In the months following a COVID infection, Olga Wehrly’s health kept deteriorating. The Dublin-based actor had trouble following conversations, even focusing for an extended period. “At one point, I was counting about 50 symptoms.”
After many doctor’s visits and failed treatments, she found a medication that helped: low-dose naltrexone, a drug best known for treating opioid overdoses.
In regular doses of 50 to 100 milligrams, naltrexone is used to treat people with substance use disorder, as it blocks the opioid receptors in the brain. In small quantities, usually 1/10 to 1/20 of a regular dose, naltrexone takes on several paradoxical qualities, relieving chronic pain and tamping down inflammation.
For decades, low-dose naltrexone, or LDN, has been used to treat a number of chronic conditions, including autoimmune disorders such as multiple sclerosis and Crohn’s disease, post-infectious conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and disorders that cause chronic pain, such as fibromyalgia. Now, as millions of people are suffering from long COVID, LDN is one of the very few treatments that can relieve their symptoms.
For Wehrly, LDN has helped alleviate her brain fog, which she compares to the feeling of getting kicked in the head by a donkey. “That feeling is mostly gone, unless I’m very overwhelmed by a lot of information or have done too much,” Wehrly said. LDN also gives her a bit more energy, staving off some of the crashes that often follow over-exertion, which has helped her care for her daughter, and return to part-time work.
“It is a remarkable drug,” said David Kaufman, a physician and founder of the Center for Complex Diseases in Mountain View, California, who has been prescribing LDN to patients since the 80’s, when it was originally used as a last-resort treatment for people with HIV. “I have a feeling we’ve only scratched the surface of what this drug can do.”
Fighting inflammation
Although naltrexone’s main mechanism of action is to block the opioid receptors in the brain, at very low doses naltrexone can tamp down inflammation in the body and brain. LDN reduces inflammation by inhibiting a molecule, called Toll-like receptor 4—that is found in a number of cells in the body, including those in the brain—and blocking it from producing factors that boost inflammation.
“Chronic inflammation is always bad,” said Jarred Younger, a neuroscientist at the University of Alabama Birmingham, whose research focuses on low-dose naltrexone. “Inflammation tends to spread, and it tends to migrate, and it tends to cause other inflammation.” As Younger notes, the advantage of low-dose naltrexone, compared to other anti-inflammatories, is that it can enter the brain in large enough quantities to have an effect.
For conditions such as ME/CFS, which is often triggered by a viral illness, and has many symptoms that overlap with long COVID, studies suggest inflammation in the brain is an issue. “That’s probably what’s causing the symptoms” such as brain fog and fatigue in long COVID patients, Younger said.
For several patients, such as Aliza Pressman, who lives in Seattle with her family, the major benefit of LDN is that it helps reduce this brain fog, restoring clarity to her thoughts. “It has helped me connect my thoughts to words better,” Pressman said. LDN can also help lessen the fatigue, giving patients a little bit more energy.
“It’s given me my life back, in that sense,” said Whitney Fox, a patient with ME/CFS who lives in Baltimore. For Fox who spent eight months in bed, unable to tolerate even the smallest stimulus, LDN enables her to tolerate sunlight and music and do more upright activities. “I can do some of the things that are rejuvenating and healing, that I couldn’t do before, with how severe my symptoms were,” Fox said. For Jennifer Dornan-Fish, an author with long COVID who lives in California, LDN has helped restore a measure of functionality. “I can write again, which gives me hope,” she said.
The other consequence of taking low-dose naltrexone is that by partially blocking the opioid receptors in the brain, it stimulates the release of endorphins—molecules produced by the body that relieve pain. It’s this property that has helped a number of chronic pain patients. For long COVID patients, this can help offset the flu-like aches and pains that many experience.
Studies are hard to fund
Naltrexone, which was developed in 1963, and received FDA approval for medical use in 1984, has the advantage of decades of research on its safety. “Overall, it has a great safety profile,” said Linda Geng, a primary care physician and co-director of the Stanford Post-Acute COVID-19 Syndrome Clinic. Since LDN is safe and has relatively few side effects, Geng estimates it helps roughly half of her long COVID patients; it is often the first medication Kaufman will prescribe for patients, usually at the first visit. “It is remarkably side effect free, and it can be remarkably helpful for patients,” Kaufman said. “It lets you hit the ground running.”
The drawback is that most research on the effectiveness of LDN is in the form of retrospective studies, which analyzes the benefits to patients who have taken the medication, rather than in the form of randomized, controlled trials, where the effectiveness of low-dose naltrexone is compared against a placebo. The lack of randomized controlled trials makes it hard to parse out what the effect of the medication was, versus what may have been from another factor.
However, a clinical trial currently underway at the University of British Columbia is looking at its effectiveness at treating long COVID patients. Further trials may help determine which patients will benefit the most from low-dose naltrexone and why, as well as the optimal dosage. “There’s a lot of nuance to this medication,” Geng said.
Access is an issue
For most of the patients that National Geographic interviewed, gaining access to LDN was a major issue. For patients such as Fox, although their doctor’s visits are paid for by insurance, their medication is not, because the doses they need aren’t commercially available, which means they need to pay to have it prepared at a specialty pharmacy. For other patients, the main issue is finding a doctor who is familiar with LDN and is willing to prescribe it.
For Wehrly, although she was initially prescribed LDN at a publicly funded long COVID clinic, it closed after several years, transferring her to another clinic that won’t prescribe LDN to their patients. Although she currently has a prescription that will last her until the end of 2023, once that runs out, she will need to pay to see a private doctor, in order to get a prescription. “It’s a generic, cheap drug,” Wehrly said. “It could be so accessible; it could be so helpful.”
