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Low Dose Naltrexone for Rheumatoid Arthritis

Posted on April 23, 2021
Medically reviewed by
Ariel D. Teitel, M.D., M.B.A.
Article written by
Emily Wagner, M.S.

Naltrexone is a drug traditionally used to treat the withdrawal symptoms associated with opioid use disorder and alcohol use disorder. However, researchers have recently looked into using low dose naltrexone (LDN) to treat inflammatory conditions, including rheumatoid arthritis (RA).

Naltrexone works by binding to specialized drug receptors in the brain, known as opioid receptors. In doing so, the naltrexone blocks other substances from binding to those receptors, thereby preventing the “high” associated with drugs and alcohol.

The first clinical trial of LDN for purposes outside of treating substance use disorders was performed in 2007, studying the drug’s effect in Crohn’s disease. The therapy has also been studied for treating severe symptoms of fibromyalgia, inflammatory bowel disease, and multiple sclerosis.

LDN therapy is currently being studied for treating rheumatoid arthritis. Only a handful of studies have been performed for LDN’s effect on the condition, and more research is needed to determine whether it is an effective RA treatment.

How Does LDN Work?

LDN therapy uses naltrexone to treat conditions other than those it was originally approved for by the U.S. Food and Drug Administration (FDA). This type of off-label drug treatment is a common practice, and there are many studies and clinical trials to support its use.

LDN uses a low dose of naltrexone, typically one-tenth of the dose used to treat opioid and alcohol use disorders. Most studies treat participants with 4.5 milligrams daily, but this amount can change depending on the condition being treated.

Effect on Immunity

When naltrexone is chemically synthesized, it can form one of two shapes, called dextro-naltrexone and levo-naltrexone. The forms have different effects on cells and receptors in the body, including the immune system.

Researchers believe that LDN therapy works because dextro-naltrexone binds to a few specialized receptors found on the surface of immune cells. When the drug binds to these receptors, it stops the release of inflammatory proteins (known as cytokines). This, in turn, dampens inflammation, which is what causes the joint damage in RA.

Levo-naltrexone also causes the release of endorphins, such as opioid growth factor (OGF). People with autoimmune diseases tend to have lower levels of OGF, which can lead to an imbalance in immune cells found in the body.

Effect on Pain

LDN seems to have other effects on the body when it is used at a low dose, including pain relief and anti-inflammatory effects. These findings are fairly recent and require more research to get a better understanding of these effects.

What Does the Research Say About LDN?

Although LDN treatment has been researched for treating some autoimmune diseases, there is currently little information for its use in RA.

One study found that people with RA who used LDN needed less medication for treating their condition, including commonly prescribed drugs such as disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and other pain relievers.

A clinical trial was also performed looking at LDN as a treatment for chronic pain from arthritis (including RA, osteoarthritis, and psoriatic arthritis). The study did not find any significant differences between participants, who were split into two groups. One group underwent LDN therapy for eight weeks, then took a placebo for the next eight weeks. The second group started with the placebo for eight weeks, then had LDN therapy for the next eight. This small, short study highlights the need for larger clinical trials that follow participants for a longer amount of time to help researchers understand the long-term effects of LDN therapy.

LDN Side Effects and Interactions

LDN appears to have few adverse side effects, including interactions with NSAIDs, which are commonly used by people with RA to help manage inflammation. In addition, LDN may be less likely than NSAIDs to cause kidney damage, blood clots, heart attack, or ulcers.

Some reported side effects of LDN include:

  • Vivid dreams or nightmares
  • Headaches
  • Increased heart rate
  • Anxiety

However, more research needs to be done to determine exactly how common these side effects are.

There is little to no research on how LDN may interact with other medications, including DMARDs (such as methotrexate) or corticosteroids. Your doctor will discuss a treatment plan with you to minimize any risks of adding LDN to your treatment plan.

Cost and Other Considerations for LDN

A main drawback to LDN treatment is that there is currently no formulation available in a low dose. Naltrexone is commercially available in 50-milligram tablets because it is only FDA-approved for treating alcohol and substance use disorders, which use higher doses. To get a low dose formula, naltrexone must be obtained through a compounding pharmacy, which may be different from where you typically get other medications or health supplies.

In general, the cost of naltrexone is very low. The average appears to be approximately $35 per month, including compounding in the low dose formula. Naltrexone is far less expensive than other treatments used for RA and other autoimmune conditions.

Connect With Others Who Understand

On myRAteam — the social network and online support group for those living with rheumatoid arthritis — members talk about a range of personal experiences and struggles. More than 148,000 members come together to ask questions, give advice, and share their stories with others who understand life with RA.

Have you used LDN to treat your RA? Share your experience in the comments below, or start a discussion on myRAteam.

All updates must be accompanied by text or a picture.
Ariel D. Teitel, M.D., M.B.A. is the clinical associate professor of medicine at the NYU Langone Medical Center in New York. Review provided by VeriMed Healthcare Network. Learn more about him here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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