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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by Lamdage22 on May 31, 2021, at 4:00:28
Hey guys,
there are several amino acids that can target NMDA recpetpors. Is this always a good idea for schizophrenia? Are there risks?
I am thinking L-or-D aspartic acid and D-Alanine.
Posted by undopaminergic on May 31, 2021, at 9:53:57
In reply to Do you agree with NMDA hypofunction hypothesis?, posted by Lamdage22 on May 31, 2021, at 4:00:28
Yes, I tend to consider the NMDA theory of schizophrenia the best one as of currently. I think low NMDA-neurotransmission leads to a *functional* (ie. not in terms of absolute concentrations) hyperdopaminergic state in the limbic system.
D-cycloserine has been tested, with inconsistent but somewhat promising results:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327448/-undopaminergic
> Hey guys,
>
> there are several amino acids that can target NMDA recpetpors. Is this always a good idea for schizophrenia? Are there risks?
>
> I am thinking L-or-D aspartic acid and D-Alanine.
Posted by linkadge on May 31, 2021, at 13:19:20
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by undopaminergic on May 31, 2021, at 9:53:57
It can work both ways too. Dopamine agonists often decrease NMDA function.
Schizophrenia is not a single disorder. The NMDA model seems to closer match the 'disorganized' subtype of the disorder. Whereas, the dopaminergic model seems to match the paranoid subtype. This being said, neither of these are likely at the core of the disorder. Dysfunction in dopamine or NMDA likely result from other dysfunctions.
Linkadge
Posted by Lamdage22 on May 31, 2021, at 13:44:11
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by linkadge on May 31, 2021, at 13:19:20
But it is worthwhile to pursue the NMDA avenue?
Posted by linkadge on May 31, 2021, at 20:10:22
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by Lamdage22 on May 31, 2021, at 13:44:11
Certainly. Although raising NMDA in a global sense may cause problems. If there are glutamatergic deficits, they may be regional. Hence, nonspecific NMDA agonists could cause excessive glutamate in certain brain regions. In schizophrenia there is evidence of both hypo and hyper function of glutamate (depending on the brain region).
Also, there are interactions with GABA. For instance, for catatonic schizophrenia, benzodiazapines are particularly effective (which is paradoxical as you'd think they would put the catatonic patient into further catatonia). This indicates an imbalance where too little gaba is actually increasing the inhibitory effect of dopamine. Increasing gaba can actually inhibit dopamine induced inhibition. Benzodiazapines can have a paradoxical excitatory effect in certain situations (such as catatonia, and in some cases coma). They can also reverse ketamine induced catatonia. NMDA antagonists tend to shift the balance between dopamine and gaba towards dopamine.
Posted by Lamdage22 on June 1, 2021, at 2:22:39
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by linkadge on May 31, 2021, at 20:10:22
So which substances would you recommend. I got D-Serine, L-Aspartic Acid and Betaine (TMG) in mind. Is the NMDA pathway also a possibility to curb positive symptoms and maybe reduce Neuroleptics? Or is it mainly helpful for negative symptoms?
Posted by Lamdage22 on June 1, 2021, at 2:23:02
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by Lamdage22 on June 1, 2021, at 2:22:39
Please no prescriptions. Just natural stuff.
Posted by linkadge on June 1, 2021, at 15:56:50
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by Lamdage22 on June 1, 2021, at 2:22:39
It's hard to say whether currently commercially available NMDA agonists are effective in schizophrenia.
I think d-serine is the most studied, and has shown some positive effects in some forms of schizophrenia. Also, l-theanine (which has glutamate enhancing and blocking effects) has also shown some benefit. Ascorbic acid (vitamin C) is also interesting. It has been shown in clinical trials to reduce the necessary dose of neuroleptics. It has glutamate stabilizing effects (acting as a co-transmitter with glutamate) and some mild dopamine reducing effects.
Glutamate modulators have the potential to improve both positive and negative symptoms (perhaps a bit more of the latter). Some recent studies found genes related to NMDA alterations in the prefrontal cortex. Here's a good article:
https://www.frontiersin.org/articles/10.3389/fnmol.2019.00185/full
Not sure if you have heard of anti-nmda autoimmune encephalitis. It is fairly rare, but it is an autoimmune condition where the body produces natural NMDA antagonists. Symptoms include the full range of symptoms of schizophrenia and, if it progresses, seizures as well.
Of course, a lot more research is needed.
Linkadge
Posted by Lamdage22 on June 2, 2021, at 2:22:57
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by linkadge on June 1, 2021, at 15:56:50
Yeah, research is really needed. And I hope that they research body-native compounds, too. It can't be that they are not researched just because companies can't make that much money with them.
Posted by Lamdage22 on June 2, 2021, at 2:24:05
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by Lamdage22 on June 2, 2021, at 2:22:57
There is a reason for every psych-diagnosis. And the reason is not that foreign chemicals are missing.
Posted by linkadge on June 2, 2021, at 15:18:23
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by Lamdage22 on June 2, 2021, at 2:24:05
Exactly. I'd much rather take, say, oxytocin spay for social phobia than paxil.
Linkadge
Posted by Lamdage22 on June 23, 2021, at 22:53:19
In reply to Re: Do you agree with NMDA hypofunction hypothesis?, posted by linkadge on June 2, 2021, at 15:18:23
So NMDA agonists should improve cognition, especially in those with a "schizo" diagnosis? That is my biggest problem right now. I surmise that this is a withdrawal problem. Trazodone has been discontinued for a week.
This is the end of the thread.
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