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.
Interesting, I'd never thought about that. Amino acids get all sorts of things attributed to them - tryptophan and glycine are also supposed to help anxiety - but it's possible lysine has some sort of theanine-like anxiety modulating effect. I'll have to look into it further.
I was curious as to why on earth they'd stick lysine in there instead of some inert filler compound. God alone knows if any of the touted health benefits actually exist but who knows? Maybe the particular bunch of rats they tested the formulation on just nommed up the lysine-laced drugs instead of other formulations and so they went with "yep, this is the one!" 😁
My guess is they *were* thinking of lysine as an inert filler compound. Amino acids are known safe chemicals; they all have a variety of biological effects but you can usually round them off to "too small to matter much". I don't know enough chemistry to know whether lysine is especially good at binding or at being removed by the liver in an orderly fashion, but probably that figured into it too.
The Vyvanse patent claims are specific to lysine, as far as I can tell, which is an odd choice for an inert filler you pulled out of a hat. I don't know that the anxiolytic effects are worth considering at the scale of a Vyvanse dose, but given how much money it's made you'd think someone would've had the bright idea to yoke amphetamines to a different amino acid by now.
Well, software patents are supposedly written to be as vague as the patent office will allow, just in case somebody else does something similar and you can gotcha them with your patent.
But not all patents have to work that way. Pharmaceutical patents might be written to be as specific as possible, so that when the evil day comes that your patent on lysine-inactivated amphetamine expires, you can patent the hot new drug, glycine-inactivated amphetamine.
I'd guess a likely scenario is that they tried sticking the amphetamine to a bunch of different harmless substances such as lysine, and the lysine compound happened to be the optimum in terms of how fast the liver enzymes break it down, combined with the acceptability of the substance.
It may be that of all the amino acids you can put on there, lysine _is_ the most inert. You're adding on a pretty big difference to a small amphetamine molecule, and want something that:
1) Liver enzymes (aminopeptidases?) still recognize
2) Doesn't change tissue distribution (e.g. hydrophobicity) too much
3) Doesn't have a different function on its own
Vivanse is ~ as hydrophilic as the amphetamine original, similar charge, plenty of enzymes recognize positive amino acids, and keeps it ionic and salt-able.
Now we're getting into the pharmacokinetics which is fascinating. Cursory noodling around gives me that L-lysine was picked because "Lisdexamfetamine is an inactive prodrug that is converted in the body to dextroamphetamine, a pharmacologically active compound which is responsible for the drug's activity. After oral ingestion, lisdexamfetamine is broken down by enzymes in red blood cells to form L-lysine, a naturally occurring essential amino acid, and dextroamphetamine. ...Lisdexamfetamine was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse. The attachment of the amino acid lysine slows down the relative amount of dextroamphetamine available to the blood stream."
It also says that "Common side effects of lisdexamfetamine include loss of appetite, anxiety, diarrhea, trouble sleeping, irritability, and nausea". So I'm wondering if lysine was picked because of touted anti-anxiety effects to offset this, or if it's simply a matter of structural isometry - this was the particular molecule that best slotted in with amphetimine. My stereochemistry isn't up to the task of working that out!
The bit about red blood cells is also capturing my attention, is that part of why an amino acid?
"Lisdexamfetamine was developed by New River Pharmaceuticals, who were bought by Takeda Pharmaceuticals through its acquisition of Shire Pharmaceuticals, shortly before it began being marketed. It was developed with the intention of creating a longer-lasting and less-easily abused version of dextroamphetamine, as the requirement of conversion into dextroamphetamine via enzymes in the red blood cells delays its onset of action, regardless of the route of administration."
I could just be going down a rabbit hole here, I think maybe the major reasons are (1) safe, available compound and (2) L-lysine is a serotonin antagonist, these damp the effects of amphetamines, this is what you want in a drug if you want to reduce addiction potential:
As an aside, the notion of giving 6 year old kids amphetamines makes me go "America, you are a wonder" 😦
"Lisdexamfetamine dimesylate (LDX) is the first long-acting prodrug stimulant indicated for the treatment of ADHD. Clinical evidence supports the safety and efficacy of LDX for the treatment of ADHD in children 6-12 years of age and adults."
On Sam Hyde's sketch comedy show World Peace there was a bit with a handful of small children throwing a football around while narrating their (somewhat off-putting) thoughts, and one of them was "I have to take 54 milligrams of Concerta every morning, and it's making me different."
It was interesting because before that I was initially unsure to what extent this was actually a problem, but the rest of the bit takes shots at how vapid this kid's parents are and it made me realize that I have no idea what the process of getting ADHD medication into a six-year-old looks like. Research papers are so bland, after all. Maybe there's a lot of direct eye contact and meaningful gestures between the physician and the mother?
Well, I was diagnosed when I was 7 and bounced around the usual meds, but mostly ended up taking a combination of up to 76mg of Concerta and an afternoon booster of normal Ritalin via a walk to the nurse's office.
My perspective is more or less just that the doctors were nice. I had a sleep study done (I had a lot of trouble sleeping, still do), took an IQ test, and did other tasks under observation. Mostly my medication management was meeting with the prescriber, both with and without my mother present, usually followed by waiting in the lobby while my mother met with the psychiatrist alone.
I know that my parents were pretty desperate to get me under control. My ADHD was then and is now pretty severe.
ex-pharmacist with somewhat outdated knowledge here:
the essential amino acids make really good promoieties when designing prodrugs. They're safe, they're well absorbed, usually actively transported and metabolised, they can be trivially bound to most drugs, and in general, we know a LOT about how they are absorbed, distributed, metabolised and excreted. This means we can make some educated guesses about which specific amino acid will create the desired effects.
Despite that, drug companies typically just synthesis 10-20 different amino acid esters of the drug in questions, and test them to see which performs best.
lisdexamphetamine is rapidly absorbed in the small intestine by high capacity carrier-mediated active transport, probably PepT1. High capacity transporters in the intestine target the 9 essential amino acids (histidine, isoleucine, leucine, lysine, methionine, threonine, tryptophan and valine). So these amino acids are typically good candidates for creating pro-drugs, and in many cases, are used to increase absorption of drugs that otherwise have low oral bioavailability.
The lysine is then cleaved off in red blood cells, presumably by one of the aminopeptidases, which are super-efficient and high-throughput. You want something super efficient here as lisdexamphetamine and dexamphetamine have some urinary excretion, and also because you want to extend duration of action, but only by a couple of hours. The nice property here is that this mechanism is not meaningfully saturated in the normal dosing range, and has linear properties, it's not affected by anaemia, sickle cell disease, or liver function - where significant variation in metabolism exists due to genetics, diet and other medications. This means that there will be few potential drug or diet interactions to worry about. It is somewhat dependent on haematocrit, but you still see high throughput in severely anaemic individuals. This effect is hypothesised to be linked to the differences reported by male/female patients.
lisdexamphetamine is also actively transported across the blood brain barrier, though in smaller amounts with saturable transport mechanisms. This is desirable as it's intended to have CNS action. It is likely transported to some extent by LAT1, and CAT3, which are heavily expressed in the brain, and minimally expressed elsewhere. There was some hope that targetting transporters in the BBB would improve the efficacy of dexamphetamine pro-drugs, and reduce cardiovascular side effects, but I have no idea whether this turned out to be clinically relevant. In terms of picking the best amino acid to use, tryptophan, tyrosine and phenylalanine are super effective, but cllinical use is limited due to population differences in metabolism and transport. Lysine is really nice because there aren't many (known) genetic or clinical variations that strongly impact absorption.
lisdexamfetamine is a really nice drug from a pharmacist perspective, there is low inter-patient and intra-patient pharmacokinetic variability. It isn't converted readily to dexamphetamine when snorted or smoked, as it needs active transport to enter the bloodstream and be activated by red blood cells. The dose can be titrated more effectively than with XR formulations of Adderall, as you can open capsules and sprinkle the drug on food or in water (and it remains extremely stable when you do so). Absorption is more uniform than dexamphetamines, so patients report less day to day variation in efficacy.
Personally, I like it as first-line therapy for adults who desire a long duration of action, where it isn't cost-prohibitive, especially in more hyperactive subtypes, as these individuals appear to have fewer adverse sleep effects.
I don't predict we'll get other dexamphetamine prodrugs soon, but think there's some clinical room for an even longer duration formulation, maybe some methylphenidate prodrugs?
I just wanted to mention that even now, years later, whenever I happen to come back by this essay, I think of this comment and how much I hate it.
I'm sorry. I like Deiseach, as a rule! Her comments are mostly just dandy!
It's just... it's just as if:
→ imagine someone asks:
"How do I know if the alternator on my truck is bad? I tried to test my batteries, and they're testing low CCAs but not toooo low, and my alternator is making a sound that [etc, etc.] [....]"
— and you respond "Well, some preliminary research has turned up the following: [copy/pasted Wiki article on history of the alternator]
"Fascinating stuff. But note that Britannica says *this* about automobile batteries: [herein you've copied over a section on cathodes and anodes]
"So I'm truly intrigued by this puzzler as well, but my automobile engineering experience isn't quite up to the task of determining too much more!"
NO. NO. YOU'RE... you're not WRONG, it's just... it's sort of not quite relevant, but it's worse than that, because you... you don't claim expertise, true, but you... but it... it's like some Vyvanse-101 boilerplate, but you've taken it and...
AAAAH, I can't even put into words why I still get mad about it two years later, okay, but I just... I had to finally say something. Forgive me.
That's an interesting reaction. So you're annoyed that I'm expressing an opinion that is not based on domain knowledge?
Okay. I think the chemist gave an explanation in a later comment as to what is going on. I was just interested in what the mechanism of action could be for an amino acid. If that irritates you because you know more of the topic, I'm sorry. No offense taken on my part, and feel free to skip any comments of mine that cause you pain!
examine.com notes a recommended dosage for lysine supplements of 2 grams per day (for herpes, oddly). So presumably if you can take 2 grams without significant effects, the amount in question here would be small, no?
Alternatively, maybe it was developed by InGen for their dinosaurs with lysine deficiencies and also ADHD.
Yeah, if you get cold sores from stress+herpes virus, the #1 recommendation is to swallow a couple of giant lysine pills, because the cold sores are apparently related to a deficiency. Works quickly and well.
Given that amino acids are present at a high level in the diet, I don't think the small levels of lysine that would be released from Vyvanse would have any noticeable effect.
Maximum daily dose of Vyvanse is 70mg, which comprises 22mg of lysine. That's <1% of the 2.64g lysine in the above referenced studies. 22mg is the amount of lysine in less than 1 oz of corn. Unlikely to have much effect.
Oh, I'm not wedded to the idea, I was just curious. It may perhaps be that if you're slightly deficient in lysine for whatever reason (cutting out animal proteins from your diet, for example) and taking Vyvanse helps bump up your levels to 'normal' that you generally feel somewhat better, so you attribute all the improvement to "this is a wonder drug!". But that is just wild speculation. I imagine you're correct that the amount of lysine is, relative to the ordinary diet, negligible. But biology is complicated and stuff happens differently in vivo, so I was just wondering.
It's possible that lysine that appears in the liver has a different effect from dietary lysine, which is released from proteins in and is absorbed by the small intestine.
Yeah. The Desoxyn comments make me curious. I wonder at the sustainability though? I've been off ADD meds for four years or so and am considering returning in order to improve productivity.
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.
There's non-stimulant ADHD medications such as guanfacine and less stimulant-y medications such as https://lorienpsych.com/2020/10/25/wellbutrin/, which might be relevant to your child's interests?
His dr has suggested guanfacine. I’m a little reluctant to add anything else right now. Especially since we might need to add some kind of appetite stimulant. He’s in this weird liminal place where he definitely has issues that are noticed by all but they aren’t so disruptive that they are causing unbearable consequences or impacting his learning (2e). I feel like in a school with a more creative and tolerant as ministration, maybe he wouldn’t need to be medicated at all. That’s probably another post, though.
The height and weight are probably temporary. My experience (started Concerta at 6) was that I grew a few years late, and was very skinny until college, but am normal size now. Modafinil (what I'm on now) might be worth trying, but I found it worked a lot more on attention than on behavior.
But I also had an extraordinarily strong light switch when I started. An hour or so after the first dose, I sat down and red a stack of books, which I hadn't been able to do before. I still remember that, and realizing that it was the day I learned to read. Your son's experience may differ.
Your situation sounds really different. My son also has that hyperattention thing going on. He’s always been able to read for long periods of time, play Minecraft for long periods of time, teach himself origami and chess and coding for long periods of time… It’s when it comes to less preferred activities and reining in his impulsivity (shouting out in class, overreacting to interpersonal issues) that he has a bigger problem.
Yeah, that does sound different. I've long suspected that ADD has a couple of different subtypes. Mine matches the classic symptoms perfectly. (Not to say I don't ever have hyperfocus on interesting things even on the days I skip the meds.) Provisionally withdraw the recommendation for Modafinil.
I definitely had a strong "light switch" experience, on my first very low dose of Ritalin (5mg), at age 34. (That was just about a year ago. I am on a higher dose now, to get the same effect, but the effect is still quite strong.) It seems very reasonable to consider the side effects not worth it, if the primary/desired effect is not obviously helping. (Personally, I am much happier when I can focus -- I expect your 10-year-old probably has an opinion on whether the meds are making his life better or worse. He's old enough that it seems like his opinion ought to have some weight.)
He did not want the meds at first but now proclaims that he doesn’t care and can’t tell a difference. His dr says he is not the best judge of his ability to focus ... it’s so hard to say because I am mainly going off teacher reports of behavior. (His school literally reports to me the %of time he is in topic and number of “shoutouts” in class.) The drug is mostly effective when he is in school so I don’t see it. And his grades have been excellent all along. Some improvements on standardized tests, but possibly attributable to small group setting/testing accommodations.
I share Glenn's experience with the light switch - I took a Concerta pill, and fifteen minutes later my brain went from a noisy house to a quiet one.
My grades were also excellent for years. I made it out of law school on the dean's list with undiagnosed ADD.
Less stimulation and things to focus on is good (as you probably know). How is organization, tidiness, things like that when he's medicated? Can he remember things he's supposed to do? Any behaviours that disappear? For example, I sing when I'm not medicated, and don't when I am, because songs don't get stuck in my head.
My 12 year old son has been on Vyvanse for a few years and the difference is night and day. What's lacking in people with ADHD isn't the ability to focus, it's the ability to control your focus and work towards goals that may not have immediate rewards. My observation is that it gives my son a sense of self awareness about his behavior that's absent without the aid of stimulants. I'm confident that both kids and adults could achieve similar benefits from Cognitive Behavorial Therapy and mindfulness meditation, but those require a regimented, disciplined approach that many ADHD patients might not be capable of.
My wife and I do stress some about his lack of appetite, but I'm not convinced that being a skinny kid is an issue as long as he isn't malnourished or grossly underweight. He essentially practices intermittent fasting, which has been shown to have long term benefits in anti-aging studies. I'm not going to go so far as to call it a silver lining, but being skinny > obese by a country mile.
It is sometimes difficult to distinguish between what's convenient for teachers (and to some extent for us parents) and what works well for the kid's development. There are many children who behave abnormally in school environment and often it is more of a problem with the school than with the kid.
Of course, often there is no other choice except to figure out how to make going to a particular school more bearable (that was my experience as a kid), but sometimes finding a different school or homeschooling is a possibility that can make things better.
I am talking from my very limited personal experience, but as someone who was very skeptical about homeschooling at first, I was really surprised how much homeschooling reduced my 8 year old kid's anxiety, improved his learning and focus and helped him develop better connection with a few friends he actually likes to spend time with.
(Not to say that it solves all problems or that medication can always be avoided; it is also very difficult to arrange if both parents work full-time + no help from grandparents).
not sure it's worth much but I took ADHD meds as a kid, it killed my appetite and likely caused long-term lower height. I don't think the tradeoff was worth it for me personally. If I could go back in time, I think I would've gotten a lot of benefit talking to a therapist. I don't know that I could've coped that much better with school without meds but that's mainly because the meds were for putting up with things that I think were ultimately not very useful.
Honestly, I really wish I'd discovered agenty duck's writing on TAPs back then and the instrumental rationality sequence. I'm not sure there's a good way for me to deal with organizing with things without some sort of TAP setup (though I'm still in the infant stages of this)
"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 ?
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?
Also could the sort of psychiatrist prescribing each drug have an impact? Maybe it's just that adderall is the default 1st line and better shrinks are more active about switching to a different drug.
My son’s dr said she does a Ritalin first because it is well-tolerated and has longest history. When they fail any Ritalin, she goes to an adderall. In our case, it was Focalin to Vyvanse. But then we switched doctors, and she thought the issue might be Focalin-specific and switched to Concerta, which I think is a Ritalin, and he is tolerating it best of all three so far. None have been massively helpful, though.
The biggest drivers in the US are insurance formulary compliance and I believe a perception of practitioners that methylphenidate is less problematic and that non-stimulants are not effective. Ultimately optimizing the med choice and dose to the individual is what is needed.
I suspect the fact that it's technically not an amphetamine and amphetamines have a bad rep is the main reason, even though the benefits seem to be largely the same and anecdotally I've heard the side effects tend to be a little more frequent and worse.
I think the other doctors' reasoning might be some combination of - maybe they work with children and I think Ritalin has better studies for kids - and Ritalin has lower addictive potential so if you're really worried about addiction and willing to to give patients less effective care to prevent it Ritalin might be a good tradeoff.
doesnt mean now (or ever) is the right time to start/try pharmacological treatments, but trying to be objective when weighing the life/societal costs versus the pros/cons with medication would seem to be reasonable.
I found that interesting to read, having recently discovered that Ritalin seems noticeably more effective for me than Adderall. (Male, age 35.) I guess "80% prefer Adderall" leaves potentially up to 20% who prefer Ritalin, which is not a small number of people, on an absolute scale.
The question of how to find "equivalent doses" for this comparison is a tough one. I'd say the answer is side effects -- the better choice is whichever one gives a better side-effect to desired-effect ratio. Of course, as a practical matter there are also "maximum doses" for each (which differ depending on who you ask), so "effectiveness at maximum dose [that you're willing to prescribe]" seems like maybe a good practical measurement, even if the documented "maximum doses" are sort of made up.
My experience is that, at the doses I've tried, Ritalin is somewhat more effective, and Adderall already seems to raise my blood pressure more (an extra ~5mm systolic, getting up into the 130s, measured VERY roughly) so I don't want to go higher on it.
(I solemnly pledge that I will not take anything you say in reply as medical advice, in the event that you want to correct or clarify anything for the benefit of other readers.)
Which is interesting to me, because I'm on Ritalin (well, a generic SR version, but still methylphenidate), and I worry about what'd happen if I ever had to go off of it. I'm a total zombie in the morning until I take my pills, like the way coffee-drinkers refer to caffeine.
I've never been on amphetamines, though(or any other addictive prescriptions), so maybe I just have a low standard for "addicted", and the real thing is much worse.
I find this fascinating because I'm an adult who takes Ritalin after being diagnosed with ADHD in my 20s. I was initially prescribed Vyvanse with the explanation that "it's everyone's favorite." I don't even know how to describe my Vyvanse experience except that it felt like a combination of a hangover (headache, lethargy, nausea, heart palpitations, inability to think) and a bad acid trip (totally dissociated from reality, bizarre quasi-hallucinatory trains of thought). I took it for two days and I had to call in sick to work both days because I didn't know what planet I was on. It was terrifying, and I have plenty of experience with psychedelics and dissociatives for comparison.
My doctor prescribed me Ritalin after that and it was like a light switch - I felt amazing. For the first time in my life my mind was calm enough to do one thing at a time and I could fall asleep easily and sleep through the night, which had basically never happened to me before. I had no side effects after the first couple days.
I've never been able to find a straight answer that explains my experience with Vyvanse vs. Ritalin - do you have any insight into how they could cause such wildly different responses, aside from the standard "different things work for different people" that I got from my doctor and the internet at large? I can't figure out how the mechanism of action of the two drugs could lead them to have such a wildly, disturbingly, different effect on me. It's almost as though I somehow metabolized all of the Vyvanse at once and got a massive dose intended to be spread out over several hours, but from what I've read that doesn't seem to be possible.
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.
So agree. I have ADHD untreated mainly because doctors refuse to prescribe stimulants. More broadly, the fact that some people snort over 500mg of X every day shouldn't mean doctors are afraid to prescribe 50mg of X per day, or even that I have to take the XR version that costs 10 times more. I'm in Alberta, but perhaps whatever makes doctors afraid to prescribe is happening all over. I'm sick of this drug war, but the shift in marijuana policy offers hope.
More pointedly, I have zero history of drug abuse. Still haven't tried marijuana. This unspoken assumption that 50mg of X would suddenly make me a junkie is unwarranted and is also why I quit going to a psychiatrist re: ADHD.
If doctors are refusing to prescribe stimulants, you might be just not a good candidate for stimulants. I have never had issues getting a stimulant prescription, and I see my ADHD as relatively mild.
There is HUGE variation between doctors, and I have a sense that certain things you say can make certain doctors feel that you're an excessive risk for them to work with. I was lucky -- I'm in the SF Bay Area, so I only had to try a few before I found a practice specializing in Adult ADHD that was able to work with me. But I got at least one vague and mealy-mouthed refusal prior to that, which I read as meaning "you said the wrong keywords, which means you know too much about stimulants, which means we're afraid you're going to abuse them and get us in trouble."
Yeah, I just assumed from his comment that he had this experience with multiple doctors. I’ve never had even a single doctor turn me down, including a doctor I met the same day and asked for vyvanse, a drug he had not heard of. I assume because (as I’ve heard from experts and laypeople alike) my inattentiveness and impulsivity are obvious in a single conversation.
Well, Vyvanse in particular is an abuse-resistant formulation, which is well-documented. (You can't make it come on any faster by crushing and snorting it, vs taking it orally, because it's inactive until it's metabolized.) So a smart doctor (which is, you know, some of them) shouldn't be too suspicious of you in that specific case, even if they've never heard of it before.
Alberta's system places you with a single specialist (psychiatrist, oncologist, etc.) chosen by your family doctor. Perhaps one can go back to the family doctor and request a different specialist, but I haven't tried it, I just quit going to the guy who wasn't being helpful.
I feel this way with respect to pain relief. Not that the spectrum of pain dealt with by the entire population requires more than what is already available over the counter, but specifically for me as a person who has had multiple discs removed and replaced with screws and rods, the overwhelming majority of the time, I'm fine with over the counter antiinflammatory and pain relief medications, but every now and again, I'm really not. Normally, this is any sort of extended travel where I need to be stuck in an unreclined seated position for more than 30 minutes, or on any day where I have any amount physical labor to do. Practically speaking, this has mostly meant I don't travel, work from home, and pay other people to do physical labor for me.
But even just putting together a piece of furniture or something can put me out, and in order to tolerate that, or tolerate a plane ride, I've been using the excess of the oxycodone I had left over from three surgeries in the span of 16 months three years ago. I'm finally down to my last pill and worry about what comes next. I guess the obvious solution is go to a pain management clinic and convince them I'm not a drug seeker, but they don't seem to accommodate non-uniform pain density (i.e. prescribe me a month's worth and I'll make it last three years). I feel like in being able to make a month's worth last three years already, I've more than proven I'm not going to get addicted, but the relative social stigma and legal consequences for physicians has gone up dramatically since 2017, and they're more likely than not just going to tell me to beat it.
Ideally, you have a good relationship with your primary care provider who will be aware of your situation and be willing to write you a script on-spec. Also, a low quantity is likely to be less of an issue for them. Asking for ~10 oxycodone at your annual checkup or whatever isn't likely to make them wig out too much.
Ideally, sure, but in reality I've never been on an insurance plan that required me to have a primary care provider, so I don't. I have only ever seen specialists.
That said, I arguably should have a primary care provider. I hit 40 last year and probably am at the point of needing regular generalized checkups unrelated to actually treating anything other than being alive and getting old.
Honestly I read this and my thoughts run in the direction of... "well, if you trust yourself, maybe you could get oxycodone or analogues through... other means?"---but honestly, I think Garret had a better line of advice. I am sorry to hear of your difficult situation.
I would consider this, but I've worked jobs for 13 years now that require a security clearance, many of which also require being regularly polygraphed, and I am not willing to lie to either the investigator or the polygrapher. So even laws that I believe to be stupid and unjust I still follow.
That makes sense to me. I use a similar guiding philosophy. It is quite liberating to know noone can make a credible claim of wrongdoing against you—even if it entails refraining from activities that, truly, are not wrong at all.
Prescribing desoxyn brings regulatory attention that could result in serious problems. It also causes things like pharmacies being unwilling to fill any prescriptions for controlled substances from you, which is of particular concern for a psychiatrist. Many doctors are simply unwilling to prescribe commonly-abused drugs, or drugs perceived to be very abuse liable, to protect themselves from potential legal jeopardy or harm to their business. For instance, my doctor will prescribe vyvanse but not Dexedrine because of the perception of reduced abuse liability. Since he isn’t a psychiatrist, he probably is more reluctant than a psychiatrist might be to go for second or third-line psychiatric meds when the abuse liability tradeoffs is in play.
The methyl group and the lysine are attached in the same place. Though I suppose you could replace the other hydrogen on that nitrogen with a lysine. Might end up forbidding some reactions though.
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?
Medical conservativism. My prior is that the thing everyone else is doing isn't dumb, my incentives are to err in the direction of doing the thing everyone else is doing *especially* when controlled substances are involved, and the evidence isn't *quite* strong enough to overcome my prior.
Its so sad that the foremost criteria is not what I think will work better but what won't get me in trouble. Doctors seem to spend all their time in a defensive crouch.
On the other hand, we had for decades an incentive structure which failed to adequately disincentivize extremely irresponsible prescribing practices. My grandmother almost died from a kidney stone because she had to be detoxed from the comical pile of mind-altering drugs she was prescribed by a particularly irresponsible doctor.
Off-target effects are regrettable. But, frankly, not every doctor is Scott and incentivizing more conservative prescribing practices around dangerous drugs is probably a good thing on balance.
When I had cancer in 1997, I read a lot of reassuring articles about how Real Soon Now, the government was going to wise up that the New Generation of pain medications weren't addictive and let doctors prescribe them more freely.
Eighteen years later, I came to suspect that old media blitz had been part of the Oxycontin push that had such unfortunate consequences.
But, still, just like the 1997 articles said, if I were dying painfully of cancer, I wouldn't mind getting an opioid prescription.
My brother couldn't get the ADHD medicine he needed. He is smart. And figured out meth was better. But then he got addicted and his life spiraled out of control.
My brother wasn't a junkie. He wasn't looking for a recreational high; he was after something functional for his debilitating ADHD.
If he had has sensible psychologists willing to prescribe a low dose with the proper ROA, he probably wouldn't have ruined his life.
Working with his psychiatrists has been maddening and bewildering.I don't understand why the evidence isn't sufficient to overcome your prior.
Why not? It's clearly a superior agent with plenty of validation? Is there actually good evidence Desoxyn leads to ruination? Or are you just inappropriately anchoring on smoked and insufflated crystal meth?
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?
Drug effects (wanted and unwanted) aren't linear with respect to dose. I would have to think about exactly why the nonlinearities make what you're saying a worse idea rather than a better one, but one possibility is because most drugs have many possible side effects and only one wanted effect.
Arguendo, if the nonlinearities manifest as zero response below some threshold dose D and linear above that (e.g., m * (d - D)), where the thresholds & slopes vary between effects, you'd expect to see very different ratios between wanted & unwanted effects at various dose levels.
In extremis, there might be a dose for each of component above the threshold for wanted effect but below that for any unwanted effects; you could then, hypothetically, add components at their individual optimal doses until the total wanted effect is attained without any unwanted effects, but you couldn't just keep adding more of any one of them and get the same balance.
The "interference effects" thing is specifically interesting to me with regard to stimulants and guanfacine. The latter is a blood-pressure-lowering medication which is also sometimes prescribed for ADHD, and indeed its main side effect (of lowering blood pressure) seemed to directly oppose some of the side effects of stimulants.
HOWEVER, in my case it took very little guanfacine to lower my BP to numbers I found a bit concerning, and some of the _other_ side effects (in particular appetite loss) are common to both drugs. And it was hard to tell whether guanfacine was actually doing anything for the ADHD symptoms. And both drugs have some effects on how nerve impulses propagate in the heart, and I think there's very little data to look at how those might interact / what their combined risks might be (although I understand them to be quite low in both cases.) And of course liver enzymes interact with practically everything in complicated ways. So any time you're adding more drugs, your risk of "some kind of thing happened that we didn't predict / don't understand" goes up.
I have read in several places that Alpha agonists (e.g. clonidine, guanfacine) actually work very well with stimulants. Their ADHD effects work together and they counter much of the side effects and limit excessive noradrenergic activity.
This also matches my experience (taking clonidine for a different reason).
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.
That is a great point, medical student disease is real. I think the vision impairment analogy above is really good. Every one (pretty much) has some vision issue impairment, but the treatment can be calibrated to the impairment very exactly. Going even further.... for specialised uses we have microscopes / telescopes, or those jewellers eye pieces. If only there were pharmaceutical equivalents.
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.
Honestly? I think somewhat worse. I remember being on Ritalin when I was younger - that was the first med I was put on, and the rebound was _terrible_ - but I was on adderall a much shorter time. I believe I was on the ER version, but I wasn't on it long, so I don't think it worked as well as my parents were hoping. This could have been due to the ER not being strong enough compared to the IR. I was also on dexedrine ER for a few months as well and it simply wasn't strong enough.
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.
I'm not sure why you're thinking Dexedrine would make you crash less than Vyvanse; it's shorter acting so I would expect it would make you crash more. You might want to look at the last link in the post for more actionable crash-related advice.
oh. yeah. good point. i mean as i said right now we're treating the crash problem by throwing more vyvanse at it, and it sort of works. but i'm definitely going to look into tyrosine. also, maybe my new psychiatrist will have some other ideas.
clinically depressed in the colloquial sense, i guess. i become unusable as a human being, i want to hide away from the world, i regress into a scared child (yes i have c-ptsd). it's really bad.
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.
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.
Also, to be clear, I only ordered legitimate things from pharmacies, not homebrewed mixtures. And I tried both the instant release and slow release versions of Adderall and Dexedrine to make sure it was a fair comparison.
There is no way to be sure “legitimate things from pharmacies” are what they claim to be on the dark web. There are many reports of counterfeit drugs, which for adderall/Dexedrine could include anything from Meth to 4-FA to different varieties of bath salts. While certain dark web mechanisms try to limit things like this, there is no way to be sure your data isn’t corrupted by it.
Be super-duper careful with this stuff. If it’s cheaper to make meth look like adderall than to divert adderall, you will get meth that looks like adderall.
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.
If they're legal in your location you can try methylphenidate (Ritalin) derivatives like IPPH and 4F-MPH.
Amphetamine has many variants on the market, methylphenidate only one. So if Ritalin worked better than amphetamine, it's worth trying its analogues. Many seem promising for ADHD and some are in clinical trials already.
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.
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?
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.
Levoamphetamine also has stronger peripheral effect, and given its weaker centrally, that should alone be a quite solid argument for sticking to dextro in treatment of adhd. Since the peripheral effects are afterall the main reasons for organic damage over time.
I guess thats what we are mainly doing in europe. Of all patients i came across getting treated with amphetamines, i never saw racemic amf or other mixtures. Ots usually dexamf as in attentin, or metamina. Or most commonly lisdex
This is very late, I know. Purity of d-amphetamine (including data from purchase and seizure) has been mostly over 50% and always over 40% since the 1980s according to a report from the Obama administration. A statista report whose veracity I can’t surmise indicated it’s been over 95% and steadily increasing since at least 2012.
This actually scans. For one, users want a crystalline product because they associate it with purity (a generally correct association). You can cut a crystal product, but it’s harder and riskier because you have to cut it with other crystals. That can cause irregular potency or even the failure of a reagent test. If your meth is in crystal form, it’s either 0% meth And 100% Epsom salt or it’s above whatever purity threshold you need to form d-methamphetamine crystals. I don’t know what that exact level is, but I’d bet at least 80%.
It also scans with the shift in production. Originally, meth was bad from methylamine by biker gangs. It was racemic, low quality powder. Then methylamine got controlled. Production switched to using ephedrine as a starting material. It gave pure d-amphetamine, which is a better product. But it was also easier to get, and easier to synthesize generally. That’s where you saw illicit amphetamine get squeezed out of the market. You just can’t compete with something that can be made from match strikers and cold medicine that can be cooked up by anyone with a remote address and a high tolerance for risk.
That new small scale meth was low purity, though, both because the market was accustomed to powders and because the people doing it were technically able to produce methamphetamine in the same way my old roommate was technically able to fix the dryer by removing the starting switch and tapping the two wires together. The product was impure, often probably too impure to crystallize well.
Then pseudoephedrine got controlled, so for well over the last 20 years, the meth business has been controlled by vertically integrated, billion dollar businesses employing professional chemists in illicit labs that rival any legitimate chemical manufacturer’s facilities. These are businesses who control the product from production to very near retail, and whose primary costs are in smuggling and protecting the product rather than in the product itself. Combined with the difficulty of consistently cutting the purity of something the market expects in crystalline form, the actual economic realities of meth, the purity of street meth is over 90% these days.
But they were always, always since the 80s snorting or smoking at least 50% pure meth by weight. And they were usually doing it every two hours for multiple days on end.
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.
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.
In the post you replied to. “Safe” being relative. Illicit drugs always carry some risk. But either having a scale accurate to the milligram or one accurate to whatever and the ability to mix a known volume of solvent with a close enough to known (relatively high) weight of chemical is all you need to be as safe as you have any chance of being. But you are also in a world where you know have access to meth in quantity and are only taking doses so low because of your judgement. Your judgement could get worse over time.
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.
I would be surprised by anyone thinking "I'm concerned about the addiction potential, can we look at some lower-risk medications" is a drug-seeking behavior? Also there's buproprion and guanfacine and some other non-stimulants.
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?
Adderall is strongly associated with being a study drug and as such is already expensive at therapeutic doses. Also consider that Adderall proper is manufactured way differently, i.e., not in home labs, and from what I know, people mainly source it with fraudulent prescriptions. I can't imagine convincing to get any psych to prescribe meth-levels of Adderall (25x by Scott's estimate), not least of all considering FDA guidelines for CII dosing would have them nailed to the cross.
I don't think that people using amphetamine pills as party drugs before the 70s war on drugs distinguished between meth and vanilla, but I'm not sure. Here's an essay on the history that doesn't answer that question.
We would, but getting such a huge dose of adderall is simply not economical. Meth is extremely easy to produce from very available feedstocks. Adderall or Dexedrine require more complex chemistry, and they’re also about 40-50% as potent by weight.
It’s pretty much the same reason you have seen the black market for OxyContin dry up as the level of control has made diversion more expensive. Also why heroin was the black market drug of choice for decades before a huge supply of oxycodone became available to divert. Oxycodone isn’t exactly super complicated to make, but it can’t be readily made in a bathtub by an afghani poppy farmer the way heroin can.
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.
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.
What he’s saying about desoxyn is based on relatively limited data. There is simply not much financial incentive to spend the research dollars, and a not-insignificant potential PR cost to trying to vyvanse-ify methamphetamine. To say nothing of the ethical concerns about the possibility that further research could actually determine methamphetamine is more dangerous in humans.
Because doing the research is ethically trickier if that considered the most likely outcome. Determining that with research means exposing real people to the potential harms. So if your starting position (or the starting position of the ethics committee) is that you’re going to confirm the conventional wisdom, the ethical approach is not to run the trial.
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.
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?)
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.
That’s a simple half-life for methamphetamine. Part of that half-life involves it being metabolized to amphetamine instead of an inactive metabolite, which then competes with the methamphetamine for metabolism/excretion. Things get wonky when you have active metabolites like this.
I'd really love to see what kind of a manufacturing plant that is. Keeping it FDA-approved as a medical-grade facility, and some bored old biochemist makes a batch the size of a chocolate bar once a year.
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.
I also find the discussion of desoxyn interesting. I wonder if it could just have a more favorable side effect profile than amphetamine? That really is my main takeaway from the difference between adderall and vyvanse. Even with the extended action, vyvanse causes me less anxiety and less sleep disturbance. Not none, unfortunately, so I do have to take temazepam with it, but I am particularly sensitive to sleep disturbance as I am phase delay to start and not permitted to wake up at noon and still pay for my life.
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.
If your personal theory held water, you would not be able to levomethamphetamine inhalers at gas stations. Since you can, your theory has some holes in it.
Yup. It’s sold uncontrolled, over the counter as a nasal decongestant. They use the German name (levmetamfetamine) on the label because they don’t want people getting ideas. But it has basically zero recreational use, and there is no reason I’m aware of to believe that levoamphetmine would be meaningfully more recreational.
I mean, in my experience with adderall vs vyvanse what I perceive is an increase in blood pressure, heart rate, and subjective anxiety. Maybe the symptathomimetic effects result in more useful or pleasant outcomes for others. But the thrust of the article is that dextro-only formulations are rated more effective and better tolerated. So, the available data (which is fairly limited) seems to imply that there’s nothing to what you’re saying at best and it’s provably false at worst.
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.
In the US, methylphenidate is most commonly known under the brand name Ritalin which Scott mentioned above. But it's not an amphetamine, so possibly outside the scope of this article.
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.
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.
Which is not to say amphetamines aren't really fun, modafinil is rather boring, I'd much rather take amphetamines for a cocktail party. But the fact that modafinil is boring would make it seem like a better candidate for clinical use.
I’ve taken modafinil, and I found it to have unacceptably high side effects compared to amphetamines, as well as lower efficacy. It caused me no less sleep disturbance, and a level of drug-induced anxiety comparable to methylphenidate with much less effectiveness.
I know that trials have been run on modafinil for adhd, and neither it nor its derivatives are approved for that indication. So, I suspect my experience generalizes.
Hmh, fair enough, I find this surprising but I had only anecdotal evidence. I'll look into it, you may well be right and my experience may have been unusual
Out of curiosity, what side effects do you find modafinil has ? The one thing I liked about it was complete lacked of side effects other than reduced sleep with prolonged consumption
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.
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.
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.
My psychiatrist recommend a home blood pressure cuff -- they're not that expensive. (Pre-COVID, I think there was still a requirement to come into the office every so often for a more official in-person check, but that seems to be getting waived right now.)
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?
The four things in Adderall are: dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate
Two of those are amphetamine, which means they're 50-50 d/l, and the other two are dextroamphetamine, which means they're 100-0. I think they're all in equal proportions, so Adderall as a whole ends up 75-25.
I love that half of the ingredients are salts of amphetamines and artificial sweeteners. Good thing they went out of their way to make to avoid abuse by making the shit taste like candy if you chew it!
"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?
I've never worried about brand. I have one patient who swears that only brand-name Adderall works for him, generics make him feel terrible, but he's taking IR.
My wife has had some really bad experiences specifically with Aurobindo and I'm pretty sure she was able to produce decent evidence that the experience generalizes, but that's just one bad brand, not all generics are bad. It's to the point that she chooses a pharmacy based on that (since they're all going to give some sort of generic).
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.
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)
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.
completely not valid. Stimulants don't help people with ADHD more than people without. Stimulants make focus easier regardless of whether you have trouble focusing. If you have adhd stimulants still might not help
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?
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.)
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.
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.
He answers a different question further down with something like “my prior is that something everyone in my field is doing isn’t stupid, and the evidence isn’t strong enough to overcome my prior yet”. Probably the same answer to this.
We have all a few , esp young, people on stimulants enter a psychotic state. For forever, the practice has been methylphenidate for teens and above to start, but is not dogma. There may be some concern the state, unscientific as they tend to be, will focus on one’s practice for showing monolithic prescription patterns. We have to log in to the state with the name of each person to assess for “doctor shopping.”
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.
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.
Unfortunately the hyper focus is usually on activities which do not stretch cognitive so much as skills which require a very narrow set of responses, eg video games instead of philosophical treatises
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.
I’m chattering too much on this thread but can’t resist here. Untreated with “speed”, ADHD kids ( the majority of JD kids I see) fall into activities with high risk consequences ranging from auto accidents, impulsive joyriding, substance use before cortical maturation is achieved, vast school underachievement and being a real pain to their families. In an adult jail setting sit so many very bright but lifelong untreated ADHD adults.
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.
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.
Thanks for bringing this up. I had never heard of ADHD inattentive, just googled it, and it basically matches my mental state exactly. I had always just ruled out ADHD as a possibility for me because I am definitely not "hyperactive", quite the opposite in fact.
FWIW, I was on Wellbutrin for about 18 months. It was effective at first for increasing my energy/focus, but I guess I built up a tolerance. Towards the end of that period I'd take it, feel nothing, and then literally take a nap. Everybody is different though, so hopefully your daughter will get some benefit.
Your daughter might need to be re-evaluated for the diagnosis. It is certainly possible but unlikely for someone with severe primary ADHD not to respond to stimulants. I would look for learning disabilities and neurological problems (a complete neuropsychological evaluation) in addition to a revision of the psychiatric diagnosis. They might recommend neuroimaging but I wouldn't do anything before the comprehensive neuropsych eval.
Stimulants (amphetamines and methylphenidate) work for both subtypes. There are variations in MOA (mechanism of action) and individual response, but they are very similar.
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."
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.
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!)
I don’t think there’s really a commercially available form of pure l-amphetamine because of the chemistry of it. There is probably a way to make it, but you would only do it if you needed a new over the counter decongestant. And l-methamphetamine is already in use for that.
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
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?
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.
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.
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.
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.
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.
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.
I sympathize. I totally changed after having children and never snapped back to my old self even after trying all sorts of meds. Dexedrine helps with my tiredness so I'm more functional but that's it. IMO, we have a crisis in psychiatry. It's being dominated by Big Pharma and psychiatrists are overly adhering to dogma and not embracing new ideas/drugs. Ketamine is a good example. The feds are another problem in being so restrictive regarding psychedelic drugs which could help many like MDMA, LSD, psylocibin. Whether it's a monitored trip or microdosing. Let us have legal choices. There are a few clinical trials but we all know that it will take years for any approvals.
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.
Is that what they teach in med schools instead of pharmacology nowadays? For the record, commonly prescribed stimulants, amphetamines and methylphenidate, do not cause addiction. Perhaps they don't last long enough with a half-life of under an hour. Instead, they are abused, which is not quite the same as addiction.
You just can’t get enough of them cheaply enough to really be “addicted”. If you like them enough that you any to take it to the next level, you need to go to illicit meth.
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.
Meth has affinity for certain serotonin receptors that increase your risk of cardiac valve hypertrophy and pulmonary arterial hypertension. Not a huge increase in risk, but not none.
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.
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.
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?
> 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"?)
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:
https://www.healthline.com/nutrition/lysine-benefits
"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.
Interesting, I'd never thought about that. Amino acids get all sorts of things attributed to them - tryptophan and glycine are also supposed to help anxiety - but it's possible lysine has some sort of theanine-like anxiety modulating effect. I'll have to look into it further.
I was curious as to why on earth they'd stick lysine in there instead of some inert filler compound. God alone knows if any of the touted health benefits actually exist but who knows? Maybe the particular bunch of rats they tested the formulation on just nommed up the lysine-laced drugs instead of other formulations and so they went with "yep, this is the one!" 😁
My guess is they *were* thinking of lysine as an inert filler compound. Amino acids are known safe chemicals; they all have a variety of biological effects but you can usually round them off to "too small to matter much". I don't know enough chemistry to know whether lysine is especially good at binding or at being removed by the liver in an orderly fashion, but probably that figured into it too.
The Vyvanse patent claims are specific to lysine, as far as I can tell, which is an odd choice for an inert filler you pulled out of a hat. I don't know that the anxiolytic effects are worth considering at the scale of a Vyvanse dose, but given how much money it's made you'd think someone would've had the bright idea to yoke amphetamines to a different amino acid by now.
Well, software patents are supposedly written to be as vague as the patent office will allow, just in case somebody else does something similar and you can gotcha them with your patent.
But not all patents have to work that way. Pharmaceutical patents might be written to be as specific as possible, so that when the evil day comes that your patent on lysine-inactivated amphetamine expires, you can patent the hot new drug, glycine-inactivated amphetamine.
I already miss the "edit your comment" feature from the old blog. :(
I'd guess a likely scenario is that they tried sticking the amphetamine to a bunch of different harmless substances such as lysine, and the lysine compound happened to be the optimum in terms of how fast the liver enzymes break it down, combined with the acceptability of the substance.
It may be that of all the amino acids you can put on there, lysine _is_ the most inert. You're adding on a pretty big difference to a small amphetamine molecule, and want something that:
1) Liver enzymes (aminopeptidases?) still recognize
2) Doesn't change tissue distribution (e.g. hydrophobicity) too much
3) Doesn't have a different function on its own
Vivanse is ~ as hydrophilic as the amphetamine original, similar charge, plenty of enzymes recognize positive amino acids, and keeps it ionic and salt-able.
Now we're getting into the pharmacokinetics which is fascinating. Cursory noodling around gives me that L-lysine was picked because "Lisdexamfetamine is an inactive prodrug that is converted in the body to dextroamphetamine, a pharmacologically active compound which is responsible for the drug's activity. After oral ingestion, lisdexamfetamine is broken down by enzymes in red blood cells to form L-lysine, a naturally occurring essential amino acid, and dextroamphetamine. ...Lisdexamfetamine was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse. The attachment of the amino acid lysine slows down the relative amount of dextroamphetamine available to the blood stream."
It also says that "Common side effects of lisdexamfetamine include loss of appetite, anxiety, diarrhea, trouble sleeping, irritability, and nausea". So I'm wondering if lysine was picked because of touted anti-anxiety effects to offset this, or if it's simply a matter of structural isometry - this was the particular molecule that best slotted in with amphetimine. My stereochemistry isn't up to the task of working that out!
https://en.wikipedia.org/wiki/Lisdexamfetamine#Chemistry
The bit about red blood cells is also capturing my attention, is that part of why an amino acid?
"Lisdexamfetamine was developed by New River Pharmaceuticals, who were bought by Takeda Pharmaceuticals through its acquisition of Shire Pharmaceuticals, shortly before it began being marketed. It was developed with the intention of creating a longer-lasting and less-easily abused version of dextroamphetamine, as the requirement of conversion into dextroamphetamine via enzymes in the red blood cells delays its onset of action, regardless of the route of administration."
https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=4509&context=open_access_pubs
I could just be going down a rabbit hole here, I think maybe the major reasons are (1) safe, available compound and (2) L-lysine is a serotonin antagonist, these damp the effects of amphetamines, this is what you want in a drug if you want to reduce addiction potential:
https://pubmed.ncbi.nlm.nih.gov/24145075/
As an aside, the notion of giving 6 year old kids amphetamines makes me go "America, you are a wonder" 😦
"Lisdexamfetamine dimesylate (LDX) is the first long-acting prodrug stimulant indicated for the treatment of ADHD. Clinical evidence supports the safety and efficacy of LDX for the treatment of ADHD in children 6-12 years of age and adults."
On Sam Hyde's sketch comedy show World Peace there was a bit with a handful of small children throwing a football around while narrating their (somewhat off-putting) thoughts, and one of them was "I have to take 54 milligrams of Concerta every morning, and it's making me different."
It was interesting because before that I was initially unsure to what extent this was actually a problem, but the rest of the bit takes shots at how vapid this kid's parents are and it made me realize that I have no idea what the process of getting ADHD medication into a six-year-old looks like. Research papers are so bland, after all. Maybe there's a lot of direct eye contact and meaningful gestures between the physician and the mother?
Well, I was diagnosed when I was 7 and bounced around the usual meds, but mostly ended up taking a combination of up to 76mg of Concerta and an afternoon booster of normal Ritalin via a walk to the nurse's office.
My perspective is more or less just that the doctors were nice. I had a sleep study done (I had a lot of trouble sleeping, still do), took an IQ test, and did other tasks under observation. Mostly my medication management was meeting with the prescriber, both with and without my mother present, usually followed by waiting in the lobby while my mother met with the psychiatrist alone.
I know that my parents were pretty desperate to get me under control. My ADHD was then and is now pretty severe.
ex-pharmacist with somewhat outdated knowledge here:
the essential amino acids make really good promoieties when designing prodrugs. They're safe, they're well absorbed, usually actively transported and metabolised, they can be trivially bound to most drugs, and in general, we know a LOT about how they are absorbed, distributed, metabolised and excreted. This means we can make some educated guesses about which specific amino acid will create the desired effects.
Despite that, drug companies typically just synthesis 10-20 different amino acid esters of the drug in questions, and test them to see which performs best.
lisdexamphetamine is rapidly absorbed in the small intestine by high capacity carrier-mediated active transport, probably PepT1. High capacity transporters in the intestine target the 9 essential amino acids (histidine, isoleucine, leucine, lysine, methionine, threonine, tryptophan and valine). So these amino acids are typically good candidates for creating pro-drugs, and in many cases, are used to increase absorption of drugs that otherwise have low oral bioavailability.
The lysine is then cleaved off in red blood cells, presumably by one of the aminopeptidases, which are super-efficient and high-throughput. You want something super efficient here as lisdexamphetamine and dexamphetamine have some urinary excretion, and also because you want to extend duration of action, but only by a couple of hours. The nice property here is that this mechanism is not meaningfully saturated in the normal dosing range, and has linear properties, it's not affected by anaemia, sickle cell disease, or liver function - where significant variation in metabolism exists due to genetics, diet and other medications. This means that there will be few potential drug or diet interactions to worry about. It is somewhat dependent on haematocrit, but you still see high throughput in severely anaemic individuals. This effect is hypothesised to be linked to the differences reported by male/female patients.
lisdexamphetamine is also actively transported across the blood brain barrier, though in smaller amounts with saturable transport mechanisms. This is desirable as it's intended to have CNS action. It is likely transported to some extent by LAT1, and CAT3, which are heavily expressed in the brain, and minimally expressed elsewhere. There was some hope that targetting transporters in the BBB would improve the efficacy of dexamphetamine pro-drugs, and reduce cardiovascular side effects, but I have no idea whether this turned out to be clinically relevant. In terms of picking the best amino acid to use, tryptophan, tyrosine and phenylalanine are super effective, but cllinical use is limited due to population differences in metabolism and transport. Lysine is really nice because there aren't many (known) genetic or clinical variations that strongly impact absorption.
lisdexamfetamine is a really nice drug from a pharmacist perspective, there is low inter-patient and intra-patient pharmacokinetic variability. It isn't converted readily to dexamphetamine when snorted or smoked, as it needs active transport to enter the bloodstream and be activated by red blood cells. The dose can be titrated more effectively than with XR formulations of Adderall, as you can open capsules and sprinkle the drug on food or in water (and it remains extremely stable when you do so). Absorption is more uniform than dexamphetamines, so patients report less day to day variation in efficacy.
Personally, I like it as first-line therapy for adults who desire a long duration of action, where it isn't cost-prohibitive, especially in more hyperactive subtypes, as these individuals appear to have fewer adverse sleep effects.
I don't predict we'll get other dexamphetamine prodrugs soon, but think there's some clinical room for an even longer duration formulation, maybe some methylphenidate prodrugs?
I just wanted to mention that even now, years later, whenever I happen to come back by this essay, I think of this comment and how much I hate it.
I'm sorry. I like Deiseach, as a rule! Her comments are mostly just dandy!
It's just... it's just as if:
→ imagine someone asks:
"How do I know if the alternator on my truck is bad? I tried to test my batteries, and they're testing low CCAs but not toooo low, and my alternator is making a sound that [etc, etc.] [....]"
— and you respond "Well, some preliminary research has turned up the following: [copy/pasted Wiki article on history of the alternator]
"Fascinating stuff. But note that Britannica says *this* about automobile batteries: [herein you've copied over a section on cathodes and anodes]
"So I'm truly intrigued by this puzzler as well, but my automobile engineering experience isn't quite up to the task of determining too much more!"
NO. NO. YOU'RE... you're not WRONG, it's just... it's sort of not quite relevant, but it's worse than that, because you... you don't claim expertise, true, but you... but it... it's like some Vyvanse-101 boilerplate, but you've taken it and...
AAAAH, I can't even put into words why I still get mad about it two years later, okay, but I just... I had to finally say something. Forgive me.
That's an interesting reaction. So you're annoyed that I'm expressing an opinion that is not based on domain knowledge?
Okay. I think the chemist gave an explanation in a later comment as to what is going on. I was just interested in what the mechanism of action could be for an amino acid. If that irritates you because you know more of the topic, I'm sorry. No offense taken on my part, and feel free to skip any comments of mine that cause you pain!
examine.com notes a recommended dosage for lysine supplements of 2 grams per day (for herpes, oddly). So presumably if you can take 2 grams without significant effects, the amount in question here would be small, no?
Alternatively, maybe it was developed by InGen for their dinosaurs with lysine deficiencies and also ADHD.
Yeah, if you get cold sores from stress+herpes virus, the #1 recommendation is to swallow a couple of giant lysine pills, because the cold sores are apparently related to a deficiency. Works quickly and well.
Given that amino acids are present at a high level in the diet, I don't think the small levels of lysine that would be released from Vyvanse would have any noticeable effect.
Except that the lysine released from Vyvanse appears in the liver while dietary lysine is released from proteins in the small intestine.
Maximum daily dose of Vyvanse is 70mg, which comprises 22mg of lysine. That's <1% of the 2.64g lysine in the above referenced studies. 22mg is the amount of lysine in less than 1 oz of corn. Unlikely to have much effect.
as someone who experienced the anti-anxiety effects of vyvanse this is extremely fascinating for me
It's worth keeping in mind that a typical dose of Vyvanse is a couple of orders of magnitude lower than the studied doses.
Max Vyvanse capsules are 70mg. According to the molar mass of the compound, lysine is about half of that dosage.
So 40mg of lysine daily very unlikely have any physiological activity.
Oh, I'm not wedded to the idea, I was just curious. It may perhaps be that if you're slightly deficient in lysine for whatever reason (cutting out animal proteins from your diet, for example) and taking Vyvanse helps bump up your levels to 'normal' that you generally feel somewhat better, so you attribute all the improvement to "this is a wonder drug!". But that is just wild speculation. I imagine you're correct that the amount of lysine is, relative to the ordinary diet, negligible. But biology is complicated and stuff happens differently in vivo, so I was just wondering.
It's possible that lysine that appears in the liver has a different effect from dietary lysine, which is released from proteins in and is absorbed by the small intestine.
this sounds like a shitty situation for anyone who’d be best helped by Desoxyn.
Yeah. The Desoxyn comments make me curious. I wonder at the sustainability though? I've been off ADD meds for four years or so and am considering returning in order to improve productivity.
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.
There's non-stimulant ADHD medications such as guanfacine and less stimulant-y medications such as https://lorienpsych.com/2020/10/25/wellbutrin/, which might be relevant to your child's interests?
His dr has suggested guanfacine. I’m a little reluctant to add anything else right now. Especially since we might need to add some kind of appetite stimulant. He’s in this weird liminal place where he definitely has issues that are noticed by all but they aren’t so disruptive that they are causing unbearable consequences or impacting his learning (2e). I feel like in a school with a more creative and tolerant as ministration, maybe he wouldn’t need to be medicated at all. That’s probably another post, though.
guanfacine can be used alone. As a replacement for a stimulant, it would likely resolve the appetite issues
The height and weight are probably temporary. My experience (started Concerta at 6) was that I grew a few years late, and was very skinny until college, but am normal size now. Modafinil (what I'm on now) might be worth trying, but I found it worked a lot more on attention than on behavior.
But I also had an extraordinarily strong light switch when I started. An hour or so after the first dose, I sat down and red a stack of books, which I hadn't been able to do before. I still remember that, and realizing that it was the day I learned to read. Your son's experience may differ.
Your situation sounds really different. My son also has that hyperattention thing going on. He’s always been able to read for long periods of time, play Minecraft for long periods of time, teach himself origami and chess and coding for long periods of time… It’s when it comes to less preferred activities and reining in his impulsivity (shouting out in class, overreacting to interpersonal issues) that he has a bigger problem.
Yeah, that does sound different. I've long suspected that ADD has a couple of different subtypes. Mine matches the classic symptoms perfectly. (Not to say I don't ever have hyperfocus on interesting things even on the days I skip the meds.) Provisionally withdraw the recommendation for Modafinil.
That's me, absolutely. Dexedrine worked for me on a low dose. All other meds either didn't work or were uncomfortable.
> Vyvanse (“empty hollow feeling”)
I get this with higher doses. Maybe 2x smaller dose would work for your kid?
He was on a super low dose already. The only lower dose had no effect.
I definitely had a strong "light switch" experience, on my first very low dose of Ritalin (5mg), at age 34. (That was just about a year ago. I am on a higher dose now, to get the same effect, but the effect is still quite strong.) It seems very reasonable to consider the side effects not worth it, if the primary/desired effect is not obviously helping. (Personally, I am much happier when I can focus -- I expect your 10-year-old probably has an opinion on whether the meds are making his life better or worse. He's old enough that it seems like his opinion ought to have some weight.)
He did not want the meds at first but now proclaims that he doesn’t care and can’t tell a difference. His dr says he is not the best judge of his ability to focus ... it’s so hard to say because I am mainly going off teacher reports of behavior. (His school literally reports to me the %of time he is in topic and number of “shoutouts” in class.) The drug is mostly effective when he is in school so I don’t see it. And his grades have been excellent all along. Some improvements on standardized tests, but possibly attributable to small group setting/testing accommodations.
I share Glenn's experience with the light switch - I took a Concerta pill, and fifteen minutes later my brain went from a noisy house to a quiet one.
My grades were also excellent for years. I made it out of law school on the dean's list with undiagnosed ADD.
Less stimulation and things to focus on is good (as you probably know). How is organization, tidiness, things like that when he's medicated? Can he remember things he's supposed to do? Any behaviours that disappear? For example, I sing when I'm not medicated, and don't when I am, because songs don't get stuck in my head.
My 12 year old son has been on Vyvanse for a few years and the difference is night and day. What's lacking in people with ADHD isn't the ability to focus, it's the ability to control your focus and work towards goals that may not have immediate rewards. My observation is that it gives my son a sense of self awareness about his behavior that's absent without the aid of stimulants. I'm confident that both kids and adults could achieve similar benefits from Cognitive Behavorial Therapy and mindfulness meditation, but those require a regimented, disciplined approach that many ADHD patients might not be capable of.
My wife and I do stress some about his lack of appetite, but I'm not convinced that being a skinny kid is an issue as long as he isn't malnourished or grossly underweight. He essentially practices intermittent fasting, which has been shown to have long term benefits in anti-aging studies. I'm not going to go so far as to call it a silver lining, but being skinny > obese by a country mile.
It is sometimes difficult to distinguish between what's convenient for teachers (and to some extent for us parents) and what works well for the kid's development. There are many children who behave abnormally in school environment and often it is more of a problem with the school than with the kid.
Of course, often there is no other choice except to figure out how to make going to a particular school more bearable (that was my experience as a kid), but sometimes finding a different school or homeschooling is a possibility that can make things better.
I am talking from my very limited personal experience, but as someone who was very skeptical about homeschooling at first, I was really surprised how much homeschooling reduced my 8 year old kid's anxiety, improved his learning and focus and helped him develop better connection with a few friends he actually likes to spend time with.
(Not to say that it solves all problems or that medication can always be avoided; it is also very difficult to arrange if both parents work full-time + no help from grandparents).
not sure it's worth much but I took ADHD meds as a kid, it killed my appetite and likely caused long-term lower height. I don't think the tradeoff was worth it for me personally. If I could go back in time, I think I would've gotten a lot of benefit talking to a therapist. I don't know that I could've coped that much better with school without meds but that's mainly because the meds were for putting up with things that I think were ultimately not very useful.
Honestly, I really wish I'd discovered agenty duck's writing on TAPs back then and the instrumental rationality sequence. I'm not sure there's a good way for me to deal with organizing with things without some sort of TAP setup (though I'm still in the infant stages of this)
"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 ?
Are the non-adderal sample sizes too small (in addition to the other potential biases)?
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?
There are other cases where weird drugs you would normally be careful prescribing get high ratings - see the stuff on MAOIs at https://slatestarcodex.com/2015/04/30/prescriptions-paradoxes-and-perversities/ . I can't remember if I checked for the general case.
While this data is not controlled in any way, anecdotal reports online support the notion that methamphetamine > amphetamine for functional use.
Generally described as smoother, with less physical side effects ("body load"), and having clearer focus.
Also could the sort of psychiatrist prescribing each drug have an impact? Maybe it's just that adderall is the default 1st line and better shrinks are more active about switching to a different drug.
A lot of doctors prescribe Ritalin first. Do you know what their reasoning might be?
My son’s dr said she does a Ritalin first because it is well-tolerated and has longest history. When they fail any Ritalin, she goes to an adderall. In our case, it was Focalin to Vyvanse. But then we switched doctors, and she thought the issue might be Focalin-specific and switched to Concerta, which I think is a Ritalin, and he is tolerating it best of all three so far. None have been massively helpful, though.
The biggest drivers in the US are insurance formulary compliance and I believe a perception of practitioners that methylphenidate is less problematic and that non-stimulants are not effective. Ultimately optimizing the med choice and dose to the individual is what is needed.
I suspect the fact that it's technically not an amphetamine and amphetamines have a bad rep is the main reason, even though the benefits seem to be largely the same and anecdotally I've heard the side effects tend to be a little more frequent and worse.
See https://lorienpsych.com/2020/10/30/adderall/#1_Is_Adderall_the_right_stimulant_for_me for a discussion of why I prescribe amphetamines first.
I think the other doctors' reasoning might be some combination of - maybe they work with children and I think Ritalin has better studies for kids - and Ritalin has lower addictive potential so if you're really worried about addiction and willing to to give patients less effective care to prevent it Ritalin might be a good tradeoff.
Less effective care sounds more likely to create addiction than the drug tradeoff
This is one of the things experts kept telling me when they were telling me to medicate my son. That untreated ADHD can lead to “self medication”.
doesnt mean now (or ever) is the right time to start/try pharmacological treatments, but trying to be objective when weighing the life/societal costs versus the pros/cons with medication would seem to be reasonable.
I found that interesting to read, having recently discovered that Ritalin seems noticeably more effective for me than Adderall. (Male, age 35.) I guess "80% prefer Adderall" leaves potentially up to 20% who prefer Ritalin, which is not a small number of people, on an absolute scale.
The question of how to find "equivalent doses" for this comparison is a tough one. I'd say the answer is side effects -- the better choice is whichever one gives a better side-effect to desired-effect ratio. Of course, as a practical matter there are also "maximum doses" for each (which differ depending on who you ask), so "effectiveness at maximum dose [that you're willing to prescribe]" seems like maybe a good practical measurement, even if the documented "maximum doses" are sort of made up.
My experience is that, at the doses I've tried, Ritalin is somewhat more effective, and Adderall already seems to raise my blood pressure more (an extra ~5mm systolic, getting up into the 130s, measured VERY roughly) so I don't want to go higher on it.
(I solemnly pledge that I will not take anything you say in reply as medical advice, in the event that you want to correct or clarify anything for the benefit of other readers.)
Which is interesting to me, because I'm on Ritalin (well, a generic SR version, but still methylphenidate), and I worry about what'd happen if I ever had to go off of it. I'm a total zombie in the morning until I take my pills, like the way coffee-drinkers refer to caffeine.
I've never been on amphetamines, though(or any other addictive prescriptions), so maybe I just have a low standard for "addicted", and the real thing is much worse.
I find this fascinating because I'm an adult who takes Ritalin after being diagnosed with ADHD in my 20s. I was initially prescribed Vyvanse with the explanation that "it's everyone's favorite." I don't even know how to describe my Vyvanse experience except that it felt like a combination of a hangover (headache, lethargy, nausea, heart palpitations, inability to think) and a bad acid trip (totally dissociated from reality, bizarre quasi-hallucinatory trains of thought). I took it for two days and I had to call in sick to work both days because I didn't know what planet I was on. It was terrifying, and I have plenty of experience with psychedelics and dissociatives for comparison.
My doctor prescribed me Ritalin after that and it was like a light switch - I felt amazing. For the first time in my life my mind was calm enough to do one thing at a time and I could fall asleep easily and sleep through the night, which had basically never happened to me before. I had no side effects after the first couple days.
I've never been able to find a straight answer that explains my experience with Vyvanse vs. Ritalin - do you have any insight into how they could cause such wildly different responses, aside from the standard "different things work for different people" that I got from my doctor and the internet at large? I can't figure out how the mechanism of action of the two drugs could lead them to have such a wildly, disturbingly, different effect on me. It's almost as though I somehow metabolized all of the Vyvanse at once and got a massive dose intended to be spread out over several hours, but from what I've read that doesn't seem to be possible.
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.
So agree. I have ADHD untreated mainly because doctors refuse to prescribe stimulants. More broadly, the fact that some people snort over 500mg of X every day shouldn't mean doctors are afraid to prescribe 50mg of X per day, or even that I have to take the XR version that costs 10 times more. I'm in Alberta, but perhaps whatever makes doctors afraid to prescribe is happening all over. I'm sick of this drug war, but the shift in marijuana policy offers hope.
More pointedly, I have zero history of drug abuse. Still haven't tried marijuana. This unspoken assumption that 50mg of X would suddenly make me a junkie is unwarranted and is also why I quit going to a psychiatrist re: ADHD.
If doctors are refusing to prescribe stimulants, you might be just not a good candidate for stimulants. I have never had issues getting a stimulant prescription, and I see my ADHD as relatively mild.
There is HUGE variation between doctors, and I have a sense that certain things you say can make certain doctors feel that you're an excessive risk for them to work with. I was lucky -- I'm in the SF Bay Area, so I only had to try a few before I found a practice specializing in Adult ADHD that was able to work with me. But I got at least one vague and mealy-mouthed refusal prior to that, which I read as meaning "you said the wrong keywords, which means you know too much about stimulants, which means we're afraid you're going to abuse them and get us in trouble."
Yeah, I just assumed from his comment that he had this experience with multiple doctors. I’ve never had even a single doctor turn me down, including a doctor I met the same day and asked for vyvanse, a drug he had not heard of. I assume because (as I’ve heard from experts and laypeople alike) my inattentiveness and impulsivity are obvious in a single conversation.
Well, Vyvanse in particular is an abuse-resistant formulation, which is well-documented. (You can't make it come on any faster by crushing and snorting it, vs taking it orally, because it's inactive until it's metabolized.) So a smart doctor (which is, you know, some of them) shouldn't be too suspicious of you in that specific case, even if they've never heard of it before.
Alberta's system places you with a single specialist (psychiatrist, oncologist, etc.) chosen by your family doctor. Perhaps one can go back to the family doctor and request a different specialist, but I haven't tried it, I just quit going to the guy who wasn't being helpful.
They'll do a second specialist. put yeah, you're kinda at your family doctor's mercy when it comes to finding a good fit with a specialist.
*But
Either that, or he's a good candidate for a new doctor.
I feel this way with respect to pain relief. Not that the spectrum of pain dealt with by the entire population requires more than what is already available over the counter, but specifically for me as a person who has had multiple discs removed and replaced with screws and rods, the overwhelming majority of the time, I'm fine with over the counter antiinflammatory and pain relief medications, but every now and again, I'm really not. Normally, this is any sort of extended travel where I need to be stuck in an unreclined seated position for more than 30 minutes, or on any day where I have any amount physical labor to do. Practically speaking, this has mostly meant I don't travel, work from home, and pay other people to do physical labor for me.
But even just putting together a piece of furniture or something can put me out, and in order to tolerate that, or tolerate a plane ride, I've been using the excess of the oxycodone I had left over from three surgeries in the span of 16 months three years ago. I'm finally down to my last pill and worry about what comes next. I guess the obvious solution is go to a pain management clinic and convince them I'm not a drug seeker, but they don't seem to accommodate non-uniform pain density (i.e. prescribe me a month's worth and I'll make it last three years). I feel like in being able to make a month's worth last three years already, I've more than proven I'm not going to get addicted, but the relative social stigma and legal consequences for physicians has gone up dramatically since 2017, and they're more likely than not just going to tell me to beat it.
Ideally, you have a good relationship with your primary care provider who will be aware of your situation and be willing to write you a script on-spec. Also, a low quantity is likely to be less of an issue for them. Asking for ~10 oxycodone at your annual checkup or whatever isn't likely to make them wig out too much.
Ideally, sure, but in reality I've never been on an insurance plan that required me to have a primary care provider, so I don't. I have only ever seen specialists.
That said, I arguably should have a primary care provider. I hit 40 last year and probably am at the point of needing regular generalized checkups unrelated to actually treating anything other than being alive and getting old.
Honestly I read this and my thoughts run in the direction of... "well, if you trust yourself, maybe you could get oxycodone or analogues through... other means?"---but honestly, I think Garret had a better line of advice. I am sorry to hear of your difficult situation.
I would consider this, but I've worked jobs for 13 years now that require a security clearance, many of which also require being regularly polygraphed, and I am not willing to lie to either the investigator or the polygrapher. So even laws that I believe to be stupid and unjust I still follow.
That makes sense to me. I use a similar guiding philosophy. It is quite liberating to know noone can make a credible claim of wrongdoing against you—even if it entails refraining from activities that, truly, are not wrong at all.
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?
Prescribing desoxyn brings regulatory attention that could result in serious problems. It also causes things like pharmacies being unwilling to fill any prescriptions for controlled substances from you, which is of particular concern for a psychiatrist. Many doctors are simply unwilling to prescribe commonly-abused drugs, or drugs perceived to be very abuse liable, to protect themselves from potential legal jeopardy or harm to their business. For instance, my doctor will prescribe vyvanse but not Dexedrine because of the perception of reduced abuse liability. Since he isn’t a psychiatrist, he probably is more reluctant than a psychiatrist might be to go for second or third-line psychiatric meds when the abuse liability tradeoffs is in play.
Uggh! What an inedequate equilibrium.
The methyl group and the lysine are attached in the same place. Though I suppose you could replace the other hydrogen on that nitrogen with a lysine. Might end up forbidding some reactions though.
??? The lysine is attached via an amide bond to the Nitrogen, the methyl group is on the alpha Carbon.
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?
Medical conservativism. My prior is that the thing everyone else is doing isn't dumb, my incentives are to err in the direction of doing the thing everyone else is doing *especially* when controlled substances are involved, and the evidence isn't *quite* strong enough to overcome my prior.
“my incentives” seems like the key part here
Its so sad that the foremost criteria is not what I think will work better but what won't get me in trouble. Doctors seem to spend all their time in a defensive crouch.
On the other hand, we had for decades an incentive structure which failed to adequately disincentivize extremely irresponsible prescribing practices. My grandmother almost died from a kidney stone because she had to be detoxed from the comical pile of mind-altering drugs she was prescribed by a particularly irresponsible doctor.
Off-target effects are regrettable. But, frankly, not every doctor is Scott and incentivizing more conservative prescribing practices around dangerous drugs is probably a good thing on balance.
When I had cancer in 1997, I read a lot of reassuring articles about how Real Soon Now, the government was going to wise up that the New Generation of pain medications weren't addictive and let doctors prescribe them more freely.
Eighteen years later, I came to suspect that old media blitz had been part of the Oxycontin push that had such unfortunate consequences.
But, still, just like the 1997 articles said, if I were dying painfully of cancer, I wouldn't mind getting an opioid prescription.
My brother couldn't get the ADHD medicine he needed. He is smart. And figured out meth was better. But then he got addicted and his life spiraled out of control.
My brother wasn't a junkie. He wasn't looking for a recreational high; he was after something functional for his debilitating ADHD.
If he had has sensible psychologists willing to prescribe a low dose with the proper ROA, he probably wouldn't have ruined his life.
Working with his psychiatrists has been maddening and bewildering.I don't understand why the evidence isn't sufficient to overcome your prior.
Why not? It's clearly a superior agent with plenty of validation? Is there actually good evidence Desoxyn leads to ruination? Or are you just inappropriately anchoring on smoked and insufflated crystal meth?
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?
Drug effects (wanted and unwanted) aren't linear with respect to dose. I would have to think about exactly why the nonlinearities make what you're saying a worse idea rather than a better one, but one possibility is because most drugs have many possible side effects and only one wanted effect.
Arguendo, if the nonlinearities manifest as zero response below some threshold dose D and linear above that (e.g., m * (d - D)), where the thresholds & slopes vary between effects, you'd expect to see very different ratios between wanted & unwanted effects at various dose levels.
In extremis, there might be a dose for each of component above the threshold for wanted effect but below that for any unwanted effects; you could then, hypothetically, add components at their individual optimal doses until the total wanted effect is attained without any unwanted effects, but you couldn't just keep adding more of any one of them and get the same balance.
The "interference effects" thing is specifically interesting to me with regard to stimulants and guanfacine. The latter is a blood-pressure-lowering medication which is also sometimes prescribed for ADHD, and indeed its main side effect (of lowering blood pressure) seemed to directly oppose some of the side effects of stimulants.
HOWEVER, in my case it took very little guanfacine to lower my BP to numbers I found a bit concerning, and some of the _other_ side effects (in particular appetite loss) are common to both drugs. And it was hard to tell whether guanfacine was actually doing anything for the ADHD symptoms. And both drugs have some effects on how nerve impulses propagate in the heart, and I think there's very little data to look at how those might interact / what their combined risks might be (although I understand them to be quite low in both cases.) And of course liver enzymes interact with practically everything in complicated ways. So any time you're adding more drugs, your risk of "some kind of thing happened that we didn't predict / don't understand" goes up.
You're not accounting for the risk of unwanted drug interactions.
I have read in several places that Alpha agonists (e.g. clonidine, guanfacine) actually work very well with stimulants. Their ADHD effects work together and they counter much of the side effects and limit excessive noradrenergic activity.
This also matches my experience (taking clonidine for a different reason).
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.
*everything
That is a great point, medical student disease is real. I think the vision impairment analogy above is really good. Every one (pretty much) has some vision issue impairment, but the treatment can be calibrated to the impairment very exactly. Going even further.... for specialised uses we have microscopes / telescopes, or those jewellers eye pieces. If only there were pharmaceutical equivalents.
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.
How does Adderall work for you?
Honestly? I think somewhat worse. I remember being on Ritalin when I was younger - that was the first med I was put on, and the rebound was _terrible_ - but I was on adderall a much shorter time. I believe I was on the ER version, but I wasn't on it long, so I don't think it worked as well as my parents were hoping. This could have been due to the ER not being strong enough compared to the IR. I was also on dexedrine ER for a few months as well and it simply wasn't strong enough.
The Sci-Hub links don't work for me, I think because they point to .se rather than, say, .st. Cheers.
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.
I'm not sure why you're thinking Dexedrine would make you crash less than Vyvanse; it's shorter acting so I would expect it would make you crash more. You might want to look at the last link in the post for more actionable crash-related advice.
oh. yeah. good point. i mean as i said right now we're treating the crash problem by throwing more vyvanse at it, and it sort of works. but i'm definitely going to look into tyrosine. also, maybe my new psychiatrist will have some other ideas.
but basically when i crash i get clinically depressed. it's much worse than what you describe on that page, i think.
clinically depressed in the colloquial sense, i guess. i become unusable as a human being, i want to hide away from the world, i regress into a scared child (yes i have c-ptsd). it's really bad.
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.
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.
Also, to be clear, I only ordered legitimate things from pharmacies, not homebrewed mixtures. And I tried both the instant release and slow release versions of Adderall and Dexedrine to make sure it was a fair comparison.
There is no way to be sure “legitimate things from pharmacies” are what they claim to be on the dark web. There are many reports of counterfeit drugs, which for adderall/Dexedrine could include anything from Meth to 4-FA to different varieties of bath salts. While certain dark web mechanisms try to limit things like this, there is no way to be sure your data isn’t corrupted by it.
Be super-duper careful with this stuff. If it’s cheaper to make meth look like adderall than to divert adderall, you will get meth that looks like adderall.
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.
If they're legal in your location you can try methylphenidate (Ritalin) derivatives like IPPH and 4F-MPH.
Amphetamine has many variants on the market, methylphenidate only one. So if Ritalin worked better than amphetamine, it's worth trying its analogues. Many seem promising for ADHD and some are in clinical trials already.
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.
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?
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 :-)
Levoamphetamine also has stronger peripheral effect, and given its weaker centrally, that should alone be a quite solid argument for sticking to dextro in treatment of adhd. Since the peripheral effects are afterall the main reasons for organic damage over time.
I guess thats what we are mainly doing in europe. Of all patients i came across getting treated with amphetamines, i never saw racemic amf or other mixtures. Ots usually dexamf as in attentin, or metamina. Or most commonly lisdex
This is very late, I know. Purity of d-amphetamine (including data from purchase and seizure) has been mostly over 50% and always over 40% since the 1980s according to a report from the Obama administration. A statista report whose veracity I can’t surmise indicated it’s been over 95% and steadily increasing since at least 2012.
This actually scans. For one, users want a crystalline product because they associate it with purity (a generally correct association). You can cut a crystal product, but it’s harder and riskier because you have to cut it with other crystals. That can cause irregular potency or even the failure of a reagent test. If your meth is in crystal form, it’s either 0% meth And 100% Epsom salt or it’s above whatever purity threshold you need to form d-methamphetamine crystals. I don’t know what that exact level is, but I’d bet at least 80%.
It also scans with the shift in production. Originally, meth was bad from methylamine by biker gangs. It was racemic, low quality powder. Then methylamine got controlled. Production switched to using ephedrine as a starting material. It gave pure d-amphetamine, which is a better product. But it was also easier to get, and easier to synthesize generally. That’s where you saw illicit amphetamine get squeezed out of the market. You just can’t compete with something that can be made from match strikers and cold medicine that can be cooked up by anyone with a remote address and a high tolerance for risk.
That new small scale meth was low purity, though, both because the market was accustomed to powders and because the people doing it were technically able to produce methamphetamine in the same way my old roommate was technically able to fix the dryer by removing the starting switch and tapping the two wires together. The product was impure, often probably too impure to crystallize well.
Then pseudoephedrine got controlled, so for well over the last 20 years, the meth business has been controlled by vertically integrated, billion dollar businesses employing professional chemists in illicit labs that rival any legitimate chemical manufacturer’s facilities. These are businesses who control the product from production to very near retail, and whose primary costs are in smuggling and protecting the product rather than in the product itself. Combined with the difficulty of consistently cutting the purity of something the market expects in crystalline form, the actual economic realities of meth, the purity of street meth is over 90% these days.
But they were always, always since the 80s snorting or smoking at least 50% pure meth by weight. And they were usually doing it every two hours for multiple days on end.
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.
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.
Where can I find detailed instructions for safe oral use?
In the post you replied to. “Safe” being relative. Illicit drugs always carry some risk. But either having a scale accurate to the milligram or one accurate to whatever and the ability to mix a known volume of solvent with a close enough to known (relatively high) weight of chemical is all you need to be as safe as you have any chance of being. But you are also in a world where you know have access to meth in quantity and are only taking doses so low because of your judgement. Your judgement could get worse over time.
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.
I would be surprised by anyone thinking "I'm concerned about the addiction potential, can we look at some lower-risk medications" is a drug-seeking behavior? Also there's buproprion and guanfacine and some other non-stimulants.
sorry, that sentence was hard to parse due to multiple negations. I agree it would hopefully not be seen as drug seeking behavior.
I had not heard of guanfacine before. Thank you!
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?
Adderall is strongly associated with being a study drug and as such is already expensive at therapeutic doses. Also consider that Adderall proper is manufactured way differently, i.e., not in home labs, and from what I know, people mainly source it with fraudulent prescriptions. I can't imagine convincing to get any psych to prescribe meth-levels of Adderall (25x by Scott's estimate), not least of all considering FDA guidelines for CII dosing would have them nailed to the cross.
I don't think that people using amphetamine pills as party drugs before the 70s war on drugs distinguished between meth and vanilla, but I'm not sure. Here's an essay on the history that doesn't answer that question.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377281/
We would, but getting such a huge dose of adderall is simply not economical. Meth is extremely easy to produce from very available feedstocks. Adderall or Dexedrine require more complex chemistry, and they’re also about 40-50% as potent by weight.
It’s pretty much the same reason you have seen the black market for OxyContin dry up as the level of control has made diversion more expensive. Also why heroin was the black market drug of choice for decades before a huge supply of oxycodone became available to divert. Oxycodone isn’t exactly super complicated to make, but it can’t be readily made in a bathtub by an afghani poppy farmer the way heroin can.
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...
https://web.archive.org/web/20180406015345/https://www.selfhacked.com/blog/worrier-warrior-explaining-rs4680comt-v158m-gene/
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.
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.
What he’s saying about desoxyn is based on relatively limited data. There is simply not much financial incentive to spend the research dollars, and a not-insignificant potential PR cost to trying to vyvanse-ify methamphetamine. To say nothing of the ethical concerns about the possibility that further research could actually determine methamphetamine is more dangerous in humans.
It’s really a touchy subject.
how would meth being determined more risky be a problem? that is literally the status quo
Because doing the research is ethically trickier if that considered the most likely outcome. Determining that with research means exposing real people to the potential harms. So if your starting position (or the starting position of the ethics committee) is that you’re going to confirm the conventional wisdom, the ethical approach is not to run the trial.
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.
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?)
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.
If everything you write here is true, then some kind of slow-release methamphetamine would be ideal.
Slow-release methamphetamine would cause significant insomnia, given its already long half-life.
Is it that different from regular amphetamine? This[0] says the half life of meth is 10 hours, and this[1] says Adderall is 9 hours.
[0] https://pubmed.ncbi.nlm.nih.gov/14586388/
[1] https://www.therecoveryvillage.com/amphetamine-addiction/faq/how-long-do-amphetamines-stay-system/
That’s a simple half-life for methamphetamine. Part of that half-life involves it being metabolized to amphetamine instead of an inactive metabolite, which then competes with the methamphetamine for metabolism/excretion. Things get wonky when you have active metabolites like this.
Though, I should have said “long action” instead of long half-life. More accurate.
I see from the writeup on Adderall that I *am* an outlier on this, and my positive response to Wellbutrin makes sense given that paper.
I believe doctors are still allowed to prescribe PCP, too
It has a manufacturing quota of 19 grams annually, so they can’t prescribe it for much.
I'd really love to see what kind of a manufacturing plant that is. Keeping it FDA-approved as a medical-grade facility, and some bored old biochemist makes a batch the size of a chocolate bar once a year.
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.
I also find the discussion of desoxyn interesting. I wonder if it could just have a more favorable side effect profile than amphetamine? That really is my main takeaway from the difference between adderall and vyvanse. Even with the extended action, vyvanse causes me less anxiety and less sleep disturbance. Not none, unfortunately, so I do have to take temazepam with it, but I am particularly sensitive to sleep disturbance as I am phase delay to start and not permitted to wake up at noon and still pay for my life.
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.
If your personal theory held water, you would not be able to levomethamphetamine inhalers at gas stations. Since you can, your theory has some holes in it.
Levomethamphetamine is different from methamphetamine?
Yup. It’s sold uncontrolled, over the counter as a nasal decongestant. They use the German name (levmetamfetamine) on the label because they don’t want people getting ideas. But it has basically zero recreational use, and there is no reason I’m aware of to believe that levoamphetmine would be meaningfully more recreational.
Right, but when I say "perceivable high", I'm not talking about it being more enjoyable - just people noticing the sympathomimetic effects more.
I mean, in my experience with adderall vs vyvanse what I perceive is an increase in blood pressure, heart rate, and subjective anxiety. Maybe the symptathomimetic effects result in more useful or pleasant outcomes for others. But the thrust of the article is that dextro-only formulations are rated more effective and better tolerated. So, the available data (which is fairly limited) seems to imply that there’s nothing to what you’re saying at best and it’s provably false at worst.
...I think we are talking past each other. My point is that those effects you name actually make people think it is "working".
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.
In the US, methylphenidate is most commonly known under the brand name Ritalin which Scott mentioned above. But it's not an amphetamine, so possibly outside the scope of this article.
Hmm, I guess methylphenidate is Ritalin. Still not sure how it fits in with the other meds discussed.
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.
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.
typo: "Richwell" should be "Richwood"
I was wondering about this, glad to see someone else noticed. They could also be two related (or unrelated) corporations.
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.
Which is not to say amphetamines aren't really fun, modafinil is rather boring, I'd much rather take amphetamines for a cocktail party. But the fact that modafinil is boring would make it seem like a better candidate for clinical use.
I’ve taken modafinil, and I found it to have unacceptably high side effects compared to amphetamines, as well as lower efficacy. It caused me no less sleep disturbance, and a level of drug-induced anxiety comparable to methylphenidate with much less effectiveness.
I know that trials have been run on modafinil for adhd, and neither it nor its derivatives are approved for that indication. So, I suspect my experience generalizes.
Hmh, fair enough, I find this surprising but I had only anecdotal evidence. I'll look into it, you may well be right and my experience may have been unusual
Out of curiosity, what side effects do you find modafinil has ? The one thing I liked about it was complete lacked of side effects other than reduced sleep with prolonged consumption
Anxiety, agitation, insomnia. Same as amphetamines.
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.
Came here to post this. It’s a clear advantage of methylphenidate. Surprised Scott didn’t mention it.
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.
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.
See https://lorienpsych.com/2020/10/30/adderall/#5_Are_there_long-term_side_effects_of_Adderall
My psychiatrist recommend a home blood pressure cuff -- they're not that expensive. (Pre-COVID, I think there was still a requirement to come into the office every so often for a more official in-person check, but that seems to be getting waived right now.)
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?
Sorry, I didn't make that clear.
The four things in Adderall are: dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate
Two of those are amphetamine, which means they're 50-50 d/l, and the other two are dextroamphetamine, which means they're 100-0. I think they're all in equal proportions, so Adderall as a whole ends up 75-25.
I love that half of the ingredients are salts of amphetamines and artificial sweeteners. Good thing they went out of their way to make to avoid abuse by making the shit taste like candy if you chew it!
"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?
I've never worried about brand. I have one patient who swears that only brand-name Adderall works for him, generics make him feel terrible, but he's taking IR.
My wife has had some really bad experiences specifically with Aurobindo and I'm pretty sure she was able to produce decent evidence that the experience generalizes, but that's just one bad brand, not all generics are bad. It's to the point that she chooses a pharmacy based on that (since they're all going to give some sort of generic).
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.
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)
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.
completely not valid. Stimulants don't help people with ADHD more than people without. Stimulants make focus easier regardless of whether you have trouble focusing. If you have adhd stimulants still might not help
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?
Nicotine makes me feel great, but unfortunately my understanding is that it is too cardiotoxic to be advisable to take frequently.
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.)
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.
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.
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.
He answers a different question further down with something like “my prior is that something everyone in my field is doing isn’t stupid, and the evidence isn’t strong enough to overcome my prior yet”. Probably the same answer to this.
We have all a few , esp young, people on stimulants enter a psychotic state. For forever, the practice has been methylphenidate for teens and above to start, but is not dogma. There may be some concern the state, unscientific as they tend to be, will focus on one’s practice for showing monolithic prescription patterns. We have to log in to the state with the name of each person to assess for “doctor shopping.”
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.
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.
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.
If you can read the entirety of one of Scott's posts, can you be suffering from untreated ADHD?
Hyperfocus is a well-known symptom of ADHD. One possible presentation might be binging SSC archive posts.
Unfortunately the hyper focus is usually on activities which do not stretch cognitive so much as skills which require a very narrow set of responses, eg video games instead of philosophical treatises
Ha
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.
Isn’t it...bad to give millions of young kids speed? I don’t know much about drugs...but it sounds bad.
I’m chattering too much on this thread but can’t resist here. Untreated with “speed”, ADHD kids ( the majority of JD kids I see) fall into activities with high risk consequences ranging from auto accidents, impulsive joyriding, substance use before cortical maturation is achieved, vast school underachievement and being a real pain to their families. In an adult jail setting sit so many very bright but lifelong untreated ADHD adults.
Scott, What drug would you recommend for a 7 year old with ADHD?
Probably the one his doctor recommends after examining him.
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.
Vyvanse has been around since 2007.
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.
Thanks for bringing this up. I had never heard of ADHD inattentive, just googled it, and it basically matches my mental state exactly. I had always just ruled out ADHD as a possibility for me because I am definitely not "hyperactive", quite the opposite in fact.
FWIW, I was on Wellbutrin for about 18 months. It was effective at first for increasing my energy/focus, but I guess I built up a tolerance. Towards the end of that period I'd take it, feel nothing, and then literally take a nap. Everybody is different though, so hopefully your daughter will get some benefit.
In my experience, this is true-ish.
Your daughter might need to be re-evaluated for the diagnosis. It is certainly possible but unlikely for someone with severe primary ADHD not to respond to stimulants. I would look for learning disabilities and neurological problems (a complete neuropsychological evaluation) in addition to a revision of the psychiatric diagnosis. They might recommend neuroimaging but I wouldn't do anything before the comprehensive neuropsych eval.
Stimulants (amphetamines and methylphenidate) work for both subtypes. There are variations in MOA (mechanism of action) and individual response, but they are very similar.
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.
https://www.smh.com.au/world/in-north-korea-meth-is-offered-as-casually-as-a-cup-of-tea-20140129-hvabv.html
> 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."
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.
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!)
Oops - I meant he's good about Schedule 3 drugs, of course. He won't prescribe Schedule 2 drugs.
I don’t think there’s really a commercially available form of pure l-amphetamine because of the chemistry of it. There is probably a way to make it, but you would only do it if you needed a new over the counter decongestant. And l-methamphetamine is already in use for that.
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
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805402/
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
https://sci-hub.se/https://www.sciencedirect.com/science/article/pii/S0091305705003722
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?
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.
For me, methylphenidate causes significantly more intense anxiety and side effects while not working nearly as well.
You just demonstrated how one can know all of the pharmacokinetics/dynamics and still not be able to explain why one works better than others
<blockquote>Why did they need four different kinds of speed?</blockquote>
Because <em>they couldn't find five.</em>
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.
Oddly, I hated Vyvanse and find Adderall delightful. Vyvanse made me jittery, even at low doses.
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.
https://www.youtube.com/watch?v=YE95y62HjZk Bugs Bunny rides "Super Upper" in 1958.
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.
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.
Sounds like you have a great psychiatrist. Count your blessings
Beta blockers are contraindicated for use with amphetamines due to some interplay between beta adrenergic and alpha adrenergic receptors.
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.
I sympathize. I totally changed after having children and never snapped back to my old self even after trying all sorts of meds. Dexedrine helps with my tiredness so I'm more functional but that's it. IMO, we have a crisis in psychiatry. It's being dominated by Big Pharma and psychiatrists are overly adhering to dogma and not embracing new ideas/drugs. Ketamine is a good example. The feds are another problem in being so restrictive regarding psychedelic drugs which could help many like MDMA, LSD, psylocibin. Whether it's a monitored trip or microdosing. Let us have legal choices. There are a few clinical trials but we all know that it will take years for any approvals.
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.
Is that what they teach in med schools instead of pharmacology nowadays? For the record, commonly prescribed stimulants, amphetamines and methylphenidate, do not cause addiction. Perhaps they don't last long enough with a half-life of under an hour. Instead, they are abused, which is not quite the same as addiction.
You just can’t get enough of them cheaply enough to really be “addicted”. If you like them enough that you any to take it to the next level, you need to go to illicit meth.
I’m what world does adderall not cause addiction? That’s plain false
I've been prescribed Adderall at 120mg/day for years and it has ruined my life
Sorry to hear that. Please tell us more if you wish to.
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.
Meth has affinity for certain serotonin receptors that increase your risk of cardiac valve hypertrophy and pulmonary arterial hypertension. Not a huge increase in risk, but not none.
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.
Do you have any thoughts on Adzenys? How does it compare to Adderall and Vyvanse?
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.
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?
> 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"?)