The ME Association, a leading UK charity for people with ME/CFS (myalgic encephalomyelitis or encephalopathy; chronic fatigue syndrome) and Long Covid, has today announced investment in an important clinical trial in Canada to test the potential benefits of low-dose naltrexone (LDN). Results from the trial should help to clarify whether LDN can affect the underlying disease processes in ME/CFS and Long Covid and improve symptoms.
Dr Luis Nacul, principal investigator at the University of British Columbia (also at the [London School of Hygiene and Tropical Medicine](https://cureme.lshtm.ac.uk/)) is leading a double-blind, randomised, placebo-controlled trial with the B.C Women’s Health Research Institute in Canada.
The trial will determine if LDN improves fatigue, pain, sleep, orthostatic intolerance and other related symptoms, reduces inflammatory markers in blood, and enhances an individual’s quality of life. The trial will test LDN or a placebo in people who meet the American Institute of Medicine diagnostic criteria for ME/CFS at three months following a COVID-19 infection.
The impact of the COVID-19 pandemic makes finding evidence for an effective and safe treatment urgent. With currently no curative treatment for ME/CFS or Long Covid, a larger number of people are predicted to be impacted by the long-term morbidity and disability associated with these conditions, with high costs to healthcare and social services.
The ME Association’s latest investment reflects its increased commitment to biomedical research that could help deliver effective treatments for ME/CFS and Long Covid.
**Dr Charles Shepherd, honorary medical advisor and trustee at The ME Association explains:**
> Large numbers of people around the world are left disabled and often unable to work because of ME/CFS and Long Covid. While estimates vary, one thing is very clear, the urgent need for effective treatments.
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> The ME Association is therefore very supportive of Dr Nacul’s clinical trial of a drug that has been long-considered a potential treatment of ME/CFS and more recently, Long Covid. A study of this nature is needed to determine if existing research relating to LDN’s use in Fibromyalgia and anecdotal evidence of its effective use in ME/CFS holds true under trial conditions.
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> Only with trials such as this one will we be able to determine LDN’s actual effect. If we see improvements in people’s symptoms then we can lobby for the drug’s use in the UK. If the trial proves LDN has little or no effect, then we can move onto other potential treatments.
Previous research has demonstrated the safety and effectiveness of LDN in other chronic conditions, such as Fibromyalgia, while existing observational studies suggest benefits in terms of increased energy, improvement in pain and sleep, with only minor adverse effects in those with ME/CFS.
Naltrexone is an opiate antagonist approved by Health Canada for treatment for alcohol and opiate use disorders. It is used off label at low doses for conditions such as ME/CFS, Fibromyalgia and Crohn’s disease, with a good safety profile and some evidence of benefit.
LDN seems to exert its effect by temporarily blocking certain opioid receptors, causing these receptors to increase in number and sensitivity. LDN also increases circulation of endogenously produced opiate-like molecules which are found to be reduced in ME/CFS. This may help to reduce pain and inflammation and improve immune function and well-being. It may also counterbalance the pro-inflammatory status that has been implicated in ME/CFS symptoms, particularly at early stages of disease, which can hamper recovery.
MRI studies also show evidence of brain inflammation, connectivity deficits, and reduced levels of brain activation in ME/CFS. A suggested brainstem dysfunction in ME/CFS, if also applied to Long Covid, could well explain many of the symptoms, such as those related to autonomic dysregulation, cognitive impairment, and reduced energy.
> We are excited by this study and delighted with the support from The ME Association. With the lack of specific treatments for Long-Covid and ME/CFS, there is a great need for trials such as this one. This is what those affected by these debilitating diseases expect from clinicians and researchers.
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> Dr Luis Nacul, the trial’s principal investigator
The clinical trial will add to the growing experience and expertise of health professionals seeing cases of Long Covid and ME/CFS. Completion is expected by 31st December 2025, and results published in early 2026.