Roughly 1 million Americans live with myalgic encephalomyelitis/chronic fatigue syndrome, a debilitating condition marked by crushing fatigue, cognitive problems, and pain that worsens after even mild physical activity. More than 35 years after it was recognized as a distinct medical condition, there is still no FDA-approved treatment. Researchers at the University of Alabama at Birmingham are now working to change that.

The team has received a $556,686 federal grant from the National Institutes of Health to run a clinical trial of low-dose naltrexone, a drug that researchers believe may calm the chronic brain inflammation thought to drive ME/CFS symptoms. The condition has become more common since the COVID-19 pandemic, as some long COVID patients develop a syndrome nearly identical to ME/CFS.

Naltrexone is already FDA-approved at higher doses for treating opioid and alcohol addiction. At much lower doses, between 0.5 and 6 milligrams per day, it appears to cross the blood-brain barrier and shift overactive immune cells in the brain from an inflammatory state to a resting one. Early evidence suggests it reduces fatigue in ME/CFS, fibromyalgia, and long COVID, but no large, rigorous trial has confirmed this.

The UAB trial is structured in three parts. The first will enroll 75 participants to find the most effective dose. The second is a 150-person randomized controlled trial comparing the drug against a placebo, testing safety and measuring the strength of the effect. A subset of participants near Birmingham will undergo brain imaging to look for biological markers that could predict who responds best to the drug. A third component will track participants over a longer period to assess how well the treatment holds up.

One notable feature of the trial is its fully remote design: participants can enroll from anywhere in the United States and complete all study tasks from home, making it accessible to patients who are homebound or bedbound due to their illness.

The researchers describe naltrexone as an especially promising candidate because it is inexpensive, widely available as a generic, and has a well-established safety profile with no potential for abuse. If this trial produces favorable results, it would lay the groundwork for a larger Phase III trial needed to pursue FDA approval.