Back from a hiatus due to computer issues and being busy with work. Typing this out on a craptop from the early 00's.
Glad to see all of the discussion! It's good seeing all of the posts looking into various different avenues of investigation. I've perused most of your posts, but there are too many for me to reply directly to them all. So I'll just discuss some of the concepts I'm seeing.
Firstly, in regards to the discussion of the NMDA Hypothesis of ADHD that I've proposed here (based on a compilation of direct studies, indirect ones, Memantine trials and experiences, circumstantial connections, etc). I currently am strongly convinced that this is indeed the root cause of the disorder, and is currently my primary area of investigation. It explains pretty much everything very neatly, compared to the very incomplete theories proposing the dopaminergic system to be the root cause. I have successfully ordered some Memantine to Canada. It will take quite a while to get here due to the way I ordered it, but it'll be worth the wait.
Now, in regards to some of your contributions to this theory: I noticed a mention of Nitromemantine. I had indeed encountered this agent during my research and pursued it, however it just isn't a viable choice at this time. It is not actually marketed anywhere yet (still in trials) and thus is not available from any pharmacy. So the only way to aquire it would be custom synthesis from a lab that doesn't check patents, which means big $$. Furthermore, dosage information is not publicly available and thus there is no way to determine how much is required for the therapeutic effect. The dosage very likely is different from regular Memantine due to the different formula and more varied MoA (acting on pre AND post synaptic NMDA receptors). So as much as I would love to try it, it doesn't seem possible at the moment. However, I welcome discussion of it, as I agree that should Memantine prove effective, Nitromemantine is the logical next-step!
As for other NMDA agents such as Ketamine, they're worth a try, but they'll likely produce a lot of undesirable side-effects, mainly reduced cognitive performance and possibly dissociation. This is because they either are full NMDA antagonists, or are also antagonists of other glutamate receptor sites. Memantine is useful for this pursuit as it binds to the magnesium channel on NMDA receptors. This means that rather than blockading the receptor, it simply increases the voltage required to activate it. So what you get is more akin to a modulatory effect, rather than blocking. This is good for this purpose, as it prevents the side effects of too little NMDA activity, which include reduced memory aquisition and working memory performance, brain fog, etc. I also some some mention of PEA being linked to the cause of ADHD. I ran into this one early on, and discounted it because there simply was very little evidence that it was actually implicated in the causality of the disorder. All there are are a few small trials noting that people with ADHD also had slightly reduced levels of PEA. This doesn't mean low PEA causes the disease, just that it happened to be low in some people who happened to have ADHD. It's very possible that having ADHD causes low production of PEA, not the other way around. The lack of clinical interest in this area, as well as the lack of efficacy supplementing it (even with MAO inhibitors, which is very risky imo) ruled this avenue of investigation out for me. I would be more interested if a large-scale trial found this link. The same applies to most precursor theories (i.e low Tyrosine, etc). They sound interesting in theory, but in practice most people do not signifigantly respond more compared to placebo, and the ones that do often report a loss of therapeutic effect after a period of time, implying that they were simply temporarily increasing dopamine production, that leveled out as rate-limited enzymes adjusted.
As for Agmatine and a few other supplements (Magnesium-L-Threonate, etc), I'm seeing a lot of hype here. I'm open to discussion of course, but please refrain from over-hyping things without providing studies backing up the hype. The placebo effect is very powerful, I've experienced it many times, only to lose the effects the initial novelty wears off (*cough* Oxiracetam). Agmatine itself has virtually no studies backing up it's efficacy treating any psychiatric disorder. It is an important compound in the brain, but people who get a decent diet have more than enough produced endogenously. I have also not seen many reliable looking case reports of people experiencing signifigant relief using it primarily. Supplementary agmatine may help augment other agents, particularly opiods and cannabinoids, but that's the extent of it's proven use right now.
Magnesium-L-Threonate got quite a bit of hype here on longecity, but actually looking at the research I'm seeing a few problems. A) There is only ONE study reporting the alleged benefits, and they used rats, which is still useful for getting an idea of a compounds possible efficacy, but there really is very little evidence supporting any claims of signifigant benefits over regular magnesium salts. B) No one knows the appropriate human dose. This is important, as it varies signifigantly between magnesium salts. The doses you see in various longecity doses are either just made up by the poster, or based on the manufacturers instructions, which are also made up, as the rat study did not include the dosage at all, let alone a human converted version. The fact that I'm not seeing any posts from people who have been using it for longer than a few weeks and still experiencing the alleged positive effects is yet another red flag suggesting bullshit. This isn't new, it's been floating around for a while. Additionally, it actually has a far lower bioavailability than cheaper forms of magnesium, which suggests you need to take much, much more. Finally, that shit is expensive for what in all likelihood is a glorified magnesium citrate.
@Ultravioletbllc: Your posts are informative, but they seem to stray from the focus of ADD/ADHD. I'm glad to hear summarized descriptions of your experiences and discoveries, but if you'd like to post in such great detail in regards to other disorders, such as mood disorders, metabolism, brain health, etc, I suggest you create a seperate thread to document them and link to it here. I'd like to keep things very on-topic and specific to the primary facets of ADD/ADHD here; attention difficulties, memory performance, motivation, hyperactivity, executive function (self-regulation), impulsiveness, etc. Too many threads devolve into more broad discussions which can be frustrating for people pursueing the threads original intent, so I'd like to keep this one on track. I do appreciate your work, and am interested in hearing more about it, I just ask that you focus on the key ADHD things here, and save the more broad discussion for a seperate thread.
Now on to Huperzine-A. I actually just ordered this, thinking I might as well give it a try since in all likelihood it's more likely to produce noticable effects than the fairly weak racetams. However, while I was waiting for it to arrive, I did some more research, and found that it does not seem like an ideal nootropic. First of all, it has a ridiculously long half-life (greater than 24 hours). This means you must be very careful with dosing, it's definitely not a daily thing. Secondly, this long half-life means that it will inevitably be active while you sleep, which is NOT desirable. Acetylcholine is naturally suppressed during certain sleep phases; it is theorized that this is part of memory consolidation. So regularly increasing acetylcholine levels with Hup-A during sleep will likely reduce long-term memory formation over time. This has very bad implications on learning processes. Finally, I've seen quite a few reports of agents that increase acetylcholine causing depression/mild dysphoria in some users, particularly after regular use. Not something I want to add on top of ADD thank you. The fact that Acetylcholine is not prominently linked to ADHD combined with all of these negatives is a dealbreaker for me.
@Stinkorninjor: Excellent find in regards to the Cannabigerol! Definitely an interesting avenue of investigation, as cannabis is fairly easily available in most parts of the world. I've experimented with micro-dosing cannabis using a vaporizer, with mixed results, but it depends greatly on the strain. Your lack of success with Hemp supplementation despite the promising levels reportedly in it is probably just the result of natural variations of it's presence. This is the problem with plant-matter supplements, the levels of active compounds can vary greatly between batches, other compounds can interfere with the efficacy, etc, etc.
Finally, wrapping things up, lets try to minimize discussion of precursor supplements (Tyrosine, Tryptophan, etc)/vitamins/minerals, as they have largely been ruled out by the medical community as not likely being the cause of the disorder. Most of the trials suggesting a benefit are confounded by simaltaneous use of active pharmaceuticals (Methylphenidate, Amphetamine, Atomoxetine, etc) by the trials' participants. Case reports on the internet are very mixed, and most do not report long-term success independent of other ADHD drugs. The bulk of the research in regards to ADHD suggests genetic issues with various receptors, neurotransmitter transporters, or the release of neurotransmitters themselves. This strongly suggests an actual dysfunction in brain circuitry, not a dietary defiency. Despite my current interest in NMDA receptors, I am definitely intrigued to hear more about specific dopaminergic issues, norepineprine, serotonin, acetylcholine, other glutaminergic targets (i.e glycine), NGF/BDNF, or any other intriguing neurocircuitry avenue of research you arrive upon. I'm still open to hearing about vitamin/precursor/mineral supplements, but please avoid making huge/multiple posts on these topics unless you have studies directly relating to ADHD backing your idea up.
LongeCity
