Metabolism, neurosteroids, ME/CFS


Senior Member
Atlanta, GA
I should start by saying that after relentlessly looking around and reading, I do not see any clear-cut consensus as to when and if it is “indicated” to supplement a small dose (say, 5mg per day, no more) of hydrocortisone for adrenal problems.

The most logical thing would be to describe what I’m dealing with now, and then maybe tread back / zoom out for the bigger picture.

Ever since moving, my new PCP has wanted me to wean off steroids. I was put on a 10mg dose of prednisone three years ago because after 17 years of suffering through morning issues with pain, stiffness, somnolence and brain fog (latter two would sometimes prevent me from focusing and learning in classes and on the job), a former doctor suggested I try prednisone.

As of today, my PCP has managed to get me to wean down to 10mg hydrocortisone. Over the past ten days, I effectively weaned down to 0mg. I have manifestly no sign of an Addisonian crisis and my blood pressure has been checked and is stable.

But the original problems are essentially back. Not the withdrawal symptoms. Not the return of the IBS, or the pain flare ups, or even the increased weakness. Though all of that has appeared.

The quite debilitating problem of feeling brain fog and a mental slowing of cognition in the morning and into the afternoon. The kind of state which was difficult to suppress (for the past 17 years) until I trialled steroids.

I am scheduled for an ACTH stimulation test in 9 days. I am already asking myself what use that test will have if, on top of withdrawal, there is that distinct return of slowed cognition.

How long does one even wait until they tell themselves: enough already, I require that 5mg hydrocortisone which evidently is helping me feel better.

There is a contradiction between theory and experience — apparently, supplementary cortisol does not improve ME/CFS because the problem is not with the adrenal glands but with brain signaling. Yet, I feel better any time I am on even the lowest dose of cortisone.

What are the interactions between cortisol and dopamine? Does the former not increase the latter? Would this not explain why one will feel less pain, less stiffness, less fatigue (all of the above) when taking things like cortisol or psychoactive agents like antipsychotics (Abilify), or SNRIs, etc? Do all these things not eventually activate the dopaminergic receptors?

Insofar as my central ME/CFS symptom (in extension of / upstream of PEM) has involved problems waking up early enough, arousal and cognition, as well as stiffness and pain, I would say that not only is my central nervous system “dysfunctional,” but that it is also obviously blunted.

In terms of my progress, I believe that re-activating neurotransmitter receptors will play a central role. Cortisol controls both metabolism and inflammation, but it is the metabolism part I find interesting. Upstream of cortisol are more hormones which regulate metabolism (the precursor cholesterol). Outside of the liver (in skeletal muscles), cortisol regulates metabolism through catecholamines (dopamine and the others).

Did aripiprazole make me feel (entirely) better because of its metabolic effects? More specifically, did it stop working because my cells were no longer able to take in whatever sugar / byproduct it was generating, thus provoking metabolic syndrome?

I think whatever Aripiprazole was triggering upstream of energy (glucose) production is what counts itself as being at the juncture (and origin point) of my ME/CFS. That primary juncture is where it all initially splits off: the path to post-exertional malaise and cellular dysfunction, but also the path to neurological slowing, neurotransmitter deficiency…

If Aripiprazole was synthesized as an atypical antipsychotic, then its constituents were meant to activate (up or down regulate) neurotransmitter activity. Yet, cortisol primarily regulates neurotransmitter activity, sort of like a “calling precedent” to whatever dopamine (or other) receptor effect Aripiprazole has.

It follows that, at least insofar as neurogenesis is concerned, cortisol takes precedent over ariprazole’s effect and it is therefore also “rate-limiting.” Cortisol also effects dopaminergic activity in skeletal muscles, so it would also have a rate-limiting effect upon Aripiprazole outside of the brain.

Neurosteroids like pregnenolone are a precursor to cortisol. If Abilify were continuously taken to the point of causing metabolic down-regulation and insulin resistance, it would not be so surprising that it would stop working. Tangentially, it would also suggest that up-regulating neurosteroids like pregnenolone and cortisol would not be such a bad thing.

Aripiprazole stops working for the same reason that cells in ME/CFS stop producing energy: there is no re-uptake of the by product (glycogen and/or glucose) which Aripiprazole helps to promote. The catecholamines which Aripiprazole agonizes (norepinephrine for example) allow the glycogen to phosphorylate, cycling through cells and driving energy. Low glycogen and absent phosphorylation mean insulin resistance.

From all this, it just seems to me that ME/CFS can only be neurological, forget neuro-immune. Neurosteroid activity, in particular, appears to be indispensable, without which several other cascading effects pain to occur.

Don’t think I’ve seen anyone do a million times better on pregnenolone and hydrocortisone, which I guess says a lot about the pathology / mechanism of this disease.

But, after the small insight which some of these medications have afforded me, my experience tells me that my ME/CFS is less metabolic and immunological than it is essentially neurological.
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Psalm 46:1-3
Great Lakes
I can't read the whole post right now...I'm brain is just not letting me. However, I did get to the point where you mentioned ACTH test in 9 days. I would say (just my opinion) that if you're off the cortisone for now maybe do the test anyway just so you have those results.

Also hydrocortisone has a much shorter half-life I believe than pred so you may want to split your dose in two and take it twice in a day. ??? Maybe something to discuss with your doctor.

You also might be able to extend it a bit (or be able to take less hydrocortisone) with things like grapefruit or licorice though grapefruit can affect levels of other medications in the blood and licorice can raise bp, lower potassium levels and is estrogenic.

You can also check interactions with other medications you might be on here for licorice and X but for some reason the site does not include grapefruit even though it does interact w/so many other things. :oh-dear:

Ahh...but this site has grapefruit on it's list of herbals so you might be able to check it here against some other meds:[]=9191 :)

Will see if I can come back sometime later and read the rest.