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Mifepristone for ME/CFS? (NK Cell Function / HPA Reset)

Jesse2233

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At end of a recent talk on Gulf War Illness (GWI) and ME/CFS, Dr Klimas mentions that a dose of the abortion drug mifepristone cured GWI in a mouse model.

This drug has been discussed previously by @Cort back in 2014 as a potential ME/CFS treatment but I have not seen much discussion of it since.

In a nutshell it supposedly boosts NK cell function and resets the HPA axis in a few doses. There are scattered reports across the internet of it greatly improving general non-specific fatigue after a handful of low dose treatments, but no mention I can find of any ME/CFS patient taking it.

Has anyone here tried it or have thoughts on its theoretical benefit?
 

Jesse2233

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From Wikipedia on its mechanism of action
It is a steroidalantiprogestogen (IC50 = 0.025 nM for the PR), as well as an antiglucocorticoid(IC50 = 2.2 nM for the GR) and antiandrogen(IC50 = 10 nM for the AR) to a much lesser extent.[30] It antagonizescortisolaction competitively at the receptor level.[31]

In the presence of progesterone, mifepristone acts as a competitiveprogesterone receptor antagonist (in the absence of progesterone, mifepristone acts as a partial agonist). Mifepristone is a 19-norsteroid with a bulky p-(dimethylamino)phenylsubstituent above the plane of the molecule at the 11β-position responsible for inducing or stabilizing an inactive receptorconformation and a hydrophobic 1-propynyl substituent below the plane of the molecule at the 17α-position that increases its progesterone receptorbinding affinity.[32][33][34]

In addition to being an antiprogestogen, mifepristone is also an antiglucocorticoid and a weak antiandrogen. Mifepristone's relative binding affinity at the progesterone receptor is more than twice that of progesterone, its relative binding affinity at the glucocorticoid receptor is more than three times that of dexamethasoneand more than ten times that of cortisol; its relative binding affinity at the androgen receptoris less than one-third that of testosterone. It does not bind to the estrogen receptor or the mineralocorticoid receptor.[35]
 

Jesse2233

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Some anecdotal accounts
I feel like I am completely over my 3-year season of lethargy and wasting. I rely on nothing to keep me going now. Before Mifepristone, I used to use Piracetam, NAC, and/or Alpha Lipoic Acid to get temporary relief. All were very good, but results were only temporary. I would force myself to go to the gym, work out, go for a 3-mile run, get good nutrition, and the wasting and lethargy persisted. My body didn't respond to anything I did, and all the lab results from my doctors showed my hormone levels at the lower end of the "normal range", so to them there was nothing wrong with me. I was incredibly sensitive to certain vitamins and minerals. I would easily overdose on a multivitamin, leaving me feeling sick and tired, leading me to believe my metabolism was incredibly low. Maybe others feel this too, but all the lethargy put me in a very negative, persistent mental state. Piracetam, NAC, and ALA alleviated negative ideation temporarily. Mifepristone definitely changed my mental state to something more positive, and did wonders for my energy level.


http://www.longecity.org/forum/topic/64289-mifepristone-for-depression-hpa-axis-dysfunction/

Cortisol is the stress hormone in our bodies...it is very important for survival but when the hypothalamus is not working right, it releases far too much cortisol and progesterone. this causes a multitude of diseases. when they gave the study participants Mifepristone, our cognitive test results soared, functional MRIs proved that cortisol was no longer drowning our brains and as a result our sickness was HEALED...not just TREATED....in 4-5 days of taking the medication.

https://www.facebook.com/PtsdHope/posts/602887143112056
 

heapsreal

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I think mifepristone increases nk function in gws by blocking high cortisol. In cfs im not sure it would work as we are blocking cortisol which is already low. But i dont think just increasing cortisol in cfsers is going to be enough.

I keep thinking of ketamine to treat neuroinflammation which is one theory they say why it puts pts with depression into remission, as they can be another group with high levels of neuroinflammation. The standard anti inflammatory drugs i just dont think work on this type of inflammation or cant cross into the blood brain barrier??
 

Martin aka paused||M.E.

Senior Member
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2,291
I think mifepristone increases nk function in gws by blocking high cortisol. In cfs im not sure it would work as we are blocking cortisol which is already low. But i dont think just increasing cortisol in cfsers is going to be enough.

I am not sure about this. That might be different in patients! Because as I mention it here http://forums.phoenixrising.me/index.php?threads/symptoms-and-cortisol-a-causal-relationship.56174/ my symptoms usually improve in the evening. And that is when cortisol is very low... But I don't know my cortisol profile yet.
 

Hip

Senior Member
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17,820
The HPA-axis reset that mifepristone is thought to achieve arises from this drug's antagonism of the glucocorticoid type II receptors. Since there is thought to be HPA-axis dysfunction in ME/CFS, this HPA-axis reset might have beneficial effects for ME/CFS patients.

In this study on patients with psychotic major depression, a short four-day course of mifepristone at 600 mg daily rapidly achieved substantial improvements, which was conjectured to arise through a HPA-axis reset. The study says:
The mechanism of clinical improvement in our patients with psychotic major depression is not entirely clear. Type II receptors are found in relatively high abundance in nonhuman, frontal cortex and primate hippocampus, and functions modulated by these regions appear to be decreased in PMD patients.

Blocking these receptors may aid in improving cognition. It also seems that the abruptly blocking type II-receptors may cause a “resetting” of the HPA axis. Cortisol levels rise when mifepristone is taken because the feedback mech- anism is partially disrupted, however, normal cortisol rhythm returns and seems to remain intact after mifepri- stone is discontinued. Short-term use of mifepristone may prove to be its most effective regimen.


However, in a clinical trial of mifepristone for Gulf War illness, there was no improvement, apart from some improvements in verbal learning. But GWI may be different to ME/CFS: GWI is associated with mitochondrial damage, and we don't know if such damage exists in ME/CFS.
 

Learner1

Senior Member
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Great. If that's your only problem....not sure it will fix immune system problems, though.

The GWI people seemed to have high cortisol, not low, right?

And, how would this fix someone with low cholesterol, low pregnenolone, low cortisol, low DHEA, low testosterone, low estrogen, and low thyroid?
 

Hip

Senior Member
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17,820
And, how would this fix someone with low cholesterol, low pregnenolone, low cortisol, low DHEA, low testosterone, low estrogen, and low thyroid?

Mifepristone is thought to be a HPA-axis resetter, not a universal panacea.
 

Jesse2233

Senior Member
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Southern California
Women may be able to get mifepristone at Planned Parenthood in the US for free if their insurance covers it. Not sure if they would offer only one pill or several. A man with a female partner, friend, or family member might be able to arrange this as well

How much does the abortion pill cost?
The abortion pill can cost between $0 to $975. The cost of a medication abortion varies and depends on where you get it and whether or not you have health insurance that will cover some or all of the cost.

https://www.plannedparenthood.org/learn/abortion/the-abortion-pill/how-do-i-get-the-abortion-pill
 

Jesse2233

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Location
Southern California
In the UK it appears mifepristone is available through the FPA. Other countries likely have similar programs
Early medical abortion (up to nine weeks of pregnancy)

Early medical abortion (sometimes called EMA) involves taking drugs to cause an early miscarriage. It does not involve surgery or an anaesthetic and you will need three appointments. The first is an assessment – the abortion will not be carried out at this visit. You will need two more appointments on two separate days. You should be able to carry out your usual activities between appointments.

At the second appointment, you will be given a tablet (called mifepristone) to swallow. This blocks the pregnancy hormone that is necessary for the pregnancy to continue.

https://www.fpa.org.uk/unplanned-pregnancy-and-abortion/abortion-your-questions-answered
 

Jesse2233

Senior Member
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Location
Southern California
I wonder if an “HPA reset” would affect other things besides cortisol (such as ADH).

Dr Klimas mentions that all of the GWI mouse model labs and testing returned to normal after taking mifepristone

This study indicates it does increase ADH (vasopressin) in primates

Increased adrenocorticotropin, cortisol, and arginine vasopressin secretion in primates after the antiglucocorticoid steroid RU 486: dose response relationships.

https://www.ncbi.nlm.nih.gov/m/pubmed/2981083/
 
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