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In a retrospective study of 230 adults at Stanford’s Long COVID Clinic, patients reported fewer symptoms and improved functioning after receiving low-dose naltrexone off-label. The study had no control group, so it cannot establish that the medication caused the changes; randomized trials are needed to test its safety and effectiveness for long COVID.
A small retrospective study of 230 adults with long COVID found that participants reported fewer symptoms and better functioning after receiving low-dose naltrexone off-label, researchers reported at the IDWeek annual meeting on October 26. The study had no control group, however, so it cannot show that the medication caused the improvements or establish that it is an effective treatment.
The researchers analyzed electronic health records from the Stanford Long COVID Clinic for adults with laboratory-confirmed COVID-19 and symptoms that persisted at least 90 days after infection. Participants needed a clinic visit before starting naltrexone and at least one follow-up visit while taking it. Their records spanned 2023 to December 2025.
After adjustment for other factors, the average seven-symptom composite score, which was 20 at baseline, fell by an estimated 5.1 points per year (95% confidence interval, -7.69 to -2.52). The mean number of reported symptoms declined by an estimated 2.4 per year (95% CI, -3.94 to -0.94). On a 1-to-5 functional stage scale, the adjusted mean score changed by -0.32 per year (95% CI, -0.57 to -0.07), indicating reported improvement on the study’s measure.
Reported improvements included fatigue, brain fog, sleep problems and post-exertional malaise. The study did not find significant improvement in headache or lightheadedness. The median final dose was 4 milligrams. The cohort’s median age was 45.4, 67% were female, and 85.2% were fully vaccinated against COVID-19. These are findings from patients’ records and reported symptoms, not evidence from a controlled test of the drug.
What the Findings Could Mean for Care
Long COVID can persist or fluctuate for months and affect daily activities. In this cohort, more than half of participants reported reduced daily activity at the initial assessment; 24.3% said they struggled with normal daily activities, and 8.3% were described as incapacitated and bedridden. The reported changes may give clinicians and patients a reason to study low-dose naltrexone further, but they do not establish that it should be used to treat long COVID.
The distinction matters because people may seek options while evidence for long COVID treatments remains limited. Naltrexone is an existing prescription medicine used for other conditions, but its use at low doses for long COVID is off-label. The study does not establish its safety or effectiveness for this condition, and patients should discuss medication decisions with a qualified health professional rather than treat these results as proof of benefit.
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How the Stanford Cohort Was Studied
Researchers included adults whose symptoms continued for at least 90 days after confirmed SARS-CoV-2 infection. The median time from infection to starting naltrexone was 606 days, and participants reported a median of 12 symptoms at the initial visit. Most had been infected with an Omicron variant, according to the study report.
Naltrexone is an opioid antagonist approved by the U.S. Food and Drug Administration for opioid use disorder and alcohol use disorder; it is also used with bupropion in an approved obesity medicine. Lower doses than the approved 50-to-100-milligram doses have been used off-label for other conditions. Researcher Brandon Aflak said possible anti-inflammatory and immunomodulatory effects could be relevant to long COVID, but the study did not test how the drug might work.
Long COVID has no FDA-approved therapy, and results from treatment studies have been mixed. The National Academies of Sciences, Engineering, and Medicine describes it as a chronic condition following SARS-CoV-2 infection that lasts at least three months and may be continuous, relapsing, or progressive. That broader clinical challenge helps explain interest in possible treatments, but it does not strengthen the causal evidence from this cohort.
Why Cause and Safety Remain Unknown
Because the analysis was retrospective and had no comparison group, it cannot separate a medication effect from the natural course of long COVID, changes in other treatments, or differences in when patients returned for care. The researchers acknowledged that these factors could confound the observations. Self-reported symptoms and functional scores also do not by themselves establish how much the changes affected patients’ health over time.
The report does not show whether people who were not prescribed naltrexone would have improved similarly, or how results might differ among patients outside this single clinic. It also does not establish a best dose, a treatment duration, or the medication’s safety profile for people with long COVID. The reported symptom changes should be read as associations, not treatment effects.
Evidence Needed Before Wider Use
Aflak said randomized, placebo-controlled trials are needed to determine whether low-dose naltrexone is safe and effective for long COVID and whether it has a place in clinical care. Such studies could compare outcomes between people assigned to the drug and those assigned to placebo, track symptoms and functioning over time, and assess harms.
The study report does not identify a specific trial start date or next research milestone. Until controlled evidence is available, the findings remain an early signal from one clinic’s patient records, and the drug’s role in long COVID care remains unsettled.
Key Questions
Did the study prove that low-dose naltrexone treats long COVID?
No. It found that symptoms and self-reported functioning improved over time among patients prescribed the drug, but the observational study had no control group and cannot show that naltrexone caused the changes.
Which symptoms showed reported improvement?
The study reported improvement in fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. It did not find significant improvement in headache or lightheadedness.
What dose did participants take?
The median final dose was 4 milligrams. This was low-dose, off-label use; the study does not establish an appropriate dose for treating long COVID.
What evidence is needed next?
Researchers called for randomized, placebo-controlled trials to assess whether the medication is safe and effective for long COVID and to clarify its possible role in care.
Source: medpagetoday.com
