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Addictive drug shows promise to eliminate long-term brain fog, fatigue

Addictive drug shows promise to eliminate long-term brain fog, fatigue

Lauren Nichols, a long-term patient with COVID, takes a break and rests in a lounger in the office at her home in Andover, Mass., on Aug. 3. Addiction drug could help those suffering from COVID. (Lauren Owens Lambert, Reuters)

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CHICAGO – Lauren Nichols, a 34-year-old logistics specialist for the US Department of Transportation in Boston, suffers from impaired thinking and focus, fatigue, seizures, headaches and pain from her Covid-19 infection in the spring of 2020.

Last June, her doctor suggested low doses naltrexone, a generic drug commonly used to treat alcohol and opioid addiction. After more than two years of living in a “thick, foggy cloud,” she said, “I can actually think clearly.”

Researchers long chasing a cure for COVID are eager to learn whether the drug can offer similar benefits to the millions who suffer from pain, fatigue and brain fog months after being infected with the coronavirus.

The drug has been used with some success in the treatment of a similar complex, post-infectious syndrome marked by cognitive deficits and overwhelming fatigue called myalgic encephalomyelitis/chronic fatigue syndrome. Building on its use in ME/CFS and a handful of long-running COVID pilot studies, at least four clinical trials are now planned to test naltrexone in hundreds of long-term COVID patients, according to a Reuters review of Clinicaltrials.gov and interviews with 12 ME/CFS and long-time COVID researchers.

It is also on a short list of treatments to be tested in the US National Institutes of Health’s $1 billion RECOVER Initiative, which aims to uncover the underlying causes and find treatments for lingering COVID, trial advisers told Reuters.

Unlike treatments aimed at addressing specific symptoms caused by COVID’s damage to organs, such as the lungs, low-dose naltrexone can reverse some of the underlying symptoms that drive the pathology, they said.

Naltrexone has anti-inflammatory properties and has been used for years in low doses to treat conditions such as fibromyalgia, Crohn’s disease and multiple sclerosis, said Dr. Jarred Younger, director of the Neuro-Inflammation, Pain and Fatigue Laboratory at the University of Alabama. in Birmingham.

At a dose of 50 milligrams—10 times the dose—naltrexone is approved for the treatment of opioid and alcohol addiction. Several generic manufacturers sell 50 mg tablets, but low-dose naltrexone must be purchased from a pharmacy.

Younger, author of a scientific review of the drug as a new anti-inflammatory, applied for a grant in September to study LDN for long-term COVID. “It should be at the top of everyone’s list for clinical trials,” he said.

However, the drug is unlikely to help everyone patients with long-term COVID, a collection of about 200 symptoms ranging from pain and palpitations to insomnia and cognitive impairment. One ME/CFS study of 218 patients found that 74% had improvements in sleep, reduced pain and neurological disturbances.

“It’s not a cure-all,” said Jaime Seltzer, a Stanford researcher and chief science officer for the advocacy group MEAction. “These people were not cured, but they were helped.”


It is not a panacea. These people were not cured, but they were helped.

–Jaime Seltzer, MEAction


‘human again’

dr. Jack Lambert, an infectious disease expert at University College Dublin’s School of Medicine, has used LDN to treat pain and fatigue associated with chronic Lyme disease.

During the pandemic, Lambert recommended LDN to colleagues treating patients with lingering symptoms after a bout of COVID.

It worked so well that he led a pilot study among 38 long-term COVID patients. They reported improvements in energy, pain, concentration, insomnia and overall recovery from COVID-19 after two months, according to findings published in July.

Lambert, who is planning a larger trial to confirm those results, said he believes LDN can repair the damage of the disease, not mask its symptoms.

Longtime COVID sufferer Lauren Nichols takes her second pill of the day of low-dose naltrexone at her home in Andover, Mass., on Aug. 3.
Lauren Nichols, a longtime COVID sufferer, takes her second low-dose naltrexone pill at her home in Andover, Mass., on Aug. 3. (Photo: Lauren Owens Lambert, Reuters)

Other planned LDN trials include one by the University of British Columbia in Vancouver and a pilot study by Ann Arbor, Michigan-based startup AgelessRx. That study of 36 volunteers should have results by the end of the year, said company co-founder Sajad Zalzala.

Scientists are still working to explain the mechanism of how LDN might work. Experiments by dr. Sonye Marshall-Gradisnik from the National Center for Neuroimmunology and Emerging Diseases in Australia suggests that ME/CFS and the long-term symptoms of COVID arise from a significant reduction in the function of natural killer cells in the immune system.

In laboratory experiments, LDN may have helped restore their normal function, a theory that still needs to be confirmed. Others believe that infections trigger immune cells in the central nervous system called microglia to produce cytokines, inflammatory molecules that cause fatigue and other symptoms associated with ME/CFS and long-term COVID. Younger believes that naltrexone calms these oversensitive immune cells.

dr. Zach Porterfield, a virologist at the University of Kentucky who co-chairs the RECOVER task force looking at commonalities with other post-infectious syndromes, said he recommended LDN be included in the RECOVER treatment trials. Other therapies being considered, the sources said, are antivirals such as Pfizer Inc’s Paxlovid, anti-clotting agents, steroids and nutritional supplements.

RECOVER officials said they have received dozens of proposals and cannot comment on which drugs will be tested until the trials are complete. dr. Hector Bonilla, co-director of the Post-Acute COVID-19 Clinic at Stanford and an advisor to RECOVER, used LDN in 500 ME/CFS patients, with about half reporting benefits.

He studied LDN in 18 long-term COVID patients, and 11 showed improvement, and said he believes larger, formal trials could determine whether LDN offers true benefit. Nichols, a patient advisor at RECOVER, was “ecstatic” to learn that LDN was being considered for government-funded trials. Although LDN hasn’t solved all of his COVID-related issues, Nichols is now able to work a full day without breaks and have a social life at home. “I feel human again.”

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