[epistemic status - Personal experience mixed with interpretation of research, don’t take this blindly as truth, though I am confident of the consensus when I express there to be consensus]
I have ADHD. If you talk to me it’s impossible not to notice.
I have tried many a stimulant over the past 8 years and acquired what I would say is a respectable amount of knowledge. I would like to share my conclusions today, because current guides on the internet are severely lacking.
Know that conclusions are based on my personal experience, YMMV, I will not keep reiterating this
This post is for the baby ADHDer, the crackheads & the stimulant curious. For the rest, feel free to skip this one
Stimulants
Stimulant medications (in practice) can be uniquely identified as a set of the following triple:1
right isomer or mixed salt/racemic mixture?
long or short acting?
amphetamine or methylphenidate?
The exception here is desoxyn. Which is meth. I would love to try it but Europe won’t let me.23
Amphetamines vs Methylphenidate
Methylphenidates work via preventing dopamine reuptake (prevents dopamine from escaping from the receptor). Amphetamines do the same but they also just flatout make you produce more dopamine.4 Also both of them increase your noradrenalin. All of this leads to a bunch of effects.
ADHD brains lack both, (but the actual truth is probably way more complicated)
So generally, amphetamines are more intense and more addicting. They’re generally slightly less tolerated, but have significantly greater effect size in ADHD symptom reduction.
right isomer vs mixed salt/racemic mixtures
So what the fuck do isomers mean? Honestly, I barely know myself.5 But to my understanding there is right handed versions of these molecules (D-amp, D-, Dextro-, etc) and left handed version of these molecules (l-, levo, etc). People generally prefer the right handed one (d) over a mix of right and left-handed ones. (we don’t sell pure left handed). D-amp makes people more alert, has less physical side effects and is more euphoric. Overall, it’s works better and is more tolerated by most people. (It’s also more addictive). L-amp has been associated with a lot of stimulant side effects I think are particularly nasty, like jitteriness and anxiety.
So why are mixes the default? This is the actual story: Some company had a patent on a pill equal parts meth and amphetamines for weight loss (glory days). Then meth got a lot of bad karma associated with it, so they reformulated. But the sixties were a weird time, people loved just mixing drugs together instead of having one active ingredient, so this impulse, mixed with patent gaming led to them patenting a mix of L-amphetamine and D-amphetamine. Simple D-amp couldn’t be patented… They named it ADD for ALL and the rest is history! Ridiculous!
They are depriving us of our D-amp glory! Making us jittery! (NOTE: a small amount of people seem to respond positively to L-amp, but I think it’s a stupid default)
Short acting vs long acting (i crash you crash)
When I take instant release (short acting) stimulants It feels way too overwhelming for me. I experience a very intense come-up, with effects too intense to allow me to focus properly, and then when I reach a flow state I am thrust into the emotional rollercoaster of the dreaded stimulant comedown. If you have never experienced a stimulant comedown, just know that it’s bad.
I’ve called this the “peakyness” problem. All instant stimulants feel too peaky to me. Long acting basically solves this for me. They also basically solve the crash by making it so gradual you don’t even notice.
If my experiences are at all general: I strongly advise you to take long acting versions of these medications, especially if you plan to be on them the entire day anyway.
The Amphetamines
There are 3 main ones:
Dexedrine: right isomer short acting amphetamine
Vyvanse: right isomer long acting amphetamine
Adderall/evekeo: mixed salt short acting amphetamine
As I said, people generally prefer dexedrine to adderall. It is kind of a mystery to me why we keep prescribing these mixed salts when people have this strong preference, nevertheless adderall is the one that everyone knows. I have not taken it, my experience is limited to right isomer amhetamine (dexedrine) and vyvanse.
If there is anything at all that you should take away from this blogpost is that lisdexamphetamine (vyvanse) consistently has the highest effect size in ADHD symptom reduction in adults compared to any other medication.6
Despite this, it’s only a third line medication in B*lgium. Worse, it is still patented, which is not the case in the land of the free. I begrudgingly pay 90 euros a month for it. It is just that good.
Vyvanse is unique (and better!) in its slow release mechanism. Long acting medication for methylphenidate is generally achieved using timed release capsules. Vyvanse solves this by attaching a lysine group to D-amphetamine. It breaks down enzymatically in your blood, causing you to absorb it nice and slowly, even on an empty stomach. And the lysine it breaks down generally has anti-anxiety effects too, but the effect size is really small. Remember that peakyness rant? Vyvanse was my salvation.
Vyvanse works so well, and has such low abuse potential that we give it to meth addicts to wean them off!
If the above paragraph was at all interesting to you I suggest you read this instead, by a psychiatrist who knows what the fuck he is talking about.
Dexedrine does last longer (~6h) than instant release methylphenidate (~4h), speaking of.
The methylphenidates
I kinda hate this drug. It makes me anxious and at the same time don’t really help with focus. I am not alone in this, the effect sizes are consistently lower for methylphenidate compared to amphetamines. But Belgian psychs still love this drug for some reason!
List of drugs:
Ritalin/Rilatine: instant mixed salt methylphenidate
Focalin: right isomer instant releast methylphenidate
Equasym: delayed mixed salt methylphenidate (30% instant, 70% delayed)
Ritalin XR: delayed mixed salt methylphenidate (50% instant, 50% delayed)
Concerta/sandoz: delayed mixed salt methylphenidate (22% instant, 78% delayed)
I have tried all of the above except focalin7 and they are all the same drug, and this drug is really fucking cursed. If you take this and you have friends who seem twacked out on like, half your dosage today I will tell you why. The bioavailability (% of how much you take that will end up in your bloodstream) for this drug varies a ton from person to person. It’s like 11%-52%.8 PURELY because of liver function (we aren’t even getting to how brains probably differ when experiencing these effects) the same dose of ritalin can be 5 times as intense for someone else compared to you, nuts!9
No lysine magic here, these capsules just work via timed release, so u have to take with food and the effect varies like that. There is a % that is instant and a % that is delayed.10 Pick equasym or similar make ups of instant vs delayed if you are not stupid. 50% instant 50% delayed does not make sense. Because of footnote, it causes it to be way more active in morning than evening.11
And whatever I do these never feel as smooth as vyvanse.
Apparently they are working on timed release D-amp methylphenidate now12, which sounds like it will make a pharmacy company 100 billion dollars and take 10+ years to be available in Europe.
meth tangent
Meth is great but they won’t let you have it. It’s just not available at all in Belgium and in the states, it is marketed as desoxyn but no one will prescribe it to you. Meth also acts on serotonin and crosses the blood brain barrier way easier. Which slightly veers into the recreational maybe, but let the patients have some fun will you?
The reason it’s still technically available in the US at all is that it was grandfathered in in 1940, no one bothered to change its legal status. But also, basically no research has come out regarding therapeutic dose efficacy for ADHD
There’s research showing that it’s neuroprotective in small therapeutic doses (little studies, in animals). People who get it prescribed overwhelmingly say it works incredibly well for them. The little research we have indicates no reason to believe it’s worse than you compared to instant release amphetamines at therapeutic doses.
Methheads mostly get addicted due to their insanely high doses, unregulated nature/purity, route of administration and general life-state they are in when they decide to start taking meth.13
No one wants to research meth for ADHD because: well, it’s fucking meth. No one wants to have the media avalanche of concluding we should give meth to children.
But it’s not only that. What if the simple unpatentable molecule turns out to work better than <newly released patented drug>, wouldn’t that be embarrassing! Our shareholder value!!!
I’m not saying meth is perfect, or even good for ADHD, I’m saying that we should research it more! Even if only because people are already taking it! A failure of the medical system!
Magnesium and tolerance
There’s some research showing that magnesium supplementation can prevent stimulant tolerance. I have not experimented with this myself, but just thought I would let you know. Although it is quite shaky, try it!
A quick shoutout to caffeine
do not drink coffee while on stimulants
It makes you jittery and all other forms of nasty. No one I know that has tried this has said this is a good idea, yet some of us keep doing it. Just avoid!
That being said: coffee by itself has actually been pretty good at treating my ADHD. I don’t think this shows in the studies or anything but I have noticed this, and thought it would be interesting to mention.
But Celeste, what do stimulants feel like?
to me: like drugs. you get put in a better mood, everything is kinda awesome and if your brain is a symphony of distractions, it takes the one violin that was playing loudest when the meds kicked in and he will be the only one you can hear for the next 12 hours. Make sure it is something useful.
This is another gripe I have with the adhd community. Everyone has talk of “the inner monologue finally shutting up” or “finally I felt calm for the first time”.
And I don’t know if this is an optics thing or what. I wonder if there’s tweakerwashing is going on in the ADHD community sometimes. I don’t want to flatout accuse people of lying but… These drugs release adrenaline and they make calm? what do you mean?14
I AM TWEAKING!!!! IT’S AWESOME!!!
If you don’t know what tweaking feels like it is hard to explain, but the feeling is just qualitatively tweaking, just quantitatively different depending on dosage.
Can I take stimulants if I don’t have ADHD? will they make me more productive
Yes, at least in the short term.
But this is probably ill-advised, especially if you don’t have severe executive dysfunction that can’t be addressed in other ways (which in those cases, you probably have ADHD). Put away your phone, or don’t. Idk, it’s complicated.
non-stimulant medication
If you can’t handle side effects of stimulants doctors will give you non stimulant medications. Off the dome I think the 4 most common ones are wellbutrin (bupropion), guanfacine (intuniv), modafinil and strattera.
They all have significantly lower effect sizes than stimulants.
I have never tried any of them so I will not talk about them further. I was going to start strattera at one point but then I discovered that in like half amount of cases or something ridiculous it would give my vegan fiber-maxxed ibs ass even more constipation. No thanks. They’re also just fairly consistently weak drugs, but they may be worth a shot if you absolutely cannot handle stimulants
A quick note on bupropion: the variance on this drug in ADHD-reduction effect size is wild, some people have a lot of symptom reduction, even better than amphetamines, for some it does nothing at all. My 2 ADHD friends who were on it said it helped them with executive function but not with concentration, make of that what you want.
TLDR
Some sane defaults:
stimulants mog non stimulants in ADHD symptom reduction effect size
bupropion is insanely high variance in efficacy, but does have a mild effect size
long acting work better than short acting, both in effect size and my subjective experience (peakyness problem)
if u are an adult, generally start with Vyvanse (lisdexamphetamine). Most prefer it and it generally works best to alleviate ADHD symptoms.
do not drink coffee on stimulants
magnesium may reduce tolerance, but evidence is shaky
if taking methylphenidate, make sure you don’t use 50-50% composition. Except if that works for you for some reason. Generally try 30-70 first (Equasym)
experiment with higher/lower doses, especially on methylphenidate
Meth is probably great and they won’t let you have it.
I’m not saying you should go and try stimulants. I am saying you can just do things.
And I personally can’t do things without my vyvanse. Long live the tweaker!
some nuance but as categories it makes sense
I am dead serious. Meth gets a super bad name but after reading the scott alexander article I would kinda love to try it.
Oh also I’d love to include it on my little graphs, but I can’t because we don’t fund RCTs on this thing because it was approved in like 1945 or something and no one wants to fund meth research. EAs should get on this.
medicine students please don’t nerd snipe me. I know it’s probably like 1000x more complicated than this but as long as this is directionally right I’m fine having it up here.
this is not medical advice or drug advice, its a secret third thing
could cite many more its a pretty consistent finding
which seems really interesting by the way. If my methylphenidate woes have been an isomer situation this entire time I’m going to fucking scream.
IF you don’t understand what this means:
person 1 is one on extreme and has 11% bioavailability, he takes 10mg of instant ritalin, and 1.1mg ends up in his bloodstream
person 2 is on the other hand of the extreme, takes 10mg of instant ritalin and 5.3mg ends up in his bloodstream
I’ve also heard this argument for why we should stop prescribing codeine to people because it has a similar problem. And if you take too much of an opioid it’s kind of a problem. But there’s seizure risk there too and it’s nuanced. Medicine is hard!
Brown sugar and white sugar differ only in molasses content. My favorite fact
this is because acute tolerance causes a non-linear experience regarding blood levels, so most people I talk to including me when they take ritalin XR just kinda feel it working really well in the morning and shittily in the afternoon. basically no one wants this so don’t do it. But again metabolism differs. IDK
kinda rly wanna try this
Insanely strongly linked to addiction by the way
apparently scott alexander had one of his clients fall asleep on adderall. Good example of why you shouldn’t assume my experiences will generalize to me
as a decade long tweaker since my college days, this is amazing. we love to see it.
Wait, I can just do things?
Thanks for the post, hopefully soon I will start the titration process for some medication; I’ll keep this in mind in case they just straight up try to put me on quick release Ritalin or something.