Hypothetical mechanisms for efficacy of Low Dose Naltrexone?

[Snow Leopard]

Hi,

I am curious as to whether anyone has some developed hypotheses as to the mechanism of 'low-dose' Naltrexone?

Much of the discourse about Naltrexone is dominated by discussion of it being a competitive inhibitor of the function of of mu-opioid receptors.

But it is known that at lower doses the target is actually filamin A which is a Actin-binding protein that anchors transmembrane proteins (specifically G-protein coupled receptors, integrins and ion channels) to the cytoskeleton. It is fairly ubiquitously expressed in many different cell types.

This means it can play role in alteration (antagonism) of diverse extraceullular signals, from mechano transduction to other G-protein coupled receptor signals, including leading to structural reorganisation of mitochondria (such as mitochondrial fission).

Hence it's effects may be quite non-specific, with a broad desensitisation of receptors in certain tissue (and possibly compensationary upregulation of those receptors in certain cells as a result). Which also means a broader range of side effects, if the dosage is high enough to stimulate them.

 

[Creekside]

It's hard to hypothesize a mechanism when the effects vary so much. For me, it worked wonderfully for blocking pain, but had no other noticeable effects. Other people have completely different responses (brainfog, sleep, etc). There could be a number of different mechanisms, working on some people and not others.

If it is the filamin A pathway, that's probably too ubiquitous to be of much help in figuring out how it's affecting which symptom(s).