NMDA receptor hypofunction?

General Discussion
#1

Hello guys,
I want to be sure before i begin explaining my „Theory“, that it is absolutely based on my opinion and i cant support any of my claims with scientific research, as there is practically non on this disease.
Please bear with me, as i know this topic is a bit sensitive for a lot of you guys (Especially the Androgen Receptor and DNA mythelation supporters)…
A lot of PFS and PSSD sufferers are mostly fixating on the „Sexual side of the story“ and forgetting the long list of mental torture that is accompanied with our disease…
Do these symptoms sound familiar? apathy, anhedonia , reduced social drive, loss of motivation, lack of social interest etc…

Im sure they are, at least for the vast majority of sufferes here…Now comparing this list of symptoms to other diseases and extrapolating that the 2 diseases have the same mechanism is a big error in the world of science, but what can one do if we are not even recognized as patients but merely as sad depressed individuals who cant stand losing their hair (BTW my hair is better than before i started balding, same as i was 14, and i still have PFS)

Now back to topic at hand…All these symptoms i mentioned i actually copied and pasted here from an article about negative symptoms in schizophrenia…What made me think about the similarity was actually the fact, that i used Ketamine before 3 weeks, cuz i was in a very very bad shape…I took it nasally, and after 10 min i felt what i can only describe as 10 times worsening of my numbness…It felt like the same thing that was causing my numbness at the first place, was getting augmented…It was like pouring gas on an existing fire…I went back to baseline 2 hours after that experience but this made me thinking (Again this is not valid science or logical thinking, as those requires million of dollars and scientific research)…What if Ketamin had the same mechanism that is causing my numbness…

Behold my new theory on what is causing at least most of our symptoms.

Its NMDA-Hypofunction…

It is thought that NMDA receptor play a very big role in causing the negative symptoms of Schizophrenia and it plays a big role in the connection and communication between neurons…I will not add any scientific research, as you can google it yourselves…Brain fog, the feeling that the penis is not connected (To me as i have complete numbness, i cant feel my skin), might be resulting from a severe hypofunction in our glutamate receptor function. Loss of memory, speech impairment etc… are controlled be those same receptors…and to the better of all of it…NMDA receptor plays a big role in sleep function, and hypofunctioning results in insomnia…NMDA controls the release of LH and FSH in the hypothalamus (Low Testosteron and hypogonadism) and it even has connections with VIt. D, which might explains why all of us have low VIt. D .

Now if you wanna ask me, why the hell im not curing myself then, well its not that easy guys…NMDA receptor cant be easily played with, and most scientists are convinced that antagonism of NMDA receptor might do depression good (Which is just a big pile of bullshit, just becuz ketmain improves depression that doesnt mean that’s antagonism at NMDA receptors long term will improve it…In Fact many studies has proved that Sarcosine a positive modulator at NMDA improved depression better than citalopram), and thats why there are not many compounds that works positively at NMDA…Recently a an indirect NMDA enhancer was be found to improve schizophrenia negative symptoms (So im staying hopeful in that regard)
So to try to prove my theory, as i wrote a couple of weeks ago, i started to take tinaeptine which is know for modulating glutamergic connectivity in the brain, and as some of you might know, i got immediate results with 80% returning of my emotion and skin sensitivity and very good libido and errection quality…Sadly this didnt stay for long and i.went back to baseline after 4 to 5 days. In the end tianeptine is a week modulator of NMDA…So i thought of other ways to enhance its effect…I remembered that Sarcosine act as well on NMDA, and when i tried it 8 months before, i had a very good response in the first week, which didnt really persist, as i ran out of it, and didnt follow up (I was on a try everything hype and literally tried 3 to 4 different things monthly)…I added Sarcosine and D-Serine (Although i wouldnt recommend it this substance for the time being) to my tianeptine regimen, a week ago, and the response is more than schoking to me…My tinnitus got better, my skin sensitivity got better, im getting rock hard nightly errection that i cant sit on the toilet to pee (Exatly like before fin)…Im feeling a lot better and my taste sense has gotten a little better…Im will say im at 30 to 35% pre PFS, coming from literally -100%…I can think a little bit more clearly, and i have no head pressure when trying to read something…Like something is connected or connecting again…

Now im ofcourse scared to to go back to baseline and i will report back on any improvements or setbacks…and i wouldnt have shared this story right now (As i would have rather to wait it at least 3 months), but i really do believe that this theory should get into the light as a possible culprit in our disease, and maybe if someone knows a researcher like meclangi, he might be interested on following or testing this theory on PFS patients…Im not a aware if there is a smart way to test for NMDA hypofunction, as i really dont have time to make proper research on that matter, but im sure there might be a way at least to test through trial and error protocol.

I hope im into something here, and that i might bring better news in 2 to 3 weeks from now…
Thx guys

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Nicotinamide Mononeuclotide
#2

Potentially great news. I’ve never heard of tinnitus improving in anyone’s endeavours. Its a v mild side in comparison but to shift that one in top of the all round uplift is v promising. I’m not promoting experimentation as it has only brought me to darker doors but keep us posted

#3

Interesting topic.

Silly question maybe… but if PFS was defined by what is thought to be a major marker in schizophrenia, why aren’t we schizophrenic?

1 Like
#4

Its not silly…I asked myself the same question…There are two main theories in schizophrenia nad they seem to be both right…The dopamine theory (Where dopamine are mostly responsible for positive symptoms)…And the NMDA theory (Where researcher believe the negative symptom are coming from…
At the end schizophrenia is a very complex disease and most of us was happy and healthy before this, our brains have many different differences than schizophrenics, but i think that at least the negative symptoms that these patients have, are mediated by the same mechanism that PFS is… (Again i have no scientific proof, only using logic and what science has to offer me in other disease modality)
THe most interesting thing and that was the last thing that made me, do post this, was that NMDA mediates sleep as well, and in some rare conditions where patients have brain inflammation caused by antibodies against NMDA receptors, these patints are unable to sleep. Like literally unable to sleep, which is exactly what i had when i crashed…

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#5

Im shocked from this as well…If this sticks i will consider my tinnitus cured…Its like 10% from where i started, and i can only hear it in completetly quiet and isolated rooms…Where before i would hear it even when im outside in traffic…This is stable like this since a week now…I do hope it sticks

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#6

Another armchair biochemist mis-linking common symptoms of health problems to fit their idea not based in science.

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#7

Im not here to trade insults with a random guy whose Master piece is „excessive Masturbation“…
If you dont want to give any insight on this matter…Just sit down and enjoy while somebody else „at least“ tries to do it for you.

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#8

I just wanted to say, as im affected by PFS, that this theory might also explain PSSD and PAS…A quick search in pubmed and you will see how SSRI alter and changes the NMDA receptor functionality (If anyone want to read he can send me a PM, as i dont want to litter the forums with endless studies)…THat is applicable as well to PAS, as isotretinion can literally cause psychosis through altering of multiple receptors, of them glutamat receptors as well…
Again not valid science but something to think about, as we have nothing else but assumptions and trial and error.
The problem that most ppl here cant get, why im doing this, is that they cant seem to understand, that NO VALID STUDIES can be done regarding PFS in the meantime…Even if its recognized, no one would be able to help us in the next 30-40 years, not at least till half of us have died of natural causes (As you cant use suicide victims in studies usually)…To be able to know what’s wrong we have to open and examine the brains of PFS victims, and as we are all young and „Healthy“, i cant see that happening any soon. So sorry for trying something other than Microbiom and stool transplant, but at least in my head im doing something.

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#9

I wouldn’t worry about “littering the forum with endless studies”. Please share.

I’d rather see someone post extensive potentially interesting and useful stuff than read about clowns getting all uppity worrying about their perineal raphes.

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#10

great read, intriguing new approach. would you be able to clarify what supplements you are taking so at least a reader can research them. thx

#11

RIght now. Im taking tineptine (3x12,5mg as a pharmaceutical, PLEASE DONT TAKE POWEDER FORM, as its highly addictive in high doses, and thats why its prohibited in many countries, not in germany at least :slight_smile: )…
Im taking 3x times 1 g Sarcosine (I might reduce it in the future)
2x 1g D-Serine (I wouldnt recommend it for the time being as i read a study that it might downregulate NMDA receptor on the long run…Im only finishing my bottle, and see where this is going)…

I might add magnesium THreonate in the near future, if i stayed stuck at 30% pre PFS, or if i declined.

Coincidentally there is a very interesting read on the PSSD forum on „ kynurenic acid“, which is upregulated while using SSRIs…You can guess what it is main target? Antagonising NMDA Receptors…Its found in high levels in schizophrenics ppl as well…There are studies that assume a correlation between kynurenic acid and anhedonia…

I would gladly link all those studies i have found here, but im at work and its easier if everyone of you, just googled any idea i presented here which he might find interesting, and i assure you that you wont be searching for too long (Like the role of NMDA in sleep, its role in cognition or LH, FSH secretion, etc … )…Otherwise you can send me a PM if you are interested, and i will try to collect all those studies and send them.

Actuallyi would appreciate it, if some of you guys would do post studies in this regard to help me…You might find something that i didnt find…

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#12

Why would we have high kynurenic acid?

#13

SSRIs are know for increasing its levels…
First result from google :slight_smile:

#14

I think it is due to eat salmon

1 Like
#15

Hi,

Thanks for sharing! Which supplement do you think you attribute your tinnitus improvements to?

I have had it from a single pill 2 months ago, and it is really impacting my everyday life

Cheers

#16

Glutamate is major excitatory neurotransmitter

GABA is the major inhibitory inhibitory neurotransmitter

These two things constantly strive to stay in proper balance with each other

You are very smart and I believe our theories go hand to hand.

If GABA receptors are “misregulated” due to improper balance of negative and positive allosteric modulators (Allopregnanolone and pregnenolone sulfate) then NMDA receptors “will not know what to do” and “do crazy things” in an attempt to “match” the glutamate (NMDA) receptors

Notice how I increased glutamate just a little bit on my neurotransmitter test and I stayed up for 9 days. Yea well that’s not normal… LOL and I think it’s because my GABA receptors are mis functional due to no pregnenolone sulfate negatively modulating them. So body pees out the positive allosteric GABA receptor modulator Allopregnanolone to try to keep the GABA receptors balanced in spite of the lack of negative modulation due to the “missing” pregnenolone sulfate

To be clear I’m peeing out highish amounts of Allopregnanolone in my urine and I have flagged low pregnenolone sulfate in my saliva . I stayed up for 9 dam days after agonizing the NMDA receptors just a little and got back to sleeping by taking 3500 MG’s of glycine nightly which is inhibitory compensating for my likely messed up/misregulated GABA receptors

So my theory is the same as yours except that I view the cause of the problem being the GABA receptors and the solution to the problem being fixing the GABA receptors. Even thisisarealbummer (who is clearly a genius) says not to go down the road of messing with the glutamate receptors and to fix the GABA receptors. Your post, insights and observations are very good. Let’s continue to explore this path

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#17

Actually glycin while might function as inhibitory on its receptor, its actually a positive allosteric Modulator of NMDA…There were study on it improving negative symptoms in schizophrenia but at much higher doses as it has terrible Bioavailability in the brain (Doses reached 60 g daily)…
While we will never be able to scientifically prove any theory for the time being, i cant see why inhibiting my brain activity would do me any good…I already feel lack of emotion and motivations and have enough cognitive problems, that can be caused bei positively affecting GABA receptor…
I posted a study a while ago, on how a german research team has found that Citalopram was able to inhibit brain activity in healthy volunteer after 30 min of taking it (Which is by the way the same duration it takes for fluoxetine to make someone penis less sensitive, there is a study about it too)…
I do believe that the excitatory circuitry is affected with all Anhedonia Patients and it can be so affected that some get not only numbness of emotion, but actual and real physical numbness as in our case. Thats why i dont believe that one medication would reverse it, if at all…we need more than one approach and a lot of hope that some researcher somewhere is trying something for negative symptoms in schizophrenia that might help us.

By the way guys im saying it again, please if anyone bumped to a reasonable way how to increase NMDA transmission (preferably increasing the receptor density), i would really appreciate it, if he can link me to it

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#18

These are some very interesting ideas. Do you think there is any way to test NMDA activity, NMDA receptor density, NMDA availability, etc…

If there is a way to measure these things, perhaps we can get an objective answer as to whether NMDA is a major factor in PFS. Did you read anything about testing (blood, spinal tap, imaging, etc.) in any of the various studies you alluded to earlier?

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#19

I havent really seen any way to test for NMDA acitivty, at least not without taking the brain out and test it ;D…
I guess our best bet, is to try to increase it and see if that solves some of our symptoms…
I have to be honest, i have the feeling that im stuck at 25% pre pfs now…Something telling me im gettin pushed back to my baseline of -100%, but im not yet there…Its a bit frustrating, but on the other hand, when i got improvements, it was the first time i felt alive in 2 years. I will report about my progress in a week or two…
You have to understand that im a really bad case (I know all think that) but i havent yet found anyone here about complete numbness of skin and loss of taste and smell senses, so i might be more affected than others…EIther way i will want all of you to wait for my experiment…I wouldnt advice testing anything for the time being

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#20

Just found this - it’s no 100% applicable to what you are saying but it is going with NMDA receptor dysfunction hypothesis and it also goes with what @LazarusRy was randomly saying the other day - that a lot of people’s neurological dysfunctions here mirror that of Magnesium deficiency .

Heart palps, muscle pain , insomnia, anxiety , GABA dysregulation , muscle atrophy , poor psychological functioning, weakness , tinnitus etc

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