LONGECITY

I finally got my hands on some Mifepristone to try.  I've suffered from chronic fatigue induced by HPA axis dysfunction, and Mifepristone is the only thing that has helped it.  It's brought my sleep cycle down from 11 hours to 7, and I feel like I'm gradually gaining energy.  I've taken a total of 5, 200mg doses thus far.  The effects of Mifepristone were apparent on the first day and caused mild, peripheral headaches, although energy was noticeably increased.  I took it the following day and the effect wasn't nearly as pronounced.  If I take it on a weekly or a biweekly basis, the benefits are always noticeable. 

I've tried piracetam, pramiracetam, and oxiracetam, but none had any effect on chronic fatigue.  Mifepristone is nice, but at $30-$40 per pill, low dose cortisol may be just as effective and more cost effective: http://www.holtorfme...ment CFS FM.pdf

I should also add that since taking Mifepristone my appetite has adjusted nicely, and I actually have little desire for junk foods oddly enough.

I know you're not taking it for an antidepressant effect, but along with the increased energy have you noticed any mood boosting effect?

Hmm, I've definitely felt more "positive" since taking it.  I would have to say it's nothing like any sort of conventional antidepressant medication, it has no direct action on serotonin, dopamine, or norepinephrine that I am aware of.  It doesn't feel like any sort of stimulant either, and there's nothing else I can think to compare it to.  But, as the articles suggest, its mode of action is much different from any other medications currently on the market.  I would be curious to see how it compares to taking low dose cortisol, from the pdf that I linked to.

Interesting

Before you started this treatment, how did you diagnose your HPA dysfunction - Have you had any ACTH or Cortisol lab work done to confirm this? is this treatment indicated for those suffering from an high cort, low cort or both?

Mifepristone is not "officially" indicated for anything other than being an abortifacient.  But typically, for fatigue due to HPA dysfunction you are talking about insufficient cortisol levels.  Chronic fatigue is still difficult to diagnose, having many possible causes.  I had tons of lab work done showing all of my hormone levels, including cortisol, at the very bottom of the "normal" range, and it's still not well established when to prescribe low dose cortisol in chronic fatigue cases.  So after a year of expensive lab work, numerous diet and excersize changes, I took matters into my own hands. 

Wow! thank you for this thread, I've read that most of the time 200mg is too low though, most studies show taking around 800mg a day and say that is on the low end? Of course better to start low to be safe. 

From my understanding using low dose cortisol doesn't really correct the dysfunctional hpa axis. What mifepristone does is temporarily redeuces cortisol, which helps to... reset the cortisol receptors so that the body starts to respond properly to cortisol signaling. I think mifepristone helps with people that have hpa hyper or hypo activity. 

This PLOS study explains it very well: http://www.ploscompb...al.pcbi.1000273

Have you ever tried low dose cortisol? I actually have quite a bit that was prescribed to me because I thought it would help, but I didn't feel any positive effects from it. 

I should also add that since taking Mifepristone my appetite has adjusted nicely, and I actually have little desire for junk foods oddly enough.

Mifepristone acts upon insulin production and probably should affect your desired dietary intake.

 

I should also add that since taking Mifepristone my appetite has adjusted nicely, and I actually have little desire for junk foods oddly enough.

 

Mifepristone acts upon insulin production and probably should affect your desired dietary intake.

 

This really seems like an incredible property of Mifepristone.  Looking back at my long-lasting, incredible lethargy and horrible diet, I feel like I've made incredible progress in so few doses.  I still haven't taken any more of it, but my sleep time stays regulated now at around 7 hours and I have no desire to eat unless I'm actually hungry, heheh.  I've also started playing sports again, which used to be incredibly difficult to have the energy for.

The restrictions on Mifepristone are so saddening, due to its status as an abortifacient.  It seems difficult to find anything that can target the HPA axis. 

Have you ever tried low dose cortisol? I actually have quite a bit that was prescribed to me because I thought it would help, but I didn't feel any positive effects from it. 

I have never tried low dose cortisol, are you also struggling with chronic fatigue?  What have you tried so far?

 

Have you ever tried low dose cortisol? I actually have quite a bit that was prescribed to me because I thought it would help, but I didn't feel any positive effects from it. 

 

 

I have never tried low dose cortisol, are you also struggling with chronic fatigue?  What have you tried so far?

 

yeah, I do, been going on for quite some time now. I've tried all kinds of things... I just take regularly now trace mineral drops, zinc, and a b complex, the thing that helped the most was just.. eating really well and reducing stress as much as possible. Eating gluten free really helped with the fatigue, as well as just cutting out sugar and excess fats. 

yeah, I do, been going on for quite some time now. I've tried all kinds of things... I just take regularly now trace mineral drops, zinc, and a b complex, the thing that helped the most was just.. eating really well and reducing stress as much as possible. Eating gluten free really helped with the fatigue, as well as just cutting out sugar and excess fats. 

 

I believe firmly that my chronic fatigue was due to chronic, uncontrolled stress, so I maintain low stress levels now as well.  I suspect I permanently down-regulated my IGF1 levels through intermittent fasting when I was young as well.  I weigh now 140 lbs, and the fatigue particularly contributed to wasting and atrophy. 

Based on my labs my pituitary is working, just at a very low level.  I think I'll try CJC-1295 as well, in one study it restored rat pituitary to normal size in Br-M3-KO mice:

Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth.

Abstract

The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinergic pathways have been implicated in regulating somatotroph function, the physiological relevance of this effect and the localization and nature of the receptor subtypes involved in this activity remain unclear. We report the surprising observation that mutant mice that selectively lack the M(3) muscarinic acetylcholine receptor subtype in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype associated with a pronounced hypoplasia of the anterior pituitary gland and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. Remarkably, treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit displayed by Br-M3-KO mice by restoring normal pituitary size and normal serum GH and IGF-1 levels. These findings, together with results from M(3) receptor/GHRH colocalization studies and hypothalamic hormone measurements, support a model in which central (hypothalamic) M(3) receptors are required for the proper function of hypothalamic GHRH neurons. Our data reveal an unexpected and critical role for central M(3) receptors in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells.

http://www.ncbi.nlm....pubmed/19332789

This article talks about the activation of growth hormone (GH & IGF1) by CJC-1295: http://www.ncbi.nlm....pubmed/19386527

The stuff is apparently popular with body builders and more readily available online than Mifepristone.  A single dose, roughly 2mg injected, lasts for about a month and costs around $25-$40 online.  Some related GH/IGF1 substances seem to be IGF1-LR3 and GHRP-6, though I'm not sure of the efficacy of these for my purpose.  My goal would be to try to induce some permanent restoration of pituitary function using CJC-1295, GHRP-6, and/or IGF1-LR3.  It's not entirely clear to me from literature how or if this is something I can acheive.  Input from others who've studied this area would be highly appreciated. 

 

 

I should also add that since taking Mifepristone my appetite has adjusted nicely, and I actually have little desire for junk foods oddly enough.

 

Mifepristone acts upon insulin production and probably should affect your desired dietary intake.

 

 

This really seems like an incredible property of Mifepristone.  Looking back at my long-lasting, incredible lethargy and horrible diet, I feel like I've made incredible progress in so few doses.  I still haven't taken any more of it, but my sleep time stays regulated now at around 7 hours and I have no desire to eat unless I'm actually hungry, heheh.  I've also started playing sports again, which used to be incredibly difficult to have the energy for.

 

The restrictions on Mifepristone are so saddening, due to its status as an abortifacient.  It seems difficult to find anything that can target the HPA axis. 

 

This was very interesting. Are you still doing great? Was it enough with 5 daily doses of 200 mg?

I believe my own chronic fatigue may be because of HTPA dysregulation. I've been hypothyroid and running on stress hormones since birth and made things worse by low-carbing, excessive endurance training, SSRI's, too much stress etc. I'm trying licorice extract right now but considering going on low dose HC/MC. Would be neat if a short abortion pill course would suffice..

What is HC/MC?

I'm still doing just fine.  I've even started a workout regimine to try to gain some weight back, I used to weigh 155 before all the lethargy knocked me down to 140.  To clarify, the first 2 doses were consecutive days, the 3rd dose was 2 weeks later, the 4th and 5th dose were each spaced a week apart.  I'm holding off taking any more of it unless I feel I'm regressing, the stuff was expensive.  After the 4th dose I felt like I had finally overcome the 11-hour sleep cycle. 

What is HC/MC?

I'm still doing just fine.  I've even started a workout regimine to try to gain some weight back, I used to weigh 155 before all the lethargy knocked me down to 140.  To clarify, the first 2 doses were consecutive days, the 3rd dose was 2 weeks later, the 4th and 5th dose were each spaced a week apart.  I'm holding off taking any more of it unless I feel I'm regressing, the stuff was expensive.  After the 4th dose I felt like I had finally overcome the 11-hour sleep cycle. 

Hydrocortisone/mineralocorticoids.. But I probably won't get on any of that stuff, even licorice root extract makes me feel worse.

Interesting to hear your report. What made you space the doses apart that way?
Where did you buy it, if you don't mind me asking? (I'll buy any you might have left btw!  )

If someone is not able to get Mifepristone, You could alternatively try Cyproheptadine

http://www.ncbi.nlm..../pubmed/8796367

or here

http://link.springer...1007/BF01184028

1. Cyproheptadine depresses neuron function in the hypothalamic arcuate nucleus, to a degree that depends on the total dose administered.

2. Under the influence of cyproheptadine release of synthesized neurohormones from AN neurons is inhibited and this may be one mechanism of its therapeutic effect in Cushing's disease.

But it seems to damage the mitochondria of this area dose depently

http://en.wikipedia....Arcuate_nucleus

This page displayed the half of the study, so also the the results of the damage, when I´ve opened it. Curiously not anymore.

Sry I have to correct my post.

Mifepristone increases Cortisol whereas Cyproheptadine decreases it.

But seemingly decreases Corticosterone as well as Mifepristone

http://www.ncbi.nlm....v/pubmed/226103

Sry I have to correct my post.

Mifepristone increases Cortisol whereas Cyproheptadine decreases it.

But seemingly decreases Corticosterone as well as Mifepristone

http://www.ncbi.nlm....v/pubmed/226103

from my understanding mifepristone helps to... reset the hpa axis. So it can actually help with either hyper OR hypo-functioning HPA axis. So it can increase or decrease cortisol levels depending on how the hpa is being affected. 

For example it might help an overactive hpa axis in depression, to help normalize cortisol levels, but would also help an under functioning hpa axis like in CFS. 

I am suffering from non-Cushing hypercorticism. I am considering a Mifepristone treatment. Seems it could be the game changer for me.

I have read some papers, including the links here on this thread. The result from those tests and studies sound very positive and encouraging.

The basic idea is that most receptors in the body tend to react to the presence of a binding antagonist, by "upregulating" or in other words they become more sensitive to their appropriate ligands. So by blocking GR, they should restore their original sensitivity after a certain time. At least that is in theory.

There is one issue however. I have read a post from an endocrinologist on a forum. He says that blocking GR with Mifepristone always lead to some ACTH rebound effect, i.e. the HPA-axis reacts by increasing ACTH secretion. This causes further increase of Cortisol secretion, which is exactly what we are fighting against. So in theory this whole approach is a bad one. But what would explain the generally positive outcomes as in those articles ?

I believe there is one key thing in this matter. As Cortisol increases because of antagonizing GR and the according ACTH rebound, we have increased plasma Cortisol levels. The key here is - PLASMA LEVELS !!! At the same time Mifepristone blocks Cortisol from binding to the GR, thus exhibiting a certain neuroprotective effect on those precious hippocampal neurons. And in the mean time, GR are undergoing expression changes to upregulate in order to cope with the increased amount of Cortisol. It sounds plausible. If true, the only thing to worry about would be possible hypokalemia, which usually comes as a result of elevated Cortisol.

computeTHIS wrote that Mifepristone it helped him with what it appeared to be hypocorticism. But will it really help with hypercorticism ? 

This explains some mechanisms behind HPA axis regulations.

http://www.biomedcen.../9/27/figure/F1

http://www.biomedcen...1741-7015/9/27/

So perhaps Mifepristone is working via increasing the negative feedback ?

Actually I dont know whether cortisol is the messenger for negative feedback

What do you think are the future directions of research into this field?

The new directions include: (1) finding the true prevalence of the syndrome in hyperandrogenism, hypertension and other conditions in which glucocorticoid resistance could be etiologically relevant; (2) exploring the interactions of the glucocorticoid signaling system and other cellular signaling pathways and their combined effect on human pathology; (3) looking further into the New World primates for nodal molecules of multiple networks related to steroid and sterol (Vitamin D) hormone actions; (4) exploring the tissue-specific changes of the glucocorticoid signaling system resulting in behavioral pathology. Tissue-specific and conditional knock-out and transgenic animals are key in this endeavor, however, soon, with the availability of sensitive and dynamic imaging methods, it will be hopefully possible to directly examine regions of the brain in which changes of the glucocorticoid signaling system could explain manifestations such as anxiety (amygdala), depression (dopaminergic reward system), and cognitive (frontal cortex) or memory dysfunction (hippocampus).

Corlux/Korlym (aka Mifepristone) had a fast track license from the FDA and was in phase III (if I recall it correctly) clinical trials to be the first in it's kind treatment for major psychotic depression. However, I don't think it ended well, I can neither find the study data nor does it still mentioned in Corcept Therapeutics pipeline.

I don't know if someone has something about the following information but I met a women once whom had a bad case of psychotic depression (psychotic depression is one of the hardest psychotic diseases to treat and has the highest suicide rate among psychotic disorders), the only thing that helped her was Mifepristone. After she was put on Mifepristone permanently she was able to have a fulfilling life without any psychotic/depressive symptoms ever again.

I've been interested in Mifepristone for years for somewhat the same reasons as the OP (and off course in the hopes it will help against psychotic symptoms) but the price is just ridiculous high.. 

There is a little bit of hope though for people who use antipsychotics, it's in clinical trials for counteracting weight gain from AP's 

Corlux/Korlym (aka Mifepristone) had a fast track license from the FDA and was in phase III (if I recall it correctly) clinical trials to be the first in it's kind treatment for major psychotic depression. However, I don't think it ended well, I can neither find the study data nor does it still mentioned in Corcept Therapeutics pipeline.

 

I don't know if someone has something about the following information but I met a women once whom had a bad case of psychotic depression (psychotic depression is one of the hardest psychotic diseases to treat and has the highest suicide rate among psychotic disorders), the only thing that helped her was Mifepristone. After she was put on Mifepristone permanently she was able to have a fulfilling life without any psychotic/depressive symptoms ever again.

 

I've been interested in Mifepristone for years for somewhat the same reasons as the OP (and off course in the hopes it will help against psychotic symptoms) but the price is just ridiculous high.. 

 

There is a little bit of hope though for people who use antipsychotics, it's in clinical trials for counteracting weight gain from AP's 

hm? I never heard of it being a fast track drug, but I have seen read clinical trials for depression using mifepristone and there were hardly any negative side effects and only positive effects. 

According to this site, its cheap i.e. 3x 200mg for 21 pounds

http://www.pharmacy2...px?packid=70279

The reason is that pharma company has used a trick.

Its reapproved it for another indication which is usually made to prolong the patent.

I guess that they did it here to raise the price.

Actually I´m not sure whether this is possible.

For major psychotic depression it was a fast track because there's still no known effective treatment for this disease. It's also weird they changed the name from Corlux to Korlym, it was known as Corlux for years.

I don't know about your pocket Flex, 3 pills 21 pounds, that's 210 for one month treatment 

Well, it has nothing to do with the patent (it has already expired) that the price is still high, here is the answer why: there are almost no generics because the product demand is not high enough..

Thanks for the Info.

My fault, I thought a few pills would be enough.

I didnt consider that You would need it for chronic usage.

But if this is not a good option, how about an alternative ?

e.g. Danshen extract 15,16-dihydrotanshinone

http://www.longecity...227#entry690227

According to this site, its cheap i.e. 3x 200mg for 21 pounds

http://www.pharmacy2...px?packid=70279

 

The reason is that pharma company has used a trick.

Its reapproved it for another indication which is usually made to prolong the patent.

I guess that they did it here to raise the price.

Actually I´m not sure whether this is possible.

Prescription only unfortunately :/

Yes I know. I´ve posted it just as a price reference

I've heard mifepristone in india is like 5 dollars per 200mg dose... or something extremely cheap, like most prescription drugs there actually. I wonder if there's a source from country like that..

According to this site, its cheap i.e. 3x 200mg for 21 pounds

http://www.pharmacy2...px?packid=70279

 

The reason is that pharma company has used a trick.

Its reapproved it for another indication which is usually made to prolong the patent.

I guess that they did it here to raise the price.

Actually I´m not sure whether this is possible.

hey, thanks for that link! looks like a good price, have you ordered from the site before? do you know if they ship  to usa?