91 replies to this topic

[civilizedsavage]

So I tried adding glutamic acid to the mix today. I used 4 grams as suggested by the bottle, is that too much? I suppose I can just take 125-250mg and get the same effect.

It feels...

subtle. I actually had major brain fog today either because I slept too little, or because I decided to take my racetams on an empty stomach with milk. Anyways, so I got home a little over an hour ago, dumped the glutamic acid in water and gulped it down. It tasted like fermented ass, no doubt about that. The mental fog seemed to clear up within the course of an hour, and right about now I feel serene, but not loopy like I normally do when I take my dose in the morning. I will give it a try in the morning tomorrow to see if it does more than just clear out the fog, though I'm happy it helped with that.

If I want to get up at 4 tomorrow, I'd better get to bed now. Good sleeping habits ftw.

So I tried adding glutamic acid to the mix today. I used 4 grams as suggested by the bottle, is that too much? I suppose I can just take 125-250mg and get the same effect.

It feels...

subtle. I actually had major brain fog today either because I slept too little, or because I decided to take my racetams on an empty stomach with milk. Anyways, so I got home a little over an hour ago, dumped the glutamic acid in water and gulped it down. It tasted like fermented ass, no doubt about that. The mental fog seemed to clear up within the course of an hour, and right about now I feel serene, but not loopy like I normally do when I take my dose in the morning. I will give it a try in the morning tomorrow to see if it does more than just clear out the fog, though I'm happy it helped with that.

If I want to get up at 4 tomorrow, I'd better get to bed now. Good sleeping habits ftw.

[Duchykins]

A lot of the information here is very useful but too one-sided. Glutamate activity in the brain is very complicated. I decided to comment here because of so many people looking to nootropics to help with various problems they have such as "anxiety", "social issues", "speech" and "attention problems". Some of the people here already have a little bit too much glutamate and/or glutamate receptors on their cells, causing insomnia (sleep-onset usually), poor eye contact, speech issues, quick learning, higher IQ (both in part due to glutamate increasing ACh in addition to providing energy), headaches/migraines, deregulation of blood sugar, difficulty discriminating background noise and deciphering speech (symptoms sometimes mistaken for auditory processing disorder), several things often mistaken for anxiety; self-stimulatory activity (not to soothe fear), "racing thoughts" (not fear-related), intellectual activity that won't "turn off" (again not fear-related), easily overstimulated - so for example, person with beaucoup glutamate activity going on might often present as a very intelligent, high functioning autistic-like person of few words or perhaps as someone with attention deficit problems.

In these cases, glutamate-GABA levels are imbalanced; GABA is way too low. Adding glutamate, glutamine, glutamic acid, aspartic acid, aspartame and related substances (as isolated supplements rather than complete protein) is the absolute last thing these types of people need. Doing such things only increases their *already increased* risk of glutamate excitotoxicity, cell death, glutathione depletion and by proxy increase inflammation due to lowered glutathione and increased histamine (which may seem paradoxical because glutathione is another thing that can decrease histamine tolerance). Even taking the noots that work significantly with glutamate can leave them worse off than before - UNLESS they take steps to simultaneously **support their GABA processes**, protecting them from glutamate excitotoxicity, lessening or abolishing many symptoms associated with excess glutamate/higher densities of glutamate receptors including headaches, excessive wakefulness, poor speech and eye contact.

Ways to approach this are varied but would include OTC supplementation of taurine, theanine, lysine, valerian, ginkgo, ashwagandha, perhaps GABA itself (some may also argue for phenibut or picamilon here, but I won't) perhaps gabapentin or related prescriptions, alteration of activities such as taking noots or any supplement or eating foods known to increase glutamate or enhance glutamate sensitivity within 6 hours of bed time. Of course this does not mean attempt to eliminate glutamate, as it is a necessary neurotransmitter and greatly beneficial when balanced.

Another reason to ward from glutamate towards the end of the day is that it increases histamine, and you need lower histamine during sleep for better memory consolidation. Some noot users that report no memory improvements or worsening memory may be taking noots or supplements that increase histamine or enhance histamine sensitivity too late in the day, too close to bed time, compromising their brain's ability to consolidate memory. Some people may already have high histamine or lowered tolerance for histamine and interpret their high histamine symptoms as excess choline/ACh including "brain fog" and/or "heaviness" especially near the sinuses, "depression", headache, among other things. I sometimes read a thread where someone asks if excess choline causes flu-like, cold-like or allergy symptoms and everyone saying no, it's not related or must be a virus, when in fact it is related- but to the noots they are taking or other things in their stack that increase glutamate and increase histamine beyond levels their bodies can tolerate. These people can benefit either from lowering whatever is increasing their histamine or adding something that has antihistamine effects.

Of course, none of this would apply to people who aren't particularly sensitive to glutamate or histamine activity, which is many people. :D

Edited by Duchykins, 01 March 2014 - 03:39 AM.

[LBGSHI]

Duchykins: Very interesting input. I had not even considered the relationship between glutamate and histamine (according to various studies, the relationship is very direct; for example - http://www.ncbi.nlm..../pubmed/1381677). Naturally, since glutamate is excitatory, I've always avoided taking it during the second half of the day, but the other potential side-effects of increasing histamine activity are well worth considering, especially if one has allergy or inflammation problems.

Nonetheless, I wouldn't dismiss it from a stack, especially if no adverse reactions are observed. That being said, I've simplified my stack to oxiracetam and a choline source (alpha-GPC and occasionally centrophenoxine), and at reduced dosage and only a single morning dose, to decrease cost and avoid the very thing you allude to several times above - hyperactivity and insomnia. Still, though I've gotten used to the difference, I do occasionally miss the intensity.

Thanks for your post.

[LBGSHI]

Oh yeah, and LBGSHI, will that Sleep as Android app try to wake me up at the right time? Just the statistics would be something i'd be interested in (and thanks for the suggestion by the way!). My sleep patterns have returned to somewhat normal, and i've been able to get 8 hours a night consistently, however I've come to accept there will just be some days where my body won't need the full 8. It would be nice if this app could keep track of those hours for me, since I always forget to update my sleep log~

Actually, yes; it can do all of those things. It's quite a useful little app.

So I tried adding glutamic acid to the mix today. I used 4 grams as suggested by the bottle, is that too much? I suppose I can just take 125-250mg and get the same effect.

4 grams is pretty excessive. 500mg is the usual dose. Isolated glutamate is nothing to toy with; although it's unlikely you'll cause yourself any harm, the potential gain from such a large dose is too small compared with the potential risk of excitotoxicity. I'd cut it down to 500mg and see if it provides the same positive effects, and scale up 500mg at a time if necessary (which it probably won't be).

[Duke318]

Anyone have any luck using N-AcetylCysteine to lower glutumate? I'm beginning to think that all of my anxiety and irritability issues stem from ADHD and excess glutumate.

Would a low-dose regimen of Lyrica (pregabalin) possibly have nootropic effects on someone with excess glutumate?

[explr9]

Duchykins - thank you for that post. I have been thinking about it all day. 

 

quote

 " a little bit too much glutamate and/or glutamate receptors on their cells, causing insomnia (sleep-onset usually), poor eye contact, speech issues, quick learning, higher IQ (both in part due to glutamate increasing ACh in addition to providing energy), headaches/migraines, deregulation of blood sugar, difficulty discriminating background noise and deciphering speech (symptoms sometimes mistaken for auditory processing disorder), several things often mistaken for anxiety; self-stimulatory activity (not to soothe fear), "racing thoughts" (not fear-related), intellectual activity that won't "turn off" (again not fear-related), easily overstimulated..."

 

This describes my typical brain state. especially the "mistaken anxiety" aspects. I had some ginkgo laying around and took it with ashwaghanda and felt relief from all the piracitam/oxi/prami tha I have been trying to understand.

 

Can you point me in the direction for more info on this glutamate false - anxiety / low GABA condition?

 

Much thanks.

[rowebil]

A lot of the information here is very useful but too one-sided. Glutamate activity in the brain is very complicated. I decided to comment here because of so many people looking to nootropics to help with various problems they have such as "anxiety", "social issues", "speech" and "attention problems". Some of the people here already have a little bit too much glutamate and/or glutamate receptors on their cells, causing insomnia (sleep-onset usually), poor eye contact, speech issues, quick learning, higher IQ (both in part due to glutamate increasing ACh in addition to providing energy), headaches/migraines, deregulation of blood sugar, difficulty discriminating background noise and deciphering speech (symptoms sometimes mistaken for auditory processing disorder), several things often mistaken for anxiety; self-stimulatory activity (not to soothe fear), "racing thoughts" (not fear-related), intellectual activity that won't "turn off" (again not fear-related), easily overstimulated - so for example, person with beaucoup glutamate activity going on might often present as a very intelligent, high functioning autistic-like person of few words or perhaps as someone with attention deficit problems.

 This definitely sounds like me... maybe I should look into this. 

Anxiety, sure, but I believe to be self-confidence. Social issues, yes, a bit. Speech (OMG yes, I will be talking in the car and see someone, or think about the speed of my speech and will totally lose track for a few minutes) and attention problems. Insomnia, sure, but it's my lack of willingness to sleep during the night, due to the night being more exciting and less bothersome. Quick learning, hell yeah, if I'm interested in the content. Headaches and migraines... yes... racing thoughts all the time... intellectual activity, if that means that my mind constantly races through different scenarios (for instance, car issues - I will go through the if else, then, logical statements) 

[formergenius]

Is there evidence for these claims that hyperglutamatergia induces these symptoms? I've seen similar symptoms being discussed in hypoglutamatergic states.
The whole "glutamate=anxiety" thing never made too much sense to me either. Sure, it's excitatory, but why would that have to lead to anxiety? Excitation of certain brain regions has shown to be anxiolytic, hence I think it's too non-specific to say that glutamate is high when one is anxious.

Anyway, like the OP, I'm also interested in activating glutamatergic receptors, although the NMDAR in specific peaks my interest. However, similar to the OP, I've seen the concerns about excitotoxicity.
Surely, there must be a way to safely, yet effectively activate these receptors? I thought I had finally found a way, albeit not yet possible due to lack of ligands; NR2A specific activation. Then, yesterday, I read "Evidence is mounting that upregulation and/or overstimulation of the NR2A receptor subtype of the NMDA receptor plays a pivotal role in the etiology of MDD" source, so that seems to exclude this as a viable means towards safe and effective NMDAR activation. Glycine, Sarcosine, et al. all seem rather meagre to be honest.

So.. any other ideas to activate NMDARs safely and effectively?

[Frigo]

A lot of the information here is very useful but too one-sided. Glutamate activity in the brain is very complicated. I decided to comment here because of so many people looking to nootropics to help with various problems they have such as "anxiety", "social issues", "speech" and "attention problems". Some of the people here already have a little bit too much glutamate and/or glutamate receptors on their cells, causing insomnia (sleep-onset usually), poor eye contact, speech issues, quick learning, higher IQ (both in part due to glutamate increasing ACh in addition to providing energy), headaches/migraines, deregulation of blood sugar, difficulty discriminating background noise and deciphering speech (symptoms sometimes mistaken for auditory processing disorder), several things often mistaken for anxiety; self-stimulatory activity (not to soothe fear), "racing thoughts" (not fear-related), intellectual activity that won't "turn off" (again not fear-related), easily overstimulated - so for example, person with beaucoup glutamate activity going on might often present as a very intelligent, high functioning autistic-like person of few words or perhaps as someone with attention deficit problems.

In these cases, glutamate-GABA levels are imbalanced; GABA is way too low. Adding glutamate, glutamine, glutamic acid, aspartic acid, aspartame and related substances (as isolated supplements rather than complete protein) is the absolute last thing these types of people need. Doing such things only increases their *already increased* risk of glutamate excitotoxicity, cell death, glutathione depletion and by proxy increase inflammation due to lowered glutathione and increased histamine (which may seem paradoxical because glutathione is another thing that can decrease histamine tolerance). Even taking the noots that work significantly with glutamate can leave them worse off than before - UNLESS they take steps to simultaneously **support their GABA processes**, protecting them from glutamate excitotoxicity, lessening or abolishing many symptoms associated with excess glutamate/higher densities of glutamate receptors including headaches, excessive wakefulness, poor speech and eye contact.

Ways to approach this are varied but would include OTC supplementation of taurine, theanine, lysine, valerian, ginkgo, ashwagandha, perhaps GABA itself (some may also argue for phenibut or picamilon here, but I won't) perhaps gabapentin or related prescriptions, alteration of activities such as taking noots or any supplement or eating foods known to increase glutamate or enhance glutamate sensitivity within 6 hours of bed time. Of course this does not mean attempt to eliminate glutamate, as it is a necessary neurotransmitter and greatly beneficial when balanced.

Another reason to ward from glutamate towards the end of the day is that it increases histamine, and you need lower histamine during sleep for better memory consolidation. Some noot users that report no memory improvements or worsening memory may be taking noots or supplements that increase histamine or enhance histamine sensitivity too late in the day, too close to bed time, compromising their brain's ability to consolidate memory. Some people may already have high histamine or lowered tolerance for histamine and interpret their high histamine symptoms as excess choline/ACh including "brain fog" and/or "heaviness" especially near the sinuses, "depression", headache, among other things. I sometimes read a thread where someone asks if excess choline causes flu-like, cold-like or allergy symptoms and everyone saying no, it's not related or must be a virus, when in fact it is related- but to the noots they are taking or other things in their stack that increase glutamate and increase histamine beyond levels their bodies can tolerate. These people can benefit either from lowering whatever is increasing their histamine or adding something that has antihistamine effects.

Of course, none of this would apply to people who aren't particularly sensitive to glutamate or histamine activity, which is many people. :D

 

Almost all of those symptoms fit me, quite a few very strongly, and yes, it was misdiagnosed several times as anxiety, depression, etc etc.

 

Glutamine takes it to a whole new level of bad: Irritability, anger, anxiety, paranoia, frontal headache, forehead overheating, strong heartbeats, and of course even more confusion, brain fog and stupidity than usual. Same with D-Aspartic Acid, and very similar with the few minutes of onset of Sarcosine, the crash 2 hours into Aniracetam, and the headache with chronic Sulbutiamine use. Pramiracetam and Oxiracetam just make me tired.

 

GABAergics do NOT alleviate any of this irritability, just add another layer of debilitating unnatural sedation, everything else stays, irritability, anxiety, headache included. Xanax, Valerian, Chamomile tea, Theanine, Taurine, Picamilon, Gotu Kola, these all just create additional problems and are worthless for treating this Glutamate related problem. I don't think this results from a hypoactive Glutamate Decarboxylase or Glutamate-GABA imbalance. In fact, higher doses of Glutamine produced the aforementioned GABAergic effect in addition to the Glutamatergic madness.

 

Things that seem to help, though a bit unreliably:

- Ketogenic diet

- Exercise

- Caffeine

- N-Acetylcysteine

- Metamizole

- Aspirin to a lesser extent

- Spinach for dinner to treat insomnia (still don't wake up refreshed)

Edited by Frigo, 12 April 2014 - 02:26 PM.

[Duchykins]

Sorry guys I didn't mean to post and run but I just moved and it took a bit to get the internet happening again (effing AT&T horrible customer service, went back to Comcast) and then I had to find my note books. I'm only just beginning to organize my notes.

Off the top of my head, low serotonin can also have the bulk of the symptoms described by everyone who replied to me. Irritability/anger, abnormal heart rates, body temperature fluctuations, insomnia and waking up feeling unrested, migraine, anxiety.

I never said glutamate is high when someone is anxious. I said very high glutamate *can* produce anxiety-like symptoms. The interrelationships between serotonin, dopamine, norepinephrine, epinephrine, glutamate, GABA, histamine and others are wildly complex and I'll try to draw (very poorly) a picture of that here with my messy notes (and I'll probably miss a few things since there are still a lot of random papers I threw in a moving box that contain pertinent information on this topic, so please forgive me)

High glutamate -> increase insomnia, decreased eye contact, high acetylcholine, increase self-stimulatory behavior, increase histamine, decreased glutathione. Often accompanied by lowered GABA as the chemical balance shifts toward glutamate. Low GABA is infamous for inducing symptoms of anxiety and anger. People carrying the mutation that impairs our ability to clear glutamate will be specially vulnerable to glutamate excitotoxicity and migraines, will have a history of true migraines.

High acetylcholine -> subdued mood, decreased or absence of pleasure, mental fatigue, memory problem, increased difficulty with higher order thought, tension, phantom body pain, tooth/jaw/joint pain or discomfort, introversion, anxiety, low serotonin, slowed heart rate **High ACh acts as depressant with decreased serotonin, decreased dopamine, increased norepinephrine. Low ACh acts as stimulant with increased serotonin, dopamine and norepinepephrine.**

High norepinephrine -> anxiety, heightened awareness of environment, vigilance or hypervigilance, anger, nonspecific anger and decreased ability to control anger and aggression, low serotonin (serotonin helps regulate norepinephrine release), low GABA (GABA works against norepinephrine, any excitatory neurotransmitter)

High histamine or histamine intolerance -> anxiety symptoms, headache, insomnia, wakefulness, poor quality of sleep, racing thoughts, memory problems (low histamine is needed for healthful sleep and memory consolidation), typical allergy symptoms including itching, inflammation, flushing, flu-like presentation, heaviness around the eyes/sinus, dry-feeling or watery eyes and sinus, 'brain fog'. Histamine is excitatory. Glutathione, NACysteine, low level and extended use of low dose zinc increase histamine (high doses of zinc can lower histamine)

Norepinephrine: increased dopamine results in increased norepinephrine, decreasing GABA results in increased norepinephrine (and decreased serotonin), serotonin regulates norepinephrine

More lysine = more GABA. Lysine also has interesting serotonin-related properties.

Caffeine inhibits GABA release.

The following will all act as excitors @ glutamate receptors: glutamate, glutamic acid, glutamine, MSG, alpha-ketoglutarate, aspartate, aspartic acid, aspartame, cysteine (except NAC), glycine IF the balance tips that way.

Glycine behaves differently depending on whether there is more glutamate than GABA, or more GABA than glutamate, it will be either excitatory or inhibitory.

Methylation plays significant roles in maintaining glutamate-GABA balance, histamine breakdown.

Dopamine plays a role in sleep regulation. Inadequate sleep causes a temporary rise in dopamine followed by downregulation of dopamine.

Inadequate sleep, 'worthless' sleep, irregular sleep cycles all compromise the body's ability to keep *any* of the neurotransmitters balanced.

Omega 3s increase dopamine by inhibiting enzymes that break down dopamine and by proxy, raise norepinephrine. Someone overdoing EPA/DHA may experience anxiety symptoms, irritability, anger. Omega 3s are also antihistamines.

Citicoline increases dopamine and norepinephrine and of course ACh, early evidence suggests that citicoline may increase dopamine receptor density with extended use (cool)

SAMe can raise dopamine and norepinephrine, acetylcholine, explains why some people get worse with SAMe. Also increases serotonin, glutathione. Increases methionine, methionine is antihistamine. Methylation. SAMe supplementation can be a wild card for a lot of people.

Misc notes on interesting nootropics: Nefiracetam enhances GABA signalling, perhaps enhances GABA uptake, one of few (to my knowledge, the only one) that has built-in properties to calm and help mitigate adverse effects of heightened glutamate and acetylcholine. Nefiracetam seems harder on the kidneys than other nootropics. Coluracetam in moderate to high doses protects from glutamate excitotoxicity, enhances choline uptake, need more info on coluracetam and GABA activity.

There's more here but I think this post is long enough. I encourage anyone interested to double and triple check anything I listed here as I could have cited outdated research or simply copied some of the notes incorrectly.

Edited by Duchykins, 14 April 2014 - 05:34 PM.

[Frigo]

Could you elaborate on these mutations? I searched for a few GAD and EAAT mutations but haven't found any conclusive information about them.

 

The Glutamate-GABA balance is a bit of a myth, it is perfectly possible to be both teeth grinding angry from Glutamate and calm and dumb from a GABAergic. It's not a very nice place to be.

 

High glutamate -> increase insomnia, decreased eye contact, high acetylcholine, increase self-stimulatory behavior, increase histamine, decreased glutathione. Often accompanied by lowered GABA as the chemical balance shifts toward glutamate. Low GABA is infamous for inducing symptoms of anxiety and anger. People carrying the mutation that impairs our ability to clear glutamate will be specially vulnerable to glutamate excitotoxicity and migraines, will have a history of true migraines.

 

[Duchykins]

1) The mutation I spoke of is a recently discovered hereditary mutation that is a cause of migraine in a great deal of migraineurs (but just one cause). We literally have more difficulty clearing glutamate than others. Only really applies to migraineurs, and the people who have noticed headaches from MSG in the past.

2) A myth, heh, speaking as a decade-long migraineur, I really wish it were a myth. You have no idea how much I wish it. You didn't pay attention to the larger picture, you didn't read carefully enough and you cherry picked. Glutamate itself does not increase anger and aggression, TOO-LOW SEROTONIN does. Of course you can dose yourself with GABAergics and still be a pissy little dopey bitch on noots (I've been there), because your serotonin is too low in part because your nootropics use has driven up your glutamate, acetylcholine, dopamine and norepinephrine, and histamine; and while GABA is certainly inhibitory, it is not serotonin and it is not the regulator that serotonin is. Don't expect yourself to be cool when you've loaded yourself up with all these different excitatory chemicals as if GABA alone can offset the adverse effects. No. High norepinephrine (not glutamate directly) is frequently the culprit for nonspecific irritability, anger, aggressive impluses and decreased ability to control anger and aggression - which typically happens when there isn't enough serotonin and/or GABA in the balance. Most noot users aren't sleeping right, some are using noots to try to make up for poor sleep and others are causing poor sleep with noots, which will result in lower serotonin and dopamine and compound all of the adverse effects of noots. Many are in high stress environments and situations (school, work, domestic, health issue, etc), which also lowers serotonin because it's being used more under stress (all different kinds of stress). Some noot users are overdoing glutamine and aspartic acid inadvertently with protein powders that have *relatively* low doses of tryptophan, phenylalanine, serine compared to glutamine and aspartic acid. I'm not even going to talk about caffeine, crap eating habits and such, I don't feel that I need to. On top of it all they're still largely sedentary and not providing a proper outlet for all that extra energy. It's just not as simple as glutamate-GABA, and I recall expressing something like that at least twice before. Many GABAergics are important for migraineurs because they really do help prevent glutamate excitotoxicity, helping us clear glutamate, and are therefore an effective part of a migraine prophylaxis stack or regimen. GABAergics help autistics whose autism is at least in part caused by excess glutamate (and by proxy, excess histamine). Serotonin is also important in both cases. The relationships between all of these neurotransmitters (and others) are very real. Most importantly, we really don't know how deeply the relationships go, nearly every year we learn something new and even counterintuitive about them. Hell, I didn't even talk about other pertinent relationships between serotonin/glutamate and serotonin/dopamine and acetylcholine/histamine. I didn't even elaborate on the things I did list because I'm too lazy to type that much. That's why I said *if you doubt, look it up for yourself*. It's easier that way anyway, especially for the cognitive dissonant since they can go look for literature that says what they like and dismiss the rest. I gotta go, have a good day

[noos]

How would you balance serotonin Duchykins?

Edited by noos, 23 April 2014 - 01:19 PM.

[Duchykins]

How would you balance serotonin Duchykins?

I'm just going to illustrate what I do, since it is so important to my daily life (partly because I will not take SSRIs). I cannot say it will work for everyone, and for some it may even be overkill since I am so sensitive to changes in serotonin.

First and most important, the not-so-glamorous chemicals that are too-frequently overlooked by noot users:

- Mangesium
- Zinc
- Calcium
- Q10
- Lysine (also involved in GABA production)

Slightly more popular supps

- fish oil
- D3
- B vitamins including inositol. Especially inositol, and especially if you are using caffeine regularly


Of course there are other things like 5-htp, St John's Wort, Rhodiola, tryptophan, I'm not advising anyone to take these daily, that will have to be something everyone should decide for themselves as there are concerns about serotonin and side effects about them that are potentially more serious than what I have already listed. Of those I have 5-htp hanging around for rare use, and rhodiola. Taurine and theanine are good stuff but they seem to be wild cards when it comes to serotonin activity, although their GABA support is pretty solid.

For people experiencing histamine intolerance:

- Q10
- EPA/DHA
- methionine (or SAMe, but I prefer methionine)
- doses of zinc in the 25-75 mg range, keep it under 100mg with long term use
- B6 but keep it under 100mg
- lower any does of folate, cobalamin, nicotinic acid, NAC you may be taking, you don't have to eliminate them

Please note that I do NOT advocate high doses of these when taken at the same time, it's really not necessary. I always recommend introducing stuff at *less* than the average recommended doses, and to be patient. And in this case to read about symptoms of high serotonin beforehand so that you can identify any signs in yourself indicating you are overdoing something (such as the dread apathy or robotic states associated with SSRI use). I think that is important especially for people who have significant doses of Aniracetam or Noopept in their stacks.


I hope I was helpful in some small way. But please don't just take my word for it before adding something to your stacks since I could have misremembered something, read as much as you can stand about these things and how they might interact with whatever you are already taking. Good luck.

[chris106]

 Would you conscider Lithium orotate to be beneficial in lowering excess Glutamate as well?

[explr9]

I recently added Li Oratate after reading a lot about it. Seems good so far, calming. I haven't read anything indicating effects particular to glutamate, etc. Lithium seems to reduce  the piracetam buzz though, so there may be some interaction.

 

The other thing I am investigating is methylation, the MTHFR (methylenetetrahydrofolate reductase)

 gene thing. Problems with methylation can cause excitability. 

[Frigo]

Did a few experiments with Taurine, and 2x500 mg seems to lessen Aniracetam + Oxiracetam + Caffeine induced irritability, but not to the degree 2x600 mg N-Acetylcysteine does. May have something to do with NMDA modulation and or redirecting Cysteine towards Glutathione synthesis instead of Taurine.

 

[Duchykins]

I tried 500mg glutamine once a day the last four days, staying low to see what happens, and I can definitely feel the dopamine and GABA support, it's very nice for a few hours, helps with irritation caused by Wellbutrin's anticholinergic side effects (which is why I'm looking for dopaminergic alternatives to Wellbutrin), then the histamine hits me later like a ton of bricks, itch like mad all over with heavy eyes. Only headache was the one yesterday evening and it's probably from a combination of a few things including cutting my wellbutrin dose in half, which was serious enough for me to take a triptan for.

I *believe* I can work glutamine into a daily stack at low doses without having headaches or mad histamine, I will just have to experiment some more. I also rcently added schizandrol a to my bedtime stack because it apparently helps keep calcium channels closed when there is an excess of glutamate outside the cells (when there is too much outside, certain channels open and allow calcium into the cell, this is part of the beginning of glutamate excitotoxicity, and the migraines for those who are prone to them -- at least, this is my current understanding / remembrance of it). Even without the glutamate issue, the schizandrol seems as useful as bacopa for anxiety and nighttime.

As for the question about lithium, I can't speak to that because I'm not comfortable advising about things I haven't tried for myself (which usually means I haven't read very much about it).

[beez]

@ Duchykins

 

Why dont you want to take ssri?

 

And since you know so much about glutamate and other transmitters, is there a way to somehow find out where exactly your issues come from, I mean which NT is involved?

I am discouraged cause I feel like even if I report my symptoms to my doc he can't really work with them or deduce something from them. I have had GAD and depression since

childhood. That's one thing issue. But what worries me much more and which is at least as bad as the depression are other abnormalities. I have symptoms which sound a bit like ADD

but ritalin didn't work for me at all it didn't cause clarity or calmness.

I suffer from brain fog. Under stress I feel like I can't think straight anymore. I almost never have clarity of mind, usually only at night when I'm alone

by myself. Other people disturb me, also sounds disturb me like ticking of a clock. I quickly become aggitated and restless inside by stress. When things stress me out I feel like I cant

concentrate anymore at all. I also feel spaced out most of the time not really knowing where to look at or what to focus on. At first I thought that this "state" is kinda cool but now it's totally

bothering me. During the day when I have things to do like going to the supermarket I always feel like I'm in a hasty mode even though I'm not under time pressure. I absolutely

hate this feeling in my head. I cannot really describe how it feels like but I absolutely know when it's there. When it's there then I can just tell that it's there.

My guess was that maybe I could suffer from excessive glutamate which causes the oversensitivity. But I tried memantine at 20mg for 5 weeks and it didn't help but caused memory side effects.

Now I dont know if memantine not working means that glutamate isn't my "issue".

 

I was offered pregabalin but since it has such a bad rep I'm really scared of it. Even if I took it and it worked at first then I could still develop dependency or it could start working and I could get withdrawals. Pregabalin is so much scarier than memantine.

Edited by beez, 20 May 2014 - 11:27 PM.

[Duchykins]

I was once given Celexa for insomnia and anxiety. About two months later, one morning, I swallowed 28 10mg ambien for no apparent reason, on an empty stomach. I just woke up, got dressed, then saw my bottle of ambien, refilled just two days before, and went "ehh, right" and took them all in one gulp. I was a robot and the apathy came on so gradually that I didn't even notice. If it had been any other drug I would probably be dead right now, but you know how loopy people can get on ambien and I'm told that I joked to some friends about it, I thought it was hilarious (I don't remember anything after taking them and then sitting down). So they saved my life for me. I still don't understand why, I wasn't thinking about anything upsetting, I wasn't upset or dwelling on dying, it was an apathetic impulse. My first and only suicide attempt. SSRIs terrify me now because if that happens again there is no way to see it coming, and from my consistent reactions to serotogenics it seems I don't need serotonin help anyway. I tried amitriptyline once, a tricyclic, for migraine prevention, but I just got more migraines.

Your sound sensitivity is something I can definitely identify with. I can get really irritiable over innocent sounds from people. I recently learned this has more to with the electrolyte imbalance (for me) than GABA. GABAergics help mask it but only fixing electrolytes makes the tinnitus go away and all of my irritability. Have you had your doctor check your potassium, magnesium, calcium and histamine? Do this before trying another supplement

[Phoenicis]

N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action

Olivia Dean et al.

 

"Glutamate

 

In addition to the effects on oxidative balance, alterations in cysteine levels have also been shown to modulate neuro-transmitter pathways, including glutamate and dopamine (DA; Fig. 1).23,24 Cysteine assists in the regulation of neuronal intra- and extracellular exchange of glutamate through the cystine–glutamate antiporter. Whereas this antiporter is ubiquitous throughout all cell types, in the brain it is preferentially located on glial cells.25 The dimer, cystine, is taken up by astrocytes and exchanged for glutamate, which is released into the extracellular space. This free glutamate appears to stimulate inhibitory metabotropic glutamate receptors on glutamatergic nerve terminals and thereby reduce the synaptic release of glutamate.26 Given that relation, the amount of cysteine in the system as well as the feedback via GSH production by neurons may directly regulate the amount of glutamate present in the extracellular space. Furthermore, GSH itself has been shown to potentiate brain N-methyl-d-aspartate receptor response to glutamate in rats.27,28 Changes in the levels of neuronal GSH may not only alter available glutamate levels, but also have direct consequences on glutamatergic function."

 

Edited by Phoenicis, 21 May 2014 - 10:42 AM.

[beez]

@ Duchykins

 

This sounds really worrying. I just started with escitalopram. Now I'm worried. I also feel a bit less moved by things which is actually good but what if you turn into somebody who doesn't care when he should care?

 

I have not had a recent measurement of electrolytes. I had magnesium measured in the past. But I also heard that measuring magnesium in the blood is not very reliable cause it doesn't show you the electrolyte levels in the cells.

I never had histamine measured. What's this good for?

[PDW]

I scanned through the 3 pages of this discussion and wanted to add. Based on the research I've done, the nootropic noopept apparently prevents the breakdown of glutamate. I found this and looked up information because everytime I used noopept I would begin to experience symptoms of excitotoxicity which I am prone to because I am sensitive to glutamate and msg. It usually begins with headaches/migraines, sore/tight jaw and anxiety for starters. If this is infact the case and the information I have read is true then perhaps adding a little bit of noopept to a racetam stack would prevent or atleast slow down a decrease/depletion of glutamate? I'm actually going the opposite and adding a little bit of Aniracetam to my stack to help even out the glutamate levels that are prevented from breaking down by the Noopept. Thats my theory atleast and I'll see how well it works out in time. It seems the combination should be pretty synergistic.   

[Frigo]

I scanned through the 3 pages of this discussion and wanted to add. Based on the research I've done, the nootropic noopept apparently prevents the breakdown of glutamate. I found this and looked up information because everytime I used noopept I would begin to experience symptoms of excitotoxicity which I am prone to because I am sensitive to glutamate and msg. It usually begins with headaches/migraines, sore/tight jaw and anxiety for starters. If this is infact the case and the information I have read is true then perhaps adding a little bit of noopept to a racetam stack would prevent or atleast slow down a decrease/depletion of glutamate? I'm actually going the opposite and adding a little bit of Aniracetam to my stack to help even out the glutamate levels that are prevented from breaking down by the Noopept. Thats my theory atleast and I'll see how well it works out in time. It seems the combination should be pretty synergistic.   

 

Are you sure about this? I'm pretty sensitive to Glutamatergics and having tried Noopept several times, it has a completely different side effect profile.

 

Also, Aniracetam is heavily Glutamatergic, especially the crash 2 hours after administration.

[LBGSHI]

I scanned through the 3 pages of this discussion and wanted to add. Based on the research I've done, the nootropic noopept apparently prevents the breakdown of glutamate. I found this and looked up information because everytime I used noopept I would begin to experience symptoms of excitotoxicity which I am prone to because I am sensitive to glutamate and msg. It usually begins with headaches/migraines, sore/tight jaw and anxiety for starters. If this is infact the case and the information I have read is true then perhaps adding a little bit of noopept to a racetam stack would prevent or atleast slow down a decrease/depletion of glutamate? I'm actually going the opposite and adding a little bit of Aniracetam to my stack to help even out the glutamate levels that are prevented from breaking down by the Noopept. Thats my theory atleast and I'll see how well it works out in time. It seems the combination should be pretty synergistic.   

 

Have you considered that you're experiencing the symptoms of an excess of choline? Adding aniracetam would likely deplete/utilize choline and reduce these symptoms, but reducing your choline intake would be a more direct approach.

[Area-1255]

ImHo, and considering how much I have researched this subject - I would say that AMPA and NMDA receptors are the most beneficial, along with the inhibitory metabatropic receptors. Kainate receptors actually have the most toxic effect, and technically, it's very difficult to get toxic in glutamate unless.

1.) You consume MSG, or are a vegetarian consuming pea protein isolate power. Which has a shit TON of glutamic acid.

2.) You have a strong GABA deficiency (which normally regulates Glut balance). 

3.) You are zinc and / or magnesium deficient.

 

And even then, NMDA receptor activation actually releases GABA, and though it has a pro-excitory effect, unless you have an overall GABA deficiency, the net effect would either be a near perfect state of concentration and enhanced sleep (REMS).

 

This is the science by which some NMDA marketers have spoken of in regards to what NMDA can do.

That it releases neurosteroids and improves sleep. ONLY with an overall glutamate toxicity (or at least moderate level) do you get extra toxic effects from NMDA...

 

Again, overall balance is key.

 

Signs and Symptoms of Low NMDA Levels/Activity

 

 

But definitely in regards to sleep, I noticed much deeper sleep when using NMDA.

 

 

 

 

[Frigo]

4) You are suffering from clinical depression, your immune system removes Zinc, Magnesium and Iron from your blood to prevent imaginary bacteria from proliferating, and releases Quinolinic Acid that potentiates Glutamate neurotoxicity in several ways.

 

And that is how you can get insane rage on free form Glutamine which is the most abundant amino acid.

 

Think about that for a moment.

 

 

ImHo, and considering how much I have researched this subject - I would say that AMPA and NMDA receptors are the most beneficial, along with the inhibitory metabatropic receptors. Kainate receptors actually have the most toxic effect, and technically, it's very difficult to get toxic in glutamate unless.

1.) You consume MSG, or are a vegetarian consuming pea protein isolate power. Which has a shit TON of glutamic acid.

2.) You have a strong GABA deficiency (which normally regulates Glut balance). 

3.) You are zinc and / or magnesium deficient.

 

And even then, NMDA receptor activation actually releases GABA, and though it has a pro-excitory effect, unless you have an overall GABA deficiency, the net effect would either be a near perfect state of concentration and enhanced sleep (REMS).

 

This is the science by which some NMDA marketers have spoken of in regards to what NMDA can do.

That it releases neurosteroids and improves sleep. ONLY with an overall glutamate toxicity (or at least moderate level) do you get extra toxic effects from NMDA...

 

Again, overall balance is key.

 

Signs and Symptoms of Low NMDA Levels/Activity

 

 

But definitely in regards to sleep, I noticed much deeper sleep when using NMDA.

 

[Area-1255]

 

4) You are suffering from clinical depression, your immune system removes Zinc, Magnesium and Iron from your blood to prevent imaginary bacteria from proliferating, and releases Quinolinic Acid that potentiates Glutamate neurotoxicity in several ways.

 

And that is how you can get insane rage on free form Glutamine which is the most abundant amino acid.

 

Think about that for a moment.

 

 

ImHo, and considering how much I have researched this subject - I would say that AMPA and NMDA receptors are the most beneficial, along with the inhibitory metabatropic receptors. Kainate receptors actually have the most toxic effect, and technically, it's very difficult to get toxic in glutamate unless.

1.) You consume MSG, or are a vegetarian consuming pea protein isolate power. Which has a shit TON of glutamic acid.

2.) You have a strong GABA deficiency (which normally regulates Glut balance). 

3.) You are zinc and / or magnesium deficient.

 

And even then, NMDA receptor activation actually releases GABA, and though it has a pro-excitory effect, unless you have an overall GABA deficiency, the net effect would either be a near perfect state of concentration and enhanced sleep (REMS).

 

This is the science by which some NMDA marketers have spoken of in regards to what NMDA can do.

That it releases neurosteroids and improves sleep. ONLY with an overall glutamate toxicity (or at least moderate level) do you get extra toxic effects from NMDA...

 

Again, overall balance is key.

 

Signs and Symptoms of Low NMDA Levels/Activity

 

 

But definitely in regards to sleep, I noticed much deeper sleep when using NMDA.

 

Well that is a good point, and that's why everyone should supplement with Zinc and Magnesium; preferably at night.

[Area-1255]

A lot of the information here is very useful but too one-sided. Glutamate activity in the brain is very complicated. I decided to comment here because of so many people looking to nootropics to help with various problems they have such as "anxiety", "social issues", "speech" and "attention problems". Some of the people here already have a little bit too much glutamate and/or glutamate receptors on their cells, causing insomnia (sleep-onset usually), poor eye contact, speech issues, quick learning, higher IQ (both in part due to glutamate increasing ACh in addition to providing energy), headaches/migraines, deregulation of blood sugar, difficulty discriminating background noise and deciphering speech (symptoms sometimes mistaken for auditory processing disorder), several things often mistaken for anxiety; self-stimulatory activity (not to soothe fear), "racing thoughts" (not fear-related), intellectual activity that won't "turn off" (again not fear-related), easily overstimulated - so for example, person with beaucoup glutamate activity going on might often present as a very intelligent, high functioning autistic-like person of few words or perhaps as someone with attention deficit problems.

In these cases, glutamate-GABA levels are imbalanced; GABA is way too low. Adding glutamate, glutamine, glutamic acid, aspartic acid, aspartame and related substances (as isolated supplements rather than complete protein) is the absolute last thing these types of people need. Doing such things only increases their *already increased* risk of glutamate excitotoxicity, cell death, glutathione depletion and by proxy increase inflammation due to lowered glutathione and increased histamine (which may seem paradoxical because glutathione is another thing that can decrease histamine tolerance). Even taking the noots that work significantly with glutamate can leave them worse off than before - UNLESS they take steps to simultaneously **support their GABA processes**, protecting them from glutamate excitotoxicity, lessening or abolishing many symptoms associated with excess glutamate/higher densities of glutamate receptors including headaches, excessive wakefulness, poor speech and eye contact.

Ways to approach this are varied but would include OTC supplementation of taurine, theanine, lysine, valerian, ginkgo, ashwagandha, perhaps GABA itself (some may also argue for phenibut or picamilon here, but I won't) perhaps gabapentin or related prescriptions, alteration of activities such as taking noots or any supplement or eating foods known to increase glutamate or enhance glutamate sensitivity within 6 hours of bed time. Of course this does not mean attempt to eliminate glutamate, as it is a necessary neurotransmitter and greatly beneficial when balanced.

Another reason to ward from glutamate towards the end of the day is that it increases histamine, and you need lower histamine during sleep for better memory consolidation. Some noot users that report no memory improvements or worsening memory may be taking noots or supplements that increase histamine or enhance histamine sensitivity too late in the day, too close to bed time, compromising their brain's ability to consolidate memory. Some people may already have high histamine or lowered tolerance for histamine and interpret their high histamine symptoms as excess choline/ACh including "brain fog" and/or "heaviness" especially near the sinuses, "depression", headache, among other things. I sometimes read a thread where someone asks if excess choline causes flu-like, cold-like or allergy symptoms and everyone saying no, it's not related or must be a virus, when in fact it is related- but to the noots they are taking or other things in their stack that increase glutamate and increase histamine beyond levels their bodies can tolerate. These people can benefit either from lowering whatever is increasing their histamine or adding something that has antihistamine effects.

Of course, none of this would apply to people who aren't particularly sensitive to glutamate or histamine activity, which is many people. :D

Excellent post, and this describes it pretty much to a tee. 

Although I should point out that histamine can technically protect against glutamate as well - but this occurs mainly when H(3)'s are blocked, and so histamine activates GABA through it's other receptors.

 

 

[PDW]

So to answer some questions. When I was using Aniracetam I rarely used choline, maybe 1 or 2 times a week and it was 250mg of CDP choline. I found it wasn't helpful and made me depressed and tired. As for aniracetam, the effects were subtle and didn't do much combined with noopept it seemed, I may revisit that experiment at a later time. The last week however I have been taking 100mg of l-theanine first thing in the morning on an empty stomach, eating 30-40 mins later and then taking my noopept. Currently I add 10mgs of noopept powder a day (from peak nootropics) into a half ounce of water and take a teaspoon at a time every 4 hours. This seems to level out the effects so it is felt consistently through the day with no ups or downs. The l-theanine seems to even out my mood so I get no irritability or anxiousness like I occasionally get from noopept. However, splitting up my noopept doses the way I have has also helped a lot with the irritability and anxiety, the theanine just seems to smooth things out as a final touch. Pea protein was also mentioned as being high in glutamic acid, my morning breakfast shake has pea protein, orange juice, and hemp oil in it, then I take my first noopept dosage afterwards. Funny enough, that pea protein has never bothered me when taken by itself and it seems to make the noopept work a lot better. But to much taken with the noopept can send me down a road of unpleasant glutamate side effects, one of which being nasty headaches. The theanine seems to prevent that though. Without the pea protein the noopept works, just less and the negative effects (anxiety and irritability) seem more prevalent. It feels like a juggling act with noopept in terms of to much or to little glutamate and finding that sweet spot for optimal effects.