7 ms·

I'd be curious about the effectiveness of atypical stimulants such as bromantane in treating ADHD. Unlike methylphenidate or amphetamine, they don't directly in

by valec 4y ago

I'd be curious about the effectiveness of atypical stimulants such as bromantane in treating ADHD. Unlike methylphenidate or amphetamine, they don't directly inhibit reuptake or induce reverse transport of dopamine but instead upregulates transcription of enzymes responsible for the production of dopamine in the CNS. Or even weak but selective DRIs like modafinil.

krono 4y ago
Anecdote warning: Tried modafinil couple of times before I was diagnosed with ADHD (automedication, baby). Whilst it did unlock some of that focus I've since been getting out of my methylphenidate regimen, it did not provide me the motivation or willpower to actually get started on something. It made me just sit still doing absolutely nothing for hours, not even really thinking about getting started on the tasks I was intending it to help me out with. Of course the dosage was my own guestimate, and this modafinil wasn't exactly sourced through a conventional route either, but that was my experience.
- emptysongglass 4y ago
  Conversely, modafinil taken as prescribed (as opposed to when-needed) transformed my life from an unproductive self-hating person for 15 plus years to a well-paid SRE within the span of a few short years. I actually needed to take less modafinil (down to 50 mg a day) to be efficaceous at work and emotionally balanced. I have recently discovered grapefruit extract transforms the experience so I am now a productive machine. Sadly, armodafinil is not available in Denmark.
  - SemanticStrengh 4y ago
    Armodafinil ships to denmark https://europechemist.com https://europechemist.com + /product/german-waklert/ I don't know if its legal there nor how much the customs let go. The reason your grapefruit extract potentiate the dose is not different from e.g. piperine. This is a mild CYP P 450 inhibitor and therefore increase the production of a drug for a same initial dose, in the liver. Grappefruit juice can be lethal with some drugs actually. The interesting question is: Is your modafinil 50mg + ??mg of grapefruit extract better than modafinil 100-200-300mg alone? I don't see how or why but please share your precise experience.
    - elcritch 4y ago
      I haven’t looked up modafinal on the site, but https://www.stuffthatworks.health/ https://www.stuffthatworks.health/ seems ideal for this sort of crowd sourced tuning! Any experience with it?
      - SemanticStrengh 4y ago
        Looks like a cool website but beware with the info you find, e.g. cannabinoids should not be the 5 most effective treatment duh.. Chronic thc use do induce ADHD like phenotype though.. For community help there is reddit stackadvice
        elcritch 4y ago
        True, grain of salt with everything. I’d suspect THC usage is more for self-medicating the emotional aspects.
        SemanticStrengh 4y ago
        Also people mix things up, they think CBD is a cannabinoid except it's actually a cannabinoid antagonist, meaning it does the pharmacological opposite of THC. (although it also do other things)
  - krono 4y ago
    Thanks for posting this, happy to see it has worked out so well for you! The main take-away from these two wildly different experiences being: people suck at fixing their own mental/behavioural problems, go the professional help route for actual results.
    - elcritch 4y ago
      Yes, professional help is critical. It was for me, I would’ve never guessed “ADHD” or believed it without clear evidence based on IQ testing. It can take a few different doctors and some work to ensure you find a good fit though. So at the same time take the medical professionals with a grain of salt. I had a psychiatrist berate me for 5 minutes for being late (though within the university health center’s allowable limit) after I had fallen into a hyper focus trance. He was working on prescribing me a medication to help with hyper focus related issues of being late. He did actually help me find one that worked, but he was kinda a dick about it. Ironic that even experts focused on treating ADHD still struggle grasping at an emotional level that “yes it’s a real physical thing”.
    - travisjungroth 4y ago
      That is quite a conclusion. Sample size of 2 for the first claim, sample size of 0 for the second!
      - krono 4y ago
        Which I realised shortly after posting, figured I was going to get called out on it sooner rather than later. Thank you for your service :p
    - kingcharles 4y ago
      If possible, get a second opinion. I was in jail and a lot of people were there because they had been prescribed a regimen of drugs, by a psychiatrist in the free world, that was subpar and caused them to behave in a way that ended with them being locked up. Psych drug prescriptions are hard to get right due to the varying combinations of mental illnesses and how difficult it is to diagnose some of them, but some psychiatrists seem to be straight quacks prescribing whateverthefuck.
SemanticStrengh 4y ago
I have expertise in ADHD pharmacology: Bromantane is an extremely atypical substance indeed. It increase dopamine level by a factor of 2 in rodents. If I remember the main effect of bromantane is via an upregulation of AADC ? If so (to be verified) then it would mean a (proportionally equal in respect to the base ratios) upregulation of serotonin, histamine and trace amine too since their precursors compete for the same enzyme. I had read bromantane increase sert but by a factor of 2? That's weird and I doubt that is the case. Hence a better explanation for what is going on would be welcome. Other interesting aspects of bromantane are the research on it being an actoprotector, indeed a very interesting concept. There was some research on its anxiolytic properties too? cons: it works better in sublingual but sublingual is annoying bromantane at non-low dose make many people feel slighlty weird, like you know on the background you are on drug. Also this psychological perception is markedly different than feeling being on a phenidate or an amphetamine. It is likely that bromantane does not significantly increase noradrenaline, which is great since this imply no cardiotoxicity nor vasocontrition however noradrenaline has an important role in fixing ADHD. It is obvious that bromantane is less effective than vyvanse although it is either an interesting augmentation in parallel or a palliation for those that can't access or tolerate stimulants. The long terms effects by taking it orally might alleviate the weird feeling though although semi unlikely. Semax and its modern derivatives are interesting too. As for modafinil and the more tolerable armodafinil, they have been tested in studies and the efficacy is much lower than stimulants. Contrary to popular belief modafinil 200mg is highly dopaminergic, almost comparable to methlyphenidate 20mg, however the reduced efficacy might be ascribed to either the D1/D2 ratio or the fact it reduce gaba levels or the action on orexins but most likely as in bromantane (although the subjective effects are very different) the lack of potent noradrenaline action. I have studied every single drug that has been tested for ADHD and the truth is, there aren't many that are promising (except as mere augmentation of a classical stim) Guanfacine is very complementary. NRI generally are less effective and cause as much side effects weirdly. Notably nobody knows it but atomotexine is neurotoxic. So if you wanna try one do reboxetine or qelbree. The interesting thing about NRIs is not that they are NRIs, it is that they act on GIRK https://en.wikipedia.org/wiki/G_protein-coupled_inwardly-rectifying_potassium_channel https://en.wikipedia.org/wiki/G_protein-coupled_inwardly-rec... and there is a drug selective only on GIRK that shows ADHD efficacy, so this could be a useful replacement or augmentation. The most potent thing people don't know though is that MAOIs (a, b) have evidence to be possibly as effective as stimulants for ADHD. See e.g. selegiline reported being as effective as methylphenidate with much less side effects: https://www.researchgate.net/publication/237845059_Selegiline_in_Comparison_with_Methylphenidate_in_Treatment_of_Adults_with_Attention_Deficit_Hyperactivity_Disorder_A_Double-blind_Randomized_Trial https://www.researchgate.net/publication/237845059_Selegilin... https://www.sciencedirect.com/science/article/abs/pii/0091305794901090 https://www.sciencedirect.com/science/article/abs/pii/009130... The main unknown with selegiline being if the efficacy works long term or not. Selegiline is BTW a potent geroprotector increasing lifespan by a very atypical mechanism (shared via the very interesting and underknown drug b-pap) but the main geroprotective effect is obvious: dopamine is oxidated by mao-b and mao-b got the good idea of being collocated to the mitochondria membrane duh which means dopamin slowly kill you mitochondria which leads to your cell dysfunction and apoptosis. Now add to the fact that mao-b increase with age.. The only downside with selegiline is that there exist one study showing it can reduce intelligence or at least increase latency in some cognitive tasks on healthy people. https://pubmed.ncbi.nlm.nih.gov/3927932/ https://pubmed.ncbi.nlm.nih.gov/3927932/ Despite other studies showing cognitive enhancement. also I don't remember if this is the exact study I was refering to. While selegiline is atypical by not only acting on mao-b (levo-meth metabolites and ppap like potentiation), maois being as effective as methyplhenidate is a consistent finding for all maois tested! Other mao-b inhibitors like rasagiline and silfenamide have not been tested. and classical maois while very effective, and actually safe, have non-negligible side effects. However the exist a middle ground, RIMAs. There exist 2-3 official RIMAs on the market (and many natural ones), one having 2 studies showing positive effect on ADHD for moclobemide. https://pubmed.ncbi.nlm.nih.gov/1546129/ https://pubmed.ncbi.nlm.nih.gov/1546129/ moclobemide is generally underdosed due to dumb FDA limit while if you watch the tyramine graph 900mg is actually mostly safe diet-free. moclobemide is remarkable by being one of the drug with the least side effects (except a theorethically worrying rem bound offset of one hour although an effect shared by stimulants too?) While I expect it to be less effective than methylphenidate, it seems like an excellent augmentation or replacement. with a diet and heart monitoring it can be combined with selegiline or afinils. So yes as always, the future of the scientific knowledge is in the past (the 90s) and will keep being ignored for eternity except for the very few meta-researchers like me. The exist many atypical drugs for ADHD, e.g. zinc allow to reduce adderall dose by 1 third, except I would not recommend taking it long term since metals accumulate in the body without chelators, and zinc is linked to oxidative stress (independently of its DRI action?) Methadoxine is a curious atypical, and is has not been marketed for this use, not because of a lack of efficacy, but because their placebo control was too effective (how tragic and ridiculous) there are many absurd results too, such as saffron being as effective as methylphenidate.. Pine bark is promising but only works on hyperactive ADHD, not on hypoactive/ADD. As for mere augmentations, I would look into regular nootropics such as racetams and cholinergics. The nicotinic GTS can make sense. Also xanthines with longer half lifes and many others. There are many research stimulants too (ppap, 4-fmph, etc) I could go on and talk about phosphodiesterases and other topics but this is HN. Beyond ADHD, consider taking magnesium l-threonate for fighting your synapse losses. Another underknown topics are the drugs that worsen ADHD such as surprisingly, Inositol. There are many studies showing potent effects of meditation which is promising although not well specified in how to reproduce. As a reminder though, vyvanse is the most effective non-polypharmacologic treatment and its patents are expiring in 2023! Unfortunately it is not prescribed in many european countries...

by valec 4y ago

krono 4y ago

Anecdote warning: Tried modafinil couple of times before I was diagnosed with ADHD (automedication, baby). Whilst it did unlock some of that focus I've since been getting out of my methylphenidate regimen, it did not provide me the motivation or willpower to actually get started on something. It made me just sit still doing absolutely nothing for hours, not even really thinking about getting started on the tasks I was intending it to help me out with. Of course the dosage was my own guestimate, and this modafinil wasn't exactly sourced through a conventional route either, but that was my experience.

emptysongglass 4y ago
Conversely, modafinil taken as prescribed (as opposed to when-needed) transformed my life from an unproductive self-hating person for 15 plus years to a well-paid SRE within the span of a few short years. I actually needed to take less modafinil (down to 50 mg a day) to be efficaceous at work and emotionally balanced. I have recently discovered grapefruit extract transforms the experience so I am now a productive machine. Sadly, armodafinil is not available in Denmark.
- SemanticStrengh 4y ago
  Armodafinil ships to denmark https://europechemist.com https://europechemist.com + /product/german-waklert/ I don't know if its legal there nor how much the customs let go. The reason your grapefruit extract potentiate the dose is not different from e.g. piperine. This is a mild CYP P 450 inhibitor and therefore increase the production of a drug for a same initial dose, in the liver. Grappefruit juice can be lethal with some drugs actually. The interesting question is: Is your modafinil 50mg + ??mg of grapefruit extract better than modafinil 100-200-300mg alone? I don't see how or why but please share your precise experience.
  - elcritch 4y ago
    I haven’t looked up modafinal on the site, but https://www.stuffthatworks.health/ https://www.stuffthatworks.health/ seems ideal for this sort of crowd sourced tuning! Any experience with it?
    - SemanticStrengh 4y ago
      Looks like a cool website but beware with the info you find, e.g. cannabinoids should not be the 5 most effective treatment duh.. Chronic thc use do induce ADHD like phenotype though.. For community help there is reddit stackadvice
      - elcritch 4y ago
        True, grain of salt with everything. I’d suspect THC usage is more for self-medicating the emotional aspects.
        SemanticStrengh 4y ago
        Also people mix things up, they think CBD is a cannabinoid except it's actually a cannabinoid antagonist, meaning it does the pharmacological opposite of THC. (although it also do other things)
- krono 4y ago
  Thanks for posting this, happy to see it has worked out so well for you! The main take-away from these two wildly different experiences being: people suck at fixing their own mental/behavioural problems, go the professional help route for actual results.
  - elcritch 4y ago
    Yes, professional help is critical. It was for me, I would’ve never guessed “ADHD” or believed it without clear evidence based on IQ testing. It can take a few different doctors and some work to ensure you find a good fit though. So at the same time take the medical professionals with a grain of salt. I had a psychiatrist berate me for 5 minutes for being late (though within the university health center’s allowable limit) after I had fallen into a hyper focus trance. He was working on prescribing me a medication to help with hyper focus related issues of being late. He did actually help me find one that worked, but he was kinda a dick about it. Ironic that even experts focused on treating ADHD still struggle grasping at an emotional level that “yes it’s a real physical thing”.
  - travisjungroth 4y ago
    That is quite a conclusion. Sample size of 2 for the first claim, sample size of 0 for the second!
    - krono 4y ago
      Which I realised shortly after posting, figured I was going to get called out on it sooner rather than later. Thank you for your service :p
  - kingcharles 4y ago
    If possible, get a second opinion. I was in jail and a lot of people were there because they had been prescribed a regimen of drugs, by a psychiatrist in the free world, that was subpar and caused them to behave in a way that ended with them being locked up. Psych drug prescriptions are hard to get right due to the varying combinations of mental illnesses and how difficult it is to diagnose some of them, but some psychiatrists seem to be straight quacks prescribing whateverthefuck.

SemanticStrengh 4y ago

I have expertise in ADHD pharmacology: Bromantane is an extremely atypical substance indeed. It increase dopamine level by a factor of 2 in rodents. If I remember the main effect of bromantane is via an upregulation of AADC ? If so (to be verified) then it would mean a (proportionally equal in respect to the base ratios) upregulation of serotonin, histamine and trace amine too since their precursors compete for the same enzyme. I had read bromantane increase sert but by a factor of 2? That's weird and I doubt that is the case. Hence a better explanation for what is going on would be welcome. Other interesting aspects of bromantane are the research on it being an actoprotector, indeed a very interesting concept. There was some research on its anxiolytic properties too? cons: it works better in sublingual but sublingual is annoying bromantane at non-low dose make many people feel slighlty weird, like you know on the background you are on drug. Also this psychological perception is markedly different than feeling being on a phenidate or an amphetamine. It is likely that bromantane does not significantly increase noradrenaline, which is great since this imply no cardiotoxicity nor vasocontrition however noradrenaline has an important role in fixing ADHD. It is obvious that bromantane is less effective than vyvanse although it is either an interesting augmentation in parallel or a palliation for those that can't access or tolerate stimulants. The long terms effects by taking it orally might alleviate the weird feeling though although semi unlikely. Semax and its modern derivatives are interesting too. As for modafinil and the more tolerable armodafinil, they have been tested in studies and the efficacy is much lower than stimulants. Contrary to popular belief modafinil 200mg is highly dopaminergic, almost comparable to methlyphenidate 20mg, however the reduced efficacy might be ascribed to either the D1/D2 ratio or the fact it reduce gaba levels or the action on orexins but most likely as in bromantane (although the subjective effects are very different) the lack of potent noradrenaline action. I have studied every single drug that has been tested for ADHD and the truth is, there aren't many that are promising (except as mere augmentation of a classical stim) Guanfacine is very complementary. NRI generally are less effective and cause as much side effects weirdly. Notably nobody knows it but atomotexine is neurotoxic. So if you wanna try one do reboxetine or qelbree. The interesting thing about NRIs is not that they are NRIs, it is that they act on GIRK https://en.wikipedia.org/wiki/G_protein-coupled_inwardly-rectifying_potassium_channel https://en.wikipedia.org/wiki/G_protein-coupled_inwardly-rec... and there is a drug selective only on GIRK that shows ADHD efficacy, so this could be a useful replacement or augmentation. The most potent thing people don't know though is that MAOIs (a, b) have evidence to be possibly as effective as stimulants for ADHD. See e.g. selegiline reported being as effective as methylphenidate with much less side effects: https://www.researchgate.net/publication/237845059_Selegiline_in_Comparison_with_Methylphenidate_in_Treatment_of_Adults_with_Attention_Deficit_Hyperactivity_Disorder_A_Double-blind_Randomized_Trial https://www.researchgate.net/publication/237845059_Selegilin... https://www.sciencedirect.com/science/article/abs/pii/0091305794901090 https://www.sciencedirect.com/science/article/abs/pii/009130... The main unknown with selegiline being if the efficacy works long term or not. Selegiline is BTW a potent geroprotector increasing lifespan by a very atypical mechanism (shared via the very interesting and underknown drug b-pap) but the main geroprotective effect is obvious: dopamine is oxidated by mao-b and mao-b got the good idea of being collocated to the mitochondria membrane duh which means dopamin slowly kill you mitochondria which leads to your cell dysfunction and apoptosis. Now add to the fact that mao-b increase with age.. The only downside with selegiline is that there exist one study showing it can reduce intelligence or at least increase latency in some cognitive tasks on healthy people. https://pubmed.ncbi.nlm.nih.gov/3927932/ https://pubmed.ncbi.nlm.nih.gov/3927932/ Despite other studies showing cognitive enhancement. also I don't remember if this is the exact study I was refering to. While selegiline is atypical by not only acting on mao-b (levo-meth metabolites and ppap like potentiation), maois being as effective as methyplhenidate is a consistent finding for all maois tested! Other mao-b inhibitors like rasagiline and silfenamide have not been tested. and classical maois while very effective, and actually safe, have non-negligible side effects. However the exist a middle ground, RIMAs. There exist 2-3 official RIMAs on the market (and many natural ones), one having 2 studies showing positive effect on ADHD for moclobemide. https://pubmed.ncbi.nlm.nih.gov/1546129/ https://pubmed.ncbi.nlm.nih.gov/1546129/ moclobemide is generally underdosed due to dumb FDA limit while if you watch the tyramine graph 900mg is actually mostly safe diet-free. moclobemide is remarkable by being one of the drug with the least side effects (except a theorethically worrying rem bound offset of one hour although an effect shared by stimulants too?) While I expect it to be less effective than methylphenidate, it seems like an excellent augmentation or replacement. with a diet and heart monitoring it can be combined with selegiline or afinils. So yes as always, the future of the scientific knowledge is in the past (the 90s) and will keep being ignored for eternity except for the very few meta-researchers like me. The exist many atypical drugs for ADHD, e.g. zinc allow to reduce adderall dose by 1 third, except I would not recommend taking it long term since metals accumulate in the body without chelators, and zinc is linked to oxidative stress (independently of its DRI action?) Methadoxine is a curious atypical, and is has not been marketed for this use, not because of a lack of efficacy, but because their placebo control was too effective (how tragic and ridiculous) there are many absurd results too, such as saffron being as effective as methylphenidate.. Pine bark is promising but only works on hyperactive ADHD, not on hypoactive/ADD. As for mere augmentations, I would look into regular nootropics such as racetams and cholinergics. The nicotinic GTS can make sense. Also xanthines with longer half lifes and many others. There are many research stimulants too (ppap, 4-fmph, etc) I could go on and talk about phosphodiesterases and other topics but this is HN. Beyond ADHD, consider taking magnesium l-threonate for fighting your synapse losses. Another underknown topics are the drugs that worsen ADHD such as surprisingly, Inositol. There are many studies showing potent effects of meditation which is promising although not well specified in how to reproduce. As a reminder though, vyvanse is the most effective non-polypharmacologic treatment and its patents are expiring in 2023! Unfortunately it is not prescribed in many european countries...