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Naltrexone
I discussed L low dose Naltrexone with my doctor. The research is showing that doses of 4.5 mg is having some positive results. I tried 4.5-6 mg in 2023. Although it seemed to help some, I stopped taking it due to the price as I have no insurance and Naltrexone is not available in such a small dose unless compounded at a special pharmacy. We discussed my trying it again, as I am desperate to feel better and function better. I started taking 25 mg of Naltrexone about a week or so ago. I took it at night. This was a mistake as I could not sleep so I changed to taking it in the morning. It does help. Just fyi...it can't hurt to try it for all of you who I know are struggling with this debilitating virus that has wrecked our bodies.
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@welchllb
Hi back,
I had much the same experience. I was on LDN for about a year and saw an improvement in breathing, fatigue, PEM and achiness but then, began to feel "not quite right." I was a bit nauseous and couldn't eat certain foods, etc. I have been off it now for about 6 months. My Cleveland Clinic doctor suggested cutting the LDN in half but I can't seem to break up the capsules accurately. I'm going through a bunch of GI tests and then, will consider what to do about the LDN. Keep in touch.
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3 Reactions@welchllb How much were you taking? I've been on it for a few months. My compounding pharmacy makes it in tablets, not capsules, for $62.50 for 90 tablets of whatever strength, so my doctor prescribed the 4.5mg and I can split it if needed.
4.5 mg capsules and am about to call my pharmacy about halving them. Thanks.
@welchllb
Did you think about a pill cutter? Amazon probably has some. Makes the cutting more accurate.
Good luck!
M
Yes, I have one and it didn't work. Thanks for the thought, though.
I have one and the outside of the capsule doesn't cut very well. Thanks, though.
@celia16
I had the same question. Here’s what I found..
Researchers believe LDN is effective because it addresses three primary physiological breakdowns: neuroinflammation, immune cell signaling, and endogenous opioid deficiency.
1. Reduction of Neuroinflammation (The "Brain Fog" Pathway)
One of the most significant reasons researchers advocate for LDN is its impact on microglia—the resident immune cells of the brain.
• TLR4 Antagonism: LDN acts as an antagonist to Toll-like receptor 4 (TLR4). In Long COVID, TLR4 can become chronically "stuck" in an active state, causing microglia to pump out pro-inflammatory cytokines like IL-6 and TNF-α (Naik et al., 2024).
• Calming Glial Cells: By blocking TLR4, LDN dampens this chronic activation, potentially reducing the "brain fog" and cognitive dysfunction associated with sustained neuroinflammation (Isman et al., 2024).
2. Restoration of Cellular Homeostasis (The "Ion Channel" Pathway)
Recent landmark research (2025–2026) has identified a specific mechanical fault in the immune cells of Long COVID and ME/CFS patients involving the TRPM3 ion channel.
• Restoring Calcium Signaling: Long COVID patients often exhibit dysfunctional TRPM3 channels in their Natural Killer (NK) cells, which impairs calcium (Ca^{2+}) influx and cellular energy regulation (Sasso et al., 2025).
• Effect of LDN: Clinical studies have demonstrated that LDN can restore TRPM3 function, re-establishing the proper calcium signaling necessary for the body to maintain homeostatic balance and clear viral remnants (Sasso et al., 2025).
3. The "Endorphin Rebound" Effect
While standard naltrexone blocks opioid receptors continuously, the low dose only blocks them for a few hours.
• Hormonal Upswing: This brief blockade triggers a "rebound" effect where the body increases its production of beta-endorphins and enkephalins while also upregulating the receptors themselves (McKenzie, 2026).
• Impact on Energy and Mood: Higher levels of these natural opioids are thought to improve pain tolerance, energy levels, and overall mood, addressing the persistent fatigue common in Long COVID (Isman et al., 2024).
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6 Reactions@celia16
Gosh, I would enjoy a glass of wine any old time, but for me part of the constellation of symptoms of LC is a near-absolute intolerance of alcohol!
I've found a German near-beer that I rather like, but with only 1/2% alcohol I can still feel its effects (tiring)!
I would love to find a non-alcoholic, full bodied red wine that is de-alocholized.
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1 Reaction@sandguy , I haven’t tried any nonalcoholic wines. The beers are pretty good though. How hoes a glass of red wine affect you now?
@debbiedsf
Thanks for taking the time and trouble to post this information--you've done us a real service. I had only been aware of the 3rd of these hypothetical mechanisms of action for LDN in treating Long COVID and am grateful to you for expanding my understanding with such well-documented clarity and concision. It's encouraging that LDN may actually be resolving some of the deep-seated dysfunction instead of merely masking it by increasing endogenous opioid levels.