Low-dose naltrexone for treatment of multiple sclerosis: clinical trials are needed.

TO THE EDITOR: Multiple sclerosis (MS) is generally thought to be an autoimmune disease. Current estimates suggest that there are up to 400 000 patients diagnosed with MS in the US.1 In all forms of MS, both inflammatory and neurodegenerative processes affect the disease. After receiving several questions regarding the use of low-dose naltrexone for MS, I performed a search of MEDLINE (1966-May 2007) and International Pharmaceutical Abstracts (1971-May 2007). One relevant article and one letter to the editor were found. The article offers a hypothesis on the potential mechanism of action of naltrexone in the treatment of MS: astrocytes and microglial cells produce peroxynitrites that inhibit glutamate transporters in neuronal cells and oligodendrocytes, resulting in excitatory glutamate neurotoxicity. Naltrexone may inhibit nitric oxide synthase activity, which may decrease the formulation of peroxynitrites, thus decreasing glutamate neurotoxicity.2,3 In this manner, naltrexone would affect the neurodegenerative processes of MS, unlike most of the currently approved treatments, which affect the inflammatory processes of the disease.1 In the letter to the editor, the author postulates that the same mechanism is the reason that naltrexone has been found to help autistic patients.4 Naltrexone is an opiate antagonist approved by the Food and Drug Administration (FDA) for the treatment of alcohol dependence and for the reversal of effects of an opioid.