Finities-infinities intro. Very strong enormous anhedonia.

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finities infinities
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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I have blood test ( next will be next 2 week or later):
Prolactin: 4,54 3,46-19,4 range
SHBG: 43,0 13,5-71,4 range
LH: 2,93 0,57-12,07 range
finities infinities
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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UPDATE:
I haven't been to this thread for a long time. But the situation seems to be clearer and clearer to me. I know my problem is reversible, the problem is that there is a problem with access to drugs ( WAY 100 135).
1.I'm currently in the care of a good neurologist who, after seeing my MRI, found a small arachnoid cyst in my left insula. He said it might stimulate my insula. Today I was to do another MRI. To see the current position of the arachnoid cysts, and perhaps I will be qualified for removal. And he mention that my epilepsy attack is from left insula.
2.I have extreme high histamine release ( severe DAO deficiency) which produce strong histamine release after food. Histamine very strong stimulate my NMDA receptor which are upregulated by CBZ and antipsychotic drugs and produce seizure attack and very worsened my all symptoms. My PSSD and CBZ PAWS are reversible, but only if I manage to get WAY 100 135 and evodiamine.

3. My PSSD post-amisulpride/mianserin symptoms very improve after 5ht1a presynaptic agonist and 5ht depletion ( buspirone, lamotrigine and fenclonine) and severe and persist detoriation after quit this drug.
I had new probe mianserin ( my PSSD induce drug) month ago. I took mianserin and I heard interesting action: acute mianserin activate presynaptic 5ht1a and reduce serotonin tone, but in very short time, few hours later my presynaptic ( and postsynaptic probably also!) receptor are strong desensitized and worsen my overempathy morality disgust feeling ( 5ht7 antagonist desensitize 5ht1a autoreceptors). Mianserin block all 5ht receptor, without 5ht1a and redirect serotonin stream to this and quickly desensitize ( alha 2 antagonist effect also potentiate serotonin flood). 5ht2a serotonin receptor is another similar pro-oxytocin receptor to 5ht1a, mianserin antagonise this and downregulate. This both receptor internalisation ( 5ht2a/5ht1a) and totally loss feedback loop induce strong AR downregulation in hypothalamus and post-orgasm state, with totally loss oxytocin and mu opioid and HPA axis/AMPAr/cannabinoid function which create ,,magic normal old me world perception". ( risperidone also the same). Both drug ar 5ht7 antagonist and histamine H1 and H2 antagonist. 5ht7 receptor antagonist upregulate NMDA receptor. H1 and H2 receptor also potentiate NMDAr, blockade both upregulate this and increase glutamate even more! ( especially in my high histamine state).
4. Corticosteroid event and adenosine A1A blockade from carbamazepine and paracetamol/salvia divinorum crash- All this drug potentiat cannabinoid release and indirectly activate Cb1 receptor ( salvia is direct Cb1 agonist+D2 and KOR agonist). Carbamazepine block A1 adenosine receptor which inhibit eCb release, carbamazepine also serotonin release and activate 5ht1a, 5ht2a and 5ht2c receptor which stimulates cortisol/ACTH secretion and endocannabinoid release, carbamazepine is also NMDA antagonist, this all action very strong activate CB1 receptor and produce crash like weed crash, and strong existential terror, depersonalization from totally disinhibit fear/OCD center in my brain by internalization post-synaptic 5ht1a and Cb1 function. Corticosteroid which I took in june year ago, practically perfect mimic carbamazepine action in me and produce tragic withdrawal- the same type of carbamazepine and weed/salvia!
5.
My PSSD and CBZ PAWS are reversible, but only if I manage to get WAY 100 135 and evodiamine. ( for upregulation both 5ht1a and restore SERT which is killed in me after mianserin/amisulpride and clomipramine/escitalopram later.
Upregulation CB1 from rimonabant ( I ordered this!).
Combination od evodiamine+WAY 100 135+rimonabant should eliminate all symptoms. Does anyone know where you can get WAY 100 135 and evodiamine at human prices?
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kpavel
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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I have seen an interesting study talking about carbamazepine tolerance.
Polyamine Modulation of Anticonvulsant Drug Response: A Potential Mechanism Contributing to Pharmacoresistance in Chronic Epilepsy
https://pubmed.ncbi.nlm.nih.gov/29789377/
Interestingly it could be linked to cb1 and nmda and ht2 receptors.
Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential
https://pubmed.ncbi.nlm.nih.gov/19594762/
Spermidine prevents high glucose-induced senescence in HT-22 cells by upregulation of CB1 receptor
https://pubmed.ncbi.nlm.nih.gov/29699000/
Serotonin receptor activation inhibits sodium current and dendritic excitability in prefrontal cortex via a protein kinase C-dependent mechanism
https://pubmed.ncbi.nlm.nih.gov/12177182/
Or glutamate and ocd/anxiety/anhedonia
Blockade of the GLT-1 Transporter in the Central Nucleus of the Amygdala Induces both Anxiety and Depressive-Like Symptoms
https://pubmed.ncbi.nlm.nih.gov/25586634/
Astrocytic glutamate transporter 1 (GLT1) deficient mice exhibit repetitive behaviors
https://pubmed.ncbi.nlm.nih.gov/32950606/
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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Yes, 5ht2a has to play a role in this, especially since it reacts very badly to the 5ht2a antagonist. But I don't know whether it is through a blockade or downregulation of adjacent 5ht1a. Activation of 5ht1a and 5ht2a releases oxytocin which mediates the effects. I tried to regulate my serotonin receptors with fenclonine but got the opposite effect. Fenclonine acted similar to buspirone with a pronounced dopaminergic effect, resulting in post-quit horrible withdrawal with horrible akathisia and complete dopamine suppression. Some of the serotonin receptors are having a very bad effect on me (maybe 5ht3 and 5ht7). This serotonin receptor other than 5ht1a/2a release also big dose vasopressin.
I'm looking to see if there are any natural substances that block 5ht1a (both post and presynaptic) but I can't find anything. Cannabigerol is also a strong alpha2 agonist which disqualifies it.
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kpavel
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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This state is totally ,,recovered" in summer 2017 when my Doctor increase carbamazepne dose from 400 mg to 800 mg. This removed SSRIS and increase dose carbamazepine totally recovered my all bad symptomss and weak PSSD- feminine-oversensitive symptoms from clomipramine. My orgasm is like fantastic dream in this time, I wanking everyday in this time, my PSSD not exist. I feel fantastic in this summer-early autumn 2017 time, I feel very masculine, narcissistic and happy! In this time I found a girlriend and was attractive to woman. My barriers and fears is dizinhibited. At that time I also had a serious infection, I took ciprofloxacin. Ciprofloxacin increase carbamazepine serum and increase state to ,,alcoholic" euphoria like for few days, but tolerance to carbamazepine growth and growth :cry: . After ciprofloxacin discontinuation my mood drastically lowered to ,,slighty dysphoric" my barriers and anxiety returned with.... strong decreasing my libido. I didn't know what was wrong with me so I suddenly reduced my carbamazepine dose to 300 mg in 25 october 2017. I found myself in hell. I returned to my terror state from 10 years ago in risperidone
It only confirms that I am heavily addicted to carbamazepine and my tolerance to it has increased cosmically because the 500 dose I am currently taking does not improve my symptoms.
I actually put the carbamazepine tolerance study (spermine is in the equation and helps reduce overactive sodium channels) above because of these your feelings reports. Activation of ht2 receptors (or ssri, also see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920646/) seems to block sodium channels and carbamazepine is about sodium channels. Or pilocarpine seizure action could be via Nav1.6 https://pubmed.ncbi.nlm.nih.gov/27670903/ (nr2b upregulation presents)? So if spermine can reduce sodium channels OVERACTIVATION, could these changes work like carbamazepine in the past or at least make possible carbamazepine to work again?
I find strange how you have empathy and irritability at the same time. And do you think you need to eliminate ht1a or upregulate it and why? By the way another potent oxytocin mediator I saw is CD38. It can deplete cellular energy since massively counsuming NAD+.
finities infinities
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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My excess empathy is probably related to vasopressin oversensitivity. ( high vasopressin, low oxytocin). I am really sure that without 5ht1a upregulation there is no chance of recovery. 5ht1a and CB1 are the key to sensitizing me to oxytocin + sexual improvement. CB1 decrease extracellural norepinephrine and serotonin, and release oxytocin, beta endrophin and block NMDA, 5ht1a reduce serotonin (presynaptic) and release oxytocin (postsynaptic). Acute oxytocin reduced my OCD and terror anxiety ( CBZ PAWS) in 75%.
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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i read about spermidine, is interesting, appear NMDA positive allosteric modulator. Maybe this is good for NMDA downregulation ( maybe better than D-aspartic acid which not cross blood brain barrier). This third happiness, sense of life molecules: oxytocin, beta-endorphin and endocannabinoid activates receptors which block NMDA receptors ( 5ht1a, Cb1, OT, MOR).
Tadalafil+ spermidine look interesting combo. ( because spermidine inhibit nNOS).
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kpavel
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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If you want to know which way it modulates NMDA/NR2B receptor - I honestly say I don't know, didn't really carefully read the study I gave you, in my blog there are 250 studies, most I've looked through for interesting moments and did automatic search for terms. It's too hard to understand and remember everything. But I can definitely tell you d-aspartic acid and spermidine/spermine have different action because they act on special polyamine site. Also DAA (+betahistine) made my hair really dry and thinner, this thing makes them grow better, and I suspect thicker! And I have best energy now. This is sort of motivational energy, not even hedonic but absence of 'noise'. Another interesting thing I read from one author from 80s is that spermidine has similar molecular build to antipsychotics. And agmatine for example is suggested by some author to be opposite. Another interesting thing about spermidine it is acetyl-CoA depletor, and this helps to induce autophagy. I read drugs like finasteride disrupt autophagy and stimulate apoptosis. Apoptosis in brain could result in suicidal thoughts as one research team suggests. Beta-endorphin is actually a laziness molecule, and memory problems on opioids occur, spermidine is known to help LTP, working memory. About nNOS inhibition I really don't understand why so, but spermine favors CX43 which seems to favor nNOS, so things are just not that obvious as we can think. Spermidine could be bought directly, stimulated with some probiotics, or eaten from food, wheat germ, mushrooms, green peas and liver are the easiet sources from what I found. Spermine is in meat. Anandamide is cx43 (proerectile and procognitive) inhibitor. The strongest cx43 inhibitor is horrible mefloquine, hydroxychloroquine and quinine do the same of course.
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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I ordered this, is interesting. Appear like NR2b positive allosteric modulator. This look good, because my NR2b is overactive in amygdala and produce ,,demonic anxiety. Kappa opioid activation dysphoria is mediated my NR2b expression in amygdala and hippocampus and ifeprodil block demonic eraserhead effect of kor agonist. I'm still looking for something that will regulate 5ht1a. (both types). There isn't a single molecule available, it breaks me down.
5ht1b receptors are interesting, appear inhibit oxytocin and produced behavior characteric to low oxytocin- https://pubmed.ncbi.nlm.nih.gov/27439030/ ( I think that post-synaptic 5ht1a play this role) Zolmitriptan is interesting 5ht1b agonist, but I don't know is presynaptic only or post-and presynaptic.
But this science look opposite: https://pubmed.ncbi.nlm.nih.gov/24025838/
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kpavel
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Re: Finities-infinities intro. Very strong enormous anhedonia.

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I will pay some time to nr2b and kappa connection with dysphoria, I attributed that more to orexin.

ht1b receptor inhibits many things besides oxytocin. Sumatriptan is known to cause anxiety of public speech. I suspect social anxiety disorder and autism can be chemically (and behaviourally?) opposite. If you look at studies on cd38 and oxytocin and put 'social anxiety' or 'autism' to search you will note that.

About ht1a sensitization, there are agonists like Nelumbo Nucifera, Or something said to upregulate it like Albizzia. Or it could be magnesium (magnesium and lithium are implicated in seizures btw). Or hormones: thyroid, estrogen, cortisol, (testosterone?, progesterone?).
But how ssri can do that? Just look at ht2 (maybe ht2c? that's a known stressogenic receptor, mcpp is an agonist for example) receptors signalling. Specifically PLA2/PKC. I think that is also true for isotretinoin.
https://pubmed.ncbi.nlm.nih.gov/11356925/
https://pubmed.ncbi.nlm.nih.gov/11750792/
https://pubmed.ncbi.nlm.nih.gov/8863849/
https://pubmed.ncbi.nlm.nih.gov/1860872/
So you may want to look at this. Anyway pla2 seem to make mitochondria fragile, cause it physically destroys phosphatidylcholine (Lands cycle).
I also read that diosgenin can inhibit pkc alpha and betaII.
Or https://pubmed.ncbi.nlm.nih.gov/32679011/
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