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Naltrexone Effective Against Ulcerative Colitis

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This first report of effectiveness in a single case study should prompt additional research and placebo-controlled trials.

Low-Dose Naltrexone Therapy Improves Active Ulcerative Colitis: A single case report. A Poster Session at AIBD 2013 Presenter: Susan Kais, Scripps Green Clinic and Hospital, La Jolla, Calif

Low-dose naltrexone has had promising results in the treatment of patients with Crohn disease, but there are no trials assessing its effectiveness in ulcerative colitis (UC). The investigator had an opportunity for a natural experiment because a patient in whom mesalamine treatment failed refused anti–tumor necrosis factor α (anti–TNF-α) agents and immunomodulators.

The patient is an 18-year-old woman with a 5-year history of UC who has been treated with 3 different oral mesalamine preparations, but usefulness has been limited by severe headaches. Recently, rectal bleeding has become severe and rectal mesalamine was tried, with minimal improvement. The patient was experiencing 5 to 10 loose, watery, bloody bowel movements daily, with nocturnal awakenings, but no abdominal pain, weight loss, fevers, chills, night sweats, or extraintestinal manifestations.

Endoscopy confirmed disease activity from the rectum to 45 cm proximal, with the most severe inflammation in the rectum; pathology confirmed UC. As above, the patient refused biologics and immunomodulators.

With poor options aside from colectomy, low-dose naltrexone, an opioid receptor antagonist, was tried. There was complete resolution of symptoms within 1 month-the patient now has 1 or 2 formed, nonbloody stools per day.

Naltrexone, currently used in the treatment of alcohol and opioid addiction, acts as a competitive antagonist at opioid receptor sites, especially the μ receptors, which may be involved in the regulation of intestinal inflammation. Blockade of these receptors leads to increased endogenous opioid levels and also may block TNF-α synthesis. The effect of these changes on immune function is thought to be the basis of naltrexone’s effectiveness in Crohn disease.

This first report of naltrexone’s effectiveness against UC in a single case study should prompt additional research and placebo-controlled trials. Fears about immunosuppression and neoplasm will lead a fair number of patients to refuse anti-TNF agents and immunomodulators. This new avenue of research could yield exciting results, with a drug now associated with serious immunosuppressive adverse effects.

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