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In a retrospective study of 230 adults treated at Stanford’s Long COVID Clinic, reported symptom burden declined and functional scores improved after patients received low-dose naltrexone. Because the study had no comparison group, it cannot establish that the drug caused those changes; randomized trials are needed to assess its safety and effectiveness for long COVID.
A retrospective study of 230 adults treated at Stanford’s Long COVID Clinic found that patients reported fewer symptoms and better functioning after receiving low-dose naltrexone, an off-label treatment. The findings, presented at the IDWeek annual meeting, show an association rather than proof that the drug caused improvement: researchers had no control group for comparison.
Researchers reviewed electronic health records for adults with laboratory-confirmed COVID-19 who had persistent symptoms at least 90 days after infection. Patients needed a clinic visit before starting naltrexone and at least one follow-up visit while taking it. The records covered care from 2023 through December 2025. The cohort’s median age was 45.4 years, 67% were female, and the median final dose was 4 milligrams.
After adjusting for other factors, the study estimated that the patients’ seven-symptom composite score, which averaged 20 at baseline, fell by 5.1 points per year (95% confidence interval, -7.69 to -2.52). The average number of symptoms also declined, by an estimated 2.4 per year. Functional stage scores improved by an estimated 0.32 points per year on a five-point scale. These are modeled annual changes based on the observed records, not results from a controlled treatment trial.
Reported improvements included fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. Headache and lightheadedness did not improve significantly in the analysis. At the start of the study period, patients reported a median of 12 symptoms; 55.7% said long COVID reduced their daily activity, while 8.3% reported being incapacitated and bedridden. The report did not establish whether changes lasted after treatment or whether participants’ experience represented that of long COVID patients more broadly.
A Possible Option Without Trial Proof
The findings matter because long COVID can substantially limit daily activity, while there are no FDA-approved therapies specifically for the condition. Some patients and clinicians are considering existing medicines for symptoms, but an apparent improvement in a medical record review does not show that a treatment works. Without a comparison group, the study cannot distinguish a drug effect from natural changes over time, other care or other influences.
Naltrexone is FDA-approved for opioid and alcohol use disorders, and in combination with bupropion for weight management. The low doses described in this study are below the approved 50-to-100-milligram doses and are being used off-label for long COVID. The results may help guide further research, but they do not establish a basis for patients to start or change medication without a clinician’s advice.
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How the Stanford Study Was Run
Long COVID is defined in different ways. 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 and remitting, or progressive, affecting one or more organ systems. The Stanford study included patients whose symptoms persisted at least 90 days after infection.
Participants had been infected a median of 606 days before beginning naltrexone. Most were fully vaccinated (85.2%), and 70.9% had been infected with an Omicron variant. The study’s starting symptom and activity measures show that many patients were experiencing persistent limitations when treatment began, but the sample came from one specialist clinic and may not reflect all people with long COVID.
Low-dose naltrexone has also been used off-label for conditions including multiple sclerosis, fibromyalgia, Crohn’s disease and pain management. Study presenter Brandon Aflak, a Stanford fellow, said the drug might have anti-inflammatory and immunomodulatory effects relevant to long COVID. That possibility is a rationale for study, not a mechanism demonstrated by this analysis.
What the Records Cannot Establish
The study did not compare patients taking naltrexone with a similar group not taking it. As a result, it cannot determine whether the observed changes were caused by the medication, reflected the course of long COVID, or were influenced by concurrent treatments or other factors. The retrospective design also relied on clinic records and patient-reported symptoms and function.
The report does not establish which patients are most likely to improve, whether the medication is safe and effective over longer periods for long COVID, or whether benefits persist after stopping it. The lack of significant improvement in headache and lightheadedness also shows that the observed changes were not consistent across every symptom assessed. These findings should not be treated as proof of benefit or as individualized treatment guidance.
Controlled Trials Needed
The next step identified by the study’s presenter is randomized, placebo-controlled research to test whether low-dose naltrexone improves long COVID symptoms and functioning, and to assess safety. Such trials could compare the drug with placebo while accounting for changes over time and other treatments. The report did not specify a trial start date or provide details of a planned study, so when those results might be available remains unknown.
For now, the Stanford findings are an observational signal from one clinic, not a treatment recommendation. People considering naltrexone for long COVID should discuss their health history and medication options with a qualified clinician, who can explain that its use for this condition is off-label and that effectiveness has not been established in controlled trials.
Key Questions
Did the study prove that low-dose naltrexone treats long COVID?
No. It found that reported symptoms and functioning improved among patients taking the drug, but its observational design and lack of a control group mean it cannot show that naltrexone caused the changes.
Which symptoms improved in the analysis?
Patients reported improvements in fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. Headache and lightheadedness did not show significant improvement.
What dose did patients receive?
The study reported a median final dose of 4 milligrams. This is below naltrexone’s approved 50-to-100-milligram doses; its use for long COVID is off-label.
What research is needed next?
Researchers need randomized, placebo-controlled trials to test whether the drug causes improvement, assess its safety for long COVID, and clarify its potential role in care.
Source: rss
