TL;DR
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A retrospective study of 230 adults treated at Stanford’s Long COVID Clinic found lower reported symptom burdens and improved functional scores after patients began low-dose naltrexone. Without a control group, the study cannot establish that the drug caused the changes; randomized trials are needed.
A retrospective study of 230 adults with Long COVID found that reported symptoms and functional limitations improved after patients received low-dose naltrexone, researchers said at the IDWeek meeting in Washington on October 26. The findings are preliminary: the study had no comparison group, so it cannot determine whether the medication caused the improvements.
The researchers reviewed electronic health records from Stanford’s Long COVID Clinic, covering patients seen from 2023 through December 2025. Participants were adults with laboratory-confirmed COVID-19 and symptoms lasting at least 90 days. Each had a baseline visit before starting naltrexone and at least one follow-up visit while taking it. The drug was prescribed off-label for Long COVID.
After adjustment for other factors, the study estimated an annual decline of 5.1 points in the average seven-symptom composite score, from a baseline average of 20. The number of reported symptoms also fell, with an estimated annual change of minus 2.4 symptoms. Functional-stage scores improved as well, with an adjusted annual change of minus 0.32 on a five-point scale. These are modeled annual changes, not a claim that every patient improved by those amounts.
Improvements were reported for fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. The study did not find statistically significant improvement in headache or lightheadedness. Patients’ median final dose was 4 milligrams. The median time between infection and starting treatment was 606 days, and the group’s median initial symptom count was 12.
Possible Symptom Relief, Not Proof
Long COVID can involve persistent symptoms that restrict daily life, and the study group included people reporting substantial limitations: 55.7% said their daily activity was reduced, while 24.3% reported difficulty with normal activities and 8.3% described themselves as incapacitated and bedridden. The reported changes may help guide further research into treatment options for patients with ongoing symptoms.
But the results do not establish that naltrexone is effective. Without an untreated or placebo group, researchers cannot separate a medication effect from natural changes over time, other treatments, or differences in who returned for follow-up. The study also does not settle questions about safety or identify which patients, if any, might benefit. Patients should discuss treatment decisions with a clinician rather than interpret these observational results as proof of benefit.
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Off-Label Use and Limited Options
Naltrexone is FDA-approved for opioid use disorder and alcohol use disorder, and in combination with bupropion for obesity. The lower doses discussed in the report are used off-label in some conditions, including fibromyalgia, multiple sclerosis, Crohn’s disease and pain management. The report’s presenter, Brandon Aflak, said the drug may have anti-inflammatory and immunomodulatory effects that could be relevant to Long COVID; that proposed mechanism was not proven by this study.
There are currently no FDA-approved therapies for Long COVID, according to the report. Previous treatment research has not produced a clear established option. The article cited a trial in which nirmatrelvir-ritonavir, sold as Paxlovid, did not outperform placebo; improvements were also seen in some placebo recipients. Long COVID definitions vary, but the National Academies definition describes an infection-associated chronic condition present for at least three months after SARS-CoV-2 infection.
“Although these findings are encouraging, this observational study design does limit causal inference.”
— Brandon Aflak, Stanford University fellow and study presenter
Cause, Safety and Patient Selection
The study cannot show whether naltrexone caused the observed changes because it had no control group. Aflak said the natural course of Long COVID and concurrent treatments could have affected the results. The report does not establish how much of the improvement, if any, was due to the medication, nor does it provide a controlled comparison of adverse effects.
It is also unclear whether the findings apply beyond this clinic’s patients, which patients might respond, or whether improvements would persist with longer follow-up. The cohort was mostly female, largely vaccinated and commonly infected with an Omicron variant, so results may not represent every person with Long COVID.
Controlled Trials Needed
The next step is randomized, placebo-controlled research that can compare low-dose naltrexone with an appropriate control, track symptoms and function over time, and assess safety. The report does not identify a specific trial or announce when one will begin. Until stronger evidence is available, the study’s findings remain a signal for further investigation rather than confirmation of a Long COVID treatment.
Key Questions
What did the study find?
In a review of 230 adults, reported symptom burden and functional scores improved after patients began low-dose naltrexone. Because the study was observational and lacked a control group, it cannot show that the medication caused those changes.
Which symptoms improved in the analysis?
The researchers reported improvements in fatigue, brain fog, sleep problems and post-exertional malaise. Headache and lightheadedness did not show statistically significant improvement.
Was naltrexone tested in a randomized trial?
No. The study reviewed clinic records and compared patients’ measures at baseline and follow-up while they were taking the drug. A randomized, placebo-controlled trial would be needed to test whether the medication itself produces a benefit.
Is low-dose naltrexone approved for Long COVID?
No. Naltrexone has FDA-approved uses for opioid and alcohol use disorders, and in combination with bupropion for obesity. Its use for Long COVID is off-label, and this study does not establish its safety or effectiveness for that condition.
Source: medpagetoday.com
