Treating Symptoms of MS With Low-Dose Naltrexone

Does the current evidence support its use?

Low dose naltrexone to treat symptoms of multiple sclerosis
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Is it possible that a drug used to treated opioid and alcohol addiction may improve the lives and outlook of people living with multiple sclerosis (MS)?

Some research suggests that it may. While not approved for such use, low-dose naltrexone (LDN) is being increasingly prescribed off-label to treat MS-related fatigue, a common and often debilitating symptom of the disease.

Approved Use of Naltrexone

Naltrexone was approved by the U.S. Food and Drug Administration 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 per day), naltrexone blocks the effect of opioids and reduces a person's desire to drink.

In both capacities, naltrexone has been shown to deliver modest to poor results in curing addition but may be beneficial when used as part of a structured, directly observed treatment program.

Off-Label Use of Naltrexone

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 by many to be caused by an autoimmune response and was among the earliest candidates for investigation. What the researchers found was that extremely low doses of the drug bolstered the production of the hormone endorphin, resulting in increased energy levels and a potent anti-inflammatory response.

It is similar to what occurs during pregnancy where increased endorphin production associated with extended periods of MS remission.

While there has yet to be any hard clinical evidence to support a hypothesis, some researchers believe that LDN may be able to reduce the severity and frequency MS symptoms such as fatigue, pain,  spasticitycognitive dysfunction, and depression.

Treatment Recommendations

When prescribed in such small doses (less than 10 percent of that used in addiction therapy), LDN is considered safe and well-tolerated.

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

LDN can be taken with or without food but should be taken between 9:00 p.m. and midnight to correspond work the body’s natural peak endorphin release.

The most common side effect of LDD is vivid dreams which tend to subside after the first week or two. Less commonly, irritability has also been known to occur.

Considerations and Contraindications

One of the main conflicts in 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 should not be used with 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 persons with hepatitis, liver disease, or cirrhosis.

LDN should never be combined with any opiate-based drugs including Oxycontin (oxycodone), Vicodin (hydrocodone).or even codeine-based cough syrups.

Reviewing the Current Evidence

While popular consensus may suggest that LDN contributes to the improved health and well-being of people with MS, the actual evidence has mostly been mixed. Among them:

  • A pilot study conducted at the University of California at San Francisco included 80 people with MS who were treated with LDN over eight weeks. While LDN did not alter the physical function or capacity of the participants, it did provide statistically significant improvements in their quality of life (including a reduction in pain and depression as well as increases in cognitive function).
  • A Phase II trial conducted in Italy in 2008 looked at 40 people with primary-progressive MS on LDN treatment for six months. In the end, there were statistical improvements in spasticity (47 percent improved, 11 percent worsened) but no improvement in either depression (56 percent improved, 33 percent worsened) or fatigue (33 percent improved, 41 percent worsened). By contrast, LDN was associated with a statistical worsening of pain (28 percent improved, 56 percent worsened).
  • A 17-week randomized, controlled study in 2010 found no statistical difference between people taking LDN or a placebo or any improvement in the quality of life variables, including pain, energy, cognitive function, and emotional well-being.
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    Article Sources
    • Cree, B.; Kornyeyeva, E.; and Goodin, D. "Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis." Annals Neurol. 2010; 68(2):145-150.
    • Gironi, M.; Martinelli-Boneschi, F.; Sacerdote, P. et al. "A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis." Mult Scler. 2008;14(8):1076-83.
    • Sharaaddinzadeh, N.; Moghtederi, A.; Kashipazha, D. et al. "The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial." Mult Scler. 2010; 16(8):964-9.