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D aspartic acid induced problems (perhaps glutamate excitotoxicity?) Please help.

d aspartic acid induced

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#1 D424friday

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Posted 12 November 2013 - 09:40 PM


Hi,

I am posting this in hopes to receive some help on what steps to take next in regards to the extreme problems supplementing with d aspartic acid has caused me, as it's currently ruining my life.
Around 2 years ago i started (stupidly) using 6 grams of d aspartic acid a day for a boost in the gym, The first week I felt great, but after that i started to get depression, anxiety and sleep problems.
I discontinued use immediately, and decided to wait to see if the problems subsided, they did not. I had to leave full time education and my Job because of the problems the d aspartic acid caused, and have not had a job or returned to education in 2 years( I'm 20 years old now.)

For the first year i had the following symptoms in a very bad way:
.Depression ( suicidal thoughts constantly )
.Anxiety (became very socially awkward because of this, I was very socially adept and confident before )
.Sleep problems(couldn't fall asleep easily, and when i did, the sleep was not very deep and not for very long, when i woke up i was very tired again)
.Brain fog
.Puffy chest, lactating nipples
.Absolutely no libido
.Memory loss, could not retain new information what so ever, and struggled to remember things i already knew
.General mental and physical fatigue
.Weight loss
.General loss of cognitive ability(I felt i was a lot less intelligent, could not contruct a sentence easily)

After a year of enduring these symptoms I finally decided to put all my energy(of which i had very very little) into doing a bit of research, my first avenue of reversing these symptoms was lowering prolactin, as raised prolactin was a side effect of d aspartic acid. I came to the conclusion i had high prolactin because of my puffy chest, lactating nipples and sleep problems. The sleep problems i linked to high prolactin because of experiences i read from people using the steroid trenbolone, they also had sleep problems exactly like mine and Trenbolone also increases prolactin.

I bought myself some cabergoline to lower my prolactin, low and behold the night i took it, my symptoms were improved around 30%. However this stopped working after a week or two, and it seemed by prolactin came crashing back. I knew this wasn't the answer, but after getting a glimpse of hope, i carried on doing a bit of research, i came to the further conclusion that D aspartic acid had damaged my nmda receptors via glutamate excitotoxicty( which can also effect prolactin secretion.)

After googling around i came across a post of someone who suffered from glutamate excitotoxicity (ketamine related) and had used NAC + Piracetam + sarcosine + niacin + vitamin c to reverse it. In desperation and willing to try anything i decided to try any of the supplements mentioned i could find, I supplemented with NAC at first 2g/day, this greatly improved my symptoms, within a week I'd say all symptoms improved 40%, i was so happy. So i decided to add vitamin C at 3g/day into the mix, My symptoms again improved around 30%. I then tried piracetam which strangely is currently making things worse.

From here i don't know where to go, I am not even sure if my conclusion of glutamate excitotoxicity is even correct, the state my brain is in at the moment makes it very hard to understand and learn new things so researching in depth the mechanisms of d aspartic acid to find out what went wrong is very difficult. All i know is something went wrong after taking d aspartic 6g/day for a week, and NAC/Vitamin C have helped greatly but are not helping any further after supplementing with them for months now. Does anyone have any suggestions on what i could try next, or what caused my problems in the first place?

Note: I was not taking any other supplements around the time of taking d aspartic acid.





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#2 nowayout

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Posted 12 November 2013 - 09:48 PM

The antidepressant Tianeptine is thought to act by making changes in glutamate pathways in the brain. You might want to read up on that and see if it could be helpful to you.

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#3 D424friday

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Posted 13 November 2013 - 12:06 AM

The antidepressant Tianeptine is thought to act by making changes in glutamate pathways in the brain. You might want to read up on that and see if it could be helpful to you.

Thanks for the reply, I will start reading up on Tianeptine asap.

#4 Kowalsteeze

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Posted 13 November 2013 - 03:35 AM

I have heard at least one anecdotal report of an individual reversing his post-DAA troubles with a high dose memantine regimen. DAA was the one supplement to make me feel "sick" in the head. The FDA should be pulling that off shelves before things like jack3d.

#5 health_nutty

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Posted 13 November 2013 - 04:01 AM

I have heard at least one anecdotal report of an individual reversing his post-DAA troubles with a high dose memantine regimen. DAA was the one supplement to make me feel "sick" in the head. The FDA should be pulling that off shelves before things like jack3d.


Really, I hardly feel anything at all from it. Is it really dangerous?

Sent from my SCH-I545 using Tapatalk


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#6 D424friday

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Posted 13 November 2013 - 01:05 PM

The antidepressant Tianeptine is thought to act by making changes in glutamate pathways in the brain. You might want to read up on that and see if it could be helpful to you.

After reading up, from my basic understanding Tianeptine stops glutamate from opening the AMPA receptors, thus stopping glutamate excitotoxicity from occurring. Would i be correct in saying this? If so, is this still benefical to me? My current understanding is that glutamate excitotoxicity has already occured from the daa, wouldn't that mean Tianeptine would just stop future excitotoxicity from occuing, whereas i need to address the damage glutamate excitotoxicity has caused. Not sure if i'm correct though.

I have heard at least one anecdotal report of an individual reversing his post-DAA troubles with a high dose memantine regimen. DAA was the one supplement to make me feel "sick" in the head. The FDA should be pulling that off shelves before things like jack3d.

Thanks for the reply. Do you perhaps have a link to the report you are talking about? If not, could you maybe point me in the direction of what sort of regimen might be of use. After reading it is used to treat nmda excitotoxicity in people with alzheimers and that it stabilizes the nmda receptors, I'd like to look further down this route.

Edited by D424friday, 13 November 2013 - 01:06 PM.


#7 YoungSchizo

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Posted 13 November 2013 - 02:06 PM

I supplement DAA in cycle's because at first (for me) it gives Sarcosine's benefits a boost, though, after a while supplementing DAA it makes me feel depressed and I stop taking DAA.

I don't know anything about glutamate excitotoxicity (I probably have it too.. however, only thing I know I have a big problem with glutamate too, I'm Schizophrenic).

And the only thing I know about Sarcosine is that it activates hypo-active NMDA receptors and that DAA is a NMDA agonist. I read somewhere that DAA is also not recommended to take for schizophrenics (I couldn't find the source though).
I don't know if it will help you out but I have great benefits from taking Sarcosine on it's own.

In this case benefits on
Depression ( suicidal thoughts constantly ) - It did little for my depression, though it has noticeable effects on my mood
.Anxiety (became very socially awkward because of this, I was very socially adept and confident before ) - it did little for my anxiety problems but I became more social again
.Absolutely no libido - my libido turned normal after Sarcosine, before it was like I was horny 24/7 :)
.General mental and physical fatigue - My overall mental health improved
.General loss of cognitive ability(I felt i was a lot less intelligent, could not contruct a sentence easily) - My overall cognition improved

Edited by YoungS, 13 November 2013 - 02:22 PM.


#8 D424friday

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Posted 13 November 2013 - 02:26 PM

I supplement DAA in cycle's because at first (for me) it gives Sarcosine's benefits a boost, though, after a while supplementing DAA it makes me feel depressed and I stop taking DAA.

I don't know anything about glutamate excitotoxicity (I probably have it too.. however, only thing I know I have a big problem with glutamate too, I'm Schizophrenic).

And the only thing I know about Sarcosine is that it activates hypo-active NMDA receptors and that DAA is a NMDA agonist. I read somewhere that DAA is also not recommended to take for schizophrenics (I couldn't find the source though).
I don't know if it will help you out but I have great benefits from taking Sarcosine on it's own.

Thanks for the reply, I'll look into Sarcosine. Also, here's a post from another member on this site that explains glutamate excitotoxicity simply:

so, first we have our AMPA receptors. once the AMPA receptor opens up, ions flow into it and start charging it. there are several different ion types that'll flow in, but the main one of concern is calcium. the AMPA receptor "fires" (aka polarizes) when the ions flowing through it charge it up to a certain threshold. once it fires, it closes up again. when your AMPAs fire, they sprout other little AMPA buddies nearby.

next, we have our NMDA receptors. we need both of these bad boys to induce long-term-potentiation, which essentially means the neuron has been "strengthened" so that it fires off just as strong with a lower amount of neurotransmitter stimulation. the NMDA receptor naturally has a magnesium "front door" or sorts blocking ions from flowing in, which is where AMPAs step in. the charge from maybe one AMPA receptor probably won't be enough to open up NMDA receptor, but after enough AMPA receptors form around the NMDA from their firing, eventually, their collective charge will be enough to knock out the magnesium blocking the way. once the magnesium is out of the way, then ions can flow through the NMDA receptor.

glutamate is the main handyman with all of this, and it does a pretty good job of prying open [aka exciting] those AMPA receptors and will get you to the front door on the NMDA receptor. now obviously, the AMPA receptors can't just stay open for ions to rush through all the time and will close once they fire, but that certainly doesn't affect whether or not glutamate will just open it up again when it can. THIS is where we get neurotoxicity. once your glutamate starts running around and partying in your brain, it'll start opening up your AMPAs more than you can handle, and more and more calcium will flow through. once you've had too much calcium flow through: poof. your neuron is zapped. gone.

so when you read something being called a "modulator," it's basically describing it's action on the receptor. what the patent that you posted basically says is that taking tianeptine is kind of like putting a really scary, shaved head, muscle-bound bouncer/doorman in front of your AMPA receptors. this way, if your glutamate gets out of hand and wants to start crashing parties in your AMPA receptors, your buddy tianeptine will be there, ready and waiting for it at the door armed with a resounding "shove off" and a nice, beefy pair of crossed arms.



#9 nowayout

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Posted 13 November 2013 - 02:55 PM

The antidepressant Tianeptine is thought to act by making changes in glutamate pathways in the brain. You might want to read up on that and see if it could be helpful to you.

After reading up, from my basic understanding Tianeptine stops glutamate from opening the AMPA receptors, thus stopping glutamate excitotoxicity from occurring. Would i be correct in saying this? If so, is this still benefical to me? My current understanding is that glutamate excitotoxicity has already occured from the daa, wouldn't that mean Tianeptine would just stop future excitotoxicity from occuing, whereas i need to address the damage glutamate excitotoxicity has caused. Not sure if i'm correct though.

AFAICR Tianeptine is thought to improve neuroplasticity via glutamate pathways and to facilitate recovery (increase in volume) of brain regions that tend to be atrophied in depressed patients. If this is true, it may well facilitate recovery of already existing damage. That is assuming your damage, if any, has to do with the pathways supposedly addressed by tianeptine. In other words, we are making a lot of assumptions.

Edited by nowayout, 13 November 2013 - 02:57 PM.


#10 BioFreak

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Posted 14 November 2013 - 03:34 PM

If your brain was damaged from DAA then I would suggest regenerative supplements:

uridine stack (ump, o3, esp DHA->important for any brain regeneration attempt, not only uridine, cdp-choline)
longvida curcumin (NO other curcumin)
NAC still stacks great with this
c60, there may be a chance it may reverse it too. Pure speculation though.

you can combine them all to my knowledge. I'm taking everything but the uridine stack atm with great success. But my brain problems are probably damage due to long term high stress. I am not suggesting these because they are good for DAA induced neurotoxicity, but because they are well known neuroprotective and neuroreparative substances. Everyone has its limits but often stacking them, because they rely on partially or completely different mechanisms, gives an extra boost.

The thing is - when the brain is damaged, its often the best way to look at substances that generally have a good effect on regeneration of the brain, its the job of the brain to heal it self, we can only support it anyways. The better the brain is at regeneration, the higher the chances of recovery.
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#11 protoject

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Posted 14 November 2013 - 10:07 PM

First you would have to prove that DAA does cause excitotoxicity when dosed orally, and how this would translate into effects in humans. Second, you would have to prove that this drug has such a profound effect on hormones that after taking it for only such a short duration of time it somehow left you with lasting hormonal changes. First of all, were you taking any other supplements around that time? Did you take any other drugs or medications, such as testosterone or steroids? (I have no reason to believe that you did but I'm just curious)/. Did you have a hormone panel before and after this incident? If not did you ever have these types of problems before at any time?

I know your conversation is only speculative and this is the approach you are taking, which is fine- because you want to find out what's wrong and treat it, and perhaps some of those things are actually beyond what doctors could diagnose. But, there are some red flags here for there being a hormonal imbalance, so why not get that tested first? ... sounds like high estrogen/ low testosterone, perhaps high prolactin like you said, perhaps a high conversion of testosterone to estrogen
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#12 nowayout

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Posted 14 November 2013 - 10:27 PM

Yes, I agree, rather than assume you know the reason it would be good to see a doctor and maybe get referred to a good endocrinologist to try to get to the bottom of this.

Lactating nipples are a big red flag. It could be a prolactinoma, which is treatable if you get it diagnosed. Get yourself to a doctor stat. You are not going to treat something like that successfully with supplements suggested to you by people on the internet.

The other red flag is thoughts of suicide. I can't emphasize enough that this is an emergency and you should go to a doctor.
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#13 D424friday

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Posted 14 November 2013 - 10:55 PM

The antidepressant Tianeptine is thought to act by making changes in glutamate pathways in the brain. You might want to read up on that and see if it could be helpful to you.

After reading up, from my basic understanding Tianeptine stops glutamate from opening the AMPA receptors, thus stopping glutamate excitotoxicity from occurring. Would i be correct in saying this? If so, is this still benefical to me? My current understanding is that glutamate excitotoxicity has already occured from the daa, wouldn't that mean Tianeptine would just stop future excitotoxicity from occuing, whereas i need to address the damage glutamate excitotoxicity has caused. Not sure if i'm correct though.

AFAICR Tianeptine is thought to improve neuroplasticity via glutamate pathways and to facilitate recovery (increase in volume) of brain regions that tend to be atrophied in depressed patients. If this is true, it may well facilitate recovery of already existing damage. That is assuming your damage, if any, has to do with the pathways supposedly addressed by tianeptine. In other words, we are making a lot of assumptions.

Thanks for the info. I'll look further into it, for now i'll be trying memantine and galantamine.

If your brain was damaged from DAA then I would suggest regenerative supplements:

uridine stack (ump, o3, esp DHA->important for any brain regeneration attempt, not only uridine, cdp-choline)
longvida curcumin (NO other curcumin)
NAC still stacks great with this
c60, there may be a chance it may reverse it too. Pure speculation though.

you can combine them all to my knowledge. I'm taking everything but the uridine stack atm with great success. But my brain problems are probably damage due to long term high stress. I am not suggesting these because they are good for DAA induced neurotoxicity, but because they are well known neuroprotective and neuroreparative substances. Everyone has its limits but often stacking them, because they rely on partially or completely different mechanisms, gives an extra boost.

The thing is - when the brain is damaged, its often the best way to look at substances that generally have a good effect on regeneration of the brain, its the job of the brain to heal it self, we can only support it anyways. The better the brain is at regeneration, the higher the chances of recovery.

I've just started looking into supplements that increase neuron growth, really appreciate the reply. I have a stack in mind i'm going to try out, including lions mane, choline,longvida curcumin , memantine and galantamine. I'll post back with the results.

First you would have to prove that DAA does cause excitotoxicity when dosed orally, and how this would translate into effects in humans. Second, you would have to prove that this drug has such a profound effect on hormones that after taking it for only such a short duration of time it somehow left you with lasting hormonal changes. First of all, were you taking any other supplements around that time? Did you take any other drugs or medications, such as testosterone or steroids? (I have no reason to believe that you did but I'm just curious)/. Did you have a hormone panel before and after this incident? If not did you ever have these types of problems before at any time?

I know your conversation is only speculative and this is the approach you are taking, which is fine- because you want to find out what's wrong and treat it, and perhaps some of those things are actually beyond what doctors could diagnose. But, there are some red flags here for there being a hormonal imbalance, so why not get that tested first? ... sounds like high estrogen/ low testosterone, perhaps high prolactin like you said, perhaps a high conversion of testosterone to estrogen

One thing i absolutely should have mentioned is that I actually tried Testosterone Replace Therapy recently(about 18 months after DAA) in desperation to see if it would help, there was no improvement in any of the symptoms(this was after trying many different dosage regimes), I also had hormone panels done during this time and according to the dr I was in normal ranges. I am now off TRT and do not feel any better/worse than when I was on it.

I don't think I'm intelligent enough to prove any of those things. I'm just going off the only other thing i can think of that has caused this in that time frame, and many of the symptoms seem to align themselves with symptoms other people have had after using DAA that i have read. As stated i was taking no other supplements and also no other medication at the time, just before i started DAA I was probably the best i'd ever felt. I have never done steroids(apart from trt after taking daa), I've also never had any of these symptoms before. It seems too much of a co incidence to me to feel really good and then the week i take DAA i start to go downhill.

EDIT: Again i apologise for missing this out the first time, as I say my memory is absolutely terrible. When i was taking DAA, every time i would take a dose i would get a feeling in my head, it felt like a pressure in the brain/headache/brain fog and this was almost immediately after taking a dose(30mins-2hours), this didn't go away until i started supplementing with NAC about a year later.

Edited by D424friday, 14 November 2013 - 11:00 PM.

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#14 Hebbeh

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Posted 15 November 2013 - 02:37 AM

Could the DAA have been either contaminated, adulterated, or laced with other substances/drugs? This is unfortunately a very common practice in the athletic performance supplement business.

Personally, I've used DAA on a regular basis for the last 10 years with nothing but positive results, although I'm 56. With DAA, I always wake with an erection but not very often without DAA (remember I'm 56) and with DAA I have more energy for physical activities. Although I don't feel it's a suitable supplement for anybody younger than probably 40. And like all things, YMMV.
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#15 Raza

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Posted 15 November 2013 - 12:51 PM

I've not come across anything that has been proven to reverse damage from excitotoxicity. I'd be interested, because being on the autism spectrum I'm very sensitive to it, and I've induced a few instances of it in myself while playing with glutamatergic nootropics before I started recognizing the symptoms. Things that prevent it are more widely available.

However, you might have some luck with general neurotropics for at least replacing the functionality of any neurons that died by forming new connections between the ones that are left. Things that enhance nerve growth factors, uridine, ashwagandha. Cerebrolysin could possibly reverse the damage, depending on how it works; that one's on my research list for this very purpose.

#16 nowayout

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Posted 15 November 2013 - 01:51 PM

I also had hormone panels done during this time and according to the dr I was in normal ranges.

Did these include prolactin and estradiol? If you have lactating and sore nipples, there is absolutely something hormonally wrong. If the doctor didn't catch that, he is an idiot and you should go to someone who is knowledgeable.
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#17 zorba990

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Posted 15 November 2013 - 04:08 PM

Re : "I also had hormone panels done during this time and according to the dr I was in normal ranges. I am now off TRT and do not feel any better/worse than when I was on it."

Post your numbers. Something is wrong and taking supplements / drugs randomly is unlikely to fix it. Bodybuilding combination supplements are sometimes (but not usually) adulterated with drugs or innocuous sounding pro hormones. I would stop taking everything fro 1-3 months and get all your hormones re-tested and test vitamins/minerals as well.

#18 protoject

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Posted 17 November 2013 - 05:20 PM

^ that's true, I think it's pertinent that we ask as well: was this pure DAA or was it DAA in a special formulation including something else?

#19 Guest_Funiture2_*

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Posted 17 August 2014 - 06:47 PM

Try including Taurine + Magnesium Glycinate, those both work for me at calming excitoxicity symptoms (plus maybe Potassium). Taurine & Magnesium have syngergy and are NMDA antagonists.

 

Also since D-aspartate is a brain osmolyte, I think what happened to you is that you depleted all the other brain osmolytes from large long-term doses. see this study:

 

http://deepblue.lib....e/2027.42/46028

"Thus, we have demonstrated an interdependence of organic osmolytes within the nerve. Abnormal accumulation of one osmolyte results in reciprocal depletion of others."

 

I've tried searching around for a definitive list of the brain osmolytes but each source seems to be different. They include:

 

Taurine

Myo-Inositol

Sorbitol (I dont think this needs to be supplemented or can even be depleted since its derived from glucose)

Betaine (I'm unsure if this refers to TMG (trimethylglycine) or something else)

D-Aspartate

Beta-Alanine (Notice that Beta-Alanine rapidly depletes Taurine, so supplementing them together is absolutely necessary)

 

 

http://www.ncbi.nlm..../pubmed/8097294

"In this work we examined the time course and the amount released, by hyposmolarity, for the most abundant free amino acids (FAA) in rat brain cortex astrocytes and neurons in culture. The aim was to evaluate their contribution to the process of cell volume regulation. Taurine, glutamate, and D-Aspartate in the two types of cells, beta-alanine in astrocytes and GABA in neurons were promptly released by hyposmolarity, reaching a maximum within 1-2 min. after an osmolarity change."

 

http://www.ncbi.nlm....cles/PMC283532/

"These include the four organic osmolyte transporters identified in mammals: the Na+/myo-inositol transporter (SMIT), betaine transporter (BGT1), taurine/β-amino acid transporter (TAUT), and system A amino acid transporter (4, 5, 7)."

 

http://www.ncbi.nlm....les/PMC2276334/

"the principal organic osmolytes in renal medullary cells are sorbitol, betaine, inositol, taurine, and glycerophosphocholine (GPC). Cells in other tissues may also experience hyperosmolality, albeit to a lesser degree than in the renal medulla. Accordingly, they also accumulate organic osmolytes. The principal ones in brain are amino acids, choline, creatine, inositol, and taurine (20). Liver cells accumulate betaine, inositol, and taurine (21)."

 



#20 D424friday

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Posted 27 August 2014 - 01:47 PM

Thanks for taking the time to reply furniture.

I will write a more detailed post when I have the time, but just to update, I have completely fixed the problem using Selegiline and Aniracetam, I only needed to take them a few times as well. Hopefully that information helps someone, I have quite a few PMs from people having similar experiences after using d aspartic acid.


Edited by D424friday, 27 August 2014 - 01:48 PM.


#21 Area-1255

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Posted 27 August 2014 - 06:15 PM

I have heard at least one anecdotal report of an individual reversing his post-DAA troubles with a high dose memantine regimen. DAA was the one supplement to make me feel "sick" in the head. The FDA should be pulling that off shelves before things like jack3d.

DAA can help treat schizophrenia naturally though, I actually like the effects of DAA as a test booster, many don't though.


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#22 Area-1255

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Posted 27 August 2014 - 06:30 PM

OP, lemme tell you a little bit about what you are missing.

#1 - NMDA-receptor modulation in general is a tricky thing, and part of the reason that DAA/NMDA is so controversial - is not so much the potential excitoxicity but the formulas themselves being called in question. What we are talking about here is both the purity of DAA and also the fact that most supplement companies don't bother to throw in sarcosine which substantially improves the tolerance for DAA and enhances the positive effects.

 

Sarcosine might as well be considered a necessary addition to DAA, without it, DAA will do very little. 

The way it works is you need something to agonize the glycine site at NMDA, as well as direct activation of NMDA-currents. 

DAA is thought to be key one and sarcosine is Key 2. Both keys are needed to open the lock (it's a double locked door), and when it is unlocked then that massive door into the other dimension is opened.

 

Read these articles/links for more information.

 

http://epharmnutriti...estforce-2.html

http://www.predatorn...rnold-15-09-11/

http://forum.bodybui...php?t=139590323

http://nootriment.com/sarcosine/

 

As you can see, I'm not the first person to bring this issue up.

 

Now let's dig a little more into what happens, assuming NMDA is properly agonized by both ligands; DAA and Sarcosine and / or Glycine.

 

When NMDA-receptors are activated, it triggers N-type calcium efflux - which leads to nNOS protein increases. nNOS is the fancy term for neuronal nitric oxide synthase or nitric oxide of the CNS/Nerves...in addition, NMDA binds directly to sites in the hypothalamus taking this mode of action on and increasing gonadotropins and testosterone by enhancing cGMP in the pituitary. Where it then has an additional downstream effect. In the testes DAA activates cAMP and sTAR, leading to enhanced testosterone secretion through that mechanism.

 

Now here's where it gets interesting, once NMDA-receptors are ACTIVATED, and then nitric oxide as I said above, now you have to look at the chemical messenger nitric oxide and how it antagonizes NMDA-induced currents/activity!!!

 

 

Which means your body would just short-circuit the effects of NMDA by means of NMDA's own pathway causing reverse/inverted feedback.

Now it will also depend on how much nitric oxide is active and how long it stays available, this period of time can be increased by adding PDE inhibitors to DAA.

But now with more nitric oxide, who's to say how much DAA is even contributing anymore????

 

I guess,

 

The question is, what does this look like in real life results, it could certainly be the reason DAA's effects wear off after the second week (aprox).

 

But now, MOST IMPORTANTLY  - DAA STIMULATES AROMATASE AND ESTROGEN SYNTHESIS FROM TESTOSTERONE!

 

OP, what this means is targeting prolactin wasn't enough, because you would just have an estrogen induced rise later that is uncontrollable by dopaminergics alone.

 

 

I too had this experience, and an AI saved me from side-effects and enhanced the DAA markedly. 

 

Moral of the story : Take BOTH an anti-estrogen (such as Erase Pro) AND an anti-prolactin with DAA always.

 

 

SOURCES : http://www.sciencedi...304394004001260

HOPPER EJN 2004 STUDIES.

 

Brain Res. 1993 Dec 17;631(1):72-6. Endogenous nitric oxide inhibits NMDA- and kainate- responses by a negative feedback system in rat hippocampal neurons.
Abstract

Involvement of endogenous nitric oxide (NO) on glutamate receptor-mediated response was investigated in neuronal cells cultured from embryonic rat hippocampus. L-NG-Nitroarginine (NOARG), a NO synthase inhibitor, augmented NMDA- and kainate-induced increase in intracellular Ca2+ concentration ([Ca2+]i) measured by fura-2 fluorometry. However, quisqualate-induced response was not affected. The potentiating effect of NOARG was blocked by L-arginine, a substrate for NO synthase. NOARG was also effective when added after glutamate-induced response had reached a steady-state. Hemoglobin itself increased the basal level of [Ca2+]i at concentrations higher than 10 mM, and treatment of the cells with 1.0 mM hemoglobin had no effect on NMDA response. 8-Bromo-cyclic GMP was not effective on NMDA response. These results suggest that endogenous NO inhibits NMDA- and kainate-induced increase in [Ca2+]i as a negative feedback system independent of guanylate cyclase activation.

PMID:   7905357   [PubMed - indexed for MEDLINE]

 


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#23 Area-1255

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Posted 27 August 2014 - 06:45 PM

One of the primary symptoms of low-NMDA activity is feeling like you have an overall lack of balance, not stimulated enough, lethargy, but yet anxious in a way as well. NMDA-hypoactivity AND hyperactivity can both contribute to Ahedonia, Dysphoria, dopamine dysregulation and other problems. Depersonalization and delirium is noted in some cases of excessive or underactive NMDA - with hypoactivity being more prominent and yielding more negative biochemical effects.

 

Another low NMDA symptom is feeling like you are out of place with reality, and feeling like people are reading your thoughts, this was also evident to me when I took agmatine supplements (which temporarily block NMDA currents) - thus yet ANOTHER great point is if you want the FULL benefits of DAA/NMDA - you need to make sure you aren't taking things that counteract it.

 

Overlooked NMDA-blockers are

-Ginkgo Biloba

-Agmatine Sulfate

-Possibly NAC* ; N-Acetyl-Cysteine.

-The Dementia drug "Memantine"

-Phenyl piracetam (but not other racetams)

-Opium chemicals.

-Kratom Leaf

 

http://en.wikipedia....ptor_antagonist

http://www.ncbi.nlm....les/PMC3817734/

 

Oh and this list is a long one.



Competitive antagonists[edit]


  • AP5 (APV, R-2-amino-5-phosphonopentanoate)[31]

  • AP7 (2-amino-7-phosphonoheptanoic acid)[32]

  • CPPene (3-[®-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid)[33]

  • Selfotel: an anxiolytic, anticonvulsant but with possible neurotoxic effects.


Uncompetitive channel blockers[edit]



Non-competitive antagonists[edit]


  • Aptiganel (Cerestat, CNS-1102): binds the Mg2+ binding site within the channel of the NMDA receptor.

  • HU-211: an enantiomer of the potent cannabinoid HU-210 which lacks cannabinoid effects and instead acts as a potent non-competitive NMDA antagonist.[47]

  • Remacemide: principle metabolite is an uncompetitive antagonist with a low affinity for the binding site.[48]

  • Rhynchophylline an alkaloid.

  • Ketamine: a dissociative psychedelic with antidepressant properties used as an anesthesia in humans and animals, a possible treatment in bipolar disorder patients withTreatment-resistant depression, and used recreationally for its effects on the CNS[49]


Glycine antagonists[edit]


These drugs act at the glycine binding site:


 


Edited by Area-1255, 27 August 2014 - 06:46 PM.

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#24 Guest_Funiture2_*

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Posted 28 August 2014 - 02:19 AM

 

One of the primary symptoms of low-NMDA activity is feeling like you have an overall lack of balance, not stimulated enough, lethargy, but yet anxious in a way as well. NMDA-hypoactivity AND hyperactivity can both contribute to Ahedonia, Dysphoria, dopamine dysregulation and other problems. Depersonalization and delirium is noted in some cases of excessive or underactive NMDA - with hypoactivity being more prominent and yielding more negative biochemical effects.

 

Another low NMDA symptom is feeling like you are out of place with reality, and feeling like people are reading your thoughts, this was also evident to me when I took agmatine supplements (which temporarily block NMDA currents) - thus yet ANOTHER great point is if you want the FULL benefits of DAA/NMDA - you need to make sure you aren't taking things that counteract it.

 

Overlooked NMDA-blockers are

-Ginkgo Biloba

-Agmatine Sulfate

-Possibly NAC* ; N-Acetyl-Cysteine.

-The Dementia drug "Memantine"

-Phenyl piracetam (but not other racetams)

-Opium chemicals.

-Kratom Leaf

 

http://en.wikipedia....ptor_antagonist

http://www.ncbi.nlm....les/PMC3817734/

 

Oh and this list is a long one.

 



Competitive antagonists[edit]


  • AP5 (APV, R-2-amino-5-phosphonopentanoate)[31]
  •  
  • AP7 (2-amino-7-phosphonoheptanoic acid)[32]
  •  
  • CPPene (3-[®-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid)[33]
  •  
  • Selfotel: an anxiolytic, anticonvulsant but with possible neurotoxic effects.
  •  

Uncompetitive channel blockers[edit]



Non-competitive antagonists[edit]


  • Aptiganel (Cerestat, CNS-1102): binds the Mg2+ binding site within the channel of the NMDA receptor.
  •  
  • HU-211: an enantiomer of the potent cannabinoid HU-210 which lacks cannabinoid effects and instead acts as a potent non-competitive NMDA antagonist.[47]
  •  
  • Remacemide: principle metabolite is an uncompetitive antagonist with a low affinity for the binding site.[48]
  •  
  • Rhynchophylline an alkaloid.
  •  
  • Ketamine: a dissociative psychedelic with antidepressant properties used as an anesthesia in humans and animals, a possible treatment in bipolar disorder patients withTreatment-resistant depression, and used recreationally for its effects on the CNS[49]
  •  

Glycine antagonists[edit]


These drugs act at the glycine binding site:


 

 


Do you mind elaborating a bit more about low NMDA symptoms? How can you distinguish this from low levels of other neurotransmitters like dopamine? The reason I ask is because I have been using Inositol on and off and whenever I do, I encounter anhedonia like symptoms, tiredness, some loss of balance, and somehow overexcitation, as in the physical manifestations of anxiety like butterflys in the stomach and slight hand tremors without the mental state, basically emotionless. Somehow I know this has to do with excess Ca+.

http://www.ncbi.nlm..../pubmed/1386623
"The N-methyl-D-aspartate (NMDA) receptor of rat cerebellar granule cells in primary culture is inhibited by Phospholipase C-coupled receptor activation."

This interests me because Phospholipase C cleaves phosphatidylinositol 4,5-biphosphate into inositol triphosphate, which in turn signals an increase in intracellular Ca+. From this I'd think that taking high doses of Inositol may increase Ca+ and lower NMDA activity, hence why alot of people experience anxiety and brain fog from Inositol despite the other beneficial effects.  I tried Sodium D-Aspartic Acid while on Inositol before with no improvement, I may have to go out and get some Sarcosine since you say NMDA activation requires both.

 

 

Could glycine replace Sarcosine as a co-agonist?

 

http://en.wikipedia....i/NMDA_receptor

"The NMDA receptor is distinct in two ways: first, it is both ligand-gated and voltage-dependent; second, it requires co-activation by two ligands: glutamate and either D-serine or glycine.[7]"

 

 

Wait, I may have answered my question:

 

http://www.ncbi.nlm....les/PMC2727032/

"We found that sarcosine is an NMDAR co-agonist at the glycine binding site. However, sarcosine differed from glycine because less NMDAR desensitization occurred with sarcosine than with glycine as the co-agonist."

 

So sarcosine seems like a better co-agonist than glycine, and considering it catabolizes into glycine anyways, it might serve dual functions.

 

 


Edited by Furniture, 28 August 2014 - 02:32 AM.


#25 Area-1255

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Posted 28 August 2014 - 02:54 AM

 

 

One of the primary symptoms of low-NMDA activity is feeling like you have an overall lack of balance, not stimulated enough, lethargy, but yet anxious in a way as well. NMDA-hypoactivity AND hyperactivity can both contribute to Ahedonia, Dysphoria, dopamine dysregulation and other problems. Depersonalization and delirium is noted in some cases of excessive or underactive NMDA - with hypoactivity being more prominent and yielding more negative biochemical effects.

 

Another low NMDA symptom is feeling like you are out of place with reality, and feeling like people are reading your thoughts, this was also evident to me when I took agmatine supplements (which temporarily block NMDA currents) - thus yet ANOTHER great point is if you want the FULL benefits of DAA/NMDA - you need to make sure you aren't taking things that counteract it.

 

Overlooked NMDA-blockers are

-Ginkgo Biloba

-Agmatine Sulfate

-Possibly NAC* ; N-Acetyl-Cysteine.

-The Dementia drug "Memantine"

-Phenyl piracetam (but not other racetams)

-Opium chemicals.

-Kratom Leaf

 

http://en.wikipedia....ptor_antagonist

http://www.ncbi.nlm....les/PMC3817734/

 

Oh and this list is a long one.

 



Competitive antagonists[edit]


  • AP5 (APV, R-2-amino-5-phosphonopentanoate)[31]
  •  
  • AP7 (2-amino-7-phosphonoheptanoic acid)[32]
  •  
  • CPPene (3-[®-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid)[33]
  •  
  • Selfotel: an anxiolytic, anticonvulsant but with possible neurotoxic effects.
  •  

Uncompetitive channel blockers[edit]



Non-competitive antagonists[edit]


  • Aptiganel (Cerestat, CNS-1102): binds the Mg2+ binding site within the channel of the NMDA receptor.
  •  
  • HU-211: an enantiomer of the potent cannabinoid HU-210 which lacks cannabinoid effects and instead acts as a potent non-competitive NMDA antagonist.[47]
  •  
  • Remacemide: principle metabolite is an uncompetitive antagonist with a low affinity for the binding site.[48]
  •  
  • Rhynchophylline an alkaloid.
  •  
  • Ketamine: a dissociative psychedelic with antidepressant properties used as an anesthesia in humans and animals, a possible treatment in bipolar disorder patients withTreatment-resistant depression, and used recreationally for its effects on the CNS[49]
  •  

Glycine antagonists[edit]


These drugs act at the glycine binding site:


 

 


Do you mind elaborating a bit more about low NMDA symptoms? How can you distinguish this from low levels of other neurotransmitters like dopamine? The reason I ask is because I have been using Inositol on and off and whenever I do, I encounter anhedonia like symptoms, tiredness, some loss of balance, and somehow overexcitation, as in the physical manifestations of anxiety like butterflys in the stomach and slight hand tremors without the mental state, basically emotionless. Somehow I know this has to do with excess Ca+.

http://www.ncbi.nlm..../pubmed/1386623
"The N-methyl-D-aspartate (NMDA) receptor of rat cerebellar granule cells in primary culture is inhibited by Phospholipase C-coupled receptor activation."

This interests me because Phospholipase C cleaves phosphatidylinositol 4,5-biphosphate into inositol triphosphate, which in turn signals an increase in intracellular Ca+. From this I'd think that taking high doses of Inositol may increase Ca+ and lower NMDA activity, hence why alot of people experience anxiety and brain fog from Inositol despite the other beneficial effects.  I tried Sodium D-Aspartic Acid while on Inositol before with no improvement, I may have to go out and get some Sarcosine since you say NMDA activation requires both.

 

 

Could glycine replace Sarcosine as a co-agonist?

 

http://en.wikipedia....i/NMDA_receptor

"The NMDA receptor is distinct in two ways: first, it is both ligand-gated and voltage-dependent; second, it requires co-activation by two ligands: glutamate and either D-serine or glycine.[7]"

 

 

Wait, I may have answered my question:

 

http://www.ncbi.nlm....les/PMC2727032/

"We found that sarcosine is an NMDAR co-agonist at the glycine binding site. However, sarcosine differed from glycine because less NMDAR desensitization occurred with sarcosine than with glycine as the co-agonist."

 

So sarcosine seems like a better co-agonist than glycine, and considering it catabolizes into glycine anyways, it might serve dual functions.

 

NMDA receptors are strange, low amounts of NMDA binding show pro-epileptic and anxiogenic effects in some studies, but hyperactivity certainly causes overstimulation as well. What I can say though, is overall, I feel better when on an NMDA agonist. More relaxed in fact, but I'm not you. Keep in mind as said before, NMDA and histamine correlates to prolactin release, so certainly high NMDA combined with low dopamine can cause a variety of issues.

 

But here's something, we knows dopamine d(2) receptors inhibit adenylyl cyclase, which means D2 agonism would reduce cAMP and thus reduce ca2+ excitability....hence why dopaminergics make people tired, their thyroid drops from less cAMP conductance.

At the same, I guess it would depend on overall adrenergic and histaminergic function as well as serotonergic.

 

Blocking A2A (as with Caffeine) and histamine H(3) receptors results in increased expression of Dopamine D(2), an effect likely happening to maintain balance and homeostasis....because by blocking A2A and constantly using caffeine and say an H3 antagonist..there would be a MASSIVE flood of cAMP, at which point the body upregulates it's key cAMP inhibiting receptor - Dopamine D(2).

 

I can only give you suggestions based on what I know and my experience.

 

And that is to look at the overall hormonal profile and not just neurotransmitters and receptors. Take an Anti-E and L-Dopa with DAA seems to result in the most favorable balance and relief of ahedonia.

 

L-Dopa > Bromocriptine (or other dopamine agonists)

 

Seeing as you would get equal agonism of D1 and D2 from L-Dopa..a process that would result in both cAMP formation and inhibition...dopamine is weird too because of this - because D1 and D5 are the direct opposite reaction of D2 type receptors.

 

My guess is it's the placement, Dopamine D(2) are expressed more in the hypothalamus and amygdala, whereas dopamine D(1) seems to be more widespread. Thus currents in regards to cAMP may be more apt to be reduced in those areas.

 

 

Prolactin inhibition leads to higher thyroid output though, so that's where it gets weird as well. D(2) activation decreases cAMP so from that level it decreases T4 production - but yet by prolactin inhibition it increases total synthesis of TSH,T4 and T3....

Unless estrogen is elevated.

 

So like I said, definitely don't let E2/Prl get all crazy. That will counter the benefits of DAA anyway.

 

 



#26 Guest_Funiture2_*

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Posted 28 August 2014 - 03:30 AM

Is that how dopamine lowers serotonin levels, by inhibiting adenylyl cyclase? Inhibition of adenylyl cyclase is how the 5-HT1 receptor family is activated. The subtype 5-HT1A, I recall, functions as the brakes on the rest of the Serotonin system, so agonism at this receptor effectively inhibits the others. please correct me if this information is wrong.

 

 

I'm gonna go ahead and supplement with Sodium DAA & Sarcosine together and report back with my experience. I already actively avoid phytoestrogen sources from soybean oil & flax, I take zinc for testostorone (that should lower estrogen right?), and low doses of Iodine+Selenium+Vitamin C for thyroid support, I also avoid goitrogen sources (which inhibit thyroid function). I read that Iodine also booosts dopamine production though that may just be an after effect of higher thyroid output.



#27 Area-1255

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Posted 28 August 2014 - 05:09 AM

Is that how dopamine lowers serotonin levels, by inhibiting adenylyl cyclase? Inhibition of adenylyl cyclase is how the 5-HT1 receptor family is activated. The subtype 5-HT1A, I recall, functions as the brakes on the rest of the Serotonin system, so agonism at this receptor effectively inhibits the others. please correct me if this information is wrong.

 

 

I'm gonna go ahead and supplement with Sodium DAA & Sarcosine together and report back with my experience. I already actively avoid phytoestrogen sources from soybean oil & flax, I take zinc for testostorone (that should lower estrogen right?), and low doses of Iodine+Selenium+Vitamin C for thyroid support, I also avoid goitrogen sources (which inhibit thyroid function). I read that Iodine also booosts dopamine production though that may just be an after effect of higher thyroid output.

That seems to be the correlation - although it's tricky because calcium channel activation and Histamine H(2) and H(3) both can inhibit serotonin / depress it's firing. It's more of a matter of which nerve terminals the associated receptor is on - e.g H(3) rests in striatum upon GABAergic terminals whereas the receptor in hippocampus rests on cholinergic terminals. H(2) in hypothalamus and frontal cortex where it co-localizes with norepinephrine and increases it's firing. D(2)R's are partly located on GABA-ergic terminals hence why they more readily release GABA and lower serotonin output. Both glutamate and GABA can inhibit serotonin output...depending on the area and cross-interactions/signaling.

 

Interestingly, postsynaptic 5-HT1A receptors have a voice of their own - having neuroendocrine effects more typical of serotonin behavior, just the presynaptic 5-HT1A inhibit serotonin, whereas PostSynaptic 5-HT1A induce oxytocin, beta endorphin, cortisol and prolactin release.

 

 


Edited by Area-1255, 28 August 2014 - 05:11 AM.


#28 stillwater

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Posted 28 August 2014 - 05:35 AM

I'm not helping in any way and adding nothing to the table, but can't help but remark how similar all the symptoms are to  "Post Finasteride Syndrome", almost exact even. I'm sure if you had taken Finasteride/Propecia/Proscar  you would have mentioned it.

 



#29 StevesPetRat

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Posted 29 August 2014 - 12:40 AM

I'm sorry to hear about the damage you've suffered, OP. I'm sure your doctor was of no help, probably with a comment like "Oh, you had a side effect? Just stop and you'll bounce back," or something along those lines. At least you have a clear indication of probable hyperprolactinemia ... um, yeah, as much consolation as that is...

I do not have much to add, but since no one has commented on it yet, choline depletion could explain your troubles with piracetam. It looks like you are already considering adding it to your stack; don't give up on piracetam just yet!

 

Best of luck.

 


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#30 Area-1255

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Posted 29 August 2014 - 12:54 AM

I'm not helping in any way and adding nothing to the table, but can't help but remark how similar all the symptoms are to  "Post Finasteride Syndrome", almost exact even. I'm sure if you had taken Finasteride/Propecia/Proscar  you would have mentioned it.

Low Testosterone/DHT and low dopamine have very similar symptoms, and tend to happen simultaneously anyway.

Usually if your testosterone and E2 ratio are in balance, as well as with thyroid hormones - dopamine levels should** be optimal.

Again, the only cases where I see a "biological override" of this hormone portrait, to where hormones can't do any more (they lay the groundwork, not supply the precursors), is in cases of heavy metal poisoning (especially LEAD) and / or severe histamine imbalances. 






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