19 replies to this topic

[Xptriate]

Hi guys, 

 

I suffer from what seems to be an overreaction to stress. I dont feel depressed, but I may well be, though it does seem atypical. It could also be from finasteride which I took in the past but I tried testosterone gel and had a good reaction, so I am looking into other avenues - namely related to atypical depression

 

At some point i developed this reckless insomnia that is connected to tension before sleep.

 

Recently I took 0.25mg of dexamethasone. Wake up next day like a totally different person, pretty much cured of all the symptoms. Happy, motivated, things from the past didn't bother me, music sounded amazing, erections back full strenght, morning erections back full strenght, reactions to meds changed for the better, mind cleared, and I felt clean ( idont know how to explain it better)... I took it 4 days in a row and I felt great appart from insomnia, which it made worse. The experience was fully reproduceable again in other isolated days.

 

I have tried equivalent dosages of Hidrocortisone to no avail.

 

I have the idea that what happened is due to an impaired glucocorticoid receptor sensitivity at the pituitary level, and an imbalance of glucocorticoid:mineralcorticoid receptor ratio, which eventually is the same. Dexamethasone broke this imbalance and activated the receptor. Pretty much like a switch it gave me back my old self.

 

I am looking to find something safer than Rx antidepressants, to restore this hyposensitivity of the receptors. Anyone has any idea of what I can try which could accomplish this?

Edited by Xptriate, 03 December 2016 - 04:31 PM.

[tunt01]

Dexamethasone suppresses CRH and ACTH, reducing cortisol output.  If you have an overreaction to stress, you might have high output of stress hormones/cortisol to psychosocial situations or whatever stimuli you are facing, but your receptor response might still be entirely normal as a feedback mechanism to stress.  You don't necessarily have impaired receptor sensitivity.

 

Mifepristone (RU486) is a glucocorticoid receptor antagonist and has been shown to have benefits in patients with excess cortisol, but I'm not sure the benefits are durable or that it is the best route for long-term health relative to alternatives like diet and exercise.  I know the manufacturer of Korlym is working on other drugs in this area that are more selective as mifepristone has activity involving progesterone.

[Armadillo Whisperer]

FWIW, there is an old classic book on the Safe Uses of Cortisol. Basically the author (an MD) treated many patients for years with typically 20 mgs of hydrocortisone spread out over the day to mimic the natural cycle for years. He found it very useful for a whole range of complaints.He found no side-effects:

https://www.amazon.c...rds=mckjeffries

 

I know you said the hydr didn't work while the dex did, which is odd, but you may want to check out the book anyway. It's a bit on the pricey side. The author died several years ago.

[Xptriate]

it is very odd that I don't get a reaction to HC but i do to DM. I initially put this down to a lack of dopamine but i tried Ropinirole and I tried testo gel and it didn't turn me on like a light switch, it did have some benefits but its not even close to DM.

 

One of the obvious difference between DM and HC is the affinity for GC is much higher for DM.

 

So these reasons are why I am thinking along the lines of hyposensitivity of GC receptors, and an impaired balance of MC:GC receptors.  Both of which been implicated in major depression. However I do not feel like I am in a major depression.

 

Unfortunately I am not confortable with mifepristone after I was left with what seems like permanent changes (damage?!) from endocrine disrupting medications. like finasteride, SNRIs, and TCAs. Do you think it can be dangerous? What other drugs do you think they are developing?

 

Any way someone knows how to do what I want but in a natural way? Or some less dangerous med?

 

Or if someone knows the mechanism by which this happens with DM? Or if someone else went through the same?

Edited by Xptriate, 04 December 2016 - 01:20 PM.

[Xptriate]

So I have come to yet another possible reason.

 

The p glycoprotein is modulated by dexamethasone at the blood brain barrier level and this regulates the access of cortisol inside, which reestablishes the inhibitory feedback of the HPA.

 

It seems antidepressants can also do this but they need time to work....

 

i will possibly try next vortioxetine at the 5ht3a blocking dosage only.

 

By the way I tried magnesium threonate and that stuff kept me up the whole night.......

Edited by Xptriate, 24 December 2016 - 01:57 AM.

[Mind_Paralysis]

So I have come to yet another possible reason.

 

The p glycoprotein is modulated by dexamethasone at the blood brain barrier level and this regulates the access of cortisol inside, which reestablishes the inhibitory feedback of the HPA.

 

It seems antidepressants can also do this but they need time to work....

 

i will possibly try next vortioxetine at the 5ht3a blocking dosage only.

 

By the way I tried magnesium threonate and that stuff kept me up the whole night.......

 

REALLY??

 

Something is definitely off inside of you... because most people report sleepiness from MagLT and other Mag-supplements - NMDA-antagonism is singled out as a possibly very valuable sleep-reinforcing effect, in Stahl's Essential Psychopharmacology, even - along with Histamine-antagonism.

 

The fact that NMDA-antagonism gives you insomnia, is something that we need to ponder further... hmm... Do you react the same to Histamine-antagonism?

 

Anyways, some of your problems could be caused by BURNOUT - a state which occurs when you have been exposed to enhanced cortisol-transmission from stress, over a long period of time - mostly ONLY, and I mean ONLY, happens to people who is either:

A) War-veterans - either as a fighter or as a fugitive, or,

 

B) people with Neuropsychiatric disorders -

 

- only the trauma from a life of issues, failures and problems caused by modern society to a person with ALTERED neurostructures can match the incredible strain brought on by WAR.

So, which, if any, category, would you classify yourself as?

 

It should be noted that there are two compounds which can help with this, which both appear to have a better side-effects-profile than most other available Antidepressants:

 

NSI-189 - created by DARPA specifically to treat the neural damage that comes from shell-shock, and get the American commando's back in top, FIGHTING shape once more.

 

TIANEPTINE - a classic, with reason. Below you can see a number of studies which confirms why Tianeptine is such a good AD - it causes somewhat more neurogenesis than 5ht-reuptakers (MAOI, SSRI, TCA, SNRI) and most importantly - it alters the patients response to stress, enhancing ones tolerance - this implies down-stream effects on glucocorticoids.

 

Tianeptine is both easier to obtain, more well-studied, and cheaper than NSI-189 - it of course takes longer to correct the damage to hippocampus from Cortisol, but still, it's faster than every other AD currently in use.

 

Of course, that depends on if you really HAVE burnout, and subsequent EXTREME biochemical damage to your hippocampus (the neural damage is so great, that the only thing non-exogenous to compare it with, is the cognitive decline caused by alcohol and methamphetamine).

 

 

References:

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

 

Tianeptine: a review of its use in depressive disorders.

https://www.ncbi.nlm...pubmed/11463130

 

Tianeptine: An Antidepressant with Memory-Protective Properties

https://www.ncbi.nlm...les/PMC2701287/

 

Neurobiological and clinical effects of the antidepressant tianeptine.

https://www.ncbi.nlm...pubmed/18072812

[Finn]

 

So I have come to yet another possible reason.

 

The p glycoprotein is modulated by dexamethasone at the blood brain barrier level and this regulates the access of cortisol inside, which reestablishes the inhibitory feedback of the HPA.

 

It seems antidepressants can also do this but they need time to work....

 

i will possibly try next vortioxetine at the 5ht3a blocking dosage only.

 

By the way I tried magnesium threonate and that stuff kept me up the whole night.......

 

REALLY??

 

Something is definitely off inside of you... because most people report sleepiness from MagLT and other Mag-supplements - NMDA-antagonism is singled out as a possibly very valuable sleep-reinforcing effect, in Stahl's Essential Psychopharmacology, even - along with Histamine-antagonism.

 

The fact that NMDA-antagonism gives you insomnia, is something that we need to ponder further... hmm... Do you react the same to Histamine-antagonism?

 

 

 

If you have really big magnesium deficit, at the beginning magnesium can be more energizing than tiring. If this happens, you can take magnesium at breakfast and lunch, sooner or later it should become more tiring, then you start to take it in evening.

[Mind_Paralysis]

 

 

So I have come to yet another possible reason.

 

The p glycoprotein is modulated by dexamethasone at the blood brain barrier level and this regulates the access of cortisol inside, which reestablishes the inhibitory feedback of the HPA.

 

It seems antidepressants can also do this but they need time to work....

 

i will possibly try next vortioxetine at the 5ht3a blocking dosage only.

 

By the way I tried magnesium threonate and that stuff kept me up the whole night.......

 

REALLY??

 

Something is definitely off inside of you... because most people report sleepiness from MagLT and other Mag-supplements - NMDA-antagonism is singled out as a possibly very valuable sleep-reinforcing effect, in Stahl's Essential Psychopharmacology, even - along with Histamine-antagonism.

 

The fact that NMDA-antagonism gives you insomnia, is something that we need to ponder further... hmm... Do you react the same to Histamine-antagonism?

 

 

 

If you have really big magnesium deficit, at the beginning magnesium can be more energizing than tiring. If this happens, you can take magnesium at breakfast and lunch, sooner or later it should become more tiring, then you start to take it in evening.

 

 

Ahh...! Now I get it - yeah, I didn't think about that! I'm so focused on Magnesium's psychiatric effects, that I forget about all of the other functions of this metal in our bodies.

 

The energizing effect is no doubt coming from increased ATP-levels, as a result of the increased availability of magnesium to the mitochondria.
 

[Xptriate]

thank you so much for the replies guys.

- Never had any traumas that I am aware of. I guess one should be aware of traumas right?

- I can related to unfulfillement and worrying about future, and frustration with some things at the time the issue developed.

- The issue also developed during a period in which I was a bit frustrated, had a stressful project and most importantly, my neighbour upstairs made a huge noise at 8 am eveyrday, which woke me up during 3 consecutive days. at the 3rd day I devleoped fear of going to bed and looking back, it felt like I crashed. I took finasteride a few months before so I dont know if its related. it probably is

 

- i tried tianeptine. it made my insomnia really worse but its one hell of an antiD. the first time i took it, it actually allowed me to go for a vigorous run, with improved performance (wtf?!), and when I came back I took a nap (marked difference because I cant nap anymore), and woke up feeling great. But the insomnia at night got way worse. I was def stimulated.

 

 

So i found a few more people with the same reaction to mag threonate, and some even worse. they all have CFS or post finasteride issues. Anyway, I tried switching it to 9AM and 1/3 of the dosage, and it doesnt break my sleep anymore it seems.

 

Im on the P Glycoprotein researching now.... as much as I would like not to pop up any Anti Depressive like SSRI or Vortioxetine, I guess will have to give it a try... just cant live like this.

 

I am happy to report :

 - I did find some good earplugs, they are from a kickstarter project, email me if you want to know the brand

 

 -  I did find one PFS sufferer who gotten around his insomnia using bright light at night (AT NIGHT), so I will give this a go.

 

 -  I am looking forward to buying some expensive Bose C25 , which everyone in the misophonia group of facebook, seems to say it is very helpful for them. noises at night startle me and keep me awake.

Edited by Xptriate, 01 January 2017 - 06:36 PM.

[world33]

I have just tried Dexamethasone (0.5mg divided in two morning and bed time doses) as well and it makes me feel like I used to be before developing general anxiety disorder. I have been taking lexapro for many years now and this new addition is a game changer.

My anxiety was not related to any cause or source and was spiking about one hour after waking up at the peak of the cortisol levels. It was so severe that I could not manage to do anything other than lying in bed and sleep waiting for the evening to come when the anxiety systematically decreased. After starting taking lexapro, apparently the best SSRI for General Anxiety Disorder, things slowly improved. I have tried so many other supplements since then that I have lost count. The ones that also helped were rhodiola, ashwagandha, theanine, sulbutiamine and dhea. Lately after regularly feeling sleepy after just one hour after waking up I decided to try something to reduce stress and cortisol. Best decision ever. I bought some very cheap Dexona 0.5mg at alldaychemist.com with no prescription and as soon as I tried it I finally felt very relaxed and stress free. I also bought cabergoline (quite expensive thought) and it also made me feel very well; I do not plan to use it on a regular basis though to avoid risking D2R dowregulation.

 

My blood tests show low dhea, low testosterone, occasionally high prolactin levels, high cholesterol and high urea. I never tested for cortisol levels though and it is something i definitely plan to do considering the amazing effects of Dexamethasone.

In terms of symptoms I experienced fatigue, very low endurance, memory problems, difficulty in concentration, low libido, daytime sleepiness, low tolerance to stress, lack of motivation and enjoyment (but not sadness or suicidal thoughts thank god).

Hopefully by reducing what seems to be chronic stress and high cortisol levels with Dexamethasone I will be able to minimize those symptoms. I wonder whether there are long term side effects by using such a low dose of 0.5mg Dexamethasone.

 

Xptriate please keep us posted on any other supplement/drug you will try and benefit from in addressing your similar cortisol related condition.

Edited by world33, 28 February 2017 - 01:41 PM.

[Xptriate]

wow this is great to hear!!ive been searching for people whk reacted like this to small dosage of DM !! have you found any other people?

in the post finasteride groups there are at least 2 more like us.

 

have you taken any of the following : metoclopramide, roacutane, finasteride,  saaw palmetto, minoxidil?

 

have youdone a 23andme test? does it show less cyp2d6  and drd2 pathogenic alleles?

 

how many days aago have you started DM? did you try hidrocortisone too? did you take cabergoline at same time as dm?

 

can you sleep on this ?

 

i dont know what to expect from low dosage dm in terms of sides. my endo advised me agaknst it but i havent found anythikng else to work like it. i am not using it out of fear of more permanent sides. 

 

i recently retried artichoke and it seems to ikncrease bile acid judging by stools getting darker on the second day. this means that it probably increased pglycoprotein too as i think both work through activation of pxr....but i saw no difference

 

i tried ritalin but only a little dosage. it helps..but its not dm...

 

im going to try fluoxetine low dosage to raise allopregnanolone

 

i tried alpha lipoic akcid and i reactrd same way as i react to mianserin: slept whole night but woke up feeling horrible. i think its the myscarinic receptors releasing adenosine or smehow affecting it.

 

theanine sometimes works and im super relaxed and Also gkycine before sleep has given me full recoveries for a day

 

no silver bullets though, nothing fixes my insomnia and lasts for long. i have moved apprtments and .it helps. sleeping outside in nature helps too

 

Edited by Xptriate, 28 February 2017 - 09:50 PM.

[world33]

Hi,
Yes I love this forum and the opportunity to share knowledge and personal experiences with conditions, drugs and supplements.
-------------
have you found any other people?
have you taken any of the following : metoclopramide, roacutane, finasteride,  saaw palmetto, minoxidil?
------------
 
No to be honest. I came to this post by searching for the keywords Dexamethasone+longecity to see other people reviews and experiences.
Among them I have used in the past and for a short time minoxidil and propecia (low dosage finasteride) but being so many years ago, in my 20s,  I doubt they had any impact on me. My issue started at 33 after a pneumonia and a stressful time of my life. I am still wondering whether the pneumonia bacterial infection or the very strong and/or long course of antibiotics could have damaged somehow my hpa axis.
 
------------
have youdone a 23andme test? does it show less cyp2d6  and drd2 pathogenic alleles?
------------
Yes indeed, I have been searching for genetic causes for a long time. I recommend selfdecode.com for analyzing the raw data and, even if not as good, livewello.com. 
I have a homozygous mthfr c677t gene mutation that does not allow me to assimilate folic acid. I supplement with the active form of folic acid but it does not have such great impact.
I did not check for those mutations you mentioned. I will check malacards.org (another very useful website) to see what human diseases are associated with those genes the most and let you know my result.
 
------------
how many days aago have you started DM? did you try hidrocortisone too? did you take cabergoline at same time as dm?
can you sleep on this ?
------------
Three days ago. I had tried it before but together with a bunch of other supplements (tyrosine, sulbutiamine and so on)  and I did not realize the unique effect it has on me. It shows that I suffer from a severe case of chronic stress. My low DHEA levels do not help either because apparently DHEA is supposed to somehow counteract cortisol. I have not tried hydrocortisone yet. I did not take cabergoline at the same time and if Dexamethasone keeps working so well I am not sure I will continue to use it (too expensive, risk of D2R downregulation in the long term, and possible side effects on the heart I read).
 
Yes I can sleep, If you notice that it does not help you sleep you can try to take it in the morning or afternoon considering it has a relatively long biological half-life.
 
------------
i dont know what to expect from low dosage dm in terms of sides. my endo advised me agaknst it but i havent found anythikng else to work like it. i am not using it out of fear of more permanent sides.
i recently retried artichoke and it seems to ikncrease bile acid judging by stools getting darker on the second day. this means that it probably increased pglycoprotein too as i think both work through activation of pxr....but i saw no difference
------------

Have you reconsidered the p glycoprotein theory since tried artichoke? I was very curious about your theory and was looking for some supplements. Are we supposed to inhibit or enhance it? 
Other supplements that reduce cortisol apparently are:
High dosage vitamin C (3000mg per day possibly in divided doses but not before bed)
Phosphatidylserine
 
------------
im going to try fluoxetine low dosage to raise allopregnanolone
 
i tried alpha lipoic akcid
------------
What about trying pregnenolone, the grand mother of all hormones, instead? or DHEA?
 
Tried ALA as well but not much effect on me. IM gluthatione injections were amazing though. Oral gluthatione also helped but not as much as IM injections.
 
 
Please consider ashwagandha to see if it helps with sleeping.
 
Keep me posted on new supplements, theories or experiences you discover.

PS I tried to multiquote your post but I got this error message:You have posted more than the allowed number of quoted blocks of text
Very annoying

[world33]

Hello Xptriate,
 
I checked my 23andme raw data through selfdecode and here my results for potentially "bad" SNPs:

DRD2 
rs1800497 GG = 47% 
rs6277 AA = 10%

CYP2D6 
rs1135840 CG = 41% 
rs1065852 GG = 63% 
rs5030867 TT = 100%

I do not understand the relation between these two genes (especially CYP2D6 which has to do with drug metabolism if I am not wrong) and our cortisol level or sensitivity.
Can you please explain what you read and researched?

I know that cabergoline (a d2r receptor agonist) has a great effect on my concentration, vision and overall mental status. The beauty of cabergoline is that has a very long half-life and you can take it once a week. Downside is that it is expensive and can lead to d2r downregulation (not sure about the dosage and time length for this to occur though).
I also read that sulbutiamine and Forskolin could help in up-regulating the d2r receptors.

Have you read anything about the relation between d2r receptors and stress/cortisol/glucocorticoid sensitivity?

Under the Glucortoid resistance (which is much more severe and certainly is not our case) page at malacards.org the genes involved are different:

http://www.malacards...d#related_genes

In particular the NR3C1 gene has a high score of correlation and impact. Once again I am not sure whether this apply to our case somehow in a limited fashion.

Under Acute Stress disorder these are the genes involved:

http://www.malacards...s#related_genes

[world33]

Unfortunately all the mutations/variations (SNPs) listed by malacards.org under Glucocorticoid Resistance are not present in the 23andme raw data:

rs104893908
rs104893909
rs104893910
rs104893912
rs104893913
rs104893914
rs121909727
rs587776832

Source: http://www.malacards...etic_variations

Malacards reports a specific genetic test on the NR3C1 gene at http://www.malacards...genetic_testing
I wonder where it is possible to take it and how much it costs.

Here an interesting publication on Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk:

https://www.ncbi.nlm...les/PMC3341031/

Another very interesting article is published by selfhacked.com (made by the same guy that publishes the gene interpretation website at selfdecode.com) at

https://selfhacked.c...icoid-receptor/

In particular in that article these are the supplements that can decreases Glucocorticoid Receptor Activity

What Decreases Glucocorticoid Receptor Activity

1) Natural Substances
•High Vitamin B6 concentration suppresses glucocorticoid receptor activation of transcription. Vitamin deficiency enhances the body’s responsiveness to glucocorticoids ®.
•Curcumin inhibits GR’s ability to induce gene transcription in HeLa (human cervical cancer) cell culture ®.
•Luteolin works to stop both glucocorticoid and progesterone signaling in human cell culture ®.

2) Drugs
•Mifepristone, a drug used for medical abortions and emergency contraception lowers GR activity ®.
•Ketoconazole and other azole drugs that treat fungal infections inhibit GR transcriptional activity ®.
•RU-43044 specifically inhibits GR activity ®.

3) Proteins
•RAP46, a mammalian protein, can bind to the glucocorticoid receptor, inhibiting its functions ®.
•RIP140 reduces GR transactivation ®.
•Daxx and Daxx-(501-740) represses GR activity ®.

4) Other

Certain cytokines can decrease glucocorticoid receptor (GR) expression, block the movement of the GR from the cytoplasm to nucleus, and disrupt GR-DNA binding. The cytokines that inhibit GR expression or function include IL-1 alpha, IL-2, IL-13, IFN-alpha, TNF-alpha, and IL-6 ®.

Edited by world33, 03 March 2017 - 02:57 AM.

[Xptriate]

Hi World 33,

 

Sorry for my late reply i have been a bit sick !

 

My genes:

DRD2
rs1800497 AA    -> this one is a pathogenic allele
rs6277 AA

CYP2D6
rs1135840 GG
rs1065852 GG
rs5030867 TT

Apparently people who react well to dexamethasone generally are found to react well to increases of dopamine activity. But this is purely anecdotal. I found some disucssion about it on a forum and I found that my psychiatrist once I mentioned dexametasone he decided to give me ritalin.

The CYP2D6 is only because dexametasone is one of the few things which increase it! I know I have a problem with this enzyme and I know that all the worse meds I tried were metabolized by this enzyme. So I was wondering if this is the culprit, but you don't seem to have a big deficiency of this enzyme?

Im not sure we fall under glucocorticoid resistance or some form of it. those people have true physical changes. but we do have some sensitivity issue probably at a very specific place in the brain ?

Regarding the compounds you mentioned, plus a couple others:
 -I have tried forskolin but i didnt feel much different.
 - I have tried recently ritalin, and I felt some positives but Im still experimenting with the dosages.
 - I have tried curcumin and it is good for some things like headache, etc..but i didnt feel any effect on mood
 - i tried high dosages of b6 p5p but i didnt feel any different
 - i tried luteolin from rutin but i didnt feel any different
 - i mixed forskolin and artichoke. maybe there is a veyr very slight positive effect on focus.
 - i tried artichoke and it does increase bile production.
 - i tried rutin forsklin and artichoke at same time but i didnt feel much difference
 - i tried inositol which seemed to work in the beggining however after a few days i was twiching before falling asleep and i couldnt sleep. any idea why is this? inositol was very powerful, and brightened my mood!
 - mifepristone i think it could work but i dont like that it acts on progesterone receptors too
 - ketoconazole i used it as shampoo only, i dont think i would take it orally, its dangerous
 - i dont know RU-43044, or the proteins you mentioned.


Did you try any of these:
- Uridine
- Ritalin
- Prednisolone instead of dexametasone
- Inositol


So now I have a flu for a few days. I can sleep! It seems when I get feverish I can sleep better. I read this is triggered by IL-B1..but this info doesnt seem useful. Someone should study this because it seems like a common trait to every human..maybe even to mammals...get fever: sleep like a comma. maybe the solution to insomnia would lie in the mechanism triggered by ILB1 that allows sleep.

Are you still on the dexametasone? any side effects or tolerance?

I have a few other ideas about what could be going on but none fits like the one i wrote here. I can post them here if you want

Edited by Xptriate, 05 March 2017 - 08:19 PM.

[world33]

Hi World 33,
 
Sorry for my late reply i have been a bit sick !
 
My genes:
DRD2
rs1800497 AA    -> this one is a pathogenic allele
rs6277 AA

CYP2D6
rs1135840 GG
rs1065852 GG
rs5030867 TT

Apparently people who react well to dexamethasone generally are found to react well to increases of dopamine activity. But this is purely anecdotal. I found some disucssion about it on a forum and I found that my psychiatrist once I mentioned dexametasone he decided to give me ritalin.

The CYP2D6 is only because dexametasone is one of the few things which increase it! I know I have a problem with this enzyme and I know that all the worse meds I tried were metabolized by this enzyme. So I was wondering if this is the culprit, but you don't seem to have a big deficiency of this enzyme?

Im not sure we fall under glucocorticoid resistance or some form of it. those people have true physical changes. but we do have some sensitivity issue probably at a very specific place in the brain ?

Regarding the compounds you mentioned, plus a couple others:
 -I have tried forskolin but i didnt feel much different.
 - I have tried recently ritalin, and I felt some positives but Im still experimenting with the dosages.
 - I have tried curcumin and it is good for some things like headache, etc..but i didnt feel any effect on mood
 - i tried high dosages of b6 p5p but i didnt feel any different
 - i tried luteolin from rutin but i didnt feel any different
 - i mixed forskolin and artichoke. maybe there is a veyr very slight positive effect on focus.
 - i tried artichoke and it does increase bile production.
 - i tried rutin forsklin and artichoke at same time but i didnt feel much difference
 - i tried inositol which seemed to work in the beggining however after a few days i was twiching before falling asleep and i couldnt sleep. any idea why is this? inositol was very powerful, and brightened my mood!
 - mifepristone i think it could work but i dont like that it acts on progesterone receptors too
 - ketoconazole i used it as shampoo only, i dont think i would take it orally, its dangerous
 - i dont know RU-43044, or the proteins you mentioned.


Did you try any of these:
- Uridine
- Ritalin
- Prednisolone instead of dexametasone
- Inositol


So now I have a flu for a few days. I can sleep! It seems when I get feverish I can sleep better. I read this is triggered by IL-B1..but this info doesnt seem useful. Someone should study this because it seems like a common trait to every human..maybe even to mammals...get fever: sleep like a comma. maybe the solution to insomnia would lie in the mechanism triggered by ILB1 that allows sleep.

Are you still on the dexametasone? any side effects or tolerance?

I have a few other ideas about what could be going on but none fits like the one i wrote here. I can post them here if you want

If I remeber well I just tried inositol but a too little dosage to have an impact on me.
I read nasty long term side effects of using prednisolone so I am not going to try it. I will also try not to go over 1mg per day of dexametasone.
Funny enough when I get sick I also feel much more relaxed and stress-free, like in a normal state of mind that should be the standard not the exception. I did not know IL-B1 was involved.
I can still sleep at night and do not suffer from insomnia but when I wake up I feel like my sleep is not restorative and I fall back to sleep after around one hour I wake up in the morning.
I wonder whether dexametasone is helping us with underlying inflammation in addition to cortisol-reducing effects. Just a speculation tough.
I definitely feel better when taking cabergoline, a D2 receptor agonist, so you might be right that the combo low dosage dexametasone and cabergoline (or other dopamine supplements/drugs) could be a winner for us.
What concerns me is dopamine receptors down-regulation in the long term.
Please share any info or idea you come across on this subject.

[Xptriate]

So I maybe have concluded something interesting

 

Dexamethasone has neglegible activity at the MineralCorticoid receptor.

 

Hidrocortisone has 1:1 affinity between MC and GC receptors.

 

As i felt recovered from 0.125mg-0.25mg of of Dexamethasone, but not from equivalent dosages of HC...I am thinking the following could have happened:

 

 -> I lost the healthy proportion of GC to MC receptors, and now the ratio is in favour of GC (gc is overexpressed), namely in hypothalamus,pituitary, Locus Coereulus, or other area that either controls HPA feedback or norepinephrine release. In other words, the GC became dominant.

 

  -> Dexamethasone, with its high GC affinity, binded to all these receptors, leaving room for cortisol and others to bind to MC receptors. Whereas before dexamethasone, these hormones would be binding to all the unbound GC receptors and the few MC receptors... Basically what Im saying is before dexametasone very little activation of MC receptors was occurring because the GC were dominant and these hormones have +- same affinity for GC that they have for MC. All the relief of symptoms would thus come from activation of MC receptors and not GC receptors

 

A low activation of MC would tie in with a lot of other symptoms and behaviours that I am experiencing - especially salt craving which I always had since a kid - and also blood exams.

 

Just leaving it out there for whoever wants to give it a go.

 

I might be trying fludrocortisone and/or vasopressin soon, in which case ill remember to post back

 

edit: This however wouldnt explain why HC didnt give me any effect at all , since it would still have blocked some of the GC receptors while activating some of the MC receptors...but ill probably still give this a shot

Edited by Xptriate, 18 April 2017 - 09:10 PM.

[Xptriate]

i think for example in the kidney the 11-bHSD is protecting the MC activation by degrading it, so unless cortisol gets too high, there wont be any activation of MC. Might be all this is an issue of imbalance between MC and GC in the HPA feedback areas of brain and / or sources of norepinephrine.

[Xptriate]

according to these guys it seems the exact opposite is happening, at least upon high dosage Dexamethasone: the MC receptors are being freed up from cortisol, since the high dosage supresses the HPA cortisol output......i doubt significant suppression occurs during 0.125mg though.

Also as it turns out, according to them HC binds 10times better to MC than GC, unlike what I thought! i read somewhere it had the same affinity, does anyone know whats the consensus?

 

Nonetheless this is where it seems to me the reaction i had to dexamethasone comes from, an imbalance between GC and MC activation. So I am happy to have found this and will keep reading.

 

Below the studies:

 

http://www.haematolo...tent/100/4/e137

http://ascopubs.org/...CO.2015.66.0761

 

 

Edited by Xptriate, 19 April 2017 - 01:34 AM.

[Xptriate]

i think for example in the kidney the 11-bHSD is protecting the MC activation by degrading it, so unless cortisol gets too high, there wont be any activation of MC. Might be all this is an issue of imbalance between MC and GC in the HPA feedback areas of brain and / or sources of norepinephrine.

 

I obviously meant 11bHSD protects MR through degradation of cortisol

 

 

I really think this MR:GR imbalance is where the problem lies. Would anyone know where to buy legit fludrocortisone in Europe? I tried to buy it in Portugal but its not available.......