Why is low-dose naltrexone beneficial for many diverse diseases?

Recently, I’ve been doing some research into Hailey-Hailey Disease (HHD).  HHD is an autosomal dominant genetic disorder that leads to severe dermatosis.  The disease causing variants are located in the ATP2C1 gene, which is a magnesium-dependent, calcium transporting ATPase.

There are unfortunately few treatment options for HHD.  Many treatment options have been tried, from corticosteroids to tacrolimus.   There are very few HHD patients, and therefore no large scale clinical trials of therapies for this disease.

I came across a paper that shows that a novel approach, low-dose naltrexone (LDN), may be an effective and low-cost therapy for treating HHD.  What is more remarkable, however, is the fact that LDN has already been used with success to treat many diseases like fibromyalgia, Crohn’s disease, and HIV. 

Here is the complete list of diseases that LDN has been used to treat with some success according to some case reports and small-scale clinical trials:

Atopic eczema

Cholestatic pruritus

Crohn’s Disease

Adenoid cystic tongue carcinoma

Fibromyalgia

HIV

Multiple Sclerosis

Chronic eczema and pruritis

Hailey-Hailey Disease

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How is LDN effective across so many seemingly unrelated diseases?  I can’t really answer that question.  We do know that naltrexone is an opioid receptor inhibitor that is used in the treatment of alcohol and opioid abuse at higher doses.  At low dose, the mechanism of action is less clear, but some studies suggest increases in beta endorphins and suppression of cytokines using LDN.

As of now, LDN remains an “off-label” use of naltrexone and in the realm of internet anecdotes until more rigorous studies can be completed.  Regardless, it is an exciting development in the potential treatment of rare diseases, like HHD.

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