by Chris Prange-Morgan

If you know anything about the the mild opioid naltrexone, it’s probably in the context of treating drug and alcohol addiction. But a growing body of research has shown that very small doses of naltrexone—less than a tenth of the amount used to treat substance abuse—can alleviate phantom limb pain and other forms of chronic pain without the unwanted side effects.

According to some estimates, chronic pain affects up to 40 percent of Americans. That figure includes the million-plus US amputees who report being challenged by phantom limb pain to one extent or another. Whether chronic pain results from limb loss or from another health condition, it takes an enormous toll on people’s relationships, job performance, and overall quality of life. It can be incredibly difficult and frustrating to treat, as pain signals remain active months or years after the precipitating injury or illness has apparently healed. These challenges are compounded by the hesitation (on the part of both patients and clinicians) to prescribe opioids for pain, due to the associated downsides.

But low-dose naltrexone (LDN) sidesteps those unwanted effects. Naltrexone binds to opioid receptors, blocking the sedative effects of opioid drugs while suppressing the cravings associated with addiction. When it’s used as a treatment for substance abuse, naltrexone is usually prescribed at around 50 mg. But a number of recent studies—including one specifically involving phantom limb pain—have demonstrated that far lower doses of naltrexone (from 1 to 4.5 mg) can alleviate many forms of chronic pain, including complex regional pain syndrome, fibromyalgia, orofacial pain, and various inflammatory and musculoskeletal conditions.

Bruce Vrooman, associate professor at Dartmouth’s Geisel School of Medicine and author of a 2018 review of low-dose naltrexone research, says LDN can be a game-changer for many chronic pain sufferers. “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,” Vrooman says. “It may truly help patients with their activities and make them feel better.”

Vrooman’s conclusions are consistent with the results of a 2021 case study published in BMJ Case Reports. In that instance, a combination of LDN and buprenorphine (another mild opioid) provided sustained relief to an amputee after a two-year battle with severe phantom limb pain. In a slightly larger case study published in Military Medicine in 2013, LDN and buprenorphine provided significant relief to four amputee veterans whose phantom limb pain had defied numerous other treatments, including nortriptyline, pregabalin, gabapentin, toradol, acupuncture, TENS, and various opioids.

And Dr. Neel Mehta, a pain specialist at Cornell Weill Medicine Center in New York City, has gotten good results from LDN with numerous patients suffering from phantom limb pain. “I see very little downside to it,” Mehta says. “We have a very good success rate of having patients try it and be pleased with it. There’s a wide variety of treatments, but LDN should be one of the mainstays.”

How Does LDN Work?

Scientists think many forms of chronic pain, including phantom limb pain, occur when 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. Researchers suspect that LDN dampens that inflammation and kick-starts the body’s production of pain-killing endorphins—all with relatively minor side effects.

Elizabeth Hatfield of the University of Michigan explains that LDN focuses on the overactive nervous system, whereas traditional pain management focuses on the site of injury or trauma. LDN targets the glial cells that keep the nervous system sensitized, thereby reducing the pain threshold and the sensitivity of the nervous system over time.

While opiates have historically been successful in dampening the sensitivity of pain receptors, it has been noted that they also come with significant risks for increased tolerance and overdose. LDN is much safer, and it’s not addictive. Patients and doctors alike tend to be much more open to less risky medications.

For all its promise, LDN hasn’t been studied widely enough to characterize it as a clinically proven cure for any type of chronic pain, including phantom limb pain. And management of phantom limb pain is never a one-size-fits-all approach. But the best outcomes result from honest communication between well-informed patients and their doctors. It’s important to weigh the risks, benefits, and realistic expectations of treating pain appropriately and effectively. LDN may be a viable part of that regimen. If you’re dealing with persistent, long-term phantom limb pain or any other type of chronic pain, it may be worth discussing the benefits and drawbacks of LDN with your doctor.

Chris Prange-Morgan is an adoptive parent, patient advocate, trauma survivor, and hospital chaplain. She co-hosts the Full Catastrophe Parenting podcast with her husband, Scott. This article originally appeared in Psychology Today.