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.
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.
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.
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.
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”.
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-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_Selegilin... 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/ 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/ 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...
then there are atypical non-addictive anxiolytics (afobazole, opipramol, etifoxine (beware liver monitoring), emoxypine, tofisopam)
As someone blessed with severe combined type ADHD (aka super ADHD) and not entirely happy with my current medication, I'm always on the lookout for this type of news in a form that is relatively digestible.
The one thing I've been running into, is that all the medication works great in that they are all more or less successful in achieving those behavioural changes I am looking for, but none of them last anywhere near as long as advertised (normal release 10mg Ritalin effects come and go within the first 30 minutes of taking), which leads to nasty rebounds and such.
Currently I'm on 30+30+20 mg of staged release methylphenidate (Medikinet) and it whilst it does (barely) last me the day, there are other things that make it not so great (which I'll spare you the details of, unless interested). Just chugging along, waiting for something better to come along in the hopefully not too distant future :)
What are your other issues with methylphen?
> What are your other issues with methylphen?
Those 80mg is what I require, on average, to get the desired effects and have them last throughout the entire day.
First problem is an inherited cardio-related risk factor. Even if not an immediate concern, it is a permanent one.
Second one is that sometimes. lasting a day or two tops, methylphenidate has no effect on me - even not that high dosage. Happens with any brand/vehicle/release I've tried. Apparently this is really weird. We went to great lengths to try and figure out the cause, but there was no correlating pattern that we could find, and the drugs and production lines tested clean and unchanged. It's a mystery.
You sharing this knowledge so freely is much appreciated. I am serious about researching and further considering every bit of it.
isopropylphenidate has not been tested, it is reputed to be clean and low potency. It might make sense for stimulant intolerant people since it has low side effects. Otherwise I'd go for low dose 4f-mph or 2-fma, at least if you can't access vyvanse.
Either way there's no harm in getting those levels checked out, cheers!
Regardless it sounds like you have built up high tolerance, which isn't surprising to me. If so, then the reason you believe your current dose isn't lasting is because you're used to that initial spike in effect. I've been there.
What works for me is to take a hiatus. Maybe a week or two if you can get away with it. Then start at a lower dose. In the past I found increasing the dose through the week and then taking a break or a reduced dose on the weekends would help fight tolerance. Avoid caffeine and other stimulants when you're on your regular dose.
If you haven't tried Vyvanse, then I encourage it. You'll want a much lower dose. Start with the 10 mg once a day and titrate up by 10mg every one or two weeks. Taking a hiatus first is a good idea otherwise you might misjudge the dose.
I currently have 40s and 10s and 40 on a Monday kicks my ass, 50 on a Friday is hardly noticable, but I take the weekends off (or 10 or 20mg each day if I need to get shit done) and the following Monday 40mg will kick my ass again.
In terms of the other things, not much you can do other than plan around the effects. Best of luck.
Good you mention Vyvanse, I need to get the ball rolling on that. Asked my GP about it a while ago, he referred me someplace for the initial prescription and titration process, but then that place stopped taking on new cases before I had a chance to set mine up. Looks like they since opened back up with a 6 to 8 months waiting list.
Tolerance and/or the "honeymoon phase" are solid mentions, but neither is at play here. Inconsistent Methylphenidate effects have been a thing for me from the very beginning. No amount of exercise, diet changes, de-stressing, lower dosages, or even month-long break have had any effect. Seems completely random, it's just weird!
Do you belong to any advanced nootropics servers by any chance ?
Do you know what CYP enzyme metabolize it ? If so then you might be able to increase its half life by playing with a CYP inhibitor? I have been banned from reddit for the stupidest and most unfair reason and I don't know how to circumvent the ban. If I manage to then send me your reddit username. BTW I recommend this sub https://www.reddit.com/r/NootropicsFrontline/
Regarding your questions I'm not certain but we can talk there . Just mention asp on generalchat and we can discuss more
I'm generally very satisfied with my Rilatine. It helps immensely, I can actually get stuff done without my thoughts branching off in multiple directions and getting stuck in inaction. I am still surprised by my lack of awareness of the (lack of) symptoms. When it wears off I don't feel different, really. I can now recognize from experience that the symptoms return, but there's no concious switch happening. It's hard to put in to words, but for me it definitely shattered the illusion of free will.
Anyway, back to methylphenidate, thankfully the side effects are very minor for me. The only annoying thing is my cold hand & feet. And the fact that I have to take 2 pills, the 2nd dose is easy to forget. I could switch to Concerta, but at twice the cost the switch is harder to justify. For some unexplicable reason ADHD medication is covered for children, but not for adults here.
Speaking of children, two different child psychiatrists recommended to try Omega 3 & 6 fatty accids (specifically "Eye q"), but I can't find much supporting evidence. IIRC one study showed an improvement in symptoms when combined with methylfenidate, but not without. Have you read anything about this?
Personally, I would like to try vyvanse, but like you said it's not prescribed in Europe. My doctor looked it up and would be willing to, but no pharmacy has it. Technically they can order it, but they would have to buy in bulk, which they understandably don't want to do for one patient. It's good to know that the patents will expire soon. The arrival of generics could make them an option, hopefully.
Omega 3 have mixed evidence, they probably help slighly as augmentations, like guanfacine.
Your cold extremities are probably because of vasocontrition, you can cancel this with low dose (1-3mg) daily tadalafil (yes the sex pill), which is available OTC btw.
As for the methylphenidate half life, if that is a huge problem you can try atypical stims cf my original comment (selegiline, amantadine, moclobemide or the inferior moda/armodafinil) or get prescribed serdexmethylphenidate (probably not yet possible in europe) or you can do the easy fix, buy 4f-mph which is an OTC methyplhenidate variants available on https://rarechems.com/ however while unlikely, it is possibly more cardiotoxic and neurotoxic. Anyway you should fight cardiotoxicity and neurotoxicity (the former via e.g. tadalafil, the latter via magnesium l-threonate, ALCAR and antioxidants such as NAC)
> Thanks for your comments. I don't understand much of it Feel free to ask any question for clarification
DDC actually.
https://www.uniprot.org/uniprot/P20711
And if this is the case, maybe many ADHD cases are caused by a B6 deficiency since B6 is the cofactor for DDC. Studies have pointed to this already:
https://pubmed.ncbi.nlm.nih.gov/24321736/
https://pubmed.ncbi.nlm.nih.gov/16846100/
If I had a kid with ADHD I would get their B6 tested.
That's interesting but we would know already if B6 was a potent cure to ADHD so either it only help slighly, either it has to be supplemented as a child and as an aldult it would be too late.
And no, we would not know if it helped. Because money. And it might only help a subset of patients since ADHD is so polygenic.
Raise of hands here for anyone with ADHD who has had a serum B6 test???
Interesting to hear about atomoxetine. I've read conflicting arguments on that but don't know enough to draw a conclusion.
Personally my adhd was best controlled by Ritalin SR 20mg. Novartis stopped making that and the generic SR I tried didn't work the same.
I can take 10mg ritalin instant release but it's harder to dose consistently.