NMDA Hypoactivity

[bell]

Does Peat speak about NMDA HYPOactivity at all?

I've seen some quotes from him about hyperactivity, but not hypo.

I would have thought that hypo would be more consistent with the "hibernation" state he speaks about.

Anyway, would love to know more about how he sees NMDA fitting in with the constellation of symptoms that he describes.

If you know of any, I'd love some references.

Thank you :)

 

[youngsinatra]

No, he did not talk about that to my knowledge.

"Antagonists of the NMDA glutamate receptor, including phencyclidine (PCP), ketamine, and CGS-19755, produce cognitive and behavioral changes in humans. In rodents these agents produce a myriad of histopathological and neurochemical changes. Several lines of evidence suggest that a large number of these drug-induced effects are dose-dependent manifestations of the same general disinhibition process in which NMDA antagonists abolish GABAergic inhibition, resulting in the simultaneous excessive release of acetylcholine and glutamate. Progressive increases in the severity of NMDA receptor hypofunction (NRHypo) within the brain produce an increasing range of effects on brain function. Underexcitation of NMDA receptors, induced by even relatively low doses of NMDA antagonist drugs, can produce specific forms of memory dysfunction without clinically evident psychosis. More severe NRHypo can produce a clinical syndrome very similar to a psychotic schizophrenic exacerbation. Finally, sustained and severe NRHypo in the adult brain is associated with a form of neurotoxicity with well-characterized neuropathological features. In this paper several of these effects of NMDA antagonists and a likely mechanism responsible for producing them will be reviewed. In addition the possible role of NRHypo in the pathophysiology of idiopathic psychotic disorders will be considered.
- https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1196/annals.1300.008

"Proper expression and regulation of NMDARs in the brain is critical for learning and memory processes as well as cortical plasticity and maturation."
- NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia

Symptoms include "Feelings of drowsiness, difficulty concentrating, dizziness, confusion, lightheadedness, “high”, exhilaration, floating sensations, parasthesias, “dream-like state”, and change in sense of time."

 

[bell]

No, he did not talk about that to my knowledge.

"Antagonists of the NMDA glutamate receptor, including phencyclidine (PCP), ketamine, and CGS-19755, produce cognitive and behavioral changes in humans. In rodents these agents produce a myriad of histopathological and neurochemical changes. Several lines of evidence suggest that a large number of these drug-induced effects are dose-dependent manifestations of the same general disinhibition process in which NMDA antagonists abolish GABAergic inhibition, resulting in the simultaneous excessive release of acetylcholine and glutamate. Progressive increases in the severity of NMDA receptor hypofunction (NRHypo) within the brain produce an increasing range of effects on brain function. Underexcitation of NMDA receptors, induced by even relatively low doses of NMDA antagonist drugs, can produce specific forms of memory dysfunction without clinically evident psychosis. More severe NRHypo can produce a clinical syndrome very similar to a psychotic schizophrenic exacerbation. Finally, sustained and severe NRHypo in the adult brain is associated with a form of neurotoxicity with well-characterized neuropathological features. In this paper several of these effects of NMDA antagonists and a likely mechanism responsible for producing them will be reviewed. In addition the possible role of NRHypo in the pathophysiology of idiopathic psychotic disorders will be considered.
- https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1196/annals.1300.008

"Proper expression and regulation of NMDARs in the brain is critical for learning and memory processes as well as cortical plasticity and maturation."
- NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia

Symptoms include "Feelings of drowsiness, difficulty concentrating, dizziness, confusion, lightheadedness, “high”, exhilaration, floating sensations, parasthesias, “dream-like state”, and change in sense of time."

Thank you - I'm curious why he didn't speak of it.

In my reading, it looks to me like serotonin might reduce NMDA function (and this is way over my head, and I might be completely misunderstanding). "We found that serotonin, by activating 5-HT1A receptors, inhibits NMDAR currents through a mechanism dependent on the motor protein-mediated transport of NMDA receptors along microtubules in dendrites." Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism

And low NMDA function, seems related to hibernation to me, which Peat speaks of often. (And logical that if a hibernation switch has been set off, then that could explain the fatigue in CFS.) Ketamine's action on NMDA lets it be used as an anesthetic (deep hibernation). And even the connection to schizophrenia, which I think is because of the hallucinations of the hyponmda state, which seems like a dream state of sleep.

Thank you so much for your thoughts, YS :)

 

[reality]

I think he would say it comes back thyroid, because the thyroid will control the neurosteroids that modulate these receptors like DHEA pregnenolone etc

 

[youngsinatra]

„Functional consequences of adult-onset hypothyroidism include an inability to produce long-term potentiation in rat hippocampus and impaired learning and memory in both rats and man. Long-term potentiation is a form of learning that is dependent on functional N-methyl-d-aspartic acid (NMDA)-preferring ionotropic glutamate receptors.“

Thyroid hormone regulation of N-methyl-D-aspartic acid receptor subunit mRNA expression in adult brain - PubMed

Thyroid hormone is an essential modulator of brain development, but little is known about its actions in the adult brain. Hypothyroidism is associated with gene expression changes in both central and peripheral nervous tissue. Functional consequences of adult-onset hypothyroidism include an...

pubmed.ncbi.nlm.nih.gov

 

[youngsinatra]

Thank you - I'm curious why he didn't speak of it.

In my reading, it looks to me like serotonin might reduce NMDA function (and this is way over my head, and I might be completely misunderstanding). "We found that serotonin, by activating 5-HT1A receptors, inhibits NMDAR currents through a mechanism dependent on the motor protein-mediated transport of NMDA receptors along microtubules in dendrites." Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism

And low NMDA function, seems related to hibernation to me, which Peat speaks of often. (And logical that if a hibernation switch has been set off, then that could explain the fatigue in CFS.) Ketamine's action on NMDA lets it be used as an anesthetic (deep hibernation). And even the connection to schizophrenia, which I think is because of the hallucinations of the hyponmda state, which seems like a dream state of sleep.

Thank you so much for your thoughts, YS :)

Very interesting. In the past I got NMDA-hypofunction symptoms only when I took magnesium and to a lesser extent zinc supplements.

The simple discontinuation of both fixed the NMDA problems for me.

 

[Highserotonin90]

Signs and Symptoms of Low NMDA-Receptor Activity

Yet another topic that is under appreciated and often not compiled in an easily searchable form. So, I've done you all the honor of finding...

area1255.blogspot.com

I found this, I don't know if it's reliable.

 

[bell]

Very interesting. In the past I got NMDA-hypofunction symptoms only when I took magnesium and to a lesser extent zinc supplements.

The simple discontinuation of both fixed the NMDA problems for me.

I know magnesium blocks it, but I hadn’t heard of zinc,
That’s interesting

I’m getting into trouble whenever I drink milk though! And it made no sense at first, because if anything, the calcium should help the channel. But I’m thinking it might be the tryptophan/serotonin, because I don’t get the same result with a calcium supplement.

 

[bell]

I think he would say it comes back thyroid, because the thyroid will control the neurosteroids that modulate these receptors like DHEA pregnenolone etc

I'm pretty sure he says everything comes back to thyroid :) But jokes aside, I've seen him mention hyper and not hypo, and trying to figure out how all the rest of his advice might shift for hypo, because I think it's a pretty different bodily state

 

[bell]

Signs and Symptoms of Low NMDA-Receptor Activity

Yet another topic that is under appreciated and often not compiled in an easily searchable form. So, I've done you all the honor of finding...

area1255.blogspot.com

I found this, I don't know if it's reliable.

There are some interesting points they made (and I wish they provided sources) ... - I bolded a few sections, and added some questions I'm asking myself...

• Things that Mimic (or cause) the State of NMDA Hypoactivity
  • Using AntiHistamine's such as Benadryl. (H1 antagonists tend to produce similar state)
  • Using Xanax, Klonopine or other GABA-A agonists (as they decrease activity)
  • Low Testosterone-Estrogen/E2 Levels (or aromatization) (as Free T/Estrogen generally facilitates NMDA function) (goes for both men and women) /* So unlike with hypo-NMDA activity might actually have too little Estrogen? Would OJ and mushrooms mess us up then?
  • Low Protein Intake
  • Abuse of Nitrous Oxide Drugs (as N.O antagonizes NMDA) /* So could the N.O. from hypothyroid state lead to Hypoactivity too? */
  • Chronic Stimulant Use (especially decongestants)
  • SSRI use, or use of Hallucinogen's (which artificially decrease glutamate). /* Another suggestion that serotonin can lead to this state */
  • High Carbohydrate Diet /* This is one where I wish really wish they provided a source. */
  • Eating foods with MSG for long periods of time, then suddenly stopping.
  • Taking NMDA-antagonists (like ketamine, PCP, and the brain booster "Huperzine-A")
  • Taking too Much Zinc and / or Magnesium Supplement.

My suspicion is the NMDA hypoactivity might be a more advanced stage of the process that Ray describes, where the organism is actually going into hibernation states. And maybe the earlier stages are a period of NMDA hyperactivity - the very high activity that would precede a hibernation state, where the organism is trying to get ready, and is pushing hard to prepare (gather food, whatever else they do) for that state. But I think the two states have different needs, and then my next question would be, what signals the organism to leave the hibernation state?

 

[youngsinatra]

There are some interesting points they made (and I wish they provided sources) ... - I bolded a few sections, and added some questions I'm asking myself...

• Things that Mimic (or cause) the State of NMDA Hypoactivity
  • Using AntiHistamine's such as Benadryl. (H1 antagonists tend to produce similar state)
  • Using Xanax, Klonopine or other GABA-A agonists (as they decrease activity)
  • Low Testosterone-Estrogen/E2 Levels (or aromatization) (as Free T/Estrogen generally facilitates NMDA function) (goes for both men and women) /* So unlike with hypo-NMDA activity might actually have too little Estrogen? Would OJ and mushrooms mess us up then?
  • Low Protein Intake
  • Abuse of Nitrous Oxide Drugs (as N.O antagonizes NMDA) /* So could the N.O. from hypothyroid state lead to Hypoactivity too? */
  • Chronic Stimulant Use (especially decongestants)
  • SSRI use, or use of Hallucinogen's (which artificially decrease glutamate). /* Another suggestion that serotonin can lead to this state */
  • High Carbohydrate Diet /* This is one where I wish really wish they provided a source. */
  • Eating foods with MSG for long periods of time, then suddenly stopping.
  • Taking NMDA-antagonists (like ketamine, PCP, and the brain booster "Huperzine-A")
  • Taking too Much Zinc and / or Magnesium Supplement.

My suspicion is the NMDA hypoactivity might be a more advanced stage of the process that Ray describes, where the organism is actually going into hibernation states. And maybe the earlier stages are a period of NMDA hyperactivity - the very high activity that would precede a hibernation state, where the organism is trying to get ready, and is pushing hard to prepare (gather food, whatever else they do) for that state. But I think the two states have different needs, and then my next question would be, what signals the organism to leave the hibernation state?

View: https://m.youtube.com/watch?v=0f2xvn7lWao&embeds_referring_euri=https%3A%2F%2Ffireinabottle.net%2F&source_ve_path=MjM4NTE&feature=emb_title

 

[bell]

There are some interesting points they made (and I wish they provided sources) ... - I bolded a few sections, and added some questions I'm asking myself...

• Things that Mimic (or cause) the State of NMDA Hypoactivity
  • Using AntiHistamine's such as Benadryl. (H1 antagonists tend to produce similar state)
  • Using Xanax, Klonopine or other GABA-A agonists (as they decrease activity)
  • Low Testosterone-Estrogen/E2 Levels (or aromatization) (as Free T/Estrogen generally facilitates NMDA function) (goes for both men and women) /* So unlike with hypo-NMDA activity might actually have too little Estrogen? Would OJ and mushrooms mess us up then?
  • Low Protein Intake
  • Abuse of Nitrous Oxide Drugs (as N.O antagonizes NMDA) /* So could the N.O. from hypothyroid state lead to Hypoactivity too? */
  • Chronic Stimulant Use (especially decongestants)
  • SSRI use, or use of Hallucinogen's (which artificially decrease glutamate). /* Another suggestion that serotonin can lead to this state */
  • High Carbohydrate Diet /* This is one where I wish really wish they provided a source. */
  • Eating foods with MSG for long periods of time, then suddenly stopping.
  • Taking NMDA-antagonists (like ketamine, PCP, and the brain booster "Huperzine-A")
  • Taking too Much Zinc and / or Magnesium Supplement.

My suspicion is the NMDA hypoactivity might be a more advanced stage of the process that Ray describes, where the organism is actually going into hibernation states. And maybe the earlier stages are a period of NMDA hyperactivity - the very high activity that would precede a hibernation state, where the organism is trying to get ready, and is pushing hard to prepare (gather food, whatever else they do) for that state. But I think the two states have different needs, and then my next question would be, what signals the organism to leave the hibernation state?

View: https://m.youtube.com/watch?v=0f2xvn7lWao&embeds_referring_euri=https%3A%2F%2Ffireinabottle.net%2F&source_ve_path=MjM4NTE&feature=emb_title

OMG THANK YOU!!! This is EXACTLY what I've been looking for. Can hardly wait to see this