Dissociative Tolerance vs. Schizophrenia Theory

[dopamimetic]

There's the theory that too little NMDA activity results in schizophrenia-like symptoms. Chronic, but less so acute administeration of PCP leads to similar changes as seen in patients, and is used in model psychosis.

Just that there's the phenomenon of dissociative tolerance which is very long lasting and can reach pretty intense levels where you aren't able to take enough K to reach dissociation. Isn't this contradictory? If NMDA receptors actually upregulate with antagonism, otherwise dissociatives should have a negative tolerance like e.g. dopamine antagonists show, don't they? Then dissociative use should acutely, but not chronically lead to these symptoms. Weird.

Indeed in times of high dissociative tolerance I had somewhat like mild negative symptoms of social withdrawal, little drive etc. but how's that possible together?

Edit:

The administration of M (Morphine) or MK801 alone, or NX (Naltrexone) together with M, caused significant upregulation of NMDA receptors. NX alone, and MK801 given concurrently with M led to a significant downregulation.

Very interesting. Strange they don'r mention morphine + mk801, maybe they cancel each other out in terms of tolerance? Source

Edit:
Unrelated, but has implications for prolonged dissociative use, especially about quitting long-term use abrutly. There is definitely something weird about rebound getting more intense and painful with increased tolerance. Organ toxicity of dissociatives, avoidable by avoiding rebound??

Or is it in the end upregulated receptors leading to toxic changes which ultimatively lead to less receptors.

Excessive Activation of NMDA Receptors in the Pathogenesis of Multiple Peripheral Organs via Mitochondrial Dysfunction, Oxidative Stress, and Inflammation
It has been well-acknowledged that N-methyl-D-aspartate receptors (NMDARs) in central nervous system play an important role in both physiological functions of neurons and the pathophysiological progression of various neurodegenerative diseases. Besides, the receptors have also been found to present extensively in peripheral organs, such as lungs, kidneys, heart, and pancreas. Under various pathological conditions, peripheral NMDARs are upregulated and excessively activated, initiating calcium influx and intracellular calcium overloading. Subsequently, mitochondrial dysfunction, oxidative stress, and pro-inflammatory signaling pathway activation ultimately aggravate tissue damage and organ dysfunction. In addition, excessive activation of NMDARs also directly initiates mitochondrial apoptosis in many organs. Here, we discuss pathophysiological roles of NMDARs in cardiovascular system, lungs, kidneys, and pancreas. Full text

 

[dopamimetic]

Somehow remarkable how both too much dopamine and too little of it do induce psychosis and delirium, respectively. Neuroleptic malignant syndrome is mostly physical but includes heavy mental changes too why it sometimes is misdiagnosed as mental illness and guess from time to time this will happen isolated without the physical symptoms if we talk about dopamine concentration changes that happen primarily in the CNS?

 

[Flower Fairy]

Just that there's the phenomenon of dissociative tolerance which is very long lasting and can reach pretty intense levels where you aren't able to take enough K to reach dissociation

I was just talking about this to someone on Bluelight it's so harsh, I'm on a tolerance break because of it lol

I'm not brainy enough to understand anything else you said, I might re read it tomorrow as it did sound interesting I'm just not that intelligent when it comes to stuff like that lol

But maybe because K increases dopamine it levels out the effects on the NMDA receptors so we all don't end up Schizo lol

 

[Schizopath]

Yes. They are co morbid. Brain = fucked.

 

[dopamimetic]

Well to my understanding the fact of dissociative tolerance = more NMDA receptors and the theory about less of them leading to psychosis and specific brain changes known under that non-scientific diagnosis aka schizophrenia are very oppositing. But maybe it is both and specific to certain brain regions. All I can say that it is probably correct that less NMDA activity = psychotomimetic but more in a psychedelic, fluid, "acute" way, is certainly not anxiogenic but anxiolytic and not like the residual symptoms of chronic shizo like the infamous voices (which are another quest to me as you can get them absolutely isolated w/o any other symptoms, and antipsychs can trigger them too while at least to me even solid doses of dopaminergics don't when used alone).
And that too much NMDA leads to irritability, rigidness, anxiety, introversion (negative symptoms and associated with autism), even more to seizures and excitoxocitiy while much too less immobilizes and anesthesizes you.

It seems to be that people with preexisting psychosis worsen under NMDA antagonists but they would too on a bunch of other psychoactive chemicals.