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Low Dose Naltrexone: An Old Drug that shows New Promise in treating many Chronic Medical Conditions.

photo credit: Delphine Ménard

Matt Weisser

"There is nothing new except what has been forgotten."

 

Marie Antoinette

Marie Antoinette's quote is a great reminder that at times, new uses can be found with old things, such is the case with the drug Naltrexone.  First synthesized as a competitive opioid antagonist in 1963, for many years research on Naltrexone remained dormant until it was FDA approved in 1984 for treatment of opioid addiction [1].  At the FDA approved doses of 50-100 mg per day, Naltrexone exhibits complete blockade of opioid receptors and thus resembles another closely related drug used emergently in acute opioid overdose; naloxone (Narcan®).

 

Low Dose Naltrexone (LDN) elicits what are referred to as paradoxical effects at these doses such that it can exert analgesic (pain relieving) and anti-inflammatory effects

Additional research with Naltrexone continued however with some researchers experimenting with daily doses approximately one-tenth (4.5mg +/- 1-2mg) of the FDA approved doses and they collected some interesting findings [2-4].  For instance, it was observed that Low Dose Naltrexone (LDN) elicits what are referred to as paradoxical effects at these doses such that it can exert analgesic (pain relieving) and anti-inflammatory effects [1]. This was startling to researchers because this is not what would be expected with an agent whose established mechanism of action is based on 'blocking' opioid receptors, hence the 'paradoxical' effect.  Additional hypotheses were clearly needed to help explain the pharmacologic effects of LDN though, because some doctors and healthcare providers were finding some success in treating their patients afflicted with chronic diseases and conditions such as fibromyalgia, complex regional pain syndrome, multiple sclerosis, and Crohn's disease. In many of these patients, they achieved some level of relief despite being unresponsive to other pharmacologic treatments.   While additional research on LDN is needed to work out its various mechanism(s) of action, an exciting possibility of this continued research is that additional insight may be gleaned in using LDN to treat other diseases and/or conditions.  Thus, despite having been around for more than 50 years, LDN continues to be relevant in treating many debilitating diseases and conditions.

 

References:

1. Younger J, Parkitny L, McLain D (2014). The Use of Low-dose Naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatol. 33:451-459

2. Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, Zagon IS (2011) Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease; a randomized placebo-controlled trial. Dig Dis Sci 56(7):2088-2097

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