In shizophrenia you want to do the following:
As first and most important is the hypoactivity of glutamate implicated in the desease, glutamate hypoactivity is at the core of shizophrenia, the evidence for this is largely based on PCP's ability to replicated not only psychosis but also cognitive deficits seen in patients. There are several ways to counteract the glutamate hypoactivity:
Nac wich increases extracellular glutamate, it does lower synaptic glutamate because of increased glutamate levels agonizing mglur2 and 3 this protects against excitoxiticy also seen in the desease while also NMDA gets potentiated due to a change in the redox site.
Sarcosine: is a glycine site agonist, the glycine site needs to be agonized before NMDA itself can be agonized, glycine and d serine are selective agonists, sarcosine is both a agonist and a glycine site reuptake inhibitor, it increases endogenious glycine levels wich then also agonize glutamate.
D asparic acid, a NMDA agonist, only has theoretical effiacy, when the glycine site is agonized NMDA can be effectively agonized.
Minocycline lowers synaptic glutamate however potentiates the mglur1 receptor, next to acting on glial cells and lowering iNOS.
Pregnenoline and DHEA (preg is much better)potently modulate glutamate, dopamine and serotonin, preg is highly effective for both positive and negative symptons.
Kynurenic acid is a endogenious antagonist at the glycine site and the alpha 7 nicotinic receptors wich causes cognitive decline, antagonists of this are oxiracetam and aniracetam.
Reduce tonic dopamine (ideally 5HT2C agonism, wich doesnt not interact with phasic dopamine levels) dopamine acts as a NMDA antagonist in the prefrontal cortex, D2 antagonism prevents this but also blocks phasic D2 levels and can cause long term movement issues like tardive dyskinesia, a positive thing about D2 blockade is that dopamine gets more shifted to receptors like D1 and D4 wich modulate the prefrontal cortex, of most importance is D1 wich also jumpstarts the glutaminergic system.
Increase phasic dopamine, ritalin or amphetamine can only do this. Ritalin works good with lexapro and mirtazepine. Stimulants do increase positive symptons and should allways be combined with something that selectively antagonize this, D2 antagonists do this and also in my case, nefiracetam and l methylfolate.
5HT2A and 5HT2C antagonism reduces impulsivity by shifting dopamine to prefrontal area's, this isnt optimal however and agonism would be preferrable as this would cause antagonism of tonic dopamine levels and an increase in phasic dopamine, 5HT3 antagonism increases cognitive symptons in shizophrenia also seen with ondansetron, 5HT6 antagonism does this tough, however 5HT6 agonism may be more beneficial against anhedonia, 5HT7 antagonism is highly antidepressive, mirtazepine does all this and covers most serotogenic targets while 5HT1A is left open wich gets agonized by the free serotonine wich on its turn increases prefrontal dopamine levels. A SSRI combined with mirtazepine will augment this, NRI's, NE releasers and stimulants will further activate the pfc by increasing dopamine levels in this area. Antipsychotics raise prefrontal serotonine by 5HT2C antagonism wich then increases pfc dopamine levels, also atypical antipsychotics have been shown to synergize with mirtazepine, and mirtazepine was found as an effective adjunct for people with this disorder.
Increase NE while antagonizing alpha 2 (like with wellbutrin) i do not take a antipsychotic atm as i find mirtazepine does the job well enough, it synergizes with ritalins ne increase due to the alpha2 antagonism, also this increases 5HT, while 5HT1A is open the baseline serotonine + the released serotonin gets targetted to 5HT1A, this increases prefrontal dopamine levels wich counteracts pfc hypofunctioning in shizophrenia.
Deplete iNOS with l-lysine or minocycline wich as well modulates glutamate, minocycline is highly effective for negative symptons, sarcosine likewise.
Increase eNOS, both resveratrol and l methylfolate do this, mfolate is way more potent and also potently acts on methylation and epigenetics, extremely important for long term improvement.
Cerebrolysine witch reverses an animal model of shizophrenia if i'm correct, stuff is expensive tough, semax may theoretically have potential too.
Oxytocin for social issues can have potential, 5HT1A induces this wich gets significantly agonized with mirtazepine treatment, a ssri will augment this.
Increasing acetylcholine and agonizing most receptors is a good thing, A7 is of most important wich togheter with D1 puts the glutaminergic system in gear. D1 agonism is great, nicotine and DHEA will help with that and stimulants are too, the most potent in fact.
Inflammation and oxidative stress play major roles in shizophrenia and contribute to the chronic decline we see in the desease, NAC provides protection against this kind of oxidative stress due to its antioxidant activity and its effects on glutathione wich is deficient in shizophrenia, for inflammation curcumin looks like a excellent supplement as it directly counteracts several pathways implicated in inflammation such as cox-2.
For anhedonia and avolition stimulants are a very effective intervention, however proceed with caution as D2 is pro psychotic (while D1 and D3 agonism are very good, D4 too for the pfc but it has nmda antagonising property's), effective treatments for the prevention of this issue are ap's, mirtazepine, l methylfolate, SSRI's, gaba reuptake inhibitors like valproate wich also has other interesting property's besides increasing gaba (wich is deficient in shizo due to nmda hypoactivity), what works best is individual, i found ap's pretty weak to counter amp induced paranoia and only benzo's, l methylfolate really effective.
Ritalin is the prefferred intervention due to its neuroprective effects and lack of negative effects on BDNF.
I looked at every proven effective treatment for shizophrenia and i conclude to look no further than the following substances:
Mirtazepine, NAC, glycine, sarcosine, d aspartic acid, aniracetam or nefiracetam, pramiracetam (it increases NO), L lysine, minocycline, DHEA, pregnenolone, l methylfolate, resveratrol, curcumin. If positive symptons are severe a antipsychotictive but those cause long term brain damage and possible permanent movement disorders. (this includes hypothised treatments like resveratrol wich also caused significant cognitive improvement in my case).
Personally im into predromal shizophrenia, a yearlong lasting phase to shizophrenia, however i am higly convinced damage can be reversed before a true unprovoked psychosis occurs.
Any contributions are welcome.
As first and most important is the hypoactivity of glutamate implicated in the desease, glutamate hypoactivity is at the core of shizophrenia, the evidence for this is largely based on PCP's ability to replicated not only psychosis but also cognitive deficits seen in patients. There are several ways to counteract the glutamate hypoactivity:
Nac wich increases extracellular glutamate, it does lower synaptic glutamate because of increased glutamate levels agonizing mglur2 and 3 this protects against excitoxiticy also seen in the desease while also NMDA gets potentiated due to a change in the redox site.
Sarcosine: is a glycine site agonist, the glycine site needs to be agonized before NMDA itself can be agonized, glycine and d serine are selective agonists, sarcosine is both a agonist and a glycine site reuptake inhibitor, it increases endogenious glycine levels wich then also agonize glutamate.
D asparic acid, a NMDA agonist, only has theoretical effiacy, when the glycine site is agonized NMDA can be effectively agonized.
Minocycline lowers synaptic glutamate however potentiates the mglur1 receptor, next to acting on glial cells and lowering iNOS.
Pregnenoline and DHEA (preg is much better)potently modulate glutamate, dopamine and serotonin, preg is highly effective for both positive and negative symptons.
Kynurenic acid is a endogenious antagonist at the glycine site and the alpha 7 nicotinic receptors wich causes cognitive decline, antagonists of this are oxiracetam and aniracetam.
Reduce tonic dopamine (ideally 5HT2C agonism, wich doesnt not interact with phasic dopamine levels) dopamine acts as a NMDA antagonist in the prefrontal cortex, D2 antagonism prevents this but also blocks phasic D2 levels and can cause long term movement issues like tardive dyskinesia, a positive thing about D2 blockade is that dopamine gets more shifted to receptors like D1 and D4 wich modulate the prefrontal cortex, of most importance is D1 wich also jumpstarts the glutaminergic system.
Increase phasic dopamine, ritalin or amphetamine can only do this. Ritalin works good with lexapro and mirtazepine. Stimulants do increase positive symptons and should allways be combined with something that selectively antagonize this, D2 antagonists do this and also in my case, nefiracetam and l methylfolate.
5HT2A and 5HT2C antagonism reduces impulsivity by shifting dopamine to prefrontal area's, this isnt optimal however and agonism would be preferrable as this would cause antagonism of tonic dopamine levels and an increase in phasic dopamine, 5HT3 antagonism increases cognitive symptons in shizophrenia also seen with ondansetron, 5HT6 antagonism does this tough, however 5HT6 agonism may be more beneficial against anhedonia, 5HT7 antagonism is highly antidepressive, mirtazepine does all this and covers most serotogenic targets while 5HT1A is left open wich gets agonized by the free serotonine wich on its turn increases prefrontal dopamine levels. A SSRI combined with mirtazepine will augment this, NRI's, NE releasers and stimulants will further activate the pfc by increasing dopamine levels in this area. Antipsychotics raise prefrontal serotonine by 5HT2C antagonism wich then increases pfc dopamine levels, also atypical antipsychotics have been shown to synergize with mirtazepine, and mirtazepine was found as an effective adjunct for people with this disorder.
Increase NE while antagonizing alpha 2 (like with wellbutrin) i do not take a antipsychotic atm as i find mirtazepine does the job well enough, it synergizes with ritalins ne increase due to the alpha2 antagonism, also this increases 5HT, while 5HT1A is open the baseline serotonine + the released serotonin gets targetted to 5HT1A, this increases prefrontal dopamine levels wich counteracts pfc hypofunctioning in shizophrenia.
Deplete iNOS with l-lysine or minocycline wich as well modulates glutamate, minocycline is highly effective for negative symptons, sarcosine likewise.
Increase eNOS, both resveratrol and l methylfolate do this, mfolate is way more potent and also potently acts on methylation and epigenetics, extremely important for long term improvement.
Cerebrolysine witch reverses an animal model of shizophrenia if i'm correct, stuff is expensive tough, semax may theoretically have potential too.
Oxytocin for social issues can have potential, 5HT1A induces this wich gets significantly agonized with mirtazepine treatment, a ssri will augment this.
Increasing acetylcholine and agonizing most receptors is a good thing, A7 is of most important wich togheter with D1 puts the glutaminergic system in gear. D1 agonism is great, nicotine and DHEA will help with that and stimulants are too, the most potent in fact.
Inflammation and oxidative stress play major roles in shizophrenia and contribute to the chronic decline we see in the desease, NAC provides protection against this kind of oxidative stress due to its antioxidant activity and its effects on glutathione wich is deficient in shizophrenia, for inflammation curcumin looks like a excellent supplement as it directly counteracts several pathways implicated in inflammation such as cox-2.
For anhedonia and avolition stimulants are a very effective intervention, however proceed with caution as D2 is pro psychotic (while D1 and D3 agonism are very good, D4 too for the pfc but it has nmda antagonising property's), effective treatments for the prevention of this issue are ap's, mirtazepine, l methylfolate, SSRI's, gaba reuptake inhibitors like valproate wich also has other interesting property's besides increasing gaba (wich is deficient in shizo due to nmda hypoactivity), what works best is individual, i found ap's pretty weak to counter amp induced paranoia and only benzo's, l methylfolate really effective.
Ritalin is the prefferred intervention due to its neuroprective effects and lack of negative effects on BDNF.
I looked at every proven effective treatment for shizophrenia and i conclude to look no further than the following substances:
Mirtazepine, NAC, glycine, sarcosine, d aspartic acid, aniracetam or nefiracetam, pramiracetam (it increases NO), L lysine, minocycline, DHEA, pregnenolone, l methylfolate, resveratrol, curcumin. If positive symptons are severe a antipsychotictive but those cause long term brain damage and possible permanent movement disorders. (this includes hypothised treatments like resveratrol wich also caused significant cognitive improvement in my case).
Personally im into predromal shizophrenia, a yearlong lasting phase to shizophrenia, however i am higly convinced damage can be reversed before a true unprovoked psychosis occurs.
Any contributions are welcome.
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