Me/Cfs caused by low dopamine / dopamine dyshomeostasis?

[Consul]

Abilify, Rexulti, Vraykar
Benzodiazepines
LDN
Carnitine
Thiamine (high dose)

These drugs and supplements are helpful to subgroups with mecfs, they all have effects on the dopamine system.

BH4 is supposedly implicated in mecfs according to Ron Davis, it is involved in dopamine metabolism

Anti-virals helps a subgroup of mecfs patients, heres a quote regarding anti-virals (see context in link) from Ron Davis /Naviaux article:

The inhibition of methylation reactions in the cell also affects neurotransmitter (dopamine, norepinephrine, and serotonin) and phosphatidylcholine membrane lipid synthesis, folate and B12 metabolism, and many other reactions. So by giving antivirals, doctors are not just inhibiting viruses, they are also inhibiting many host cell metabolic functions.

The gene PDE10A has been found to be implicated in males with mecfs (mentioned in Dibble et al 2022), it is mostly expressed in the striatum. quote:

The striatum, or corpus striatum[5] (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamatergic and dopaminergic inputs from different sources; and serves as the primary input to the rest of the basal ganglia.

Mecfs appears to have partial overlap to other diseases such as IBS (or functional dyspepsia), fibromyalgia, insomnia, and i think there are elevated depression rates. The link here could be that all of these disorders have troubles with neurotransmitters. These things are not properly established by research (yet) but a suggestion could be:
IBS/functional dyspepsia - trouble with gut serotonin.
Depression - serotonin
Fibromyalgia - endocannabinoid (supposed to regulate pain)
Insomnia - melatonin

Another question would be why women are 3-4 times more likely to have mecfs than males. Thats an unknown but there are gender differences that possibly could explain it, for example it seems like the dopamine system is more active in males and maybe this could be protective. The gender differences are complex though so this is just a suggestion.

Some studies also indicate increased peripheral inflammation in mecfs and iirc this is something that can whack the dopamine system.

These are just a few observations. Theres lots more info on this in some of healthrisings blogs or mepedia. But there seems to be lots of connections imo.

 

[hapl808]

I definitely seem to have some neurotransmitter function connection. Almost all my PEM crashes follow any kind of cognitive 'flow' or energy. Something that stimulates me in any way is likely to lead to a multi-day crash. Not sure how to treat those issues, though.

 

[Consul]

I definitely seem to have some neurotransmitter function connection. Almost all my PEM crashes follow any kind of cognitive 'flow' or energy. Something that stimulates me in any way is likely to lead to a multi-day crash. Not sure how to treat those issues, though.

I think stimulation intolerance is pretty central to the disease. Sound, screen,light etc. Seems more like a neurotransmitter problem than mitochondrial problem imo

 

[Oliver3]

Doesn't Ron say that our neurotransmitters are being eaten

 

[linusbert]

Doesn't Ron say that our neurotransmitters are being eaten

i just want to throw in that the brain is the organ with most energy demands in the body, so everything which requires it might "sap" energy.

i have mainly muscle cramping. i get it first in the muscle i have overused, for example in the legs. but if i continue i also get cramps in muscles i didnt use in the exercise, like arms. it seams that some kind of exhaustion happens in the whole body affecting systems which didnt exhaust.

this could be true for brain too, over exert brain, get problems in other body parts later too.

what is the actual cause of exhaustion? eaten up ressources... like sugar (liver) ... or eaten up neurotransmitters, i dont know. but mitochondria do not cope too well with chronic energy deficiency like too less substrate to burn. but opposite is true as well, too much substrate hurt as well.

 

[lyran]

I think it's low endorphins in general, mostly beta-endorphins and met-enkephalins but also dopamine. Not the cause but an outcome.

 

[Oliver3]

I'm pretty sure Ron's working hypothesis is that the shift in energy use means neurotransmitters are used for fuel.
If course just one idea

 

[pattismith]

I agree Dopamine dysfunction is a problem in ME and Fibro.

It's also a problem in ADHD and iron deficiency is an ADHD risk factor because iron is needed for Dopamine and Norepinephrin production

BH4 depends on iron for function!

Iron, neuro‐bioavailability and depression - Berthou - 2022 - eJHaem - Wiley Online Library

 

[hapl808]

I think it's low endorphins in general, mostly beta-endorphins and met-enkephalins but also dopamine. Not the cause but an outcome.

One thing I noticed immediately after my viral onset was an almost total lack of endorphins. Things like exercise that used to give me an endorphin rush just stopped doing so. Doctors just shrugged of course - no real interest in that. Frustrating because I used to be very active in the gym because I loved that post-workout endorphin high. That ended.

 

[Oliver3]

I know what you mean about that endorphin rush....lack of any meaningful feeling at all is what happens to me now.
Interestingly, when I started using cannabis at first, the top of endocannabinoids helped with those feelings...for a while. I just couldn't tolerate whatever was in that weed for long. Seemed to build up

 

[lenora]

Well then, if we take that one step beyond....wouldn't dopamine have something to do with a lot of mental illnesses? I wonder how much research has been done on them that we aren't aware of? Yours, Lenora

 

[physicsstudent13]

I suffer horribly from dopamine blockade and dopamine receptor problems and low dopamine after being punched, strangled, robbed, beaten, drugged, and sexually assaulted. dopamine is supposed to be very controversial because it can cause arrythmias at least at higher dosages

 

[MeMeMe]

yes a lack of dopamine seems to play a big role. I noticed today that it seems to have the opposite effect as stress on my symptoms. I had very little sleep last night (just been experimenting with phenylpiracetam which I’ve found amazing but I think left my nervous system feeling overstimulated and in discomfort, hence the poor sleep).

I was dreading a phone interview I had to conduct with someone today. The anxiety brought my symptoms on even stronger. After the call, which went quite well, I had a noticeable dopamine response and my symptoms eased off massively for a while.

It’s like the flip side of the stress. Makes me think I should trial Abilify.

Mega dosing thiamine hcl a couple of weeks ago was also very effective but only for a few days. That’s a tool in my arsenal to keep trying.

 

[Oliver3]

Im still surfing the thiamine wave. I've had up days and down days but it's still having some effect...I'm not megadosing. I'm trying to add other nutrients in.
I went for a twenty minute walk twice today and to the launderette today and recorded some music tonight.
I've been almost totally wiped out before I started thiamine. I've upped the dose.
My main problem is keeping hydrated. Thiamine burns through a lot of hydration it seems.
Wierdly, if I take a walk after ten mins of taking thiamine it seems to push my kidney s or the body into function and I'm less dry.
I'm still experimenting.
Whenever I'm increasing the dose I feel, almost, almost normal for an hour.
I woke up a week or so ago.
No poisoned feeling, no dread, no malaise, no inner voice of doom...just experiential and happy.
It didn't last at that level.
I've noticed of I isolate myself it can lead to a drought of dopamine and it's a vicious circle.
If I get out and do smthg different, it seems to squeeze a bit if dopamine out which is aided by the thiamine.
Rambling. Sorry.

 

[hapl808]

I was dreading a phone interview I had to conduct with someone today. The anxiety brought my symptoms on even stronger. After the call, which went quite well, I had a noticeable dopamine response and my symptoms eased off massively for a while.

Yeah, a weird thing for me is that things that will crash me (music, cognitive tasks, social interactions) also give me a massive temporary relief, followed by a huge crash. That adrenaline stimulation or dopamine or whatever feels great, but leads to days of PEM for me.

 

[Consul]

The loss of butyrate microbes finding in mecfs is very well documented now. Does it result in a whacked dopamine system?

It seems uncanny how all the mecfs drugs can have effects on dopamine signalling.

A few quotes from the paper below

Overall, these findings show that butyrogenic microbes play a major role in maintaining adequate dopamine concentrations by protecting against dopaminergic neuronal loss.

Overall, gut microbiota that produce butyrate have a myriad of effects on dopamine and contribute significantly to attenuating deficits seen in neurodegenerative disorders.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962300/

 

[Forummember9922]

Well if you had a sudden onset and your case is autoimmune, then maybe you can't make dopamine because beta 2 receptors are not working properly. The list of beta agonists is quite short, including pseudoephedrine or inhalers and not much else outside of clinical testing enviorment.
https://pubmed.ncbi.nlm.nih.gov/26399744/
I went from POTS to CFS not too long aog---- and with that change I went from never depressed, feeling like I am going to explode if I eat a sandwich, (having to lay down wait for my body to chill tf out)
To ....depressed and empty, no blood flow. Almost like I went from beta 2 agonist antibodies to beta 2 antagonist antibodies. No i dont think thats the entire picture but I feel confident that based on what an overnight change things were that autoimmunity plays a role in some

 

[Oliver3]

It could also be that you went over the edge totally into a much deeper " dauer state".
I've had moments usually after prolonged stressors, where I've broken a bit more. It's a marked change.
I'm not sure it's necessarily autoimmune but just the system shutting down to protect

 

[cheeseater]

Another way to look at all the very popular seratonin and noradrenaline boosters is that by boosting those chemicals, they are in effect lowering the ratio of dopamine. Same for GABA. The noradrenaline boosters are really just seratonin/noradrenaline boosters, or rebranded discards of the Rx business. Drugs like cocaine and amphetamines are dopamine boosters, so really seratonin boosters are just turning people into slow moving zombies.

 

[hapl808]

Well if you had a sudden onset and your case is autoimmune, then maybe you can't make dopamine because beta 2 receptors are not working properly. The list of beta agonists is quite short, including pseudoephedrine or inhalers and not much else outside of clinical testing enviorment.
https://pubmed.ncbi.nlm.nih.gov/26399744/
I went from POTS to CFS not too long aog---- and with that change I went from never depressed, feeling like I am going to explode if I eat a sandwich, (having to lay down wait for my body to chill tf out)
To ....depressed and empty, no blood flow. Almost like I went from beta 2 agonist antibodies to beta 2 antagonist antibodies. No i dont think thats the entire picture but I feel confident that based on what an overnight change things were that autoimmunity plays a role in some

This is interesting - I feel like I missed this before. Actually when I've taken real Sudafed a few times over the years when I had bad congestion colds, I always felt 'better' overall than when I didn't have a cold. Always just assumed the stimulant nature of pseudoephedrine, but the beta agonist element is interesting. Yet when I once tried albuterol, I felt pretty awful.

I wonder if there are other ways to approach this aspect.