Links To Resources On Low Dose Naltrexone In Myalgia Encephalomyelitis/Chronic Fatigue Syndrome

In this post, I link to some articles on low-dose naltrexone in Myalgia Encephalomyelitis/Chronic Fatigue Syndrome.

Low-dose naltrexone as a treatment for chronic fatigue syndrome [Full-Text PDF]. : Bolton MJ, Chapman BP, Van Marwijk H. BMJ Case Rep 2020;13:e232502.


Naltrexone is used as an off-label treatment in low doses for several chronic immune-modulated disorders in many countries. Although only small-scale clinical trials have been performed, these suggest efficacy in several diseases including Crohn’s disease,fibromyalgia and Gulf War Illness. Despite numerous internet reports of response to low-dose naltrexone
(LDN), no clinical trials exist in people with chronic fatigue syndrome. This condition is characterised by chronic profound fatigue, postexertional malaise, pain and autonomic and neurocognitive disturbances. This series of three case reports compiled by people with long-term ill-health due to chronic fatigue syndrome shows the range of responses they observed when taking LDN, from life changing to a reduction in some
symptoms only. Treatment doses ranged from 4 to 12mg. Clinical trials may be warranted to explore the potential use of naltrexone in people with these debilitating illnesses which currently have no licensed treatments available.

Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)  [Full-Text HTML] [Full-Text PDF]. Published online: 19 Nov 2019abstract


Background: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a common medical condition that limits physical and cognitive functions, with no known effective medical treatment.

Methods: We report on the safety and effectiveness data accumulated in clinical practice when treating ME/CFS with low-dose naltrexone (LDN, 3.0 – 4.5 mg/day). The medical records from 218 patients who received ar diagnosis of ME/CFS and LDN treatment during 2010–2014 were retrospectively analyzed.

Results: Outcome data were available in 92.2% of patients with an average follow-up time of 1.7 years. A positive treatment response to LDN was reported by 73.9% of the patients. Most patients experienced improved vigilance/alertness and improved physical and cognitive performance. Some patients reported less pain and fever, while 18.3% of patients did not report any treatment response to LDN. Mild adverse effects (insomnia, nausea) were common at the beginning of the treatment. Neither severe adverse effects nor long-term adverse symptoms were reported.

Conclusions: The high frequency of treatment response and good safety profile observed in this retrospective open label study could prompt prospective controlled studies to confirm the feasibility of LDN in alleviating ME/CFS symptoms.

KEYWORDS: Chronic fatigue syndromemyalgic encephalomyelitisnaltrexonetherapypharmacology

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 [PubMed Abstract] [Full Text] [Full-Text PDF]. Front Immunol. 2021 Jul 13;12:687806.

There are 39 similar articles in PubMed Central.


Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multisystemic 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 (m)-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 potentialbenefi 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 ioniccurrents 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.

Keywords: low dose naltrexone, transient receptor potential melastatin 3, calcium, opioid receptor, myalgic encephalomyelitis/chronic fatigue syndrome, natural killer cells, whole-cell patch clamp electrophysiology

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