Low-Dose Naltrexone May Be Opioid Replacement for Chronic Pain

For people who live with chronic pain, it can be a difficult decision to start taking medication to manage pain. People who take opioids for chronic pain may run the risk of developing opioid addictions.

But researchers have found that low-dose naltrexone, a medication traditionally used to help people who have struggled with substance abuse, may be helpful in treating widespread chronic pain conditions. Some of these conditions include:

• Fibromyalgia
• Complex regional pain syndrome
• Chronic pelvic pain
• Interstitial cystitis.

The systematic review included eight articles for evaluation that all looked at low-dose naltrexone's ability to reduce the intensity of chronic pain. The review was published in the December 2020 issue of the Journal of the American Dental Association.

The researchers believe that low-dose naltrexone (LDN) can also be used to manage orofacial pain—the pain of the face and the mouth. "LDN has use as a management tool that dental care providers can offer chronic facial pain patients," the researchers wrote.

What Is Low-Dose Naltrexone?

Naltrexone is a medication traditionally used to help people with substance abuse issues avoid drinking alcohol or taking non-prescribed medication. Naltrexone is not considered addictive. It is given in a tablet, when taken at home, and is usually taken once a day.

Research from the last decade shows low-dose naltrexone is helpful in managing pain from chronic conditions. A 2014 study published in the Clinical Rheumatology journal, for example, found that in patients with fibromyalgia (FM), low-dose naltrexone has anti-inflammatory markers. "Individuals with greater [erythrocyte sedimentation rate] at baseline experienced a greater drop in pain when taking LDN, despite that fact that FM is not considered to be a classic inflammatory disorder, and ESR values were in the normal to high-normal range," the researchers wrote.

Ilan Danan, MD, MSc, sports neurologist and pain management specialist at the Center for Sports Neurology and Pain Medicine at Cedars-Sinai Kerlan-Jobe Institute in California, tells Verywell that he would consider giving low-dose naltrexone to people with chronic pain who have a history of substance abuse issues. "For those that have struggled with addiction undoubtedly, that would be a patient base where one would consider it," Danan says.

Proof of Pain Reduction

The December systematic review highlighted how across four studies, people self-reported feeling a reduction in or an increased tolerance of chronic pain when taking 4.5 milligrams (mg) of low-dose naltrexone for fibromyalgia.

In his own practice, Medhat F. Mikhael, MD, pain management specialist and medical director of the non-operative program at the Spine Health Center at MemorialCare Orange Coast Medical Center in California, has witnessed the effectiveness of low-dose naltrexone in his own patients.

"Two mg to 3 mg once a day has been effective in some patients. We have gone as high as 4 or 5 mg," Mikhael tells Verywell. "It is a very safe drug to use, and the side effect profile is very, very low."

While major side effects from low-dose naltrexone are uncommon, Mikhel says that the few of his patients who experienced them were able to continue taking this medication as prescribed. "Some patients reported some fatigue and some anxiety, some dizziness, but [it was] very, very rare," he says.

The systematic review also looked at the role low-dose naltrexone can play in decreasing pro-inflammatory cytokine levels. Cytokines affect the growth of blood cells and other cells that help the body produce normal immune and inflammation responses. If there are high levels of inflammation in cytokines, the body will have an improper immune response.

The review highlighted a 2017 study that looked at cytokine levels of people with fibromyalgia who had been on low-dose naltrexone for eight weeks. The study found that low-dose naltrexone helped decrease inflammation in cytokines.

Managing Chronic Versus Acute Pain

When treating acute pain like musculoskeletal injury and post-surgical pain, Danan does not recommend that people be prescribed low-dose naltrexone. The review only looked at studies that reviewed low-dose naltrexone's effectiveness in people with chronic pain, not acute pain.

"It's really for those who are dealing with high levels of pain, day in and day out, where it's affected their quality of life," Danan says. "Medications such as naltrexone may be more helpful for those that are going to be exposed to a certain degree of a lifetime of pain."

A 2013 paper published in the American Family Physician journal recommended that the following pharmacologic treatments be considered for acute pain:

• Acetaminophen is the first-line treatment for most mild to moderate acute pain.
• Ibuprofen and naproxen are good first-line nonsteroidal anti-inflammatory drugs (NSAID) for mild to moderate acute pain based on effectiveness, adverse effect profile, cost, and over-the-counter availability.
• Cyclooxygenase-2 selective NSAIDs are second-line medications for mild to moderate pain based on their similar effectiveness to non-selective NSAIDs and greater costs.

Combining Low-Dose Naltrexone With Other Medication

Instead of replacing one medication used to treat chronic pain with another, Mikhael uses a multimodal approach. "We always say that pain is like a monster," he says. "The only way to kill the monster is to shoot at it from different angles and different mechanisms of action. 

Mikhael may prescribe low-dose naltrexone to treat a patient who has fibromyalgia. If the patient's pain is still not managed, Mikhael may prescribe pregabalin, a nerve pain medication, in addition. "Sometimes also we use low-dose naltrexone, we see some results, but there are other factors that we need to push it further, or help with other things that the low-dose naltrexone did not achieve," he says. "However, a combination of both can be very safe and complementary and get us good results."

Multimodal treatment for chronic pain of non-opioid is more effective in treating chronic pain than just taking an opioid medication for numerous reasons, according to Mikhael. One of the reasons is that chronic pain patients may develop hyperalgesia, an increased sensitivity to pain.

People who take opioids to manage chronic pain may also develop a dependency on them. "These patients go on narcotics...they think it's giving them good results," Mikhael says. "Three years later, the pain is way up back to an eight on a scale of zero to 10...It's because the central nervous system gets acclimatized."

Mikhael also finds that gabapentin, an anticonvulsant and nerve pain medication, and tricyclic antidepressants can be helpful when combined with low-dose naltrexone to manage chronic pain.

Non-Pharmacological Treatments for Chronic Pain

In addition to taking medication to help manage chronic pain, there are treatments beyond drugs that people can pursue. The Centers for Disease Control and Prevention suggests recommends that people with common chronic pain conditions pursue the following:

• If you have lower back pain, you should limit bed rest, exercise, do cognitive behavioral therapy (CBT), and do interdisciplinary rehabilitation.
• If you have migraines, you should avoid your migraine triggers, do CBT, relax, get biofeedback, and do exercise therapy.
• If you have osteoarthritis, you should exercise and try to be at a healthy weight.
• If you have fibromyalgia, you should do low-impact aerobic exercise, CBT, get biofeedback, and participate in interdisciplinary rehabilitation.