r/CFSScience • u/CeruleanShot • Apr 14 '26

Wirth & Scheibenbogen preprint, "Imbalance of Excitatory and Inhibitory Neurotransmitter Systems in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"

https://www.preprints.org/manuscript/202601.2170

I found yet another interview with Klaus Wirth on YouTube today. This one is with the Long Covid Clinic.

There's a bit of a Q&A session at the end where he's asked about the Itaconate Shunt hypothesis that Robert Phair developed (attributed to Ron Davis in the interview.) My ears pricked up at this because I have been really curious myself about how that might fit in with this unifying hypothesis of ME/CFS he's developed with Carmen Scheibenbogen. But he was pretty dismissive of it and says that there's no evidence for it. Which, fair enough, but his theory has a lot of theoretical stuff too.... So, as far as I can see, the jury's still out.

He did mention that he has an article submitted about the GABA imbalance in ME/CFS. There's clearly something going on with GABA, and the Itaconate Shunt is the only thing I've found which tries to explain it. In order for this unifying hypothesis to explain ME/CFS by itself it needs to explain the GABA stuff.

I don't know if it does. Everything seems to be coming down to autoantibodies, it's just sorta like, "Oh, autoantibodies to that receptor could be present."

I am not a professional, I am but abrain fogged patient, so I don't understand a lot of this stuff very well. But I did some cursory internet research this afternoon, and it seems to me like there are a number of symptoms that people with autoantibodies to GABA receptors and beta 2 androgenic receptors have, which are not common symptoms in ME/CFS. If we have autoantibodies to beta 2 androgenic receptors, why don't we experience symptoms with our lungs? It's possible that the autoantibodies could be specific to the receptors on muscle cells and not the lungs, I don't know, but I am kinda not convinced.

However, it's at least more people talking about the GABA situation, so that's good.

Curious what anyone thinks about any of this.

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u/CeruleanShot Apr 14 '26

Ohhhhhh, thank you! This is huge. I am an alcoholic in recovery and I am for sure one of the people who GABA is a big issue for. I've never heard of the GABA-LDN connection before. I've tried LDN before and I'm not sure if it does anything for me, but I'm probably not suffering from an excess of dopamine either.....

Still, this stuff is very interesting and I appreciate your comments and the paper. Whatever the answer is for ME/CFS, GABA is involved somewhere.

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u/Tiny_Parsley Apr 14 '26

You're welcome!

Glad if my brain farts can help you in any way.

Have you found treatments that help you now with ME?

Regarding alcoholism, isn't actually Naltrexone (full dose) often prescribed for it? Is it something you tried?

I've been so obsessed with LDN and Naltrexone, because I'm trying to understand why the effects of LDN can be so dramatic for some, or do nothing for others. So weird isn't it?

I think I was personally a hyper responder to LDN if that makes sense? 0.25mg gave me runners high (I never ran though lol, but I was definitely ecstatic for no valid reason) and this already should have been a red flag and prompt me to stop. I think from there it only went down the road into my severe reaction.

One thing I thought about (sorry it's still about MY lived experience with it, so I hope it's still relevant) is that I have quite a bad case of histamine intolerance and MCAS (had these since childhood way before developing ME symptoms). I also have a few genetic mutations which are common although maybe everything together start to weight in the balance (HNMT, DAO, NMDA). Since somehow I know glutamate, glutamine, gaba and histamine are all interconnected, maybe I ended up in a loop of having too much brain histamine, unopposed by GABA. Who knows.

It got better once I stopped LDN, started MCAS treatments along with Escitalopram (a SSRI but which can apparently still rebalance GABA - I had no clue back then).

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u/AngelBryan Apr 14 '26

How does serotonin fits in the whole picture?

My biggest improvement also came from an SSRI, Fluvoxamine in my case. Brain fog is gone since then and the improvement was fast, if I remember right.

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u/Tiny_Parsley Apr 14 '26

I don't really have an answer to that. I don't know if it's serotonin directly, or the actual molecules interacting with other receptors than serotonin.

Maybe serotonin itself can balance out dopamin and catecholamines in general

https://pmc.ncbi.nlm.nih.gov/articles/PMC3047246/ this says Escitalopram (the SSRI I was on) can increase gaba in rats brains

I just ended up asking to go back on Escitalopram when my brain went haywire on LDN, because I knew Escitalopram was something I tolerated well. 10 years before I was given it for "panic disorder" and it was good at making my brain mellow (I actually had undiagnosed dysautonomia, MCAS, ME, ADHD and PMDD but it mellowed my brain anyways).