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In a retrospective study of 230 adults at Stanford’s Long COVID Clinic, patients reported fewer symptoms and better functioning after receiving low-dose naltrexone. The study had no control group, so it cannot show that the drug caused the changes; randomized trials are needed to establish its safety and effectiveness for long COVID.
Adults with long COVID reported fewer symptoms and better functioning after receiving low-dose naltrexone in a retrospective study of 230 patients at Stanford’s Long COVID Clinic, researchers reported at the IDWeek annual meeting. Because the study had no comparison group, it cannot establish that the drug caused the improvements.
The researchers reviewed electronic health records for adults treated at the clinic from 2023 through December 2025. Participants had laboratory-confirmed COVID-19, symptoms lasting at least 90 days after infection, a baseline clinic visit before starting naltrexone and at least one follow-up visit while taking it. The median age was 45.4, and 67% were women. The median final dose was 4 milligrams.
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; P<0.001). The number of symptoms fell by an estimated 2.4 per year (95% CI, -3.94 to -0.94; P=0.001). Functional-stage scores also improved, with an adjusted annual change of -0.32 on a scale from 1 to 5 (95% CI, -0.57 to -0.07; P=0.011).
Reported gains were seen in fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. The study did not find statistically significant improvement in headache or lightheadedness. These are changes observed in the records, not proof of a treatment effect; the researchers did not compare patients taking the drug with a similar untreated or placebo group.
What the Patient Reports Suggest
The findings offer a preliminary signal about a drug some clinicians have prescribed off-label to people with long COVID, a condition for which no FDA-approved therapies were identified in the report. Long COVID can persist or fluctuate and affect multiple organ systems, limiting daily activity for some patients. In this cohort, 55.7% reported reduced daily activity, 24.3% struggled with normal daily activities and 8.3% were described as incapacitated and bedridden.
That burden makes possible treatment options relevant to patients and clinicians, but the results should not be read as a recommendation to use naltrexone. Without a control group, improvements could reflect natural changes over time, other treatments or differences in who returned for follow-up. The study also does not establish whether the observed changes are clinically meaningful for every patient or whether they would occur in a broader population.
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How the Stanford Cohort Was Studied
Naltrexone is an opioid antagonist approved by the U.S. Food and Drug Administration for opioid use disorder and alcohol use disorder. In combination with bupropion, it is also used in an approved medicine for weight management. Doses below the standard 50- to 100-milligram range have been used off-label for other conditions, but that history does not establish efficacy for long COVID.
The study’s participants had been ill for a median of 606 days before starting naltrexone. Most were fully vaccinated against COVID-19 (85.2%), and 70.9% had been infected with an Omicron variant. Their median initial symptom count was 12. The findings reflect this clinic population and follow-up design, rather than a randomized trial that assigned treatment and compared outcomes.
Study presenter Brandon Aflak said naltrexone might have anti-inflammatory and immunomodulatory effects that could be relevant to long COVID. That is a proposed explanation, not a mechanism established by this study. The report also points to prior treatment research in which some approaches have not shown a clear advantage over placebo, underscoring the difficulty of identifying effective care.
What the Records Cannot Establish
The retrospective design cannot separate a possible drug effect from natural symptom changes, concurrent treatments or other confounding factors. There was no placebo group or untreated comparison group, and patients’ symptoms and functional status were self-reported. The analysis therefore does not show what would have happened to the same patients without naltrexone.
The report does not establish the drug’s safety or effectiveness for long COVID, which patients might benefit, how long any improvement lasts, or whether the results apply outside this specialist clinic. It also does not provide randomized evidence that the proposed anti-inflammatory or immunomodulatory effects explain the observed changes. Those questions remain open.
Evidence Needed From Controlled Trials
The next step identified by the study presenter is randomized, placebo-controlled research that can test whether low-dose naltrexone improves symptoms compared with placebo and assess safety. Such trials would also help establish which outcomes matter, how long participants should be followed and whether any effects persist.
The available report does not specify a planned trial, its start date or when new results might be expected. Until controlled evidence is available, the Stanford findings remain an observational association, 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 that patients reported improvements while taking the drug, but its retrospective design and lack of a control group mean it cannot establish that naltrexone caused those changes.
How many people were included?
The analysis covered 230 adults with long COVID who received care at Stanford’s Long COVID Clinic and had a baseline visit before naltrexone and at least one follow-up visit while taking it.
Which symptoms improved in the study?
Researchers reported improvements in fatigue, brain fog, unrefreshing sleep, difficulty sleeping and post-exertional malaise. They did not find significant improvement in headache or lightheadedness.
Is low-dose naltrexone FDA-approved for long COVID?
No. The report describes its use for long COVID as off-label. Naltrexone has other FDA-approved uses, but this study did not establish its safety or effectiveness for long COVID.
What evidence is needed next?
The study presenter called for randomized, placebo-controlled trials to test whether the drug causes improvement and to evaluate its safety and possible role in care.
Source: medpagetoday.com
