Low-Dose Naltrexone Therapy Improves Active Ulcerative Colitis (Abstract)

P-015 YI Low-Dose Naltrexone Therapy Improves Active Ulcerative Colitis

Inflam Bowel Dis
01 December 2013

Low-dose naltrexone (LDN) has shown promise in several clinical studies as a safe and effective treatment for Crohn’s disease (CD). Naltrexone is an opioid receptor antagonist. It acts as a competitive antagonist at several opioid receptor sites, showing the highest affinity for mu receptors. Studies have shown that opioids have immunomodulatory activity, including modulation of the inflammatory response and healing and repair of tissues. Short-term blockade of opioid receptors leads to increased endogenous levels of opioids, which is the basis for naltrexone use in CD. The belief is high levels of opioid receptor antagonism leads to a complete block of the receptors and prohibit the effect of the endogenous opioids. LDN therapy has been studied in the adult population with CD, but not in ulcerative colitis (UC). We describe a case of active UC treated with LDN in a young adult. An 18-year-old Caucasian female with a history of UC diagnosed in 2007 and treated initially with various mesalamine therapies (Asacol, Pentasa, Lialda) with intolerance due to increased rectal bleeding and severe headaches. Rectal mesalamine (Rowasa) was tried with minimal improvement. Endoscopic involvement consisted of continuous disease activity from the rectum to 45 cm with the most severe area of inflammation in the rectum. Pathology was consistent with active UC. Symptoms being endorsed were 5–10 loose, watery, bloody bowel movements along with nocturnal awakenings, but no abdominal pain, weight loss, fevers, chills, night sweats, or extraintestinal manifestations. Patient requested minimal therapy; hence, biologics and immunomodulators were not an option. LDN was tried with dramatic results within 1 month: 1–2 formed, non-bloody bowel movements per day and complete resolution of symptoms. The role of opioids and opioid receptors in the immune regulation has been a center of growing attention over the past decade. Pharmacological evidence has revealed that it has the highest affinity for mu receptors and also been shown to block TNF-alpha synthesis, suggesting that naltrexone may have anti-inflammatory effects. One study demonstrated the physiological role of mu opioid receptor (MOR) in the regulation of intestinal inflammation and the potential therapeutic benefit of using selective peripheral MOR agonists in IBD. This study investigated LDN as a potential treatment for CD in which 17 adult patients with endoscopic and histologic evidence of CD were enrolled and given 4.5 mg naltrexone/day in addition to their ongoing medications. Crohn's Disease Activity Index (CDAI) was assessed before the initiation of the LDN therapy and at follow-up visits 4, 8, 12, and 16 weeks after initiation. The results showed that with LDN therapy, CDAI scores decreased significantly (P < 0.001). Improvement was also recorded in both quality of life surveys compared with baseline. To the best of our knowledge, this is the first reported case of naltrexone effectiveness in the treatment of UC in a young adult. More studies are needed to evaluate its potential role in the management of IBD.