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Low-Dose Naltrexone


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Naltrexone is approved by the U.S. Food and Drug Administration (FDA) for the treatment of addictions to opioids and alcohol. At the full recommended dose, Naltrexone blocks opioid docking sites on cells.

At significantly lower doses, Naltrexone has been prescribed as a treatment for a variety of diseases, including various types of cancers, HIV/AIDS, Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), emphysema, as well as multiple sclerosis (MS) and other autoimmune diseases. There has been limited clinical study of low-dose Naltrexone (LDN) to treat MS.

Studies examining LDN & MS

A pilot clinical trial involving 60 people with all types of MS testing low-dose Naltrexone suggested that it may improve several measures of mental health quality of life and pain, and that further testing in larger numbers of individuals may be warranted.

  • The study, by Bruce Cree, MD, Douglas Goodin, MD, and colleagues (MS Center, University of California at San Francisco), was published in the Annals of Neurology (Volume 68, Issue 2, pages 145–150, August 2010).
  • Some participants were using standard disease-modifying therapies during the trial and some were not. All participants received both the LDN for eight weeks and inactive dummy pills (placebo) for eight weeks in a study design known as “crossover,” with one week free of treatment in between. Some received the LDN during the first eight-week period and some during the second eight-week period.
  • Participants were given a Web-based battery of quality of life tests called the MS Quality of Life Inventory (MSQLI) before the first treatment period and after each study period. The MSQLI asks the individual to report on mental and physical aspects of their condition including mental health, pain, perceived cognitive deficits, fatigue, and visual, bladder and bowel symptoms and sexual satisfaction.
  • The investigators found that LDN significantly improved quality of life (specifically, mental health, pain and self-reported cognitive function), but no impact was observed on aspects of physical quality of life (such as fatigue, bowel and bladder control, sexual satisfaction, and visual function). Vivid dreaming was reported during the first week of treatment by some patients, but no other adverse effects were reported. The investigators emphasized that the results did not support the use of LDN instead of proven MS treatments.
  • The investigators suggest that LDN may provide symptomatic relief for MS. Based on some published laboratory studies, the investigators cite the possibility that LDN increases levels of endorphins in the brain, which are the body’s natural pain relievers. Unfortunately, as noted by the investigators, due to dropouts and incomplete data, they had complete data on only 60 of the 80 original participants, which weakened the statistical power of the trial results. They suggested that their findings require confirmation in a larger, multi-center clinical trial.

Results of a small trial of LDN were presented by Dr. Gianvito Martino (San Raffaele Hospital, Milan, Italy) at the 2008 Academy of Neurology meeting. The team administered 5 mg of LDN to 40 people with primary-progressive MS for six months, evaluating its safety and effects on spasticity, pain and fatigue. Five patients dropped out. Significant improvements were shown in fatigue and depression. Transient increases in liver enzymes, urinary tract infections, mild agitation and sleep disturbance were the most common adverse events.

A 17-week randomized, controlled study of low-dose naltrexone in 96 people with MS, published in 2010, found no statistically significant differences between the naltrexone-treated and placebo-treated groups on any of the following quality of life variables: pain, energy, emotional well-being, social cognitive and sexual functions, role limitations, health distress and overall quality of life. The authors concluded that although naltrexone appears to be a safe treatment option, a controlled trial of longer duration would be needed to demonstrate its effectiveness in improving quality of life for people with MS. 

LDN has also been investigated to a limited degree in animal models of MS. The National MS Society funded a pilot study by Ian Zagon, PhD (College of Medicine at Pennsylvania State University) looking at the effects of both low- and high-dose Naltrexone in mice and impacts on the MS-like disease, EAE. Based on earlier findings that opioids (which occur naturally on cells in the nervous system) may regulate immunity, wound healing and cell renewal, Dr. Zagon and colleagues were looking to see if mice treated with Naltrexone demonstrate any changes in their MS-like symptoms or underlying disease activity. His team found that low-dose naltrexone, but not high-dose naltrexone, was somewhat protective against the development of EAE. (Exp Biol Med (Maywood). 2009 Nov; 234(11):1383-92.)