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What are some CRF1 antagonists?

crf1

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#1 farshad

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Posted 24 March 2018 - 07:17 PM


Corticotropin-releasing factor (CRF), also known as Corticotropin-releasing hormone, is an endogenous peptide hormone released in response to various triggers such as chronic stress . This, then, triggers the release of corticotropin (ACTH), another hormone involved in the physiological response to stress. Chronic release of CRF and ACTH is believed to be directly or indirectly involved in many of the harmful physiological effects of chronic stress.

 

So I wonder why there are no CRF1 antagonists widely in use for anxiety? Why are doctors not prescribing the good stuff??

 

list of CRF1 Antagonists:

 

Antalarmin 

Pexacerfont

CP-154,526

Verucerfont 

Emicerfont 

 

 

CRH antagonist (both CRF1/CRF2) can buy on Amazon:

 

Astressin-B 

 

-------------------------------------

 

Miconazole  is an antagonist of the glucocorticoid receptor- can get on Amazon too- Dont know if this will reduce CRH activity or not.

 

 

olanzapine (zyprexa) inhibit stimulated CRH release from the hippocampus

 

 

 


Edited by farshad, 24 March 2018 - 07:18 PM.


#2 farshad

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Posted 24 March 2018 - 09:20 PM

apparantly Alcohol  has some effect on the CRH...



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#3 tunt01

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Posted 24 March 2018 - 11:31 PM

Doctors are not prescribing drugs like antalarmin because they have not made it through clinical trials and are not FDA approved.  I've personally met with scientists investigating some of these drugs and interviewed them.  There are some huge downsides to basically killing off cortisol signaling internally.



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#4 tunt01

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Posted 25 March 2018 - 12:50 AM

What cortisol tests have you done and what gives you reason to believe that cortisol is your problem?



#5 farshad

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Posted 25 March 2018 - 01:06 AM

  .  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.

 

Doctors are not prescribing drugs like antalarmin because they have not made it through clinical trials and are not FDA approved.  I've personally met with scientists investigating some of these drugs and interviewed them.  There are some huge downsides to basically killing off cortisol signaling internally.

 

 

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..


Edited by farshad, 25 March 2018 - 01:07 AM.


#6 farshad

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Posted 25 March 2018 - 03:27 AM

Ginkgo Biloba may slow down the secretion of corticotropin releasing hormone (CRH) by the hypothalamus that directs the production of cortisol by the adrenal gland, though take it lightly as it is an animal study with chronic administration of Ginkgo Biloba;

Effect of chronic administration of Ginkgo biloba extract or Ginkgolide on the hypothalamic-pituitary-adrenal axis in the rat; Life Sci. 1998;62(25):2329-40.
Marcilhac A, Dakine N, Bourhim N, Guillaume V, Grino M, Drieu K, Oliver C.
[...]Chronic i.p. injection of Ginkgolide B reduced basal corticosterone secretion without alteration in the subsequent CRH and AVP increase. However, the stimulation of CRH gene expression by insulin-induced hypoglycemia was attenuated by Ginkgolide B. These data confirm that the administration of EGb 761 and Ginkgolide B reduces corticosterone secretion. In addition, these substances act also at the hypothalamic level and are able to reduce CRH expression and secretion.[...]

#7 tunt01

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Posted 25 March 2018 - 03:40 AM

  .  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.

 

Doctors are not prescribing drugs like antalarmin because they have not made it through clinical trials and are not FDA approved.  I've personally met with scientists investigating some of these drugs and interviewed them.  There are some huge downsides to basically killing off cortisol signaling internally.

 

 

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..

 

This is a bunch of confused nonsense.  Even if you had 'too many CRF1 receptors', the feedback mechanism in cortisol would shut down secretion.  Unless you have serious hypertension/insulin resistance and persistent cortisol release, you don't have a cortisol problem.  You'd have to have like a benign tumor or something more serious.

 

Doctors do not measure CRH and even ACTH may not be worth even looking at.

 

You don't have a cortisol problem.  Stop "speculating".


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#8 farshad

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Posted 26 March 2018 - 01:27 AM

 

  .  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.

 

Doctors are not prescribing drugs like antalarmin because they have not made it through clinical trials and are not FDA approved.  I've personally met with scientists investigating some of these drugs and interviewed them.  There are some huge downsides to basically killing off cortisol signaling internally.

 

 

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..

 

This is a bunch of confused nonsense.  Even if you had 'too many CRF1 receptors', the feedback mechanism in cortisol would shut down secretion.  Unless you have serious hypertension/insulin resistance and persistent cortisol release, you don't have a cortisol problem.  You'd have to have like a benign tumor or something more serious.

 

Doctors do not measure CRH and even ACTH may not be worth even looking at.

 

You don't have a cortisol problem.  Stop "speculating".

 

hmm Maybe I do have an benign tumour... Where would the benign tumour be located   to cause an overactive CRH system? like where are the CRH located in the brain? Becuase I felt worse as  I grew up... meaning more cells in my brain built up-


Edited by farshad, 26 March 2018 - 01:28 AM.

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#9 farshad

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Posted 27 March 2018 - 10:50 PM

what are some drugs  that have studies showing them inhibit CRH?



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#10 farshad

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Posted 07 May 2018 - 11:43 PM

magnesium inhibits crh 



#11 farshad

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Posted 12 May 2018 - 04:16 PM

Anyone know of any stuff that inihibts CRH, CRF1,CRF2 etc ?



#12 farshad

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Posted 12 May 2018 - 07:54 PM

polygala extract reduced crh, acth, and Cort in the stressed rodents



#13 farshad

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Posted 13 May 2018 - 01:22 AM

Tribulus – Lowers CRH and cortisol 



#14 farshad

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Posted 15 May 2018 - 03:17 AM

growth hormone

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

 

St John's wort

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

 

 



#15 farshad

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Posted 17 May 2018 - 05:42 AM

heres a list of things that decrease CRF1 https://www.selfdeco...o-decrease-gene & https://www.selfdeco...o-decrease-gene


Edited by farshad, 17 May 2018 - 05:43 AM.


#16 farshad

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Posted 17 May 2018 - 11:19 PM

Schisandra chinensis and Rhodiola rosea 

 

The aim of the present study was to investigate the effects of Schisandra chinensis (S. chinensis) and Rhodiola rosea (R. rosea) on rats subjected to 5 h of stress,  Rats were distributed into four groups: S. chinensis (n=12), R. rosea (n=10), stress control (n=10) and quiet control (n=8). The results indicated that S. chinensis and R. rosea markedly decreased the stress-induced elevation of CRH and peripheral CORT levels. 



#17 farshad

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Posted 17 May 2018 - 11:44 PM

  • Curcumin inhibited the glucocorticoid receptor’s ability to change cellular production in a human cell study (R).

 

Glucocorticoid Receptor Activation Decreases the Expression of: CRH: human corticotropin-releasing hormone ®

 

  • Dexamethasone (a synthetic glucocorticoid/steroid medication) has a high affinity for glucocorticoid receptors (R)
  • Selective glucocorticoid receptor agonists and modulators (SEGRAM) are experimental drugs that trigger certain glucocorticoid receptor mechanisms. However, they are still in development and not much information is known (R)
  • Antidepressants, like clomipramineamitriptylineparoxetine, etc., enhance glucocorticoid receptor function in cell studies, especially in combination with dexamethasone (R)

Edited by farshad, 17 May 2018 - 11:48 PM.


#18 farshad

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Posted 18 May 2018 - 08:25 AM

Progesterone and Pregnenolone decrease CRH.

 

GHB too.

 

Licorice increases cortisol which should inhibit CRH.


Edited by farshad, 18 May 2018 - 08:30 AM.


#19 farshad

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Posted 18 May 2018 - 07:34 PM

fluoxetine ( Prozac) decreases CRH https://www.ncbi.nlm...pubmed/12865894


Edited by farshad, 18 May 2018 - 07:35 PM.


#20 farshad

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Posted 20 May 2018 - 11:56 AM

whats the difference between hippocampus and hypothalamus? zyprexa inihibt crh release from the hippocampus but CRH is created in the hypothalamus so would inhibiting the CRH in hippocampus even help? how are the 2 connected.



#21 farshad

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Posted 22 May 2018 - 05:46 PM

A Corticotropin-Releasing Hormone Antagonist (CRH antagonist) is a specific type of receptor antagonist that blocks the receptor sites for Corticotropin-releasing hormone (also known as Corticotropin-releasing factor (CRF)), which synchronizes the behavioral, endocrine, autonomic, and immune responses to stress by controlling the hypothalamic-pituitary-adrenal axis (HPA Axis).[1] CRH Antagonists thereby block the consequent secretions of ACTH and cortisol due to stress, among other effects.
 
 
There are four subtypes of the CRH receptor known at present, defined as CRF-1, CRF-2a, CRF-2b, and CRF-2g. Three of these receptors are expressed only in the brain: CRF-1 in the cortex and cerebrum, CRF-2a in the lateral septum and hypothalamus, and CRF-2g in the amygdala. CRF-2b is expressed in the choroid plexus and cerebral arterioles in the brain, but is expressed mainly peripherally on the heart and skeletal muscle tissue.[2] Extensive research has shown that overactivity in the brain CRF-CRF1 signaling system contributes to the onset of anxiety disorders and depression. It's been hypothesized that patients with clinical conditions that are causally related to HPA hyperactivity, including major depression and post-traumatic stress disorders, may benefit from CRH receptor antagonist treatment. CRH antagonists are believed to work by blocking the consequent secretions of ACTH and cortisol that occur following activation of CRH and lowering the stress-induced rise of CRH in CSF. There is increased clinical interest in CRH receptor antagonists that can cross the blood-brain barrier for the treatment of depression and anxiety, along with other conditions related to HPA hyperactivity, including treatment of irritable bowel syndrome, which is exasperated by stress.[3][4]
 
 
CRH is produced by parvocellular neuroendocrine cells within the paraventricular nucleus of the hypothalamus and is released at the median eminence from neurosecretory terminals of these neurons into the primary capillary plexus of the hypothalamo-hypophyseal portal system. The portal system carries the CRH to the anterior lobe of the pituitary, where it stimulates corticotropes to secrete adrenocorticotropic hormone (ACTH) and other biologically-active substances (β-endorphin). ACTH stimulates the synthesis of cortisol, glucocorticoids, mineralocorticoids and DHEA.[7]
 
In the short term, CRH can suppress appetite, increase subjective feelings of anxiety, and perform other functions like boosting attention. Although the distal action of CRH is immunosuppression via the action of cortisol, CRH itself can actually heighten inflammation, a process being investigated in multiple sclerosis research.[8]
 
The CRHR1 gene is alternatively spliced into a series of variants.[8][11] These variants are generated through deletion of one of the 14 exons, which in some cases causes a frame-shift in the open reading frame, and encode corresponding isoforms of CRF1.[8][10] Though these isoforms have not been identified in native tissues, the mutations of the splice variants of mRNA suggest the existence of alternate CRF receptors, with differences in intracellular loops or deletions in N-terminus or transmembrane domains.[10] Such structural changes suggest that the alternate CRF1 receptors have different degrees of capacity and efficiency in binding CRF and its agonists.[8][10][11] Though the functions of these CRF1 receptors is yet unknown, they are suspected to be biologically significant.[10]
 
 
 
CRF1 is expressed widely throughout both the central and peripheral nervous systems.[10] In the central nervous system, CRF1 is particularly found in the cortex, cerebellum, amygdala, hippocampus, olfactory bulb, ventral tegmental area, brainstem areas, and pituitary.[8][9][12] In the pituitary, CRF1 stimulation triggers the activation of the POMC gene, which in turn causes the release of ACTH and β-endorphins from the anterior pituitary.[8] In the peripheral nervous system, CRF1 is expressed at low levels in a wide variety of tissues, including the skin, spleen, heart, liver, adipose tissue, placenta, ovary, testis, and adrenal gland.[8][9][11]
 
In CRF1 knockout mice, and mice treated with a CRF1 antagonist, there is a decrease in anxious behavior and a blunted stress response, suggesting that CRF1 mechanisms are anxiogenic.[8][12] However, the effect of CRF1appears to be regionally specific and cell-type specific, likely due to the wide variety of cascades and signaling pathways activated by the binding of CRF or CRF-agonists.[12] In the central nervous system, CRF1 activation mediates fear learning and consolidation in the extended amygdala, stress-related modulation of memory formation in the hippocampus, and brainstem regulation of arousal.[12]
 
The corticotropin-releasing hormone receptor binds corticotropin-releasing hormone, a potent mediator of endocrine, autonomic, behavioral, and immune responses to stress.[13]
 
CRF1 receptors in mice mediate ethanol enhancement of GABAergic synaptic transmission.[14]
 
Variations in the CRHR1 gene is associated with enhanced response to inhaled corticosteroid therapy in asthma.[16]
 
CRF1 triggers cells to release hormones that are linked to stress and anxiety [original reference missing].Hence CRF1 receptor antagonists are being actively studied as possible treatments for depression and anxiety.[17][18]
 
Variations in CRHR1 are associated with persistent pulmonary hypertension of the newborn.[19]
 
Corticotropin-releasing hormone receptors (CRHRs), also known as corticotropin-releasing factor receptors (CRFRs) are a G protein-coupled receptor family that binds corticotropin-releasing hormone (CRH).[1] There are two receptors in the family, designated as type 1 and 2, each encoded by a separate gene (CRHR1 and CRHR2 respectively).
 
 
CRHRs are important mediators in the stress response.[2] Cells in the anterior lobe of the pituitary gland known as corticotropes express the receptors and will secrete adrenocorticotropic hormone (ACTH) when stimulated. This binding of corticotropin releasing-hormone (CRH) activates the hypothalamic-pituitary-adrenal (HPA) axis, one of the two parts of the fight-or-flight response to stress.[3] CRHRs are also present in other brain areas such as the amygdala, locus coeruleus and hippocampus. Within the hippocampus, the CRHR1s are most abundant, residing mainly on the pyramidal cells of CA1 and CA3. Chronic activation of CRHR1s by CRH induced by early life stress has been shown to underlie memory deficits and learning impairments and anxiety in adulthood.[citation needed]
 
 
 
 
 
 
 
 
 
 
 

 


Edited by farshad, 22 May 2018 - 06:17 PM.

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#22 farshad

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Posted 23 May 2018 - 11:58 AM

dexamethasone inhibits CRH.

 

probiotics - https://www.ncbi.nlm...les/PMC2095678/

 

 

Increasing ACTH will increase cortisol which will inhibit CRH? (correct me if i am wrong):

 

Stimulants (Caffeine (R),  Nicotine (via Acetylcholine…Increases ADH, ACTH, Cortisol) (R), Yohimbine (R), etc..)

 

https://www.selfhack...tisol-low-high/

 

https://www.selfhack...e-role-of-crh/ 

 

https://www.selfhack...tress-response/

 

https://www.selfhack...ation-baldness/

 

https://www.selfhack...tisol-low-high/

 

https://www.selfhack...backed-science/

 

https://www.selfhack...effects-stress/

 

https://www.selfhack...icoid-receptor/

 

https://www.selfhack...-to-break-down/

 


Edited by farshad, 23 May 2018 - 12:32 PM.


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#23 farshad

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Posted 23 May 2018 - 07:05 PM

GABA inhibits CRH.

 

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

 

alpha lipoic acid https://www.ncbi.nlm...pubmed/20423821

 



#24 farshad

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Posted 31 May 2018 - 11:38 AM

1. Polygala tenuifolia  (Have yet to try)
2. St John's wort   (takes long  for full effect) >(not recommended)
3. alpha lipoic acid (short effect)  
4. Ginkgo Biloba (chronic high dosage needed)
5. tribulus (effect is very subtle) > (not recommended)

Edited by farshad, 31 May 2018 - 11:38 AM.


#25 farshad

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Posted 01 June 2018 - 04:51 PM

 NVM ST JOHNS WORT IS STARTING TO WORK VERY GOOD... ONLY Day 4 (now recommended)

 

btw heres the source for tribulus lowering crh https://www.ncbi.nlm...pubmed/23789222

 

polygala tenuifolia review coming soon.


Edited by farshad, 01 June 2018 - 04:58 PM.


#26 farshad

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Posted 02 June 2018 - 12:59 PM

 Im wondering are there any diseases that can make you have too much CRH (cortisol releasing hormone)? I think my anxiety is caused my too much CRH but someone said that is unlikely becuase there is a feedback loop if there is too much CRH then cortisol will be increased which will shut down CRH release. But I started looking up and I found a rare case of Cushings syndrome, rare case of CRH-secreting tumors (without ACTH secretion) have been reported, which stimulates pituitary ACTH production. There is like 15 reports of CRH tumor very rare.
So this would be the only plausible explanation for which there is too much CRH that there is not enough cortisol that would be able to inhibit it. A tumor that secrets CRH. 
 
If we look at this picture: https://bengreenfiel...._HPA_Axis.jpeg
 
If there is a CRH tumor that would mean it releases CRH 24/7, which would be impossible for the cortisol to inhibit becuase CRH would make you in a constant fight/flight mode and your anxiety would just get worse and worse and eventually the ACTH would go down becuase the anxiety would be so much the pituitary would give up. The cortisol would just stay high. But the CRH would still keep being released. Any experts here that can explain to me more about this CRH-secreting tumor? Im just trying to learn more about this CRH stuff. 
 
I read this SelfHacked article and everything fits how I feel: https://www.selfhack....e-role-of-crh/
the article also mentions there is In Hashimotos and UC(Ulcerative colitis?), inflamed tissues contained large amounts of CRH.
Im gonna have an full body MRI soon. I had a Brain scan Only and it was fine but im thinking the tumor is somewhere else.
 
What else can cause so much CRH that your body can not handle? just a tumor? 
 
Also Is it more plausible to have a CRH or CRF1 secreting tumor? Is the second even possible? CRH is a peptide hormone and CRF1 is a protein.. have not seen any study with CRF1 secreting tumor just CRH.


#27 farshad

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Posted 02 June 2018 - 10:24 PM

Nobody knows of any other CRH-Inhibitors that have not been mentioned yet?



#28 farshad

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Posted 03 June 2018 - 03:13 AM

Adrenal glandular has cortisol and Grapefruit Juice increase cortisol, which inhibits CRH, the first part of the stress response. Cortisol inhibits CRH but not neuronal excitation .


#29 farshad

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Posted 03 June 2018 - 01:48 PM

studies have shown that supplemental phosphatidylserine reduces anxiety measures by reducing CRH and blunting cortisol levels.18,19

 

 

The amygdala, a key component of the limbic system, is activated by fear. This activation causes increased levels of serotonin and sympathetic nervous activity, with resultant increases in norepinephrine and serotonin. In a feed-forward loop, elevations of these neurotransmitters further activate the amygdala and contribute to feelings of anxiety. This situation is aggravated in the context of dopamine deficiency, which exerts a counter-regulatory effect on serotonin. On the other hand, oxytocin quiets amygdalar activation, and reduced oxytocin has been linked to a worsening of anxiety issues.6 A therapeutic goal with GAD is, therefore, to increase oxytocin.7

Oxytocin is decreased under the influence of elevated corticotrophin-releasing hormone (CRH). In turn, hyperactivity of the amygdala potentiates hypothalamic release of CRH. Elevated CRH, itself, is highly implicated in anxiety.8 When both CRH and serotonin are high, the HPA axis’ dynamic responsiveness to stress is restrained. Chronically, this restraint leads to unchanging cortisol, which results in decreased sensitivity of the pituitary and hypothalamus to negative feedback from cortisol. This, in turn, leads to sustained elevation of CRH and aggravation of anxiety.



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#30 farshad

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Posted 04 June 2018 - 01:19 PM

carnitine has some effect  https://www.ncbi.nlm...pubmed/29346768

Cordyceps ? https://www.scienced...02194981630182X

 

Forgot everything iv'e said only   Ginkgo Biloba very high dosage worked so far. 

polygala tenuifolia yet to try.

Edited by farshad, 04 June 2018 - 01:42 PM.






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