The unique action of Low Dose Naltrexone (LDN) was discovered in 1979 by Dr. Ian S. Zagon and Dr. Patricia McLaughlin at Hershey Medical Center, Penn State University College of Medicine.

Dr. Zagon and Dr. McLaughlin were working together to understand the effect of opioids on the growth of neuroblastoma, one of the most common solid cancer-tumors in children. When they realized that specific opioids suppressed the cancer’s growth, they devised an experiment to ensure that the results were due to the opioids themselves and not any other unaccounted for effect.

They performed a study in which they used naltrexone to block the effects of the opioids. To verify the results, they also used naltrexone on its own to verify that blocking the cells’ access to opioids actually stimulated the cancer’s growth. Whilst testing different doses of naltrexone, they discovered an unexpected effect – that a very low dose of naltrexone on its own inhibited the growth of neuroblastoma.

Extensive experimentation between 1979 and 1981 clarified the precise mechanism of action of LDN, and the results were published in Science in August 1983 (Science 1983;221(4611):671-3). A detailed history of the discovery of LDN may be found in this interview with Dr. Ian S. Zagon.

The 1983 Science publication caused great interest amongst researchers and physicians. The significance of the findings was noticed by a bright physician, Dr. Bernard Bihari, then the director of the Division of Alcoholism and Drug Dependence, SUNY/Health Science Center at Brooklyn, New York. Dr. Bihari followed Dr. Zagon’s advice on the ideal dose for LDN and in 1985, once convinced of its safety, began prescribing it to AIDS patients who had no other treatment options.

Unable to obtain research funding or the interest of drug manufacturers, Dr. Bihari began prescribing LDN for multiple sclerosis patients (MS) in the mid 1990s. Word of the successful results with LDN began to spread, and it is now estimated that over 20,000 patients worldwide have LDN prescribed by their physicians to manage their MS.

In 2003, Moshe Rogosnitzky and Dr. Ian S. Zagon instigated a clinical trial of LDN for Crohn’s disease at Hershey Medical Center, Penn State University College of Medicine, under the direction of Dr. Jill P. Smith, Professor of Gastroenterology. The results of the successful trial were published in the American Journal of Gastroenterology in early 2007 (Am J Gastroenterol 2007;102(4):820-8). Since then two additional Phase II trials have been launched at Hershey Medical Center, one for adult Crohn’s disease and the other for pediatric Crohn’s disease. A case report has also been published by the Cleveland Clinic describing successful use of LDN in a child with treatment-resistant duodenal Crohn’s disease (Inflamm Bowel Dis 2009)

In 2008, researchers from Italy published successful results of a trial to treat MS with LDN (Multiple Sclerosis 2008;14(8):1076-83).

In 2009, Drs. Sean Mackey and Jarred Younger of Stanford University completed a successful trial of LDN in patients with fibromyalgia. The successful results were published in Pain Medicine in April 2009 (Pain Med 2009;10(4):663-72).

Whilst the mechanism of action of LDN in autoimmune disorders is assumed to be through upregulation of OGF production and interaction (as supported by a clinical trial in Europe which showed that OGF ameliorates MS and other autoimmune disorders), Dr. Zagon and his team have several studies underway in order to determine the precise molecular cascade that leads to the beneficial effects.  For details of these studies, please click here.