Low-Dose Naltrexone for Treating MS Symptoms

What evidence says about using this opioid addiction drug off-label

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Low-dose naltrexone (LDN), a drug used to treat opioid addiction, is getting a lot of attention as an off-label treatment for multiple sclerosis (MS)—namely, for the reduction of symptoms and relapses. It's a popular treatment among MS patients, but scientific evidence supporting its use is just beginning to take shape.

That's not because early results haven't been promising—they have. Instead, it's because this is an inexpensive medicine that's been on the market for decades, meaning pharmaceutical companies have little financial interest in researching it.

In spite of that obstacle, scientists have learned a fair amount about LDN in recent years, and its use as an MS drug has now got a fairly compelling, although still preliminary, body of evidence behind it.

Woman holding a glass of water and pills, detail
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Naltrexone was approved by the U.S. Food and Drug Administration (FDA) in 1984 for the treatment of opioid addiction, and in 1994 to treat alcohol use disorder (AUD). At the full recommended dose—50 to 100 milligram (mg) per day—naltrexone blocks the effect of opioids and reduces a person's desire to drink.

Off-Label Use

While these are the only two FDA-approved uses for the drug, it is used for several other health issues in an off-label capacity.

At the time naltrexone was first developed, researchers at the Penn State College of Medicine began studying its use in treating autoimmune disorders (where the immune system mistakenly attacks the body's own cells). Multiple sclerosis is believed to be an autoimmune disease, with the immune system attacking and destroying the myelin coating of nerve fibers, impeding nerve functioning.

Some research supports the use of LDN for reducing the severity and frequency of MS symptoms. This drug is not considered a disease-modifying therapy.

The suspected effect of LDN is similar to what occurs during pregnancy, in which increased endorphin levels lead to extended MS remissions.

LDN is also being used off-label and/or researched as a treatment for:

In addition, it's been proposed as a treatment for multiple other conditions, including:

Effectiveness in MS

Researchers are beginning to understand the mechanisms of action in LDN, which are significantly different from that of full-strength naltrexone.

LDN is made up of two molecules. One of the molecules, dextro-naltrexone, binds to immune cells. The other, levo-naltrexone, attaches itself to opioid receptors. These actions are dose-dependent, meaning they happen in low doses but not higher ones.

The result of those molecular attachments includes several mechanisms that may lead to improvements in MS symptoms, including:

  • Alterations in immune function, including suppression of T cells and B cells, due to increasing endorphin, enkephalin, and opioid growth factor levels
  • Lowered neuroinflammation due to the altering of glial cell action in the central nervous system and down-regulating of TH17
  • Lowered inflammation in the rest of the body due to the inhibition of proinflammatory immune cells (including cytokines, TNF-a, NF-kB, and TH17)

A review of LDN research published in 2018 noted several beneficial outcomes from peer-reviewed studies using the drug to treat MS, including:

  • Safe and well-tolerated
  • Significantly reduced spasticity
  • Significant benefits for mental health
  • Improvement in quality of life
  • Reduced fatigue
  • Use as a single therapy resulted in stable disease state

However, not all results have been positive or consistent. The review cited:

  • One study showing LDN treatment resulted in no significant differences in quality of life, which conflicts with a later study
  • One study reporting side effects of insomnia and nightmares in a minority of cases
  • A survey that found treatment with LDN didn't reduce the amount of disease-modifying therapies people were prescribed


LDN is most commonly taken in pill form. Liquid sublingual (under the tongue) and transdermal (through the skin) forms are also available.

The dosages commonly prescribed in people with MS range from 1.5 milligrams (mg) to 4.5 mg per day. It is advised that people with any form of spasticity take no more than 3 mg daily, as it may contribute to muscle stiffness.

Typically, when prescribing doses higher than 1.5 mg, healthcare providers recommend starting at 1.5 mg and gradually increasing the dosage. Be sure to follow your practitioner's instructions and note any increase in side effects when you increase the dose.

Not Available at Standard Pharmacies

Low doses of naltrexone aren't available from standard pharmacies. You'll have to get it through a compounding pharmacy where it's specially made. Some local options may be available, depending on where you live, or you can try a trusted online option.

LDN can be taken with or without food. Some healthcare providers recommend taking it between 9:00 p.m. and midnight to correspond with the body’s natural peak endorphin release.

Side Effects

Naltrexone side effects are infrequent at low doses. The most common side effects include:

  • Vivid dreams
  • Sleep disturbance/insomnia
  • Nausea (typically subsides after about two weeks)
  • Constipation or diarrhea
  • Headache
  • Morning stiffness
  • Dry mouth

Ask your healthcare provider about the sublingual or transdermal forms of LDN if intestinal problems persist; these forms don't pass through the intestinal tract.

If sleep-related side effects are a problem for you, your healthcare provider may adjust the timing of your dosage.

In rare cases—less than 10 percent—symptoms may temporarily increase. This increase may last for a few weeks or, rarely, up to three months. If this happens to you, talk to your healthcare provider. You may be advised to lower your dosage temporarily.

Considerations and Contraindications

One of the main issues with using LDN is its interaction with many of the disease-modifying drugs used to treat MS. Based on the pharmacokinetic action of the drugs, LDN may interact with interferon drugs, including Avonex, Rebif, or Betaseron. By contrast, there appear to be no conflicts with Copaxone.

Because it is excreted from the body through the liver, LDN is not recommended for people with hepatitis, liver disease, or cirrhosis.

Studies haven't been done on the use of LDN and opioid medications together. Because of regular-strength naltrexone's effect on opioid receptors, it's recommended that you don't combine LDN with opioid drugs such as OxyContin (oxycodone), Vicodin (hydrocodone-acetaminophen), Ultram (tramadol), or codeine-based cough syrups.

So far, very little data exists on LDN during pregnancy or breastfeeding. Be sure to talk to your healthcare provider if you become pregnant or want to become pregnant while taking this drug.


LDN costs range from about $45 to $100 dollars for a month's supply, depending on which compounding pharmacy you go through. Because it's off-label for MS and considered an experimental treatment, your insurance may not cover it. Be sure to check with your carrier.

Refill Tip

The pharmacy may make this drug to order rather than keeping it in stock, so you may need to call in refills earlier than you're used to.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

By Julie Stachowiak, PhD
Julie Stachowiak, PhD, is the author of the Multiple Sclerosis Manifesto, the winner of the 2009 ForeWord Book of the Year Award, Health Category.