Potential therapeutic benefit of Low Dose Naltrexone

Hufsamor

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https://www.frontiersin.org/article...IEsMBLuI5b559lIUhyWhXoxWs19gmugwqf2tPD0Fm7lko
The discovery of the widely expressed Transient Receptor Potential Melastatin 3 (TRPM3) as a nociceptor channel substantially targeted by certain opioid receptors, and its implication in calcium (Ca2+)-dependent Natural Killer (NK) cell immune functions has raised the possibility that TRPM3 may be pharmacologically targeted to treat characteristic symptoms of ME/CFS.
 

Pyrrhus

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Full abstract of this new paper by Staines, Marshall-Gradisnik and folks:

Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment (Cabanas et al., 2021)
Helene Cabanas, Katsuhiko Muraki, Natalie Eaton-Fitch, Donald Ross Staines and Sonya Marshall-Gradisnik

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multi-systemic chronic condition of unknown aetiology classified as an immune dysfunction syndrome and neurological disorder. The discovery of the widely expressed Transient Receptor Potential Melastatin 3 (TRPM3) as a nociceptor channel substantially targeted by certain opioid receptors, and its implication in calcium (Ca2+)-dependent Natural Killer (NK) cell immune functions has raised the possibility that TRPM3 may be pharmacologically targeted to treat characteristic symptoms of ME/CFS.

Naltrexone hydrochloride (NTX) acts as an antagonist to the mu (μ)-opioid receptor thus negating its inhibitory function on TRPM3. Based on the benefits reported by patients on their symptoms, low dose NTX (LDN, 3.0–5.0 mg/day) treatment seems to offer some potential benefit suggesting that its effect may be targeted towards the pathomechanism of ME/CFS.

As there is no literature confirming the efficacy of LDN for ME/CFS patients in vitro, this study investigates the potential therapeutic effect of LDN in ME/CFS patients. TRPM3 ion channel activity was measured after modulation with Pregnenolone sulfate (PregS) and ononetin in NK cells on 9 ME/CFS patients taking LDN and 9 age- and sex-matched healthy controls using whole-cell patch-clamp technique.

We report that ME/CFS patients taking LDN have restored TRPM3-like ionic currents in NK cells. Small ionic currents with a typical TRPM3-like outward rectification were measured after application of PregS, a TRPM3-agonist, in NK cells from patients taking LDN. Additionally, PregS-evoked ionic currents through TRPM3 were significantly modulated by ononetin, a TRPM3-antagonist, in NK cells from ME/CFS patients taking LDN.

These data support the hypothesis that LDN may have potential as a treatment for ME/CFS by characterising the underlying regulatory mechanisms of LDN treatment involving TRPM3 and opioid receptors in NK cells. Finally, this study may serve for the repurpose of marketed drugs, as well as support the approval of prospective randomized clinical studies on the role and dose of NTX in treating ME/CFS patients.
 
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I only took one dose of LDN but it made me feel much worse.
well, I have taken 3.5 mgs LDN for about 5 years now. I must be already receiving these benefits.

so: well I guess I should try to better appreciate these benefits...

I did get much much worse ME CFS. ON LDN....(I went from mild to moderate bad over a new six month period of time...maybe got hit with Virus #2).
 

Marylib

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So now there is evidence of several things, if you want to read the most recent paper for yourself. I'll post a link. I find it valuable to subscribe to a newsletter on psychopharmacology. Considering the many posts about low dose abilify, I wonder about high dose naltrexone. If you want to watch an interesting video, here's one. It's focused on alcohol-use disorder and there was a thread at one point about those who felt better drinking alcohol. We all know what alcohol does to the human body and brain, so that's not up for debate. Obviously naltrexone changes something metabolically or immunologically. Also discussed is a disulfram and one I haven't heard about called acamprosate. Neurotransmitters also feature in the video:

https://www.frontiersin.org/articles/10.3389/fimmu.2021.687806/full

https://psychopharmacologyinstitute...ampaign=FREE-4306&ck_subscriber_id=1331366510
 

Marylib

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@Rufous McKinney I had no idea that it was being used in MS at 50 mg. But it looks like I missed where this conversation actually is happening from @Pyrrhus
Related discussion:

Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment (Cabanas et al., 2021)
https://forums.phoenixrising.me/threads/potential-therapeutic-benefit-of-low-dose-naltrexone.84779/
 

Marylib

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Shame it's not an in vivo study. I only took one dose of LDN but it made me feel much worse.

Also if they saw calcium channel issues again, wouldn't nimodipine also work? With its extra effects on calming microglia inflammation and increasing blood flow to the brain?
I think they already did the in vivo (the lab) and this is in the humans (in vitro). But anyway, I was discussing some thing else on another thread and I didn't know this one was here. I guess it will take one of our overworked admins to move the threads around. I wonder how much they used in the lab (in vivo) and @Rufous McKinney was saying they use 50 mg in MS patients, which I didn't know. I posted some other links that were interesting in the other thread. We just assume that low dose is the thing because this study involved those already using low dose naltrexone, rather than a higher dose.
 

Marylib

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LOL - I keep getting those two mixed up. At this point my brain might work better in a glass jar (in vitro) than it does in my head. ;) But yeah, I get your point. Who knows what the higher dose would do...
 
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This is how I remember it:

vivo is latin for alive. as in viva la vida, viva las vegas, viva la revolucion, etc.

in vitro is in glass, as in in vitro fertisilation (IVF) , aka test tube babies.