Low-Dose Naltrexone (LDN)

Naltrexone is an oral medication typically used to treat alcohol and opiate addiction. Some have suggested that low-dose naltrexone (LDN) might prevent MS attacks, help treat symptoms, and slow the overall course of the disease. Similar claims have been made for the use of LDN for treating AIDS, cancer, Crohn’s disease, and rheumatoid arthritis. Dr. Bernard Bihari, a New York physician, was the first to suggest LDN treatment for many diseases, including MS.

Treatment Approach

Regular doses of Naltrexone are around 50 milligrams per day; LDN is between 1.5 and 4.5 milligrams per day. There are several theories about how LDN might produce beneficial effects. LDN may increase the production of endorphins, thus alleviating pain and improving mood. Alternatively, LDN may provide therapeutic benefit by decreasing the formation of free radicals, harmful chemicals that may damage nerve cells and other tissue.

Evaluation in MS and Other Conditions

Until recently, only anecdotal evidence for LDN treatment of MS was available. Several recent studies involving MS and EAE, an animal model of MS, have produced preliminary findings. Two recent studies in EAE have suggested that LDN decreases nervous system inflammation, immune cell activation, and overall disease severity.

A study of 80 people with MS was recently conducted at the University of California-San Francisco (UCSF). This study suggested that LDN treatment does not affect physical functioning, but does improve several measures of mental health and pain. A smaller Italian study focused primarily on the safety of LDN was recently published in the journal Multiple Sclerosis. LDN was generally well tolerated. This study also reported that LDN treatment was associated with decreased spasticity and increased pain. LDN did not affect fatigue, depression, or quality of life.

The results of LDN research are suggestive, but not definitive. Many of these results are preliminary and have yet to be published. Both clinical studies mentioned are limited in size and scope: the Italian study did not include a placebo group and the UCSF study was not designed to evaluate disease activity. Furthermore, EAE research results often cannot be applied directly to MS, so these studies must be interpreted cautiously. Further research needs be completed to determine the safety and effectiveness of LDN in MS.

Adverse Effects

Safety data for LDN treatment in MS is not currently available. The two clinical trials conducted have suggested that it is usually well tolerated. Some people have reported “vivid dreaming” when they begin treatment. LDN appears to be associated with mild abnormalities of cholesterol, blood count, and liver function in some people. It may also cause irritability.


Although definitive information on LDN and MS is not currently available, some people may be interested in pursuing LDN therapy. Those interested should be aware of the limitations of the available research and should carefully discuss LDN with a health care professional before pursuing treatment.

References and Additional Readings


Bowling AC. Complementary and Alternative Medicine and Multiple Sclerosis. New York: Demos Medical Publishing, 2007, pp. 163-164.

Journal Articles

Agrawal YP. Low dose naltrexone therapy in multiple sclerosis. Med Hypotheses 2005;64:721–724.

Cree BA, Goodin DS, Ross M, et al. Low dose naltrexone improves quality of life in patients with multiple sclerosis: a randomized, masked, placebo-controlled trial. Mult Scler 2008;14:S295.

Cree BA, Ross M, Violich I, et al. A single center, randomized, placebo-controlled, double-crossover study of the effects of low dose naltrexone on multiple sclerosis quality of life. Neurol 2008;70,Suppl1:A88.

Gironi M, Martinelli-Boneschi F, Sacerdote P, et al. A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis. Mult Scler 2008;14:1076-1083.

Rahn KA, Bonneau RH, Turel AP, et al. Opioid growth factor (OGF) and low dose naltrexone (LDN) inhibit immunological responses associated with EAE. Mult Scler 2008;14:S234.

Rahn KA, McLaughlin PJ, Bonneau RH, et al. Low-dose naltrexone (LDN) prevents development or delays onset and severity of experimental autoimmune encephalomyelitis in mice. Mult Scler 1008;14:S84-S85.

Smith JP, Stock H, Ringaman S, et al. Low-dose naltrexone therapy improves active Crohn’s disease. Am J Gastroenterol 2007;102:1-9.

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