TL;DR
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A retrospective study of 230 adults at Stanford’s Long COVID Clinic found lower reported symptom burden and improved functional scores after patients were prescribed low-dose naltrexone. Without a control group, the study cannot establish that the drug caused the changes; researchers say randomized trials are needed.
Adults with long COVID reported fewer symptoms and better functioning after receiving low-dose naltrexone in a small retrospective study presented at the IDWeek annual meeting, adding to reports on long COVID’s effects on the body. The findings, based on records from 230 patients at Stanford’s Long COVID Clinic, show changes over time but do not establish that the medication caused them, because the study had no comparison group.
Researchers reviewed electronic health records for adults with laboratory-confirmed SARS-CoV-2 infection and symptoms lasting at least 90 days. Patients needed a clinic visit before starting naltrexone and at least one follow-up visit while taking it. The analysis covered care from 2023 through December 2025; the median final dose was 4 milligrams.
After adjustment for other factors, the seven-symptom composite score declined by an estimated 5.1 points per year from a baseline average of 20. The reported number of symptoms fell by an estimated 2.4 per year, while functional-stage scores improved by 0.32 points per year on a five-point scale. These are modeled annual changes from the study, not evidence that every patient improved by those amounts.
Reported improvements included fatigue, brain fog, sleep problems and post-exertional malaise. The researchers did not find statistically significant improvement in headache or lightheadedness. Participants had a median age of 45.4; 67% were female, and 85.2% were fully vaccinated against COVID-19. More than half reported reduced daily activity at the initial assessment.
What the Findings May Mean for Patients
The results add observational evidence about a treatment some clinicians have tried off-label for persistent symptoms, at a time when no FDA-approved therapy specifically treats long COVID. The reported changes across several symptoms and functional status may help shape questions for future research, including which patients might benefit and which outcomes should be measured.
But the findings do not show that naltrexone is an effective treatment. Symptoms can change over time, and patients may receive other care while taking the drug. Without a control group, those influences cannot be separated from a possible medication effect. The study also does not establish the medication’s safety or efficacy for long COVID.
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How the Stanford Clinic Study Was Conducted
The analysis included adults with persistent symptoms at least 90 days after infection and at least two clinic visits. The median time from infection to starting naltrexone was 606 days, and the median initial symptom count was 12. Most participants had been infected with an Omicron variant, according to the study report.
Naltrexone is an FDA-approved opioid antagonist used to treat opioid use disorder and alcohol use disorder; in combination with bupropion, it is also used in an approved medication for obesity. Lower doses than the approved 50-to-100-milligram doses have been used off-label for other conditions. The study presenter, Brandon Aflak of Stanford, said anti-inflammatory and immunomodulatory effects are possible explanations for interest in the drug, but the study did not test how it might work.
Other potential long COVID treatments have also faced challenges in trials. The report cited a study in which nirmatrelvir-ritonavir, sold as Paxlovid, did not outperform placebo on the outcomes assessed. That history underscores why results from a clinic cohort should not be treated as proof of benefit.
“Although these findings are encouraging, this observational study design does limit causal inference.”
— Brandon Aflak, a Stanford University fellow and study presenter
What the Study Cannot Establish
The study had no untreated or placebo comparison group, so it cannot determine whether naltrexone, natural changes in symptoms, other treatments or a combination of factors explains the reported improvements. Its retrospective design also relies on clinic records and patient-reported symptoms, rather than a trial in which treatment and outcomes are assigned and tracked under a common protocol.
The findings do not establish which patients, if any, are most likely to benefit, whether improvements last, or what dose would be appropriate. The study report does not provide a controlled safety assessment for low-dose use in long COVID. Aflak said randomized, placebo-controlled trials are needed to answer questions about both safety and efficacy.
Controlled Trials Are the Next Test
The next major evidence step is a randomized, placebo-controlled trial that can compare outcomes among people receiving low-dose naltrexone and those receiving placebo. Such research would need to track symptoms, daily functioning, treatment duration and safety to clarify whether the changes seen in the Stanford records reflect a drug effect.
No trial schedule or results were specified in the study report. Until stronger evidence is available, the cohort findings remain an early observational signal, not confirmation that low-dose naltrexone treats long COVID.
Key Questions
Did the study prove that low-dose naltrexone treats long COVID?
No. It found self-reported improvements over time among patients prescribed the drug, but its retrospective design and lack of a control group mean it cannot show that naltrexone caused those changes.
Which symptoms improved in the study?
Reported improvements included fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. Headache and lightheadedness did not show statistically significant improvement in the analysis.
How many people were included?
The researchers analyzed records from 230 adults seen at Stanford’s Long COVID Clinic. Participants had laboratory-confirmed infection, persistent symptoms and clinic visits before and after starting naltrexone.
Is low-dose naltrexone FDA-approved for long COVID?
No. Naltrexone is approved for other uses, but the study describes its use for long COVID as off-label. The report says randomized, placebo-controlled trials are needed to establish safety and efficacy for this condition.
Source: medpagetoday.com
