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7 Things To Know About Low-Dose Naltrexone for Rheumatoid Arthritis

Updated on October 03, 2022
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 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, 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 on Crohn’s disease. The therapy has also been investigated for treating severe symptoms of fibromyalgia, inflammatory bowel disease, and multiple sclerosis.

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

1. LDN Therapy Uses a Low Dose of Naltrexone as Treatment

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.

2. LDN Affects the Immune System

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 joint damage and pain 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.

3. LDN Has Been Studied for Potential Effects on Inflammation and 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.

4. The Research on LDN for RA Is Currently Limited

Although LDN treatment has been researched for treating some autoimmune disorders, there is currently little information on 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 randomized groups. One group underwent LDN therapy for eight weeks and took a placebo for the next eight weeks. The second group started with the placebo for eight weeks and 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.

5. So Far, There Are Few Reported Side Effects of LDN

LDN appears to have few adverse side effects, including interactions with NSAIDs, which are commonly used by people with RA to help manage pain and 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.

6. LDN Has To Be Obtained Through a Compounding Pharmacy

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

7. LDN Is Inexpensive Compared To Other RA Medications

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

If you’re struggling to maintain a good quality of life with RA, talk to your rheumatologist or another health care provider. They can answer your questions and concerns and help determine if you need to switch rheumatology treatments to better control your RA symptoms.

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 197,000 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? How did it affect your RA symptoms? 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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