Low-Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients (Sasso et al., May 2025)

[bad1080]

Introduction: Long COVID is a multisystemic condition that includes neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations, independent of the severity or duration of the acute SARS-CoV-2 infection. Dysfunctional Transient Receptor Potential Melastatin 3 (TRPM3) ion channels are associated with the pathophysiology of long COVID due to reduced calcium (Ca2+) influx, negatively impacting cellular processes in diverse systems. Accumulating evidence suggests the potential therapeutic benefits of low-dose naltrexone (LDN) for people suffering from long COVID. Our study aimed to investigate the efficacy of LDN in restoring TRPM3 ion channel function in natural killer (NK) cells from long COVID patients.

Methods: NK cells were isolated from nine individuals with long COVID, nine healthy controls, and nine individuals with long COVID who were administered LDN (3–4.5 mg/day). Electrophysiological experiments were conducted to assess TRPM3 ion channel functions modulated by pregnenolone sulfate (PregS) and ononetin.

Results: The findings from this current research are the first to demonstrate that long COVID patients treated with LDN have restored TRPM3 ion channel function and validate previous reports of TRPM3 ion channel dysfunction in NK cells from individuals with long COVID not on treatment. There was no significant difference in TRPM3 currents between long COVID patients treated with LDN and healthy controls (HC), in either PregS-induced current amplitude (p > 0.9999) or resistance to ononetin (p > 0.9999).

Discussion: Overall, our findings support LDN as a potentially beneficial treatment for long COVID patients by restoring TRPM3 ion channel function and reestablishing adequate Ca2+ influx necessary for homeostatic cellular processes.

https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1582967/full

 

[Rufous McKinney]

Given recent discussions in other threads here in PR, I was curious whether this study mentions any side effects or issues with dosing, for the LDN group. The paper seems to not go into that.

It says the LDN group(n=9) received 3.0-4.5 mgs of LDN per day. Nobody was given 0.0001. Or 0.5.

Nobody was gradually increasing their dosage I assume.

wonder what we all think about that?

Its pretty cool to find out LDN is helping the calcium channels which seem important.

 

[andyguitar]

I was curious whether this study mentions any side effects or issues with dosing, for the LDN group. The paper seems to not go into that.

Could'nt find any mention of adverse effects.

Its pretty cool to find out LDN is helping the calcium channels which seem important.

Yes this is interesting.

 

[cfs since 1998]

Seems congruent with a 2024 paper by Klaus Wirth which discussed TRPM3 dysfunction:
https://pubmed.ncbi.nlm.nih.gov/38970055/

Wirth also found LDN improved NK cell function but only in test tube experiments.

edit: Just to clarify, he only performed test tube experiments. I think this new paper is the first to show LDN treatment in Long COVID patients improves their NK function, presumably the same would be true for ME/CFS. It's looking more and more like they're the same thing.

 

[kushami]

It's a bit unclear, but it seems as though the people they recruited for the active group were already taking LDN: "To be included in the LDN group, participants must be in treatment with a daily dose of 3 to 5 mg of NTX for at least 4 weeks (prescribed by their physicians)."
(My emphasis)

So anyone who had had untenable side effects and had already stopped would not have been eligible to participate.

 

[andyguitar]

It's a bit unclear, but it seems as though the people they recruited for the active group were already taking LDN: "To be included in the LDN group, participants must be in treatment with a daily dose of 3 to 5 mg of NTX for at least 4 weeks (prescribed by their physicians)."
(My emphasis)

Yes that's correct, some of them for months. Also worth saying that the tests were done on cells removed from the patients. So it's a test tube test. Some useful info about how effective LDN was can be seen here...

 

[andyguitar]

As it says here the significant difference between patients who had been on LDN and those who were not was in their scores for mobility.

 

[cfs since 1998]

Yes that's correct, some of them for months. Also worth saying that the tests were done on cells removed from the patients. So it's a test tube test. Some useful info about how effective LDN was can be seen here...

Well then every test is a "test tube" test. That's not what I meant. You can't test blood while it's still inside the patient.