Saturday, June 2, 2012


Opioid boost may ease Crohn’s symptoms

There is a lot of talk around the IBD community about the potential benefits of low-dose naltrexone (LDN) as a novel treatment for Crohn’s disease. The interest stems from two small pilot and follow-up studies by researchers Dr. Jill Smith and Ian Zagon at Pennsylvania State University, which suggest that a low dose of the generic drug naltrexone can improve symptoms and quality of life for some Crohn’s patients.

What is LDN therapy and is it a legitimate treatment option for IBD patients to consider?

Naltrexone hydrochloride is a blocker of the body’s natural opioid system. It was developed in the 1960s and later approved by the FDA to treat drug and alcohol dependence. With low-dose naltrexone therapy, patients receive a 4.5 milligram (mg) dose daily, about one-tenth of the normal FDA-approved dose of 50 mg for treating drug addiction and overdose.

Researchers don’t know exactly how LDN works. The proposed theory is that a low dose of the drug stimulates the body to make more of its endogenous (or “home-grown”) opioids, known as endorphins and enkephalins. A low dose is used because it blocks opioid receptors only temporarily, resulting in a rebound effect where more opioids are produced to compensate for a perceived deficiency. (A high dose blocks receptors continuously, which would prevent therapeutic effects from the opioids.) The higher opioid levels produced by the low dose of naltrexone help to control and reduce inflammation in the gut, and may have other beneficial effects on the immune system.

Dr. Keith Sharkey is the Crohn’s and Colitis Foundation of Canada Chair in IBD Research and well-known for his research on the role of the nervous system  in IBD at the University of Calgary. Dr. Sharkey is encouraged that LDN shows promise in controlling inflammation and improving symptoms in some patients with Crohn’s disease, but cautions that the findings are preliminary and limited to a small number of patients treated for only 12 weeks at a single research centre.

“The encouraging aspect is that beneficial effects were seen in some patients and this suggests the endogenous opiate system is important in Crohn’s disease. Further clinical trials are absolutely warranted and low-dose naltrexone has to be tested in a multi-centre study,” he says.
Dr. Sharkey emphasizes that there isn’t enough information yet to know whether LDN is effective, or who is most likely to benefit from the treatment. “This is not necessarily going to benefit everybody. We don’t know the optimal dose or the optimal way the drug should be used in Crohn’s patients. We don’t know for sure that it doesn’t do harm and an important question is whether it would interfere with existing therapies,” he says.

Despite those caveats, Dr. Sharkey believes it is worthwhile for patients interested in LDN to consider and discuss this treatment option with their doctors. “Talk to your doctor and ask whether it’s safe and appropriate for you,” he says.

One major benefit of these preliminary LDN studies is as a stimulus for more research in this area.

“This is a very exciting development from my perspective as a researcher. The promise is that we could target sites in the endogenous opioid system, and perhaps better regulate and control inflammatory conditions in the body. The ultimate would be to never get inflammation in the gut,” says Dr. Sharkey.

“If we can understand the endogenous opioid system better, we could perhaps prevent relapses from occurring as often or at all. If remission lasts longer, that’s as good as a cure.”  

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