Im convinced I have extremely high Glutamate levels, life is hell.

[dannybex]

Eventually the answer did come in the form of the anti-inflammatory supplements (especially N-acetyl-glucosamine) detailed in my thread. These supplement I believe work by reducing the brain inflammation that releases glutamate, which in turn I believe can cause incredibly intense anxiety.

...

Myself, I had terrible IBS-D, and the inflammation in my gut was ramping up anxiety levels a lot. I found that probiotics and prebiotics improved gut health, likely reducing gut inflammation, which in turn substantially reduced by anxiety levels. I have thread on using probiotics and prebiotics to treat anxiety here.


If you have any chronic inflammation in your nasal or sinus cavities, this can also ramp up inflammation in the brain, and again I believe thereby increase anxiety levels. In this case, it is the trigeminal nerve that detects the inflammation in nose and sinus cavities, and just like the vagus nerve, the trigeminal nerve then signals to the brain, and the brain then responds by ramping up brain inflammation levels. I found that treatments which reduce sinusitis and nasal or sinus inflammation would noticeably reduce anxiety.

I mentioned the other day how NAG raises f. prausnitzii levels. Just found a few studies (which maybe you've seen already) that show it's an anti-inflammatory bacterium:

https://www.ncbi.nlm.nih.gov/pubmed/26045134

https://www.ncbi.nlm.nih.gov/pubmed/18936492

http://aem.asm.org/content/81/21/7582.full

https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-015-0400-1

 

[rossho]

What can I do to try lower it? as a test?

I always had issues throughout my life but nothing like this, I had fatigue and focus issues, 4 years ago I tried to treat 'hpa-axis dysfunction/adrenal fatigue' with MEDROL after receiving bad advice and it terrorized my mind (picture constant crying and charging back and forth), coming off of the drug my brain never calmed down.

I am 4 years deep into this -
I wake up, there is a CHAOS in my mind, a powerful energy/force - constantly overthinking, like my brain is overfiring too much and theres no brakes so it never ends, hopping from topic to topic, deep stressful and obsessive thinking patterns sometimes mixed with a spaceyness but doesnt really feel like adrenaline. Its very hard to explain, it really does not feel like a typical anxiety or stress feeling. I constantly pace up and down.

I have tried things such as Alpha Blockers, in high dose. Didnt touch Anxiety whatsoever but it did stop orgasms which tells me the drugs did a good job of blocking adrenaline but adrenaline isnt whats causing my mental struggle.

My diet is now filled with vegetables, meats and decent carb sources like basmati rice. no refined sugars.
I had vitamins and minerals tested and I am deficient in them all
I also have SIBO and Candida. I did Stool tests, Amino Acid and organic acid tests.
I have really high Beta-alanine, Anserine and Carnosine levels.


I Take all the B Vitamins, Folate, Zinc, Copper, Iron, Vit D, E, A, K and selenium to replace what im low in aswell as Bile Acids and Betaine HCl.

Im not getting anywhere with this, I just dont know what to do.
Could it be a GABA/Glutamate issue and what can I do ? i get the impression my brain is overstimulated to a rediculous degree.
Ive tried memantine, L-theanine and Phenibut didnt do anything unfortunately.
I tried Lamotrigine, but got a small rash before I reached 200mg so I had to quit it.

I sometimes wonder if im in a state of overmethylation as people like to talk about but I dont understand it well. i take 500mg Niacinamide, will this have the same effects on calming down the methylation cycle as Niacin?

Jack... did you ever get to the bottom of this problem? Did you come right? are you coping?

 

[pattismith]

That

And for some reason, the drug amiloride 5 mg (a diuretic) helped a lot with my psychosis symptoms. For the last few years I have taken amisulpride 12.5 mg every day, and if I feel that I am getting a return of some mild psychosis-y symptoms that I used suffer a lot with, I will take amiloride 5 mg once daily, and this does help. I am not sure why though. Amiloride affects the electrolyte levels within cells.

Amiloride is a well-known non-selective inhibitor of ASICs.

ASICs channels are activated by extracellular acidity (increased lactic acid) in brain or peripheral nerves (small fibers) or Dorsal root ganglia.

Here a recent study :

Front. Neurol., 12 March 2019

Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro
Fei Zhu1,2,3,4†,

Wei Shan1,2,3,4†,

Qinlan Xu1,2,3, Anchen Guo2,3,

Jianping Wu1,2,4 and

Qun Wang1,2,3*

• 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• 2National Center for Clinical Medicine of Neurological Diseases, Beijing, China
• 3Beijing Institute for Brain Disorders, Beijing, China
• 4Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China

Objectives: Despite the long-term efficacy of antiepileptic drug treatments, frequent attacks of drug-resistant epilepsy necessitate the development of new antiepileptic drug therapy targets. The ketogenic diet is a high-fat, low-carbohydrate diet that has been shown to be effective in treating drug-resistant epilepsy, although the mechanism is yet unclear. In the ketogenic diet, excess fat is metabolized into ketone bodies (including acetoacetic acid, β-hydroxybutyric acid, and acetone). The present study explored the effect of ketone bodies on acid-sensing ion channels and provided a theoretical basis for the study of new targets of antiepileptic drugs based on “ketone body-acid sensing ion channels.”
Methods: In this study, rat primary cultured hippocampal neurons were used. The effects of acetoacetic acid, β-hydroxybutyric acid, and acetone on the open state of acid-sensing ion channels of hippocampal neurons were investigated by the patch-clamp technique.
Results: At pH 6.0, the addition of acetoacetic acid, β-hydroxybutyric acid, and acetone in the extracellular solution markedly weakened the currents of acid-sensing ion channels. The three ketone bodies significantly inhibited the opening of the acid-sensing ion channels on the surface of the hippocampal neurons, and 92, 47, and 77%, respectively.
Conclusions: Ketone bodies significantly inhibit the opening of acid-sensing ion channels. However, a new target for antiepileptic drugs on acid-sensing ion channels is yet to be investigated.

 

[Hip]

Amiloride is a well-known non-selective inhibitor of ASICs.

Does not seem to be any ASIC link to psychosis or schizophrenia though.

 

[pattismith]

Does not seem to be any ASIC link to psychosis or schizophrenia though.

or maybe research didn't look for this link yet...

Some papers were released last year showing a possible role of ASICS in peripheral nerves in fibromyalgia

https://forums.phoenixrising.me/thr...use-model-of-fibromyalgia.79183/#post-2258904

And the link between Fibro and small fiber neuropathy is already done.

I personally came to the conclusion that my muscle pain from exercising (and post exercising) is linked to hyperexcitability of my small nerve fibers to the muscle via ASICS (not the ASICS in DRG).

I think that muscle biopsy to test small nerve fibers going to the muscle would be a better test for us than the skin biopsy they do for SFN diagnosis.

I wrote to one scientist in this area to share my "theory" and he said he just agree.

So if ASICS are a key in peripheral small nerves damages to the muscles, I just think we should look into their role in the brain too.
The fact you had good result from amiloride just convinced me I should share that with you.
edit:
This study shows peripheral ASICs are not only sensitive to protons but also to other ligands:

https://www.frontiersin.org/articles/10.3389/fnmol.2017.00282/full

It means that CNS ASICs probably do as well.

ASICs also bind Chloride which lower their excitability state. Lack of extracellular Cl increases their excitability.
And last, there is a kind of link between ASICs and P2X receptors that necessary8 already noticed, but I havn't investigated much on it.

 

[Hip]

@pattismith, years after I found that amiloride has some beneficial anti-psychosis effects, I discovered that this drug is a regulator of adenosine receptors. Now one explanation of schizophrenia is the adenosine theory of schizophrenia; so it may be by its effect on the adenosine receptors that amiloride reduces my mild psychosis symptoms.

 

[strepliferuiner]

Wow, I've never read of someone else describing the exact headspace I lived in for the first 23 years of my life so accurately. Torture is exactly how I would put it and I honestly have a bit of PTSD from it.

These were the factors that contributed to that headspace for me.

1. Lactic Acid - my symptoms greatly diminished within days after starting ampicillin for a severe streptococcus overgrowth and moderate bifidobacterium overgrowth in my gut. Both are lactic acid producing bacteria. My symptoms would also get worse after exercise, I had terrible PEM and foods with high acid content made me worse.

2. Histamines/amines/glutamate - the particular strain of streptococcus was also a huge histamine producer. I for whatever reason also do not tolerate high amine or high glutamate foods in my diet. I can induce that headspace back by eating foods like soy sauce and salami. Growing up, I ate very high histamine foods everyday and I've noticed a very potent cumulative effect with it. Nowaways, I can have a bit of soy sauce here and there without too much distress, but if I have even just 2 meals in a row with these aggravating elements I my mind starts to slide back into the bad place.

3. Food intolerances (linked to both of the above probably) - whether this is causing a histamine flare or an inflammation flare leading to a histamine flare or an increase in Lactic acid or whatever, I have no clue. But on top of avoiding histamines/amines/glutamates I also do not tolerate grains (wheat being the absolute worst), all dairy except for butter, eggs, nuts, seeds, legumes, most additives/flavours/colours. I could only figure this out doing a strict elimination diet after I had done the gut protocol, because it knocked the intensity of my symptoms back so that I could actually start to pick up on the nuance of my reactions. I'd tried elimination diets before but it was just loud screamy torture no matter what I did.

4. Deficiencies - none of mine budged until I changed my diet, probably due to continually aggravating my gut. The nutrients that made the biggest difference for me were zinc (took 2 months of 90mg a day for me to start feeling the positive effects, as I was so deficient), tryptophan, niacin, inositol, iron (I was consistently deficient) and b1. All excluding the b1 helped me reach a peaceful mental equilibrium for the first time in my life. The b1 I added later and it took away most of my orthostatic intolerance and heat intolerance symptoms, further inducing calm by no longer having heart palpitations and tachycardia all the time.

I found periodic use of phenibut to be absolutely wonderful, a great way to blow off some mental steam, but unfortunately the Australian gov has banned it here due to people using it irresponsibly, doing what they always do. A friend has a prescription of Baclofen for fibro and while it's not as good as phenibut it's enough to blow off steam once every couple of weeks, since I am highly intolerant of alcohol and cannot drink for some relaxation. Both work on GABA receptors.

 

[DrUniverse]

Same for me 1:1.

I also expect a high amount of Glutamat in my brain.
Life is hell really matches the description.
I have reactivated EBV Infection and CFS. And 1000 other Symptoms of course.

You have to try NDMA Antagonist, NDMA releases the Glutamat in Brain. So inhibtion might work.
I figured out S-Ketamin worked for me as it blocks the NDMA Receptors.
The permanent fire in the brain calms down.
But as S-Ketamin is also a psychotrop and disassociative Drug, im heading for Memantin (N-Methyl-D-Aspartat) which is also a NDMA Antagonist. Its common used in dementia.
But i just read u tryed it, well i would give S-Ketamin one try though.

An alternative would be Hypericum perforatum Extract, as it also decrease the Glutamat concentration and also works for me.

L-Theanin works for me like 1%.

Did u try THC/CBD? I also got some good effects.

Valerian officals as a GABA Modulator works too.