EFFICACY OF LOW DOSE NALTREXONE IN PATIENTS WITH CROHN’S COLITIS AND ILEITIS
Authors: Weinstock Leonard 
Published: January 2022

Abstract
In a Phase 2 placebo-controlled trial, low dose naltrexone (LDN) improved inflammation of the gastrointestinal mucosa and improved clinical activity scores in patients with mild to moderate Crohn’s disease (CD). We present two patients with symptomatic CD with a rapid clinical and endoscopic response to LDN: 1) Crohn’s colitis with prolonged maintenance to LDN which had failed mesalamine with immunomodulator therapy; and 2) Crohn’s ileitis with prolonged remission with addition of LDN to biologic and immunomodulator therapy. CASE 1: A 43-year-old male with a 23-year history of Crohn’s colitis of mild-to-moderate severity was previously treated with 150 mg mercaptopurine and mesalamine. Despite this treatment he had left-sided abdominal cramping, urgency, and 8-12 loose bowel movements with bleeding. Colonoscopy showed severe rectal ulcerations and normal ileum (Figure 1A). He started 1 mg oral naltrexone daily which was increased to 4 mg daily over 1 mo and a tapering course of budesonide. Mesalamine was continued. Six mo later, he stated he had 2 to 3 semi-formed bowel movements daily without bleeding or urgency. He was maintained on mesalamine and LDN 4.5 mg daily for 3 years. Colonoscopy showed dramatic improvement of rectal ulcerations and 3 small erosions in the proximal ascending colon which were not present on the previous colonoscopy (Figure 1B). At the time of this colonoscopy he was doing well clinically with a plan to augment LDN therapy with a probiotic and an anti-inflammatory diet. This case demonstrates favorable clinical and endoscopic response to an LDN-based regimen that was rapid and durable, with a short exposure to steroid. CASE 2: A 42-year-old female with a history of severe CD of the colon and ileum starting at age 27. She required total colectomy and end ileostomy at age 36. Three years after surgery she developed recurrent ileal ulcerations and strictures leading to further ileal resection. Later that year, ileoscopy demonstrated ileal ulcers (Figure 2A) and she was started on infliximab and mercaptopurine. She was stable for 3 years but then developed higher ileostomy output and fatigue. Methotrexate was substituted for mercaptopurine which helped reduce symptoms for 2 years. With increasing ostomy output, infliximab dosing interval was reduced from 8 weeks to 5 weeks which led to less output and less fatigue. After a year, symptoms returned, and naltrexone was added with 1 mg increasing to 4.5 mg over 1 month. Within 4 months, her symptoms were in remission and ileoscopy showed flat scars where ulcers had been seen in the past (Figure 2B). Her disease remained in endoscopic remission for 3 years documented by two more ileoscopies. The patient maintained clinical response to the combination of infliximab (6 week intervals), methotrexate, and LDN. Owing to a change in insurance she was lost to follow up at this point.
Figure 1. Rectal images before starting LDN for CD (A) and 3 years of maintenance therapy with LDN (B)

Figure 2. Ileal ulcers seen after the second surgery (A) and scar tissue seen at the ulcer sites at the time the patient with on infliximab, methotrexate, and LDN (B)