9 replies to this topic

[gamesguru]

mPFC Biomarker [cause → symptom]
hypoDOPAMINErgic [Attentional deficits → social impairment]
[COMT valine polymorphism → COMT hyperactivity → prefrontal hypodopamine]

 

COMT inhibitors

• Quercetin [1]
• EGCG [might unfortunately inhibit dopa decarboxylase] [2a] [2b]
• Rosmarinic acid [thx to DevinThayer]
• Cichoric acid [also has antiviral properties, and is recommended by DevinThayer due to its lack of DNA modulating effects. however it inhibits tyrosinase, which is critical for melanin and skin health]

Misc dopamine boosters

• ginkgo acts as NDRI, prevents NET from sucking up dopamine [3]
• ginsenoside Re [well to supplement with Rg1 and Rd] [4]
• bacopa prevents DA/5-HT depletion while allowing NE depletion [examine.com]
• tyrosine

See this post for a final word on manipulating dopamine

 

hyperNORADRENErgic [Irritability or aggression → social impairment]

 

DBH inhibitors

• wheat [1]
• California poppy [2]
• St John's Wort [3a] [3b]
• ginseng [watch out for tyrosine hydroxylase inhibition too tho] [4]
• low copper[5] and high iron, zinc, magnesium diet

I'll try to find more information on NE, I just wanted to post what I found in March. The DA/Glu sections are less incomplete.

 

hyperGLUTAMATErgic [Affective flattening, social anhedonia, face recog → social impairment]

[PKA hypoactivity and PKC hyperactivity → hyperglutamate]

the increase in synaptosomal PKC activity is paralleled by increased glutamate but not GABA release[!]

 

PKC inhibitors

• Piceatannol [1]
• Michellamine [2]
• Xestocyclamine A [3]

Glutamate release inhibitors

• NAC? possibly?
• theanine [4]
• taurine, NGF/BDNF [5]
• curcumin [6]
• riluzole [inhibits glutamate synthesis and GABA breakdown] [7]

GABA antagonists

1. Ginkgo acts as presynaptic GABA(A) antagonist
2. ginsenoside Rc acts as presynaptic GABA(B) antagonist
3. generally anything recommended for maintenance of Social Anxiety Disorder

final word: long-term low dose presynaptic NMDAR inhibition may mitigate long-term hyperglutamatergic states by sensitizing autoreceptors

• magnesium [not very effective]
• memantine [seems to lose efficacy after months-years]
• DXM [not recommended]

[normalizing]

memantine and DXM are two recent things i have taken in experimental phase to achieve more "feel to life" and as dissociative as those two are, they have long term subtle effect in achieving what i aim for but are seriously problematic in short term memory formation and concentration.

DXM i took last week and while it wasnt very pleasant the night, the next day social interactions seemed to flow at ease and i didnt feel angry anymore. but for days after, memory impairment is quite bad and concentration is just not good. I dont think its something to take too often at all!

memantine, i just took it today with coffee and few other things, and the dissociative effect is just as strong as DXM for me, but without the euphoric and other mental stimulative and sedative properties. I must say, it feels like DXM in the same negative aspect too, memory impairment is quite bad and concentration is horrible! as seen in this one study i dug up; A recent study demonstrates therapeutically-relevant doses of memantine in the mouse can lead to disruption of cognitive flexibility' http://www.ncbi.nlm....pubmed/21860092

 

what is the conclusion? NMDA antagonism is not something to fuck with too often. in fact, im not sure its good idea to even bother with those, or perhaps it just affects me differently and nobody else had those memory, concentration problems? big problem for me, how do i avoid these serious side effects and get that feeling of life, fluid social life thing going?

Edited by normalizing, 30 March 2016 - 05:31 AM.

[Sleepdealer]

Useful information, thank you gamesguru. But couldn't the glutamate activity also be HYPOactive rather than HYPERactive in schizophrenia/schizotypal PD? Hence why sarcosine seems to help a lot of schizophrenics with their negative symptoms.

[gamesguru]

its interesting you got impaired memory for days, but at the same timeframe, "social flow"

 

yeah they are used most commonly for amphetamine tolerance, but they might find a niche in negative schizophrenia too.

research goes both ways on kynurenic acid, being both good for memory and bad. magnesium might be too weak to be good or bad. the goal of the glutamate antagonist strategy is to upregulate presynaptic autoreceptors and restore balance, this goal it may not achieve. something as simple as a low glutamine diet might be more effective (btw i also mention homocystein in my bipolar/borderline thread, its another thing i thinks worth considering)

high levels of serum  homocysteine  and glutamate might be considered as a trait mar ker for schizophrenia.

 

ketamine doesnt really produce negative symptoms, but dizocilpine produces both negative and positive.

what's going on here? two chemicals can hook into the same receptor, but have very different effects. for example serotonin and LSD are two chemicals hooking into the 5-HT2A receptor, yet with profoundly different effects. never could intracerebral serotonin injections or other serotonergic manipulation result in a spectrum of effects like LSD. subtle differences in signalling cascades can lead to profound state changes

 

take schizophrenia for example. the level of glutamate depends on the region. in the frontal lobe and accumbens, there is too much glutamate, but in the hippocampus there is not enough. this idea is supported by the fact that ketamine injected to the mPFC and NAc is antidepressive while that injected to the hippocampus is not [!].

 

so if my posts suddenly become more insightful, you know what to assume (i jumped on something new, haha jk)

 

 

 

re: sarcosine

 

Its probably the same reason acute dizocilpine increases symptoms: short-term, postsynaptic activity. (Although dizocilpine is associated with chronic worsening of symptoms too)

so idk maybe then it comes down to selectivity for the postsynaptic site over the presynaptic autoreceptors [!].

Its also possible glycine targets the presynaptic site, or is a NMDA agonist associated with chronic worsening. I also didn't look into if it selectively addresses positive, or negative symptoms

It increases glycine concentrations in the brain thus causing increased NMDA receptor activation and a reduction in symptoms

Edited by gamesguru, 30 March 2016 - 01:43 PM.

[normalizing]

im thinking of just going to selegiline for dopamine benefits. i know ive used it before with not much success but maybe it was too short term and low dose (has low bioavailability) or i can just switch to this one; https://en.wikipedia...pylaminopentane

[gamesguru]

im wondering how rasagaline and ladostigil are coming along.

selegiline has a lot of reports of side effects, even cropping up months into a cycle. you could try it, but i would first do a little more reading around

 

as far as natural options, area has one DRI. ill try to dredge up more later, but im running out of leads

• Shilajit is known to decrease Serotonin, increase Dopamine and 'mimic' glycine thereby improving memory, libido and motivation (1) (2).
• Mucuna Pruriens (the second image link) contains a natural dopamine precursor ; L-DOPA - which is also a compound used to treat Parkinson's disease (3) (4).
  • Also contains minor DMT analogues which, theoretically, can have additional euphoric effects. 
• Mu  GUA ('Common Flowering Quince') - acts as a DRI; Dopamine Reuptake Inhibitor - thereby reversing the transport and 'locking' dopamine back into the synapse...similar to the mechanism of amphetamine but without any effect on noradrenaline or serotonin which means it is VERY SAFE (5).

[normalizing]

i was just reading this new article; http://www.medicalne...ases/308510.php and its nothing new or surprising they just solidify that being said before. it depresses me a lot since they only look at one drug that might cause such long perm damage but never mind the combination of other stimulants to the mix... 

Edited by normalizing, 31 March 2016 - 06:57 PM.

[gamesguru]

paxil was recently ruled unsafe for teens too

eli lilly admitted to greatly downplaying olazapine's side effects

blah blah blah, all these consumers are trusting an institution to do their research. i say above 110iq, no excuse not to do all your own research and answer your own questions and trust yourself. i feel badly for these consumers, but its not my job to help.

 

and btw, i doubt the selegiline side effects are because of its amphetamine metabolites, its mostly selegiline itself. one guy here developed really bad insomnia and brain fog, maybe it was building up in his system. but in small doses, over short periods, few side or tolerance effects. its kind of something to cycle

Dizziness, abdominal pain, dry mouth, nausea, stomach upset, trouble sleeping, and headache

[Londonscouser]

 Vitamins C & E may help with negative symptoms http://www.ncbi.nlm....pubmed/23105377

[gamesguru]

Good point, several studies come up in google with keywords "schizophrenia antioxidant".

I wonder if lipoic acid (also maybe ALCAR+PS) might be a good choice. Then something as simple as blueberries (proanthocyanins), broccoli (lutein, zeaxanthin, & more), or walnuts might lessen schizophrenic symptoms.

Alpha-lipoic acid alone and combined with clozapine reverses schizophrenia-like symptoms induced by ketamine in mice: Participation of antioxidant, nitrergic and neurotrophic mechanisms.
ALA presented an antipsychotic-like profile reversing KET-induced positive- and negative-like symptoms. The mechanism partially involves antioxidant, neurotrophic and nitrergic pathways. The combination of ALA+CLZ2.5 improved most of the parameters...
when combined with ALA a lower dose of CLZ is required.

 

here are references quantifying dietary sources of common mitochondrial antioxidants (why mitochondria? inspired by this google query.)

• melatonin [1] (rice, oats, corn. kiwis apparently no good for melatonin, but tall fescues great if you know what im talking about)
• PQQ [2] (iirc black/red/pinto beans are also a fair source, plus theyve various antioxidants)
• CoQ10 [3]
• lipoic acid [4]

 

endoplasmic stress also plays a role in most psychiatric conditions, but as to how much it is involved, the literature is more of a maze (literally! btw these references are not to dietary quantities)

• luteolin [1]
• quercetin [2]
• rutin [3]
• genistein [ad addendum, study 3 actually refs all six]
• daidzein
• biochanin A

Edited by gamesguru, 02 April 2016 - 05:27 PM.