Low Dose Naltrexone for Long COVID: Is an Old Drug Finally Showing Promise?

There is still no FDA-approved treatment for long COVID, even though millions of people struggle with fatigue, brain fog, poor sleep and debilitating symptoms after exertion. Now researchers at Stanford University have reported encouraging new evidence that an inexpensive old medicine might help. Their study of 230 patients suggests that low dose naltrexone for Long COVID may reduce some of the most troublesome symptoms.

Before you start celebrating, the latest research does not prove that LDN (low dose naltrexone) is a cure for long COVID. The Stanford research was observational, not a randomized placebo-controlled trial. But it adds to a growing body of evidence suggesting that LDN deserves a much closer look.

New Stanford Data on Low Dose Naltrexone for Long COVID:

Researchers reviewed electronic health records from 230 adults treated at the Stanford Long COVID Clinic between 2023 and December 2025. The findings were presented at the 2026 IDWeek annual meeting.

All the patients had laboratory-confirmed COVID-19 and persistent symptoms for at least 90 days. They had been prescribed low dose naltrexone off-label and had follow-up evaluations after treatment.

The median age was about 45 years and two-thirds of the patients were women. They had been dealing with long COVID for a long time. The median interval between their COVID infection and starting naltrexone was 606 days.

The median final dose was just 4 mg daily. That is dramatically lower than the usual 50-mg dose of naltrexone prescribed for alcohol or opioid dependence. Low dose naltrexone is an opioid antagonist. That is why doctors prescribe higher doses to treat people who are trying to overcome dependence on alcohol or narcotics. Lower doses, however, are sometimes prescribed to treat fibromyalgia, nerve pain, chronic fatigue syndrome and autoimmune and inflammatory conditions.

Patients reported significant improvement in several classic long COVID symptoms, including:

• Fatigue
• Brain fog
• Unrefreshing sleep
• Difficulty sleeping
• Post-exertional malaise

They also reported fewer symptoms overall and better day-to-day functioning. Headache and lightheadedness, however, did not improve significantly.

Perhaps most important, the researchers themselves emphasized that these results do not prove that naltrexone was responsible. There was no placebo group. Long COVID symptoms can wax and wane over time, and some people may improve spontaneously.

Study presenter Brandon Aflak emphasized that randomized, placebo-controlled trials will be needed to determine whether low dose naltrexone is truly safe and effective for long COVID. That seems like an especially important caution. Encouraging observations are a reason to conduct a good clinical trial. They are not a substitute for one.

This Is Not the First Stanford Study:

The latest findings build upon earlier research from Stanford. In 2023, Stanford investigators reported on 59 long COVID patients who had been treated with low dose naltrexone (International Immunopharmacology, Nov. 2023). Patients experienced fewer symptoms and improvements in fatigue, post-exertional malaise, unrefreshing sleep and functional status.

Once again, though, this was not a randomized placebo-controlled trial. The authors themselves concluded that their observations warranted rigorous clinical testing.

A 2026 Meta-Analysis Adds More Evidence:

An even more interesting development came in July 2026, when researchers published a systematic review and meta-analysis of low dose naltrexone for long COVID in BMJ Open (July 16, 2026). They screened nearly 400 reports but found only four observational pre-post studies that met their criteria, involving a total of 155 patients.

The pooled results suggested improvements in:

• fatigue
• brain fog
• sleep
• pain
• daily functioning

Sadly, though, the researchers found no randomized controlled trials among the published studies they reviewed.

Their conclusion was appropriately cautious: the available evidence suggests that low dose naltrexone may help some long COVID symptoms, but the certainty of the evidence remains low. Larger, well-designed randomized trials are still needed.

In other words, we now have several different studies pointing in roughly the same direction. What we still do not have is the kind of randomized placebo-controlled evidence that could tell doctors with confidence whether the drug really works.

The Fascinating Story of Low Dose Naltrexone:

We have been writing and talking about naltrexone for many years. The drug was first approved by the FDA under the name Trexan in 1984. It was initially given a green light to help treat opioid dependence. A decade later the FDA granted the drug company the right to promote naltrexone for the treatment of alcohol dependence. The brand name became ReVia. The dose was 50 mg.

Generic naltrexone continues to be prescribed for alcohol use disorders and opioid dependence. As mentioned, this drug is categorized as an opioid antagonist. That means it blocks opioid receptors. This is also why people taking opioid pain medicines or those who are physically dependent on opioids should not simply start naltrexone on their own. The FDA-approved labeling makes it clear that doctors should not prescribe naltrexone for people receiving opioid analgesics or those who are currently opioid-dependent.

What Is Low Dose Naltrexone?

Doctors have been experimenting with low dose naltrexone for a variety of conditions. One of the first studies was carried out in mice and published in Science (Aug. 12, 1983).

The authors reported that the low doses of naltrexone could inhibit the growth of the brain cancer neuroblastoma:

“These results show that naltrexone can modulate tumor response and suggest a role for the endorphin-opiate receptor system in neuro-oncogenic events.”

We were intrigued to discover an article in the journal Advances in Therapy (Feb. 2021) titled:

“Naltrexone’s Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures.”

The authors concluded:

“This review emphasizes the value of potential future research on NTX [naltrexone] in cancer therapy, and warrants need for a better understanding of underlying mechanisms. Future controlled studies with more robust sample sizes, particularly in humans, are needed to fully elucidate its potential in cancer therapy.”

A New York City physician, Dr. Bernard Bihari, started treating patients with low dose naltrexone (LDN) in the mid-1980s. He used doses of 3 mg to treat patients with HIV, autoimmune diseases and some cancers. Remember, the FDA-approved dose is much higher: 50 mg.

Other Uses for LDN:

Here are some of the articles we have written about low dose naltrexone (LDN):

Low Dose Naltrexone (LDN) Provides Surprising Pain Relief 

What do you know about low dose naltrexone (LDN) for pain? This drug has been around for decades and it just might help some people in pain.

Low Dose Naltrexone for Fibromyalgia and Other Nasty Conditions

Can Naltrexone Help Symptoms of Sjogren’s?

Low Dose Naltrexone Worked for Pain

We do not want to suggest that low dose naltrexone is some sort of all-purpose treatment for autoimmune disorders or pain problems. But there is growing interest in the drug for a variety of hard-to-treat conditions. We just wish there were bigger and better randomized controlled trials.

A Pilot Study Tests Low Dose Naltrexone for Long COVID:

There has been little to offer patients with long COVID. In case you have not been following the tale of woe and intrigue around this condition, here is a link that will provide an overview. Four years ago a pilot study suggested that there might be some benefit to trying low dose naltrexone for long COVID (Brain, Behavior, & Immunity – Health, Oct. 2022).

The authors introduced their study of low dose naltrexone for long COVID by stating:

“Up to 37.7% of patients experience symptoms beyond 12 weeks after infection with SARS-CoV-2. To date care for people with long covid has centred around multidisciplinary rehabilitation, self care and self pacing. No pharmacotherapy has been shown to be beneficial.”

The pilot study involved 52 patients.

“Patients who enrolled in the study received LDN 1 mg once daily for one month, the dose was increased by 1 mg monthly to a maximum of 3 mg.”

The authors reported that low dose naltrexone for long COVID helped with:

“…activities of daily living, energy levels, pain levels, levels of concentration, sleep disturbance and overall recovery from COVID-19…”

People also reported less chest tightness and cough. The authors acknowledged that this was not a placebo-controlled trial and called for larger, more robust studies.

In this study, patients took only 1 to 3 mg. Ideally, the NIH would sponsor a large, randomized controlled trial (RCT) of low dose naltrexone for long COVID. There are millions of people suffering. If there is something helpful, we need to know about it as soon as possible. Why hasn’t the government pursued this kind of research?

Final Words:

Long COVID remains a serious medical problem with few proven treatment options. Fatigue, brain fog, disturbed sleep and post-exertional malaise can interfere with work, family life and even basic activities of daily living. The accumulating evidence on low dose naltrexone for Long COVID is encouraging enough that we think it deserves serious scientific attention. But “encouraging” is not the same thing as “proven.”

The latest Stanford study had no control group. Neither did most of the earlier studies. A 2026 systematic review found suggestive benefits but rated the certainty of the evidence as low. That is exactly why a well-designed randomized, double-blind, placebo-controlled trial is so badly needed.

Naltrexone is an old, generic drug. At low doses it is inexpensive, and there is no blockbuster pharmaceutical market waiting to be created. Perhaps that helps explain why definitive trials have been slow to materialize. For people suffering from long COVID, though, the question is far from academic. If an old medicine costing relatively little really can reduce fatigue, brain fog or post-exertional malaise, patients and physicians deserve to know.

And if it doesn’t work better than placebo, they deserve to know that too.

If you have had any experience with low dose naltrexone, positive or negative, please share it in the comment section below.