149 replies to this topic

[YOLF]

Have you been genotyped with 23andMe? I'd like to take a look and see what you mean by speed mode... You can cut off adrenaline output with several things, or increase receptor competitors that are also anxiolytics.

 

 

  .  I believe I have too many crf1 receptors/activation in the brain and this is causing my anxiety and increasing ACTH. I have an appointment with my doc in like 3 weeks. is it possible to test ACTH levels? Is it possible to measure CRH?,is it true you cant test for crf1? 

This is all just speculations based on my SNPS/genes and various drugs ive tested.

 

Well dont have to nessicary kill it off 100% but just balance it . is there a video of these interviews?

 

 

and my grammar is horrible becuase of this .. im in a constant speed mode .. this all relates to CRF activation..

 

Have you ever taken protein with added BCAAs? Lots of other GH releasers.

 

growth hormone

https://www.ncbi.nlm...pubmed/16912060

 

St John's wort

https://www.ncbi.nlm...pubmed/11526469

 

 

Of Astressin-B:

 

 

In 2011, research showed that treatment with astressin-B caused the sudden growth of hair in mice bred for a propensity for stress.

 

That's pretty cool, the product also has copper containing peptides. Have you tried it? It would seem that it could address a variety of aging issues and depending on what Astressin-B peptide is, it could even reach circulation when applied topically like other hair treatments. I'm guessing that even if you're wrong, this one would be a useful purchase.

Edited by YOLF, 06 June 2018 - 04:49 AM.

[kurdishfella]

Have you been genotyped with 23andMe? I'd like to take a look and see what you mean by speed mode... You can cut off adrenaline output with several things, or increase receptor competitors that are also anxiolytics.

 

 

 

Have you ever taken protein with added BCAAs? Lots of other GH releasers.

 

 

Of Astressin-B:

 

That's pretty cool, the product also has copper containing peptides. Have you tried it? It would seem that it could address a variety of aging issues and depending on what Astressin-B peptide is, it could even reach circulation when applied topically like other hair treatments. I'm guessing that even if you're wrong, this one would be a useful purchase.

yes ive used 23andme. i ran it trough a site and it says I have mutation in my CRF1 gene which I have no idea what they are.

CRHR1-IT1 (CRHR1 intronic transcript 1) & MGC57346-CRHR1 2.35. All the info I have is they are both  associated with Corticobasal Degeneration®. It is reported to increased association with Corticobasal degeneration. Does that mean lower CRF1 activity? Anyway I suspect I have excess CRF1 levels due to a tumor that secrets it.

https://www.longecit...ve-crh-or-acth/

 

Astressin B blocks CRH I tried to order it but not allowed where I live for some reason.

I doubt it will get absorbed tho..

 

yes I have taken protein with BCAA , why?

[YOLF]

You mentioned GH, I was wondering how the BCAAs affected your 'speed mode.' I've skimmed the study now though... it'll need more attention.

[kurdishfella]

I think bcaa helped a little with my  headache other than that I don´t think I noticed anything else.

[kurdishfella]

pregnenolone decreases CRH by converting to progesterone which then converts to 5α-DHP then allpregnenolone which is how it inhibits CRH.

 

There is a guy that sells plain 5α-DHP on Raypeat gonna try it out. This has to be the best way to inhibit crh.

 

[YOLF]

They make progesterone creams for women. Application on sensitive areas will make it to the bloodstream in sufficient quantities.

 

It looks like progesterone was also used once upon a time as a partially effective hair loss treatment. I image there are combination therapies that could rival finasteride.

[kurdishfella]

whats the difference between the 50:1 extract and  the dry powdered ginkgo?

[kurdishfella]

 sulforaphane increases the expression of the enzyme 3alpha-HSD which is responsible for converting DHP into allopregnanolone (GABA-A modulator, inhibits CRF release)

 

 

https://www.ncbi.nlm...pubmed/26923074

[kurdishfella]

Hi, probably last update, this is the best combo I have ever had for my social anxiety:

 

1. 5A-DHP: Precursor to allopregnanolone which increases GABA-A & indirectly inhibits CRH. (5mg-10mg dosage day)

 

2. St. John's Wort: Lots of fake stuff out there, a real brand I found is Gaia Herbs, I take 3 capsules a day.

Takes 8 weeks for full effect, but decreases CRH activity. Possible to decrease to 2 capsules a day.

 

3. Ginkgo Biloba: Again, find a good brand, slows down the secretion of CRH but high dosage needed (1 gram a day or depends on

the person).

 

thats it, rest of the CRH blockers I posted here are weak or don't work. If anyone has any suggestions for a CRH antagonist not 

mentioned yet i'm all ears.

[Hyperflux]

What are the nootropic and hormonal benefits of 5a-DHP? There's a 36 page thread on Ray Peat forums.

[kurdishfella]

https://en.wikipedia...ogical_function

 

 

Allopregnanolone possesses a wide variety of effects, including, in no particular order, antidepressant, anxiolytic, stress-reducing, rewarding,^[21] prosocial,^[22] antiaggressive,^[23]prosexual,^[22] sedative, pro-sleep,^[24] cognitive and memory-impairing, analgesic,^[25] anesthetic, anticonvulsant, neuroprotective, and neurogenic effects.^[2]

Increased levels of allopregnanolone can produce paradoxical effects, including negative mood, anxiety, irritability, and aggression.^[29][30][31] 

5a-dhp main effects come from this, 5a-dhp on its own I don't think it does much.

Edited by farshad, 24 June 2018 - 11:21 PM.

[kurdishfella]

dunno if NAG inhibits  crh but helps a little with my anxiety.

[kurdishfella]

are ginkgo biloba faked a lot? Im taking capsules now but before I took  a powder with juice, but the capsules doesen'´t seem to be working..is powder absorbed different/better?

[Hyperflux]

So that's why it's used as a first-line treatment for PFS?

[kurdishfella]

1g+ ginkgo biloba didn't work but 2g+(20 capsules) did ..... too many capsules and expensive to take everyday.. gonna skip ginkgo biloba.

Edited by farshad, 26 June 2018 - 07:47 AM.

[kurdishfella]

it is the hypericin content not Hyperforin that decreases CRH: https://www.ncbi.nlm.nih.gov/pubmed/12865894

Edited by farshad, 06 July 2018 - 05:59 PM.

[kurdishfella]

GABA receptors are significantly involved in fear memory and fear conditioning.

GABA receptors regulate a stress response hormone (corticotropin) when GABA receptors are excited

GABA (GABA-A? OR B?) is the main inhibitory neurotransmitter in the brain, meaning that it prevents our neurons from over-firing and being over-stimulated. 

 

 

[kurdishfella]

picamilon should inhibit crh

[kurdishfella]

GABA and Cortisol  (good read)

https://www.drlam.co...out-gaba/15864/

 

Btw I think fasting increases GABA which would lower crh.

Edited by farshad, 16 July 2018 - 02:09 PM.

[kurdishfella]

to my surprise, GABA-B doesen't inhibit CRH release, only GABA-A does.

GABA-A Indirectly supress the amygdala, which in turn prevents the release of CRF: 

I know GABA-A and GABA-B are receptors of GABA, so on its own does GABA have any function or is it just there to activate the two receptors?

[kurdishfella]

so I have figured out my situation a little more.. as Ive been saying I have increased CRF1 activity (not CRH OR CRH2) , cause at the moment : unknown but refer to my other post to see some possible causes: https://www.longecit...th/#entry854058 #post 15

may update later if I find other possible causes.

 

Anxiety is more affected by GABA-a agonism than CRH antagonism. CRH antagonism have more effect on how well you handle stress.

Now my plan was to take 5a-dhp a precursor to allopregnanolone  potent modulator of GABA-A, BUT... it will not decrease the CRF1 activity it will only inhibit its release and help with anxiety. But it will not help me handle anxiety better. So I need a CRF1 Antagonist.......... IE antalarmin (dunno where to get these)

 

second, Ginkgo biloba has been shown to reduce CRH , so this could possible slow down my CRF1 activity, only problem is I dont know if it is CRH only or CRF1 too. study says only CRH.

https://www.gaiaherb.../32/Ginkgo-Leaf

 

third: st johns worth has been shown to reduce CRH by 20% after 8 weeks, again studies only mention CRH not CRF1 so dunno if that will help either.

https://www.gaiaherb.../St.-Johns-Wort

 

Edited by farshad, 30 July 2018 - 11:42 PM.

[kurdishfella]

HDAC inhibitors downregulate CRH expression.

 

Transcription of the CRH gene requires recruitment from histone deacetylace 4 (source). Therefore, substances that inhibit histone deacetylace 4 (sodium butyrate and thymoquinone from black seed oil/nigella sativa  both do) should decrease transcription of the CRH gene.

studies have shown the HDAC inhibitor valproic acid (depakote) can decrease CRF1 binding in the amygdala and hypothalamus.

 

https://imgur.com/8I1q3gf

 

HDAC inhibitiors:

 

Vorinostat

Curcumin

tacedinaline

gamma-hydroxy-butyrate (GHB)

beta-hydroxy-butyrate (BHB)

Cl-994

Crebinostat

phenibut

egcg

granny smith green apples affect gut butyrate which may act as hdac inhibitor.

RG2833

trichostatin A

pterostilbene

resveratrol

Parmesan cheese 

butter

Bacopa

Metformin

Berberine

Indole-3-carbinol

L-Carnitine

sulforaphane

Apple cider vinegar

 

 

 

 

[kurdishfella]

ok heres the ultimate fear extinction stack ive come up with lemme know your thoughts:

 

tribulus - possible reduce crh

st johns worth - reduce crh by 20%

ginkgo biloba - slows down crh secretion

 

memantine - alpha  7 antagonist (alpha 7 nicotinic receptor controls amygdala activity but memantine is weak need a stronger one but it has a long half life) alternative BNC-210 or somth if you can get it.

5a-dhp / progesterone / pregnenolone - precursor to allopregnenolone potent modulator of gaba-a which inhibits crh

Vorinostat/ black seed oil/sodium butyrate etc - HDAC inhibitors decrease fear a lot

valproic acid (depakote) - decrease CRF1 binding in the amygdala and hypothalamus.

marijuana or synthetic cb1 drugs -CB1 agonists decrease anxiety

Antalarmin or Pexacerfont or astressin b - Antagonist on CRF1 and CRH(ie both crf1/crf2)

 

[kurdishfella]

Valproate (depakote) decreased CRH release in rats, whereas lamotrigine stabilized ACTH/cortisol secretion. Moreover, felbamate was found to inhibit stress-induced corticosterone release in mice. Interestingly, recent data suggest that felbamat and some other new antiepileptic drugs may inhibit transcriptional activity of glucocorticoid receptors. Summing up, the above data suggest that traditional antiepileptic drugs may cause endocrine disturbances, especially in gonadal hormones.

 

Carbamazepine (CBZ) is a widely used therapeutic agent in seizure, pain, and mood disorders. Although CBZ has been shown to inhibit hypothalamic CRH ...

 

 

they  are HDAC inhibitors too.

 

I wanna try these 3:

 

valproate 

lamotrigine

carbamazepine

 

Edited by farshad, 02 August 2018 - 04:09 PM.

[kurdishfella]

i wonder would wellbutrin + memantine together potently block alpha niconic receptor 7? both are antagonists on that but weak especially wellbutrin.

[kurdishfella]

Allpha-7's (α7-Containing nicotinic acetylcholine receptors) are located on the interneurons of the basolateral amygdala, which controls and regulates how hyphy your neuro-network is going to be for the moment,   also   Notch receptors, trkB and trkC receptors, and androgen receptors; and any ligand that stimulates the dorsolateral prefrontal cortex will decrease activity in the amygdala. 

[kurdishfella]

Local repeated corticotropin-releasing factor infusion exacerbates anxiety- and fear-related behavior: differential involvement of the basolateral amygdala and medial prefrontal cortex.

https://www.ncbi.nlm...pubmed/21093544

 

Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects

https://www.journalo...0070-0/abstract

 

 

in terms of anxiety, the central factor regulating that axis, CRH, seems to increase anxiety via acting at the amygdala and BNST. 

[kurdishfella]

Clonidine, Cabergoline, Raloxifene inhibit HPA axis, leading to lowered CRH and ACTH.

CRH/ACTH inhibitors

Serotonin antagonists: cyproheptadine, ketanserin, ritanserin, metergoline

Dopaminergic agonists: bromocriptine, cabergoline Catecholamine depletors: reserpine GABAergic agents: valproic acid

Somatostatin analogues: octreotide, lanreotide, pasireotide Peroxisome proliferator-activated receptor (PPAR-c) agonists: pioglitazone, rosiglitazone

Steroid synthesis inhibitors Single enzyme inhibitors: metyrapone, trilostane Multiple enzyme inhibitors: mitotane, aminoglutethimide, ketoconazole, fluconazole, etomidate

Glucocorticoid receptor antagonists Mifepristone (RU486)

You want to read this:

Drugs and HPA axis (2008)

Pharmacological modulation of HPA axis in depression - new avenues for potential therapeutic benefits (2013)

 

 

?prednisolone?

 

 

more hdac inhibitors

https://en.wikipedia...ylase_inhibitor

Edited by farshad, 04 August 2018 - 03:57 PM.

[kurdishfella]

does lithium decrease CRH?

 

''Lithium administration decreased CRF(1) mRNA expression in both the amygdala and frontal cortex''

 

https://www.ncbi.nlm...pubmed/12606697

[kurdishfella]

Alprazolam(xanax), a benzodiazepine derivative, stimulates specific gamma-aminobutyric acidA receptors and has been found to inhibit CRH activity in the brain.

 

In this patient, the acute drop in serum cortisol might be due to overdose of clonazepam that can inhibit CRH

 

+ more benzos possibly

Edited by farshad, 09 August 2018 - 08:57 AM.