Low Dose Naltrexone a ‘Game Changer’

By Alex Smith, Kaiser Health News

Lori Pinkley, a 50-year-old from Kansas City, Mo., has struggled with puzzling chronic pain since she was 15.

She has had countless disappointing visits with doctors. Some said they couldn’t help her. Others diagnosed her with everything from fibromyalgia to lipedema to the rare Ehlers-Danlos syndrome.

Pinkley has taken opioids a few times after surgeries, but they never helped her underlying pain. Recently she joined a growing group of patients using an outside-the-box remedy: naltrexone. It is typically used to treat addiction to opioids or alcohol, in pill form or as a monthly shot.

As the medical establishment attempts a huge U-turn after two disastrous decades of pushing long-term opioid use for chronic pain, scientists have been struggling to develop safe, effective alternatives.

When naltrexone is used to treat addiction in pill form, it’s prescribed at 50 milligrams. But chronic pain patients say it helps their pain at doses of less than a tenth of that.

Low-dose naltrexone (LDN) has lurked for years on the fringes of medicine, and its zealous advocates worry it may be stuck there. Naltrexone, which can be produced generically, is not even manufactured at the low doses that seem best for pain patients.

Instead, patients go to compounding pharmacies or resort to DIY methods — YouTube videos and online support groups show people how to turn 50 mg pills into a low-dose liquid.

Some doctors prescribe it off label even though it’s not FDA-approved for pain.


University of Kansas pain specialist Dr. Andrea Nicol recently started prescribing LDN to her patients, including Pinkley. Nicol explained that for addiction patients it works by blocking opioid receptors — some of the brain’s most important feel-good regions. So it prevents patients from feeling high and can help patients resist cravings.

At low doses of about 4.5 mg, however, naltrexone seems to work differently.

“What it’s felt to do is not shut down the system, but restore some balance to the opioid system,” Nicol said.

Some of the hype over low-dose naltrexone has included some pretty extreme claims with limited research to back them, like using it to treat multiple sclerosis and neuropathic pain or even using it as a weight-loss drug.

In the past two years, however, there’s been a significant increase in new studies published on low-dose naltrexone, many strengthening claims of its effectiveness as a treatment for chronic pain, though most of these were small pilot studies.

Dr. Bruce Vrooman, an associate professor at Dartmouth’s Geisel School of Medicine, authored a recent review of low-dose naltrexone research.

Vrooman said that, when it comes to treating some patients with complex chronic pain, low-dose naltrexone appears to be more effective and well-tolerated than the big-name opioids that dominated pain management for decades.

Those patients may report that this is indeed a game changer. It may truly help them with their activities, help them feel better.
— Dr. Bruce Vrooman

“Those patients may report that this is indeed a game changer,” Vrooman said. “It may truly help them with their activities, help them feel better.”

So how does it work? Scientists think that for many chronic pain patients the central nervous system gets overworked and agitated. Pain signals fire in an out-of-control feedback loop that drowns out the body’s natural pain-relieving systems.

They suspect that low doses of naltrexone dampen that inflammation and kick-start the body’s production of pain-killing endorphins — all with relatively minor side effects.

Drug Companies Not Promoting LDN

Despite the promise of naltrexone, its advocates say, few doctors know about it. The low-dose version is generally not covered by insurance, so patients typically have to pay out-of-pocket to have it specially made at compounding pharmacies.

Advocates worry that the treatment is doomed to be stuck on the periphery of medicine because, as a 50-year-old drug, naltrexone can be made generically.

Patricia Danzon, a professor of health care management at the Wharton School at the University of Pennsylvania, explains that drug companies don’t have much interest in producing a new drug unless they can be the only maker of it.

“Bringing a new drug to market requires getting FDA approval, and that requires doing clinical trials,” Danzon said. “That’s a significant investment, and companies — unsurprisingly — are not willing to do that unless they can get a patent and be the sole supplier of that drug for at least some period of time.”

And without a drug company’s backing, a treatment like low-dose naltrexone is unlikely to get the promotional push out to doctors and TV advertisements that has made household names of drugs like Humira and Chantix.

 “It’s absolutely true that once a product becomes generic, you don’t see promotion happening, because it never pays a generic company to promote something if there are multiple versions of it available, and they can’t be sure that they’ll capture the reward on that promotion,” Danzon said.

The drugmaker Alkermes has had huge success with its exclusive rights to the extended-release version of naltrexone, called Vivitrol. In a statement for this story, the company said it hasn’t seen enough evidence to support the use of low-dose naltrexone to treat chronic pain and therefore is remaining focused on opioid addiction treatment.

Lori Pinkley said it’s frustrating that there are so many missing pieces in the puzzle of understanding and treating chronic pain, but she, too, has become a believer in naltrexone.

She’s been taking it for about a year now, at first paying $50 a month out-of-pocket to have the prescription filled at a compounding pharmacy. In July, her insurance started covering it.

“I can go from having days that I really don’t want to get out of bed because I hurt so bad,” she said, “to within a half-hour of taking it, I’m up and running, moving around, on the computer, able to do stuff.”

A recent review by British researchers found that LDN is safe to use and more clinical studies are needed on its potential uses. PNN readers have shared their positive experiences using LDN to treat Interstitial Cystitis and fibromyalgia.

The LDN Research Trust includes a list of LDN-friendly doctors and pharmacies on its website.

This story is part of a partnership that includes KCUR, NPR and Kaiser Health News, a nonprofit news service covering health issues. KHN is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

Naltrexone ‘Changed Life’ of Fibromyalgia Patient

By Donna Gregory Burch

The pain in Janice Hollander’s legs was so excruciating that she wanted to cut them off. Diagnosed with fibromyalgia in 2013, she’d progressed through the normal litany of prescription drugs doled out by physicians – Lyrica, Cymbalta, gabapentin, muscle relaxers and narcotics – all without finding relief.

Then she happened to catch an episode of the Dr. Oz Show where a guest discussed using low-dose naltrexone (LDN) as a treatment for chronic pain. A few days later, she convinced her doctor to write a prescription and took her first dose of LDN.

“After about seven days, my pain lessened,” said Hollander of Michigan. “It lessened by 10 or 20 percent. That was huge! Even just that little bit of lessening was huge.”

After four weeks, the depression that had been stymying her for years lifted. At six weeks, she saw a noticeable increase in her energy levels. Her brain fog improved, and her memory returned.

Hollander has been taking LDN for about year now, and she’s probably one of its biggest fans within the fibromyalgia community. She regularly shares her success story in online support groups.

Hollander still has fibromyalgia symptoms, but they are more manageable thanks to LDN.

“I would say my leg pain is pretty much gone,” she said. “[LDN] has completely changed my life. I don’t know that I would be here today if it wasn’t for it. I don’t think I could go for another year in the misery I was in.” 

A growing number of fibromyalgia sufferers like Hollander are finding relief using LDN. It’s an unusual discovery since LDN is best known in the addiction treatment community. The U.S. Food and Drug Administration approved LDN to treat addiction to certain opiate drugs in 1984.

janice hollander

janice hollander

Dr. Jarred Younger, who conducted two LDN/fibromyalgia studies at Stanford University, believes LDN has an anti-inflammatory effect on the brain.

“This is one of the few drugs that can do that in the brain because it crosses the blood-brain barrier,” Younger said.

In simple terms, the brain contains microglial cells that look for problems within the central nervous system. When they discover an abnormality, these cells release chemicals into the body that cause fatigue, pain, cognitive disturbances and other symptoms common among fibromyalgia patients. In a healthy person, these chemicals are intended to slow down the body, to force it to rest, so that it can heal from whatever has caused the abnormality. In fibromyalgia, some researchers hypothesize this normal central nervous system response gets activated and doesn’t shut off.

“It’s like the central nervous system thinks you have an infection when you don’t,” Younger explained.

Fibromyalgia sufferers often speculate about what caused their condition, and researchers have debated various triggers for years. Viruses (herpes, Epstein Barr, etc.), chronic stress, genetics, obesity, aging and pollution are suspects, but according to Younger, it could be all of these.

He believes LDN works because it calms the microglial cells and reduces brain inflammation.

Penn State University researcher Ian Zagon posits a different mechanism behind LDN. Zagon’s opioid blockade hypothesis surmises that LDN blocks the brain’s opioid receptors, essentially tricking the body into increasing production of natural pain-suppressing chemicals.

Theoretically, both hypotheses could be correct.

Younger’s two Stanford University studies showed LDN outperformed Lyrica, Cymbalta and Savella, the three drugs currently approved to treat fibromyalgia in the U.S., and it did so with minimal side effects. The most common side effects are headache, insomnia, vivid dreams and nausea – all of which usually disappear over time.

“Probably 65 percent of people get an appreciable decrease of symptoms,” Younger said.

But more research is needed to confirm these early findings.

Next year, Younger will conduct at least two LDN/fibromyalgia studies at his new facility, the Neuroinflammation, Pain and Fatigue Lab at the University of Alabama at Birmingham.

One study will try to parse out the most effective dose of LDN for fibromyalgia. Most LDN users are prescribed the drug off-label, between 1.5mg and 4.5mg daily. But some rheumatologists have shared anecdotal accounts that certain patients respond better to higher doses, ranging up to 9mg.

A second trial will pair LDN with dextromethorphan, a common cough suppressant that’s believed to work similarly to LDN.

But many fibromyalgia sufferers aren’t waiting for the research. They’ve found ways to secure a prescription and try LDN for themselves.

Linda Elsegood, founder of the U.K.-based LDN Research Trust, has helped thousands of people gain access to LDN. She credits LDN with stabilizing her multiple sclerosis. At her worst, Elsegood was wheelchair bound, had no control of her bowels or bladder and had lost much of her sight and hearing. After 18 months on LDN, she was able to walk again on her own and had a reversal of most of her symptoms.

After her remarkable recovery, she wanted to educate others on the benefits of LDN.

“I wanted people to know that there is a choice, if you’ve been told, like me, that there’s nothing else that can be done for you,” she said. “Look into LDN. Do your research. … It is amazing the number of people who’ve found LDN works for them for so many different conditions.”

In addition to fibromyalgia, early research has found LDN to be useful in reducing the symptoms of certain autoimmune and central nervous system conditions, including multiple sclerosis, Crohn’s disease, rheumatoid arthritis and others.

But few doctors know about LDN as an emerging treatment, so it can be difficult to get a prescription.

“Some doctors are too busy to read the information,” Elsegood explained. “Some will not think outside of the box. It’s not what they learned in medical school, so they’re not prepared to consider something that is alternative. Other doctors won’t prescribe it because there aren’t enough trials.”

Unfortunately, it’s unlikely that any of the major drug companies will ever study LDN because it’s an older, generic drug and little profit can be made from it. So it falls to innovative researchers, like Younger, who secure donations and grants to fund trials.

Patients often encounter doctors who refuse to prescribe LDN even though it has a proven safety record and a low risk of side effects. The LDN Research Trust includes a list of LDN-friendly doctors and pharmacies on its website. For those who can’t find an LDN-friendly doctor locally, there are physicians who offer phone and online LDN consults.

“My advice is to always research it yourself, and then address it with your doctor,” Hollander said. “And if your doctor won’t agree to letting you try it, then find a doctor who will.

“I would drive to Florida to get it if I had to. It makes that big of a difference. I just wish more doctors would prescribe it, and more people would find help with it.”

For a list of helpful LDN resources, visit www.fedupwithfatigue.com/low-dose-naltrexone.

Donna Gregory Burch was diagnosed with fibromyalgia in 2014 after several years of unexplained symptoms. Donna is the founder of Fed Up with Fatigue, a blog devoted to helping those with fibromyalgia and ME/CFS live better with these conditions.

Donna is an award-winning journalist whose work has appeared online and in local newspapers and magazines throughout Virginia, Delaware and Pennsylvania. She lives in Delaware with her husband and their many fur babies.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.