letter to the Editor re: Agrawal 2005

Medical Hypotheses  2006;67:671-672

Low-dose naltrexone for multiple sclerosis and autism:

Does its benefit reveal a common cause?

Agrawal [1] proposed that low-dose naltrexone helps multiple sclerosis (MS) patients by reducing the activity of inducible nitric oxide synthase, thought responsible for harmful concentrations of the inflammatory molecule nitric oxide in MS brains. It is no coincidence, I believe, that low-dose naltrexone has also helped patients with autism [2]. The rationale for this treatment is that naltrexone antagonizes endogenous opioids suspected to play a role in autistic behavior, but because nitric oxide is also high in autism, the benefit of naltrexone in both disorders may be primarily anti-inflammatory.

Vargas and colleagues [3] detected chronic inflammation in autistic brains – activated microglia and astroglia, and elevated levels of cytokines. Microglia and astroglia are also highly proliferated in multiple sclerosis. In MS, acute inflammation is usually detectable by MRI, while chronic inflammation is evident in the growth of plaques at their periphery. CNS demyelination, the hallmark of multiple sclerosis, has been observed in autistic brains.

Autism and MS have other features in common, notably liver pathology, intestinal inflammation, and glutathione disturbances, but the most provocative association may be evidence that mercury and other metals cause both diseases. The high incidence of MS following hepatitis B vaccinations, thought to be due to the mercury preservative thimerosal in the vaccine, has revived interest in the role of mercury in MS, proposed by Baasch in 1966, Ingalls in 1983, and others since. Thimerosal is also suspected to cause autism. Not only do the signs and symptoms of autism greatly resemble mercury poisoning [4], they have much in common with multiple sclerosis, including emotional disturbances, ataxia, and tremor.

One argument contra is that lymphocytes are often detected in MS lesions but not in autistic brains. Yet lymphocytes are not always present in the earliest MS lesions, as Roizin, Haymaker and D’Amelio, and Barnett and Prineas, observed. But if lymphocytes do play a pathogenic role in multiple sclerosis, the explanation could lie in the proposal that MS is a “metal-induced autoimmunity” [5].

Do autistic children develop MS as they get older? Some do, although this association has not been reported in the literature. One explanation may be the extreme sex difference between the diseases. Autistic children are usually male; multiple sclerosis is twice as common in women. Are male children more vulnerable to mercury neurotoxicity [6], adult females more vulnerable to mercury-induced autoimmunity?

Peter Good

Multiple Sclerosis Studies

Bend, OR


  1. 1.Agrawal YP. Low-dose naltrexone therapy for multiple sclerosis. Med Hypotheses 2005;64:721-724.

  2. 2.Cazzullo AG, Musetti MC, Musetti L, et al. Beta-endorphin levels in peripheral blood mononuclear cells and long-term naltrexone treatment in autistic children. Eur Neuropsychopharmacol 1999;9: 361-366.

  3. 3.Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005;57:67-81.

  4. 4.Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism: a novel form of mercury poisoning. Med Hypotheses 2001;56:462-471.

  5. 5.Stejskal J, Stejskal VD. The role of metals in autoimmunity and the link to neuroendocrinology. Neuro Endocrinol Lett 1999;20:351-364.

  6. 6.Geier MR, Geier DA. The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity. Med Hypotheses 2005;64:946-954.