On the 30th April 2026, a new paper was published in the journal ‘Advances in Therapy', titled ‘Low-Dose Naltrexone: What is the Evidence? A Narrative Review.' This is a comprehensive narrative review of current evidence on the safety and efficacy of using LDN to treat a variety of medical conditions, including ME/CFS.
Extracts from the Abstract:
Naltrexone is prescribed off-label at low doses, typically 0.5–6.0 mg, for a variety of therapeutic indications. This review evaluates the clinical evidence for low-dose naltrexone (LDN).
A literature search was conducted in February 2026 across PubMed, Embase and CINAHL for studies published from 1989 to 2026.
Title and abstract searches for “low dose naltrexone” identified peer-reviewed English-language studies using doses of ≤ 12.5 mg in humans.
A total of 105 studies were reviewed, including 15 randomised controlled trials (RCTs) in chronic pain, autoimmune and neuroimmune disorders, gastrointestinal disease, dermatological conditions, post-infectious syndromes, mental health and oncology.
Across these fields, early positive findings from uncontrolled studies were rarely replicated in placebo-controlled trials. Most available evidence consists of case reports and small feasibility studies that are prone to publication bias and rely heavily on subjective outcomes.
LDN is generally safe, inexpensive and well tolerated, with most studies using a daily dose of 4.5 mg.
Although these features contribute to its appeal, current evidence does not support routine clinical use.
LDN may have a pragmatic role in treatment-resistant cases where standard therapies have failed, provided its experimental status and uncertain efficacy are clearly explained.
Larger, well-designed RCTs with objective endpoints, along with N-of-1 approaches to identify potential responders, are needed to clarify its true clinical value.
MEA Comment:
The MEA is currently funding a clinical trial into the use of LDN in ME/CFS. The trial is now completed and the results are being analysed.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
