Addiction drug shows promise lifting long COVID brain fog, fatigue

A 34-year-old American logistics specialist named Lauren Nichols Since contracting COVID-19 in the spring of 2020, Department of Transportation in Boston has been afflicted with problems with her memory and concentration, fatigue, seizures, headaches, and pain.

Her doctor recommended naltrexone, a generic drug typically used to treat alcohol and opioid addiction, in low doses last June.

She remarked that she could now think clearly after more than two years of living in "a thick, foggy cloud."

If the medication can provide similar benefits to millions of people experiencing pain, fatigue, and brain fog months after a coronavirus infection, it would be a welcome development for researchers searching for long-term COVID cures.

The medication has been used to treat a similar complex post-infectious syndrome known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is characterized by cognitive deficits and extreme exhaustion.

According to a Reuters review of Clinicaltrials.gov and interviews with 12 ME/CFS and long COVID researchers, there are currently at least four clinical trials planned to test naltrexone in hundreds of patients with long COVID, drawing on its use in ME/CFS and a few short-term pilot studies.

It is also among the few treatments that will be tested in the United States. According to trial advisers, the National Institutes of Health's $1 billion RECOVER Initiative seeks to identify the root causes of long-term COVID and develop treatments for it.

Low-dose naltrexone (LDN) may reverse some of the underlying pathology causing symptoms, they said, in contrast to treatments intended to address specific symptoms brought on by COVID damage to organs like the lungs.

According to Dr. Jarred Younger, director of the Neuro-inflammation, Pain and Fatigue Laboratory at the University of Alabama at Birmingham, naltrexone has anti-inflammatory properties and has been used for years in low doses to treat conditions like fibromyalgia, Crohn's disease, and multiple sclerosis.

Naltrexone is approved to treat alcohol and opioid addiction at a dose of 50 milligrams, which is 10 times the low dose. A compounding pharmacy is the only place to get low-dose naltrexone, which is available from a number of generic manufacturers in 50mg pills.

In September, Younger, who wrote a scientific review of the medication as a cutting-edge anti-inflammatory, submitted a grant application to research LDN for long COVID. It ought to be the first clinical trial that everyone considers, he said.

However, it is unlikely that the medication will help all of the patients with long COVID, a group of about 200 symptoms that includes everything from pain and heart palpitations to insomnia and cognitive impairment. In one ME/CFS study of 218 patients, sleep quality, pain levels, and neurological disturbances all improved in 74% of the patients.

Jaime Seltzer, a Stanford researcher and the organization MEAction's head of scientific outreach, said, "It's not a cure-all." "These people received assistance, not a cure."

Dr. Jack Lambert, an infectious disease specialist at University College Dublin School of Medicine, used LDN to treat the pain and exhaustion brought on by chronic Lyme disease in his book "HUMAN AGAIN."

Lambert advised LDN to coworkers caring for patients experiencing persistent COVID symptoms during the pandemic.

He conducted a pilot study with 38 long COVID patients because it worked so well. According to research results released in July, they reported enhancements in energy, pain, focus, insomnia, and general recovery from COVID-19 after two months.

Lambert said he thinks LDN may repair disease damage rather than just mask symptoms and he is planning a larger trial to confirm those findings.

A trial by the University of British Columbia in Vancouver and a pilot study by the Ann Arbor, Michigan-based startup AgelessRx are two additional LDN trials that are in the works. Sajad Zalzala, a co-founder of the company, predicted that the 36 volunteer study's findings would be available by year's end.

Researchers are still trying to pinpoint the mechanism by which LDN might operate.

Dr. Sonya Marshall-research Gradisnik's at the National Centre for Neuroimmunology and Emerging Diseases in Australia suggests that the symptoms of ME/CFS and long-term COVID are caused by a marked decline in the immune system's natural killer cell activity. Laboratory tests have shown that LDN may havehelped them regain their normal function, a hypothesis that needs to be verified.

Some people think infections cause immune cells called microglia in the central nervous system to produce cytokines, which are inflammatory molecules that cause fatigue and other symptoms of ME/CFS and long COVID. Younger thinks that naltrexone can reduce the sensitivity of these immune cells.

It has been suggested that LDN be included in RECOVER's treatment trials, according to Dr. Zach Porterfield, a virologist at the University of Kentucky and co-chair of a task force for RECOVER looking at similarities with other post-infectious syndromes.

According to sources, antivirals like Paxlovid from Pfizer Inc. (PFE.N), anti-clotting medications, steroids, and nutritional supplements were among the other treatments being considered. Officials from RECOVER stated that they have received numerous proposals and could not yet comment on the specific drugs that will be tested due to ongoing clinical trials.

About half of the 500 ME/CFS patients who received LDN treatment from Dr. Hector Bonilla, co-director of the Stanford Post-Acute COVID-19 Clinic and RECOVER adviser, reported positive results.

Eleven of the 18 long-term COVID patients he studied who received LDN showed improvements, and he said he believes larger, more official trials could determine whether LDN actually has a benefit.

When Nichols, a patient adviser to RECOVER, learned LDN was being considered for the government-funded trials, she was "ecstatic."

Nichols can now work all day without taking breaks and maintain a social life at home, even though LDN hasn't solved all of her COVID-related issues.

"I feel like a human again," she said.