overtly effective but fixed the depression I didn't know I had so that's nice.

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I believe doctors are still allowed to prescribe PCP, too

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The vyvanse vs Dexedrine thing you mention was my hypothesis about my preference for vyvanse over adderall. Adderall has unacceptably high side effects for me that vyvanse does not. When I did comedy I wrote a joke about how I had to stop taking adderall because “it made people follow me when I was walking behind them”. This was from one incident where I realized I was following a guy for like six blocks and wondering why he was following me.

I may try to provide this to my doctor to see if he would be willing to try Dexedrine, as it is much cheaper than vyvanse but he has been pretty reluctant to prescribe it.

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My person theory is that levoamphetamine creates a more perceivable high, hence aids with user's perception that the medication is "doing something".

The problem with meth (or Desoxyn if we must), is that it lacks the feedback mechanism amphetamines have. If you take more than your prescribed amount of amphetamines, eventually the uncomfortable physical effects will be way too much for you to take more. Meth has no such feedback mechanism and taking a large dose can be neurotoxin since it lasts so long. Not saying this isn't a reason just to use it, just that it is potentially way easier to abuse.

I'm curious why people haven't looked more into basing drugs off Thozalinone and Pemoline. Pemoline is Schedule IV (what the creators of Vyvanse wanted all along!) and has no sympathomimetic effects like lack of appetite, racing heart, dry mouth etc. Thozalinone is fairly similar to Pemoline and apparently animals did not build tolerance over time to it. Pemoline was removed from market due to liver issues, but I think the statistics used to justify the removal were very suspect.

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How does methylphenidate (Metadate) fit in with these others? That's what our clinic gave our family for ADHD. Seemed to help somewhat, not a miracle cure for sure.

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Hmm, I guess methylphenidate is Ritalin. Still not sure how it fits in with the other meds discussed.

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I think the popularity of methamphetamine on the black market is likely explained by its relatively simple synthesis, for both racemic and stereo specific formulations, and helped by its double potency by weight. Like, as best I can tell, adderall can’t be made from cold medicine in a buried school is with equipment you could steal from a high school.

Basically, it’s the exact same situation that made heroin, and not oxycodone, the black market leader among opioids for decades. We also erroneously assigned basically the same false attribution, that being increased addictiveness rather increased accessibility by markets that serve addicts.

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Very interesting to learn both the history and pharmacology of ADHD stimulants. My son has had inattentiveness issues since kindergarten with (mercifully) almost no hyperactivity. He did OK with Adderall but much, much better after being switched to Vyvanse. His dosage is low and has increased over time only with body weight. He still runs out of gas by the end of the day and has a low dosage of Ritalin prescribed as an as-needed booster. He doesn't take it very often.

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typo: "Richwell" should be "Richwood"

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I still fail to see the value of amphetamines in generating any positive outcome in regards to AHDH when modafinil and co are on the table.

The main effect of amphetamines always seemed to be that of making you "feel" productive, with a bit of added productivity on top, maybe.

It seems that for the purpose of productivity/focus modafinil is much better suited.

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I feel like this might be tied to the propensity of people with ADHD to experience methamphetamine psychosis (https://doi.org/10.1016/j.psychres.2013.06.030). Regular amphetamines also seem more likely to cause psychosis in ADHD sufferers than methylphenidate (https://www.nejm.org/doi/full/10.1056/NEJMoa1813751), and methylphenidate probably doesn't significantly increase rates of psychosis in and of itself.

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A little bit off topic from the white-market pharma approach, but it's important to note how there are a substantial number of people who turn to substituted amphetamine research chemicals to deal with ADHD. A substantial amount of people who use these alternate chemicals do so since they aren't covered by insurance for adderall and access to chinese RCs turn out to be cheaper, which is a terrible indictment for the american healthcare system.

Notably, chemicals like 2-FMA, 3-FPM, 2-FA, Isopropylphenidate, 4F-MPH, etc are used in low doses. There are other substituted amphetamines in this class like 4-FA or 3-FEA, but these tend to have mild serotonin releasing effects (think MDMA) so they're used more recreationally than for productivity. (IIRC, 4-FA also has mild 5-HT2a neuroreceptor agonism so it's also mildly psychedelic, although it's been a while since I read up on this stuff so I can be wrong).

I think the mild serotonergic action for some of these, as opposed to being a pure DNRI/dopamine releaser, helps with the perceived efficiency of these drugs. That being said, my pet theory at the moment is that a substantial amount of people with ADHD also have mild depression, and something fucky with messing with the SERT transporter helps alleviate depression symptoms in conjunction with just the stimulant effect for ADHD, causing people to be more productive.

Shout out to r/drugnerds for a slightly more erudite discussion source than the average druggie forum "herr durr i took a massive hit of meth and im totally spun bro".

Ultimately, for people who can't afford medication from a pharmacy, a lot of people end up buying amphetamine from the darknet. It used to extremely cheap (as low as $50ish for 7g of amphetamine sulphate powder), although I haven't looked at the darknet markets for this in a few years so I could be wrong nowadays. You would ideally want to test the powder with a chemical (particularly Simon's reagent, which turns blue in the presence of methamphetamine), to make sure it's amphetamine. And then do an anhydrous acetone wash of the powder in order to purify it. You lose a significant amount of material that way, but it allows for much more precise dosing.

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What are your thoughts on the cardiac risks of amphetamines? I meet the DSM critera for ADHD but have never got psychological testing because I don't want to increase my risk of MI (or brain damage). I actually started to resent people in my classes who were taking ADHD meds becase I thought they were unfairly setting the curve.

I know of some psychiatrists who seem to hand out stimulants to anyone who says they have ADHD, while others insist on getting an EKG for every patient. It used to be fairly normal practice to check vital signs for anyone on stimulants, but that hasn't been happening much over the last year for obvious reasons, and I don't think there'll be much of a shift away from telepsychiatry even when the pandemic ends.

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It would be good if we could see the number of ratings for Desoxyn.

Also, I'd like to see exactly what ends up going into Adderall: you mention the 75/25 split as if it's spelled out earlier, but I don't think it is, and it's not clear what the other two ingredients are. Also, are the sulfates and saccharides relevant to the action of the drug?

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"Yes! Yes! This is the psychiatry blogging I subscribed for." - Sickos, me.

I worked on a mixed amphetamine salts ER patent case, which went sideways because of an FDA freak-out that the time release profiles turned out not to be completely bioequivalent. Don't remember how that all shook out.

When you prescribe time release MAS, do you try to prescribe a particular generic (or brand) extended release drug, and if not do you worry about pharmacy substitution to a manufacturer with potentially different profile?

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As someone who's used both methamphetamine and adderall plenty, this is not quite correct. Methamphetamine is unequivocally a better high. And yes, i've taken both in comparable doses using comparable routes of administration.

My personal theory for the biochemical explanation is this: Meth crosses the BBB more effectively, as you stated. But this has a second order consequence. It changes the ratio between CNS stimulation (pleasure) and PNS stimulation (heart rate, blood pressure, etc.). When you are consuming drugs like these, you are effectively rate limited by the side effects on your peripheral nervous system. Think of it as a 'budget' in heart rate increase.

Due to the increased permeability of the BBB to methamphetamine, the ratio between pleasure/heart rate is much better, and allows you to achieve significantly more of the pleasurable effects per unit heart rate increase.

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Jan 26, 2021Liked by Scott Alexander

Recent conference speakers’ comments about immediate release of any stimulant being ( ironically to me) more helpful with mood symptoms than extended release of any stimulant has been borne out in my practice 100%. ( None took AD’s)

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Somewhat off topic: do you think adults can self diagnose themselves for ADHD quickly by buying a bunch of ADHD drugs on the black market and trying them to see if it improves performance? If performance is consistently better, you probably have ADHD. If no difference beyond the high given by the drug, you probably don't.

That's what I did personally to confirm I don't have ADHD (just laziness and procrastination I guess), but I'm always wondering if that was a valid approach.

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Do you have any thoughts about self-medicating nicotine to treat ADHD symptoms? I was diagnosed with ADHD as a kid, but hated the "feeling like a robot" symptoms, so I discontinued it on my own (and my opinion at the time was that if my teachers wanted me to pay any attention, they should teach something vaguely interesting instead of just reciting facts that I successfully regurgitated in exams).

After becoming an adult and getting a job as a programmer, I didn't really have any problems, because I was genuinely interested in my work, so focusing while at work wasn't an issue. Working from home has been a lot harder for me, though: more easily available distractions and no social pressure from sitting next to people that can see me slacking off makes staying focused more difficult.

I didn't really feel like having to go shopping for a psychiatrist to find one willing to prescribe me drugs that were gleefully forced upon me as a child, so I decided to try nicotine via gum, and it seems fairly effective, although not the magic bullet that I've heard some people call adderall etc.

The cost benefit tradeoff seems pretty good, at least compared to no treatment: it seems like there's a clear benefit, and it's cheap and easily accessible. I think the addictiveness of nicotine is massively overblown, at least in my personal case: I used it pretty liberally (~20mg/day) until the holidays, and then quit cold turkey for a month and a half, with only a mild headache on day one.

Do you think that it'd be worth scheduling an appointment with a doctor to try to get a prescription for actual drugs?

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I've been on ADHD drugs for years to pretty marginal effect—was diagnosed (inattentive) as a kid but never medicated, then rediagnosed as an adult in 2012 after my usual coping strategies became inadequate in grad school. For me stimulants (Ritalin for years, both IR and ER, then Focalin, now Adderall IR) have always been much better for my mood than they are getting me to do the things I need to do. Never tried one of the non-stimulant options, but they seem more likely to benefit people on the hyperactive side.

One strange thing about ADHD is that frequently extremely productive people who know I have it will talk to me about how much trouble they always have focusing and getting work done and do they think they should talk to a doctor about it. Obviously I don't know what it's like to be them, so I tell them to go for it, but the degree of impairment I have even medicated compared to what they are able to accomplish (however it feels to them internally) is so much higher than it almost makes me think *I'm* misdiagnosed. (I made it into grad school, but it's a fine arts degree in fiction, so that really just meant that over my two years focusing almost exclusively on fiction I was able to write three good stories for my portfolio.)

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This is tangential to all the discussion below, but I've been following you for nearly a decade and I've never seen you more engaged with commenters (judging by your comment count). It's exciting to see.

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I'm curious if there are any others out there who responded very poorly to stimulants for ADHD and went on something else, like say, Clonidine.

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I was surprised that at the end of the article, your first choice of prescription is still Adderall; out of curiosity, why not start with dexedrine if all signs indicate it to be a 'better choice? Cost? Patient preference/name recognition? I know I personally sometimes conclude something is

'better' but go on doing the old thing anyways sometimes. Curious if I'm missing something.

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Very interesting article, thanks! Can't help but wonder why the tables are pictures instead of tables. Screenshots from an article? This is probably not important in the grand scheme of things, but, having recently fixed some accessibility problems on a website, I now _notice_ things like that.

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I'm a freshly starting teacher in Germany and all my life I struggled with procrastination. I always had the disposition to have my body keep it's own house but if there is a possibility a drug could help me with starting important tasks earlier and keep focus that would be life changing. I always managed in the end but everything was close and everything took longer than it had to. This blog post want's me to look into ADHD and how it relates to chronic procrastination. If there is a link between those I never picked up on it. My current bias was to assign ADHD to kids who 'need to calm down', not adults who 'need to get important shit done and not just last minute again'.

My experience with procrastination is that it is mostly perceived by others as a problem of choice and laziness. I actually am not sure anymore what laziness as a social concept really is. I'm sure at this point that my susceptibility to procrastination is hard-coded and if there are drugs helping with this they would be not just a huge benefit to me personally but also could set free the lost potential of a lot of people struggling with this. Maybe there is already a bigger discussion about this that I am not aware off but I would be thankful for any personal experiences and recommendations from people who can relate and might have had success or not with medication.

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The big issue for most kids with the Dexedrine Spansules is that they don't last well enough to cover them throughout the school day.

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If you can read the entirety of one of Scott's posts, can you be suffering from untreated ADHD?

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A while back you made a joke along the lines of "This study was in the 1950s, before people invented being responsible," and every time you post something else about the 50s I realize more and more that it wasn't a joke.

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Isn’t it...bad to give millions of young kids speed? I don’t know much about drugs...but it sounds bad.

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Scott, What drug would you recommend for a 7 year old with ADHD?

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Great post. I'm glad that this blog is just as good now as it was before.

Methamphetamine is absolutely the best amphetamine analog out there. Amphetamine works for about 40% of the time as methamphetamine, and methylphenidate (Concerta, Medikinet) just makes people jittery for an hour or two and then crash. Adderall is about the same as Medikinet.

But who am I to judge?

I'm bemused that people are now talking about Vyvanse in the same way that people were talking about Lyrica 10 years ago. Lyrica killed people. That stuff is going to kill people.

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One thing I didn't see here is a discussion of the difference between ADHD hyperactive presentation and ADHD inattentive presentation. My teenage daughter has a severe case of the latter, and absolutely no medication that we have tried (Strattera, Vyvanse, Concerta, Focalin, Adderall) has done a damn thing. She is on Wellbutrin now, but I honestly don't think it is doing much. My sense is that these amphetamine-type ADHD meds work with the hyperactive kids, but not so much the inattentive ones. I know, N=1, but it is deeply depressing.

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I'm reminded of that story a few years back about methamphetamine's widespread popularity in North Korea. Starkly different from what an American would picture as "widespread meth use", but pretty much what we'd expect "widespread Adderall use" to look like.


> North Koreans say there is little stigma attached to meth use. Some take it to treat colds or boost their energy; students take it to work late. The drug also helps curb appetites in a country where food is scarce. It is offered up as casually as a cup of tea, North Koreans say.

"If you go to somebody's house it is a polite way to greet somebody by offering them a sniff," said Lee Saera, 43, of Hoeryong, also interviewed in China. "It is like drinking coffee when you're sleepy, but ice is so much better."

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Meth supposedly (sorry, no reference handy) has more 5-HTergic (serotonin) activity than regular amph. This might very well be part of the explanation for the greater efficiency, and also fits well with the anecdotal reports of an anxiolytic effect.

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Re Evekeo, as a physician, can't you simply prescribe a half-dose of d- and l- amphetamine, so your patients can pay for cheap generics instead of the on-patent Evekeo?

I've wanted to try Adderall or similar for decades - mostly to give my aging brain (I'm 59) a boost back to where it was 30 years ago. My MD won't prescribe it, even tho I'm on Wellbutrin and Effexor (he's good about Schedule 2 drugs, but he's terrified of the DEA and losing his license...).

Any suggestion re how to try it?

(BTW, welcome back to the Internet - I really missed your posts!)

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There's a take that dopamine depletion is driven entirely by dopamine just hanging out in the synaptic cleft for longer, and getting oxidized faster... so therefore the thing to do is to take MAO-B inhibitors, which coincidentally also help with neurotoxicity. I personally have found this to be relatively underwhelming, but a friend swears by it and says it lets them be productive for most of the day off 10mg dexamphetamine IR + rasagiline with much less crash than otherwise.

Their supporting literature:

Combining Stimulants and Monoamine Oxidase Inhibitors: A Reexamination of the Literature and a Report of a New Treatment Combination


Newton, T. F., De La Garza, R., Fong, T., Chiang, N., Holmes, T. H., Bloch, D. A., … Elkashef, A. (2005). A comprehensive assessment of the safety of intravenous methamphetamine administration during treatment with selegiline. Pharmacology Biochemistry and Behavior, 82(4), 704–711. doi:10.1016/j.pbb.2005.11.012


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How much do you think you would have to surcharge patients to provide adequate indemnity against the lawsuit risks of misuse of substances like this? Like a kind of compulsory insurance you force your patients to hold against the risk of them becoming addicted and harming themselves?

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Why the hesitance on Ritalin? I take it and think it's got a serious edge over Adderall. My reasoning that methylphenidate feels like a better option over Adderall because 1) it's easier to control timing (mainly the timing of side effects, like appetite suppression and wakefulness, both very important to be able to time; e.g. I can take a small dose when I leave for work at 8, come down enough to relax and enjoy lunch at noon, take another, then be back down and ready to relax for dinner/evening), 2) fewer/less intense side effects generally, particularly irritability/aggression, 3) my pharmacological knowledge is poor, but doesn't it act as a non-competitive dopamine/noradrenalin reuptake inhibitor (rather than competitive) and thus theoretically in a weird and poorly-understood and possibly unimportant (or even counter-intuitively deleterious) way, not disrupt the natural biology of the synapse quite so much, because the catalysis of the enzyme's reaction is slowed rather than just completely blocked? Idk, I majored in econ.

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<blockquote>Why did they need four different kinds of speed?</blockquote>

Because <em>they couldn't find five.</em>

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Vyvance had a very strong effect on me. Mind you, i was actively abusing uppers for fun such as esctacy pressies and coke. I took one pill. and immediately felt like i was "rolling" i was so fucked up. Within 2 weeks i was covered in scabs from picking at my skin until 4am spun out. Vyvance was hell for me i might as well have been smoking meth that whole time. my brain has not been the same since and i still have weird anxiety i never had before.

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Oddly, I hated Vyvanse and find Adderall delightful. Vyvanse made me jittery, even at low doses.

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Regarding the Desoxyn getting higher patient ratings -- to the extent it is used in only really extreme cases I think we might expect higher ratings regardless of comparative efficacy. I would guess those types of patients would see a more noticeable difference and be happier about it. If it were applied to a broader base of people I would expect the ratings to go down.

Same kind of thing as when an NBA player's usage rate goes up, usually their efficiency goes down. If you are only taking wide open shots, you are going to look extra-efficient.

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https://www.youtube.com/watch?v=YE95y62HjZk Bugs Bunny rides "Super Upper" in 1958.

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From personal experience, I've found that adjusting the medication to the right dosage and managing caffeine intake has made a greater impact on my functioning than any one medication with regard to the side effects. At least for me, the therapeutic window is ridiculously tiny.

I tend to advise other people with ADHD that neurologically normal people also have to learn how to concentrate and be disciplined, and that nobody has perfect focus.

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I'm TRD and I've tried Adderall, Dexedrine, Desoxyn, Modafinil. Here's my personal take as medications affect people differently. Adderall affects both the CNS and PNS whereas Dexedrine only affects the CNS which is why Adderall can make people physically jittery. I prefer Dexedrine for this reason and I continue to take it to this day. Modafinil was just OK, just kept me more awake than usual, I find the effect is unpredictable for me. Recommended for jet lag though. I tried a script of Desoxyn based on the description by the psychiatrist ("Best thing ever") and was not impressed. Didn't do anything really, perhaps the dosage was too low. I have a great psychiatrist who's very willing to script me most anything I want because I do my research and can talk to him about it, he learns from me sometimes and I'm not a drug abuser.

One drug I want to alert people to is Memantine. From blog comments I noticed that some people claim it helps to lower amphetamine tolerance, the problem of increasing dosage to continue the same effects. For me, it does exactly that. I find that I take much less Dexedrine than before. I often skip dosages as it has a long term effect and I'm only taking 5mg Memantine as a PRN. Sometimes every other day, sometimes every few days. I'm pretty sensitive to drug dosages so I trend to low dosages, YMMV. I'm taking only 5 mg of Dex every day or twice a day. Depends on how I feel. Memantine is sometimes used as a nootropic and it can sharpen your focus. But I have to warn you on starting out on it. It must be titrated up and you should start even lower than the doctor recommends because it can cause very disturbing nightmares when you first start. I recommend 2.5mg to start.

The other thing I'll add is that I find that a beta blocker like propranolol helps take the sharp edge off Dexedrine. My psychiatrist claims that propranolol can be used during times of grief like a death in the family to suppress long term memories that might cause PTSD. He had actually prescribed it initially because my daughter committed suicide due to Covid isolation. I'm not sure it helped with the grief but the calming effect was beneficial.

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I’ve been on a long and emotional rollercoaster of discovering myself and my mental health issues. I’ve always been quite hyper as a kid and as an adult, mixed with anxiety it’s been confusing to say the least. After my divorce at 25 I went into a deep depression and GAD. It took years to come out of it, following a lot of the advice that Dr Rhonda Patrick suggests in her various talks and podcasts. There was still something unresolved and I just couldn’t place what it was, I remember kids at school asking me if I had adhd and I passed it off as a joke. So as an adult I thought maybe… asked for a adhd test and got a simple questionaire at the doctors which I scored highly likely on and was referred to a psychiatrist to explore further. The following year (NHS) I had my first appointment with a psychiatrist and we did a full adhd survey questionnaire which took 2 hours. It was suggested that I scored highly likely to have adhd around 96%. I’m still unsure whether I have it or not but I lean towards having it. I’ve tried everything and dexa amphetamines and lisdexaamphamines were among the best but the side effects kept me off of them and I only used it while doing heavy studying and college and workload. I try and use natural methods now to improve my cognition form meditation to exercise and multi vitamin supplementation. I’m still unsure about how I feel and who I really am but I think I’m finding life much easier since I’ve had my diagnosis and my divorce. But my bubbly gregarious teenager self has definitely been put on the back burner as lives stresses blossomed.

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Im a med student who really enjoys your writing on psychiatry. I would like to suggest that you use language like "patient with stimulant disorder" instead of "addict". I'm not sure how big your medical readership is but there are numerous studies showing that provider attitudes toward (and hypothetical treatment of) patients with SUDs differ based on how they are framed in clinical vignettes.

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I've been prescribed Adderall at 120mg/day for years and it has ruined my life

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AnonymousFeb 20, 2021

I think the gradient going from l-amph to meth is how much norepinephrine is being released in addition to dopamine. Phenmetrazine was also a stimulant in the 60s, and apparently people preferred it over meth! And the difference is also that phenmetrazine is less adrenergic than meth (which is less adrenergic than r-amph which is less adrenergic than l-amph).

The clean euphoria and the ability to focus are more related to dopamine than norepinephrine, so this story is consistent with subjective reports of the drugs. I've read that meth users describe amphetamine as "meth + coffee" which of course would make you feel more anxious/experience a lot more body load.

My takeaway is that if heart health is something you care about, chances are that psychoactive-equivalent doses of meth are just better than amphs. The problem is more on the "how do I avoid not redosing when this feels so great?" side than on "meth is worse physiologically" side.

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Aug 3, 2022·edited Aug 3, 2022

This will sound a bit off-topic but I really want to bang this in people' thick skulls. When you read the word Modafinil, its precursor, or similar chemical substances, you need to understand that you can get crucified for importing it. Don't import drugs for that matter, I will say. Don't import substances. These laws change all the time. I know people can get despaired and seeking self-medication. That is ok, that is really ok. Just don't import substances. Especially forbidden substances that are innocuous. Some substances classed as supplements in some countries are classed as controlled highly addictive substances in other countries. Don't get crucified. Just search for sports shops in your country. You don't want to have to deal with customs. You don't want to be subject for a contraband investigation. Sometimes the substances are legal. Except it's illegal to import without a license and you get crucified for that.

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Do you have any thoughts on Adzenys? How does it compare to Adderall and Vyvanse?

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Pitching in my 2c as an oddball ADHD patient.

I began my adventures orally dosing questionably pure d/l amphetamine sulfate up to 15 mg/day. The compound was readily water soluble so I compounded it into nasal spray at 2.5 mg/spray. I would also dose up to 15 mg/day but this route was significantly more effective. I think shooting such low doses into my nostrils was actually sensitizing because I never seemed to develop a tolerance. The spray was tolerable, dealt zilch nostril damage and had the pleasant side effect of decongesting my nose like a budget Benzedrine.

(Un)fortunately I decided to get my life together for my professional career since we get occasional drug tests. I went to a shrink, got an ADHD diagnosis and received an Adderall prescription. I've never been 100% happy with this pharmaceutical formulation, you eat lots of it for less effect and it's full of filler so I've never tried sending it up my nose. But this stuff gives me an air of legitimacy so I keep using it. My dosage ballooned to 30 mg/day and I've developed a noticeable tolerance. Adderall gets the job done but I definitely miss the Evekeo being made in Dutch kitchens.

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If amphetamine and methamphetamine have nearly identical pharmacodynamics except meth crosses the blood brain barrier more easily, that implies meth could achieve the same CNS effect with lower doses and fewer side effects. So wouldn’t most of the kids on Adderall probably be better off microdosing meth?

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Dec 21, 2023·edited Dec 21, 2023

> It's lisdexamphetamine - ie Dexedrine attached to a random inactive molecule called lysine. As long as the lysine is attached, it can't stimulate anything. The body removes the lysine at a slow, consistent rate, which means that you get a slow, consistent release of stimulant into the bloodstream.

Can someone explain this to me? If the lysine-removal-rate is fixed, then it shouldn't be possible to vary effect by varying dosage, because you'd get the same dexamphetamine dosage independent of lisdexamphetamine dosage (which would only control the duration, not the intensity of effect). The fact that the conversion factor between dosage of other stimulants and dosage of lisdexamphetamine is a fixed constant (different for each other stimulant, of course) suggests that maybe the removal rate is linear in concentration? But then the release of stimulant should be exponentially decaying, not constant. (But maybe you call an exponential decay "consistent"?)

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