88 replies to this topic

[Area-1255]

So we all should know one hypothesis of schizophrenia is low NMDA-activity (or NMDA hypoactivity) - this is because NMDA helps to filter dopamine in the brain and shuffle it into the correct area's, low NMDA leads to a significant change in DAT (Dopamine Transporter) and low calcium channel activity that leads to disturbing personality changes, ahedonia/dysphoria can be possible, DEpersonalization and delirium, along with other classic low glutamate symptoms such as Insomnia, Fatigue etc ...and feeling like people are reading your thoughts, usually coupled with paranoia.

But you see, NMDA is the most important glutamate receptor and carries the widest range of physiological and psychotropic effects.

It also is a major signaling conductor and cross-talks with histamine.

Super HIGH NMDA has not really been studied without the presence of glutamate at other receptors, but I highly doubt that NMDA itself (and studies are lacking as well) can cause any excitotoxicity ALONE.

 

 

However, in the presence of glutamate binding at other receptors that are mostly excitory (with the exception of two metabotropic Glut receptors), there is a potential for ultimate calcification and destruction of brain neurons and myelin sheaths. Also a notable reduction in BDNF would be there.

 

NMDA can also enhance GABA release and releases pregnenolone and IGF-1; which can have pro-anabolic effects altogether, AND, NMDA acts as a major gonadotropic signaler, where it can massively increase testosterone and other sex hormones.

However, NMDA ALSO activates aromatase...leading to more estrogen production.. 

 

http://area1255.blog...a-receptor.html

 

http://www.ncbi.nlm..../pubmed/9751147

 

http://apt.rcpsych.org/content/8/3/189.full

 

http://www.ncbi.nlm....les/PMC3677126/

 

http://bit.ly/1vrVnjv

Most likely, NMDA enhances GABA release to short-circuit it's own actions to an extent or to trigger homeostasis in cross talk.

GABA-A antagonists will enhance NMDA-stimulated neurosteroid synthesis. As well as gonadotropin.

Edited by Area-1255, 29 August 2014 - 02:40 AM.

[Flex]

Whats about laughing ?

Leads NMDA activation or Inhibition to Laughing  ?

The question sounds strange but I´m interrested because I lack sometimes of laughing

and it would be nice when I would know the a possible cause or correlation.

 

Btw:

The abstracts who I found point out a NMDA casued toxicity.[*]

And Your posted study did confirmed this:

Specifically, in the case of complicated mental disorders that manifest in a variety of symptoms including psychosis, the NMDA receptor pathway comes into play. Alterations in its activity lead to either hypofunction or hyperfunction and related excitotoxicity.

http://www.ncbi.nlm....les/PMC3677126/

 

[*]

http://www.chemie.de...s-involved.html

http://jcs.biologist...2/4083.full.pdf

 

Could You explain why NMDA activation is safe ?

Edited by Flex, 29 August 2014 - 07:52 PM.

[Area-1255]

Whats about laughing ?

Leads NMDA activation or Inhibition to Laughing  ?

The question sounds strange but I´m interrested because I lack sometimes of laughing

and it would be nice when I would know the a possible cause or correlation.

 

Btw:

The abstracts who I found point out a NMDA casued toxicity.[*]

And Your posted study did confirmed this:

Specifically, in the case of complicated mental disorders that manifest in a variety of symptoms including psychosis, the NMDA receptor pathway comes into play. Alterations in its activity lead to either hypofunction or hyperfunction and related excitotoxicity.

http://www.ncbi.nlm....les/PMC3677126/

 

[*]

http://www.chemie.de...s-involved.html

http://jcs.biologist...2/4083.full.pdf

 

Could You explain why NMDA activation is safe ?

 

 

It is safe as long as you aren't glutamate toxic; ingesting MSG and combining that with NMDA is no good. What's sad is most people who are fairly supplement savvy don't always realize the undocumented MSG additions to many foods as the ingredient "Spices". Spices on the label of prepackaged foods (unless organic) usually = MSG or analogues of it.

 

NMDA itself actually has protective effects, and releases GABA, again, assuming you aren't already glutamate toxic. ALOT of people are today, toxic in glutamate and / or histamine.

 

In regards to laughing, I would presume NMDA could do both; decrease or rapidly increase.

Think about nitrous oxide (whip-its,nitrous inhalants)  which is a fairly common street drug, it induced laughing and is even named "laughing gas" for that reason.

 

I've noticed ridiculous laughing when I've taken potent nitric oxide activators. It seems ultimately, that nitric oxide is key in being able to feel normal emotions and enjoy activities as well as laughter.

 

Yet ironically, because N.O inhibits NMDA currents (likely by negative feedback), I guess you can have the opposite effect if other N.O Inhibitors are in your system.

 

Thus, NMDA is one mechanism by which the body releases N.O, but isn't likely to be a continuing one without a bounce back.

 

It's a very strange and complex concept indeed, NMDA supplementation is now taken about by bodybuilders and fitness enthusiasts, being told by companies that it will raise endogenous N.O levels - again, I would call this into question based on the feedback inhibition.

 

However, when coupled with other glutamate and NMDA site potentiators, such as Testosterone and some nootropics, we can theorize that NMDA would then release one hell of a lot of Nitric Oxide.

[Flex]

Thx

[Flex]

To make things clear:

 

in the Study above:

http://www.ncbi.nlm....les/PMC3677126/

They stated that direct NMDA agonism is not safe, but glycine-site agonist are taken in account for health condition.

 

And MonoSodiumGlutamate does not cross the Blood Brain Barrier. Although some brain parts do not have a BBB (see below)

 

This explains studies that show that the BBB is impermeable to glutamate, even at high concentrations, except in a few small areas that have fenestrated capillaries (circumventricular organs).

 

The blood-brain barrier and glutamate

http://www.ncbi.nlm....les/PMC3136011/

Edited by Flex, 30 August 2014 - 03:43 PM.

[Nemo888]

 

It is safe as long as you aren't glutamate toxic; ingesting MSG and combining that with NMDA is no good. What's sad is most people who are fairly supplement savvy don't always realize the undocumented MSG additions to many foods as the ingredient "Spices". Spices on the label of prepackaged foods (unless organic) usually = MSG or analogues of it.

 

NMDA itself actually has protective effects, and releases GABA, again, assuming you aren't already glutamate toxic. ALOT of people are today, toxic in glutamate and / or histamine.

 

I

Your body is has over 4 pounds of glutamate in it. It is the most common amino in your body.  A single chicken breast has almost 9 grams of glutamic acid. This doesn't make any sense to me. My understanding is NMDA is an artificial compound that is excitotoxic, Could you explain?

[Area-1255]

 

 

It is safe as long as you aren't glutamate toxic; ingesting MSG and combining that with NMDA is no good. What's sad is most people who are fairly supplement savvy don't always realize the undocumented MSG additions to many foods as the ingredient "Spices". Spices on the label of prepackaged foods (unless organic) usually = MSG or analogues of it.

 

NMDA itself actually has protective effects, and releases GABA, again, assuming you aren't already glutamate toxic. ALOT of people are today, toxic in glutamate and / or histamine.

 

I

Your body is has over 4 pounds of glutamate in it. It is the most common amino in your body.  A single chicken breast has almost 9 grams of glutamic acid. This doesn't make any sense to me. My understanding is NMDA is an artificial compound that is excitotoxic, Could you explain?

 

No, N-Methyl-D-Aspartate is naturally taken up as a separate compound, with a separate receptor, though its comprised of glutamate and glycine as agonists for the receptor - it can also use aspartic acid and glycine which will be co-activators.

NMDA is not excitotoxic alone, but together with and EXCESS of glutamate it can be, it can also promote free radical damage in high amounts by leading to Ca2+ release and subsequent nitric oxide production. Your body will take up glutamate into many receptors (metabatropic,NMDA,AMPA,Kainate) but the reason is that if studied alone - NMDA itself has no direct negative effect.

 

NMDA is a particular Glutamate receptor involved in fear conditioning and contextual fear responses, with low NMDA activity being linked to excessive fear, and / or startling, or ....a lack of general emotions and fear responses. Whereas high NMDA activity is associated with improved fear conditioning (adapting to and facing fears). Thus it can be said that high NMDA individuals are high metabolism persons with high potential - if only they utilize their adaptation techniques.

 

http://learnmem.cshl...t/17/6/289.full

http://www.ncbi.nlm....pubmed/15959918

http://www.ncbi.nlm....pubmed/15617772

http://www.nature.co...l/388471a0.html

Edited by Area-1255, 30 August 2014 - 05:25 PM.

[Flex]

I´ve heard that here in Germany some thug uses DXM to decrase their anxiety and nociception before a fight.

 

So nmda blockade leads supposedly to anti-anxiety

http://www.bluelight...sts-for-anxiety

[Area-1255]

I´ve heard that here in Germany some thug uses DXM to decrase their anxiety and nociception before a fight.

 

So nmda blockade leads supposedly to anti-anxiety

http://www.bluelight...sts-for-anxiety

NMDA receptors mediate inflammation, and NMDA blockers tend to have a pain alleviating / narcotic type effect.

Think about PCP rage, PCP (Angel Dust) is a street drug and powerful form of NMDA-glutamate blocker, it carries the most euphoria out of almost all drugs, but the worst side effects. PCP rage, these fuckers can't even be touched with a tazer, it won't do anything to them.

 

[Sciencyst]

Edit; redundant post

Edited by katuskoti, 31 August 2014 - 07:57 AM.

[Area-1255]

Edit; redundant post

So what do you think about this concept?

[Area-1255]

Interestingly though, NMDA seems to positively promote endorphins...but this effect subsides in high concentrations.

[mono]

I'd love to hear your thoughts on this.

In regards to someone with a schizo affective psychotic disorder who is mainly experiencing mania, anxiety/panic, insomnia but generally no negative symptoms (such as anhedonia, amotivation) - what do you think is going on in the glutamate system there? Or are these kind of symptoms more likely to be related to other parts of the brain?

From what I've read NMDA dysfunction is more closely related to the negative symptoms of schizophrenia, whereas glutamate hyperactivity is more related to mania, OCD and perhaps positives?

http://www.elsevier....n-schizophrenia

Thoughts??? I don't quite understand the correlation between glutamate, the NMDA receptors and symptoms that are presented.

I've noticed glycine reduces some of this manic energy but tolerance develops fast.

[Flex]

Afaik Nmda inhibition helps to fall asleep.

From my view its not everything related to Nmda or glutamate.

[mono]

Yeah it's weird I don't completely understand it but I'd like to know more, in particular about how the glutamate system relates to schizophrenia. As far as I remember (don't quote me) the glutamate, GABA and dompaminergic systems are all linked.

 

NDMA antagonists are used in the treatment of anxiety so it doesn't make sense why a dysfunction of the NMDA receptors would do the opposite in schizophrenia....

 

This study does show however that antagonizing NDMA receptors increases extracellular glutamate:

http://www.ncbi.nlm....ubmed/15379899/

 

And as posted above (http://www.elsevier....n-schizophrenia) glutamate receptor agonists reduces glutamate release.

 

Interesting that glutamate is also thought to be involved in ADHD - www.corepsych.com/2010/11/adhd-and-glutamate-neurotransmitters/#axzz3Ezuucdht - and that dopamine release in the prefontal cortex inhibits glutamate release. Once again we see dextroamphetamine reduces mania - http://www.ncbi.nlm..../pubmed/3312177 - suggesting that this hyperactivity of glutamate does indeed contribute to the manic / obsessive symptoms.

 

This one shows reducing glutamate reduces OCD symptoms: http://www.ncbi.nlm....pubmed/16490414

 

It's pretty complex stuff but I'd love to hear others input!

 

------

 

This is really relevant:

 

http://cdn.intechope...fs-wm/44752.pdf

 

Studies of signaling interactions between the dopaminergic and glutamatergic systems dem‐

onstrate that the NMDA receptor is crucial in activating dopamine neurons in the VTA/SN

[17

,

18

]. Also, it has been found that stimulation of the D

2

-class dopamine receptor is in‐

volved in the downstream inhibition of the NMDA receptor, weakening the excitatory re‐

sponse to those neurons [

19

]. Likewise, it was found that activation of D

4

receptors

depressed AMPA receptor-mediated excitatory synaptic transmission in PFC pyramidal

neurons, which was accompanied by a D

4

-induced decrease of AMPA receptors at the syn‐

apse [

20

]. These results provide substantial evidence that the dopamine and glutamate neu‐

ronal systems work in tandem to create a balance of neurotransmission in these regions.

The hypodopaminergic theory of ADHD asserts that the hyperactive and inattentive behav‐

iors are caused by low levels of either tonic or phasic dopamine. If true, decreased dopamine

released in the striatum and PFC would then be expected to lead to more active NMDA and

AMPA receptors based on the studies mentioned above resulting in increased glutamatergic

output to the striatum and SN/VTA, as well as an increased glutamate signal to the PFC.

Glutamate coming into the SN/VTA would normally go on to release more dopamine [

17];

however, in the ADHD brain, this feedback does not seem to occur.

 

 

---

 

So what's interesting is that NMDA receptor is crucial in activating dopamine neurons, as there have been quite a few studies suggesting negative symptoms are a lack of dopamine in the PFC but hyperactivity in mesolimbic pathway.

D2 stimulation results in NDMA inhibition, so essentially D2 antagonism (which is how most APs work) would be activating NDMA receptor? which is very very interesting.

Edited by mono, 02 October 2014 - 03:02 PM.

[Area-1255]

NMDA's positively correlate with GABA release, and no OCD is not a hyperactivity of these glutamate receptors, in fact, some people with OCD actually have low NMDA-glutamate receptors, or such high levels everywhere that the other receptors over ride the beneficial effects of NMDA activation.  NMDA also is crucial in not just dopamine production, but is a major on switch in testosterone production, which is why many bodybuilding and test booster supplements now add in d-aspartic acid or even pure NMDA.

Also obsessive compulsive disorders are worse in those with an estrogen receptor alpha variant, likewise, high estrogen levels can contribute to OCD pathology and can be hard to treat without lowering the estrogen level.  Low estrogen may be an issue in those with more transient, "calm" OCD... but both high and low estrogen levels cause the same issue - glutamate dysfunction.

http://www.longecity...inergic-system/

http://www.currentps...8877267fc5.html

http://www.ncbi.nlm....les/PMC2746669/

http://www.ncbi.nlm....pubmed/22433450

http://www.ncbi.nlm....pubmed/20850223

 

 

 

Psychoneuroendocrinology. 2011 May;36(4):473-83. doi: 10.1016/j.psyneuen.2010.07.022. Epub 2010 Sep 17.

Variants in estrogen receptor alpha gene are associated with phenotypical expression of obsessive-compulsive disorder.

Alonso P1, Gratacòs M, Segalàs C, Escaramís G, Real E, Bayés M, Labad J, Pertusa A, Vallejo J, Estivill X, Menchón JM.

Author information

 

Abstract

Compelling data from animal and clinical studies suggest that sex steroids may play a role in the etiopathology of obsessive-compulsive disorder (OCD). The aim of this study was to investigate whether variants in estrogen receptor genes ESR1 and ESR2 may contribute to the genetic susceptibility to OCD, through a case-control association study using an extensive linkage disequilibrium-mapping approach. Twenty tag single-nucleotide polymorphisms (tagSNPs) covering the ESR2 region and nine tagSNPS from regions of ESR1 reported to be related to transcriptional control were genotyped in 229 OCD patients and 279 controls. SNP association and haplotype analysis were performed. The association of these genes and OCD subphenotypes was tested, considering early-onset OCD, comorbid tic and affective disorders, and OCD symptom dimensions. No significant difference in the distribution of alleles or genotypes was detected between controls and OCD subjects. Nevertheless, on analyzing OCD subphenotypes, SNP rs34535804 in ESR1 and a five SNPs haplotype, located at the 5' end of intron 1 of ESR1, were associated with the presence of contamination obsessions and cleaning compulsions. Specifically, carriers of the ACCCG haplotype, a combination of functional alleles related to higher ER alpha expression, showed a reduced risk of suffering from these symptoms. Our results suggest that the ESR1 gene may contribute to the genetic vulnerability to certain OCD manifestations. The dissection of OCD into more homogeneous subphenotypes may well help to identify susceptibility genes for the disorder.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID:   20850223   [PubMed - indexed for MEDLINE]

http://en.wikipedia....ulsive_disorder

 

 

Schizophrenia is by  a lack of homeostasis in glutamate regulation, usually equates to NMDA hypoactivity as well, but not gene specific like with OCD...what I mean by that is the hypoactivity in schizophrenia can be overall a low glutamate level; resulting in low nmda activity whereas OCD is exclusive and includes high glutamate levels but for some reason low NMDA...or with the gene mentioned above in the y2 subunit.

[Area-1255]

NMDA is also involved in not only increasing GABA, but also increasing neurosteroids...and let me be clear, I've had severe OCD as a child and fit dr.kaslow / pfeiffers and rivers high histamine phenotype....yet, after years of supplementing with anti histamines (herbals) ive had a nice reduction of symptoms, but now ive tipped it to the other end, and just recently began feeling better and some of my OCD symptoms are alleviated with d-aspartic acid and / or NMDA...as well as histamine h3 antagonists..which of all things improved my ocd the most....which is odd...but then it isn't. :D

 

Most of the side effects or unwanted central nervous system disturbances from histamine come from histamine h3 receptor.

Although blocking this receptor results in more histamine being released and active, it also results in a super potent increase in gaba, serotonin etc

THUS, in my humble opinion, ocd 's pathology, even in severe cases, comes from a bad shift in glutamate / gaba balance.

A shift that is corrected by h3 antagonism and NMDA agonism...but this works even better when lowering glutamate levels and histamine slightly...but not too much.

[mono]

Yes I didn't mean to say OCD was hyperactivity of these receptors, but the study I posted suggested that OCD could be treated by reducing these high levels of glutamate in the brain. The other study suggested that hyperactivity of glutamate could be treated by agonizing the glutamate receptors themselves. But indeed the disorders are extremely complex and thanks for sharing some of your knowledge on the topic as my understanding is quite basic.

 

Interesting, not only do I have pretty good testosterone levels but I don't suffer from the typical negative / cognitive symptoms of schizophrenia, despite fitting on the schizo spectrum. My schizo affective is characterized by hypo mania and slight trend towards OCD and ADHD. So one, perhaps, could assume that I'm not suffering from a dysfunction of NMDA given that I don't present the symptoms of NDMA inhibition?

 

Using the findings in this thread however: http://www.longecity...nefits-from-it/

I would assume that I do have in fact have high levels of glutamate. As mentioned above high levels of glutamate correlate with OCD, mania and ADHD, all things of which I suffer from. So one might again, perhaps, assume I do have a hyperactivity of glutamate in my brain...

 

I've tried the standard routes of NDMA activation such as sarcosine, glycine, nefiracetam but none have given significant results, and my thoughts as mentioned above may explain why? I'm really stabbing in the dark here but would love to get a deeper understanding of this.

 

What are your thoughts?

 

I'm really just trying to understand my own disorder and how I can go about treating it. Amphetamine seems like a viable option for now if dopamine release in the PFC will reduce glutamate levels, but I'm definitely interested in understanding this further and looking at other methods of treatment.

 

P.S. Thanks for the links, checking them out now!

 

 

 

 

Edited by mono, 02 October 2014 - 03:42 PM.

[mono]

NMDA is also involved in not only increasing GABA, but also increasing neurosteroids...and let me be clear, I've had severe OCD as a child and fit dr.kaslow / pfeiffers and rivers high histamine phenotype....yet, after years of supplementing with anti histamines (herbals) ive had a nice reduction of symptoms, but now ive tipped it to the other end, and just recently began feeling better and some of my OCD symptoms are alleviated with d-aspartic acid and / or NMDA...as well as histamine h3 antagonists..which of all things improved my ocd the most....which is odd...but then it isn't. :D

 

Most of the side effects or unwanted central nervous system disturbances from histamine come from histamine h3 receptor.

Although blocking this receptor results in more histamine being released and active, it also results in a super potent increase in gaba, serotonin etc

THUS, in my humble opinion, ocd 's pathology, even in severe cases, comes from a bad shift in glutamate / gaba balance.

A shift that is corrected by h3 antagonism and NMDA agonism...but this works even better when lowering glutamate levels and histamine slightly...but not too much.

 

Interesting, if NDMA activation increases GABA, why are NMDA antagonists used in the treatment of anxiety?

 

So you are saying that supplementing d-aspartic acid / NDMA has reduced some of your symptoms through activating the NMDA receptor? How does this actually work? Is the activation of NMDA reducing hyperactive glutamate levels, or is it supplementing for low glutamate levels? What is the activation of NDMA actually doing that alleviates the symptoms?

 

Any suggestions on methods to lower glutamate levels?

 

 

[Flex]

Tumeric lowers afaik glutamate

[Area-1255]

 

NMDA is also involved in not only increasing GABA, but also increasing neurosteroids...and let me be clear, I've had severe OCD as a child and fit dr.kaslow / pfeiffers and rivers high histamine phenotype....yet, after years of supplementing with anti histamines (herbals) ive had a nice reduction of symptoms, but now ive tipped it to the other end, and just recently began feeling better and some of my OCD symptoms are alleviated with d-aspartic acid and / or NMDA...as well as histamine h3 antagonists..which of all things improved my ocd the most....which is odd...but then it isn't. :D

 

Most of the side effects or unwanted central nervous system disturbances from histamine come from histamine h3 receptor.

Although blocking this receptor results in more histamine being released and active, it also results in a super potent increase in gaba, serotonin etc

THUS, in my humble opinion, ocd 's pathology, even in severe cases, comes from a bad shift in glutamate / gaba balance.

A shift that is corrected by h3 antagonism and NMDA agonism...but this works even better when lowering glutamate levels and histamine slightly...but not too much.

 

Interesting, if NDMA activation increases GABA, why are NMDA antagonists used in the treatment of anxiety?

 

So you are saying that supplementing d-aspartic acid / NDMA has reduced some of your symptoms through activating the NMDA receptor? How does this actually work? Is the activation of NMDA reducing hyperactive glutamate levels, or is it supplementing for low glutamate levels? What is the activation of NDMA actually doing that alleviates the symptoms?

 

Any suggestions on methods to lower glutamate levels?

 

Well it's very complex, yes NMDA receptors increase GABA , but they also increase all other neurotransmitters associated with the induced calcium influx - and Ca2+ channels will lead to the release of norepinephrine, glutamate and acetylcholine, thus the net effect in a state of overall glutamate toxicity is actually so many neurotransmitters flooding around from the excess calcium voltage.

However NMDA itself seems to more potently affect GABA, it's just so difficult to predict because you would have to consider the parameter's of the study likely aren't coinciding with the outcome for this particular agenda...Most people in urban societies do have some sort of glutamate toxicity, and a lot of this comes from stress induced release of calcium channels and the neurotransmitters that regulate it.

 

It's very complex indeed, NMDA blockers help in some individuals because it's likely enough to reduce some degree of calcium channel voltage, but the irony, if you go on forums where people are trying to raise their t levels..they all describe profound mental clarity from nmda activators and d-aspartic acid...it's only at really high doses that overstimulation occours..so it seems it's like a threshold/adaptation response, little to moderate levels unlock the focus and clarity, from nmda, assuming you don't have excess glutamate everywhere else.

 

But in itself it's not a big deal..it's just that most people aren't looking at the whole picture...and how many things are involved and interact.

Another interesting pathway is the beta-adrenergic to histaminergic regulation of calcium channels..and sets another example, or poster child, for the bodies homeostatic regulation of calcium channels.

 

Beta activation leads to ca2+ faciliatation, but ironically, also over time (such as with asthma drugs), both beta adrenergic receptors are reduced from chronic agonism, AND...in the meantime, every use of a beta agonist also downregulates histamine h1 receptors which happen to be almost as potent, if not MORE potent calcium channel stimulators than nmda and beta receptors....

 

 

Ultimately, less H1 HISTAMINE mRNA, leads to more agonism at the histamine h3 receptor, which then further decreases calcium channel output....

 

Always try to predict how your body will ellicit homeostasis...only then can we find the keys to the great puzzle.

[mono]

Very interesting read. Thanks for posting.

[Area-1255]

Very interesting read. Thanks for posting.

Haha, I hope to inspire and inform my friend. A lot of what I research comes following or preceding me being my own guinea pig...so it works out well.,

 

One of the most important things is to know YOURSELF, your genes, your predispositions etc

That's only way to know what you need and what will benefit or enhance you is having a look within yourself and being in tune with your own body and it';s signals.

 

23 and me is nice , too.

[mono]

So for someone experiencing hypomania, panic, ADHD and OCD like symptoms what would you put this down to in relation to the glutamate system?

[mono]

Reports indicate there are elevated levels of glutamate in the left dorsolateral prefrontal cortex of adults with BPAD during the manic phase (Michael et al., 2003).

http://www.ncbi.nlm....les/PMC3677126/

[mono]

The effective NMDA receptor antagonism by atomoxetine at low micromolar concentrations may be relevant to its clinical effects in the treatment of ADHD.
http://www.ncbi.nlm....51/#!po=60.9244

[Area-1255]

Reports indicate there are elevated levels of glutamate in the left dorsolateral prefrontal cortex of adults with BPAD during the manic phase (Michael et al., 2003).

http://www.ncbi.nlm....les/PMC3677126/

I wouldn't doubt the elevated whole system glutamate elevation during the manic phase, however, I think copper dominance and estrogen fluctuations in both men and women contribute the most to bipolar type symptoms - which makes more sense....

Based on what I read, all vain and erratic personalities have some type of estrogen elevation and / or copper elevation - and also if not estrogen then yes, glutamate toxcitity or over function at the metabatropic receptors and possibly the kainate receptors as well

 

On the other hand, hypomania and not hypermania or classic mania is a highly anticipated and well-cherished state...I should know. :D

It's also more controlled - and even ideal in some cases unless you are irritated..it can help get some work done...that's just me, most intellectuals and writers have a hypomanic phase. It helps us get far down the road and supplies the type of enthusiasm and ideology needed to set up such a strong grounded, persistent and powerful display of knowledge .

 

All the while being unique and innovative relative to the passion for success.

 

It's to mirror my objectives but that I have consistently found my place, and I hope others do too., anyway, was getting off-topic. But that brings up another good point, psychology vs chemicals ....many of us can ellicit changes in glutamatergic function as I said by simply choosing to think a certain way...we can control our stress hormones by the mindset we embrace.

 

Hypomania certainly doesn't involve as much the glutamatergic system but it must be fine-tuned...

 

Noradrenergic systems also play a role and account for the heightened sense of alertness and even hyper vigilance, but passive hyper vigilance in some of these fellas.

 

Dopamine plays a mild, transient, passive role but is pretty insignificant until you throw around the noradrenergic neurohormones which are the majority of these changes.

 

And whether we are talking about hypo or classic mania, the science and altitude of such behavior begs that noradrenaline be involved ...and to the same point, we are just talking different levels of efflux.

 

Of course it's not irony when people who get drunk frequently also develop hypomanic phases, they usually are overstimulated personalities to begin with - while the benzo activation leads to a reduction in excess cns activity, it may also in some, simply modulate the efflux of the excess.

In which case instead of getting hyper mania or classic mania, the response of benzo modulation of neuron firing doesn't result in a reduction of excess, but rather the thunderous hypomania resultant from noradrenaline and / or glutamate re-modulation/// taking that pulse wave from the high and bringing it to a medium gravitation...that' doesn't change the amount of it, it just shifts the level of stimulation....lowers it a bit.

 

Which is exactly why diet and protein intake come into all of this...we produce neurotransmitters and hormones proportional to the amount of raw materials we get (should at least)..if not a good conversion rate then this is an example of everything not set in balance...homeostasis my friend....!

[Area-1255]

Seems the amygdala is another primary target of both histamine and glutamate...makes sense though.

[Senka Lowris]

Hello area. Thank you for all your great work.

 

I'm currently attempting to treat my long term anxiety and have a few questions pertaining to NMDA.

Okay, so, for maybe 3-4 years now i have noticed a drastic decrease in anxiety, coupled with extreme clarity and hugely improved verbal articulation skills during extreme hangovers from alcohol. 
Of course, i don't feel fantastic physically at the time, but honestly i'd still rather be in that state all of the time due to the positive mental effects.

I have also found some other people online who experience the same thing... There is actually a thread about it on this forum here: http://www.longecity...ohol-hangovers/

Anyways...my current belief is that it has something to do with NMDA upregulation during the hangover phase... This theory was also postulated by the OP of that thread.. but it didn't seem to be his problem, although he didn't have anxiety...

 

One thing that intrigues me is that normally i have horrible anxiety/psychotic behaviour when smoking marijuana. I always used to joke to myself that smoking marijuana is the ultimate test to see if my deep anxiety is gone. This anxiety is eliminated 100% during an acute hangover.

 

Interestingly, marijuana has some kind of interaction with NMDA and glutamate too. On a side note I always suspected id be very prone to going schizophrenic if i kept smoking that stuff over a long period in high amounts.

I also learned that hypo function of NMDA is involved with schizophrenia too.....Actually you mentioned it int he first lien of this thread :p

This all has to be linked somehow, i dunno if you have any input regarding this, but i'm thinking of buying sarcosine etc to test on myself, but i don't have much spare funds so i'd really like to hear if you have any opinions on this before i do, whether it's worth a try.

Again, thanks for your help regardless of whether you respond or not, you're a good guy.

 

.

Edited by Senka Lowris, 09 October 2014 - 02:49 AM.

[Area-1255]

Hello area. Thank you for all your great work.

 

I'm currently attempting to treat my long term anxiety and have a few questions pertaining to NMDA.

Okay, so, for maybe 3-4 years now i have noticed a drastic decrease in anxiety, coupled with extreme clarity and hugely improved verbal articulation skills during extreme hangovers from alcohol. 
Of course, i don't feel fantastic physically at the time, but honestly i'd still rather be in that state all of the time due to the positive mental effects.

I have also found some other people online who experience the same thing... There is actually a thread about it on this forum here: http://www.longecity...ohol-hangovers/

Anyways...my current belief is that it has something to do with NMDA upregulation during the hangover phase... This theory was also postulated by the OP of that thread.. but it didn't seem to be his problem, although he didn't have anxiety...

 

One thing that intrigues me is that normally i have horrible anxiety/psychotic behaviour when smoking marijuana. I always used to joke to myself that smoking marijuana is the ultimate test to see if my deep anxiety is gone. This anxiety is eliminated 100% during an acute hangover.

 

Interestingly, marijuana has some kind of interaction with NMDA and glutamate too. On a side note I always suspected id be very prone to going schizophrenic if i kept smoking that stuff over a long period in high amounts.

I also learned that hypo function of NMDA is involved with schizophrenia too.....Actually you mentioned it int he first lien of this thread :p

This all has to be linked somehow, i dunno if you have any input regarding this, but i'm thinking of buying sarcosine etc to test on myself, but i don't have much spare funds so i'd really like to hear if you have any opinions on this before i do, whether it's worth a try.

Again, thanks for your help regardless of whether you respond or not, you're a good guy.

 

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Yes, cannabinoid receptors interact with glutamate channeling.

CB active substances, such as forms of THC have differential effects on glutamate. 

Delta9-thc tends to decrease excitory currents.  http://www.ncbi.nlm..../pubmed/9882692

 

However , in one study, extracellular glutamate had increased and GABA had decreased, selective for the prefrontal cortex. http://www.ncbi.nlm....pubmed/12383968

Considering cannabinoids generally increase philosophical thinking, and this is evident when I have smoked it as well - and also in eating aka "munchies" this is all more connected with increased glutamate imHo. However, they also increase dopamine and have a number of other effects.

 

http://www.ncbi.nlm....les/PMC1575338/

 

It seems though that decreases in serotonin in the VTA may also occur due to THC's ability to inhibit zone specific GABA and glutamate interneurons...it's all very interesting.

 

In regards to sarcosine...yes I've always had positive effects from sarcosine plus d-aspartic acid...and I am probably one of the few who isn't going crazy with the concept of NMDA blockade; in fact , I take a far different view in this regard.

 

I believe that blocking NMDA's is generally counter-effective and not a good idea in the long-run, even though short-term it might have some benefits by positively affecting dopamine reuptake transporters and endorphin release....

In the long-run, NMDA blockade leads to several unfavorable effects, including decreased testosterone, neurosteroids, GABA and cholinergic activity, and messed up opioid receptors. It also produces a notable transient but possibly controlled, psychotic / psychotomimetic effect.

 

Now let's be clear, I've had chronic OCD, anxiety and tourette's as a child...as well as a long list of experimentation in substances and chemicals....

 

I can tell you that all in all...NMDA agonism has an excellent effect; including with sarcosine plus d-aspartic acid....and it actually decreases incidences of intrusive thoughts and gives a general sense of mental clarity and even restores excitement and counteracts anhedonia.

 

 

However, I should also mention that although NMDA agonism has favorable effects, this is probably not the case if you are consuming MSG and / or are already glutamate toxic; in this case, the benefits are probably over ridden by kainate / AMPA / metabatropic glutamate receptor overactivation.

 

Hence why I see the best effects (different as well, not exclusive to the diet, tested separately and together) when on a clean diet and avoid MSG containing foods.

Edited by Area-1255, 09 October 2014 - 03:18 AM.