Lori Pinkley, a 50-year-old from Kansas City, Mo., has struggled with puzzling chronic pain since she was 15. She's had endless 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 says they never helped her underlying pain. "I hate opioids with a passion," Pinkley says. "An absolute passion." Recently, she joined a growing group of patients using an outside-the-box remedy: naltrexone. It is usually used to treat addiction, in a pill form for alcohol and as a pill or a monthly shot for opioids. As the medical establishment tries to do 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 mg, but chronic-pain patients say it helps their pain at doses of less than a tenth of that. Low-dose naltrexone has lurked for years on the fringes of medicine, but its zealous advocates worry that it may be stuck there. Naltrexone, which can be produced generically, is not even manufactured at the low doses that seem to be 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 liquid dose. Some doctors prescribe it off-label even though it's not FDA-approved for pain. Dr. Andrea Nicol has recently started prescribing it to her patients, including Pinkley. Nicol explains 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 mgs, however, naltrexone seems to work completely differently. "What it's felt to do is not shut down the system, but restore some balance to the opioid system," Nicol says. 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 big increase in new studies published on low-dose naltrexone, many strengthening its claims as a treatment for chronic pain, though most of these were still small pilot studies. Dr. Bruce Vrooman, an associate professor at Dartmouth's Geisel School of Medicine, was an author of a recent review of low-dose naltrexone research. Vrooman says 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," Vrooman says. "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. Despite the promise of low-dose 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 says. "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 big promotional push out to doctors and TV advertisements that have turned drugs like Humira or Chantix into household names. "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 says. 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 says 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. Pinkley says she is frustrated 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 has 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 says, "to within a half-hour of taking it, I'm up and running, moving around, on the computer, able to do stuff." Source