Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial.

BACKGROUND: Cannabis is often used by patients with ulcerative colitis, but controlled studies are few. We aimed to assess the effect of cannabis in improving clinical and inflammatory outcomes in ulcerative colitis patients. METHODS: In a double-blind, randomized, placebo-controlled trial, patients received either cigarettes containing 0.5 g of dried cannabis flowers with80mgTetrahydrocannabinol (THC)or placebo cigarettes for 8 weeks. Parameters of disease including Lichtiger disease activity index, C reactive protein (CRP), calprotectin, Mayo endoscopic score and quality of life (QOL) were assessed before, during and after treatment. RESULTS: The study included 32 patients. Mean age was 30 years, 14 (43%) females. Lichtiger index improved in the cannabis group from 10.9 (IQR 9-14) to5 (IQR 1-7), (p<0.000), and in the placebo group from 11 (IQR 9-13) to 8 (IQR 7-10)(p = 0.15, p between groups 0.001). QOL improved in the cannabis group from 77±4 to 98±20 (p = 0.000) but not in the placebo group (78±3 at week 0 and 78±17 at week 8;p = 0.459; p between groups 0.007). Mayo endoscopic score changed in the cannabis group from 2.13±1 to 1.25±2 (p = 0.015) and in the placebo group from 2.15±1to 1.69±1 (p = 0.367, p between groups 0.17). CONCLUSION: Short term treatment with THC rich cannabis induced clinical remission and improved quality of life in patients with mild to moderately active ulcerative colitis. However, these beneficial clinical effects were not associated with significant anti-inflammatory improvement in the Mayo endoscopic score or laboratory markers for inflammation.(clinicaltrials.gov NCT01040910).

Cannabinoid receptor 2 agonist promotes parameters implicated in mucosal healing in patients with inflammatory bowel disease.

BACKGROUND: Cannabis benefits patients with inflammatory bowel disease (IBD). Cannabinoid receptors are expressed in gut immune cells and in epithelial cells of inflamed guts. Mucosal healing (MH) requires epithelial layer restoration. OBJECTIVE: To analyze the effects of CB2 agonist on parameters implicated in gut inflammation and MH. METHODS: Mucosal samples from areas of inflamed/uninflamed colon from 16 patients with IBD were cultured without/with cannabinoid receptor 2 (CB2) agonist (JWH-133, 10 µM, 6 hours (hr)), and analyzed for epithelial/stromal cell proliferation, apoptosis (secretome matrix metalloproteinase 9 (MMP9) activity, which impairs epithelial permeability) and interleukin-8 (IL-8) levels (n = 5-9). In addition, Caco-2 (colon carcinoma epithelial cells) were cultured with biopsy secretomes (48 hr), and analyzed for phenotype and protein markers of proliferation (proliferating cell nuclear antigen), autophagy (LC3IIB) and permeability (Zonula occludens-1) (n = 4-6). RESULTS: Uninflamed tissue had higher epithelial proliferation (Ki67: 50%↑, p < 0.05), and reduced secretome MMP9 activity and IL-8 levels (>50%↓, p < 0.05) compared to inflamed tissue. Treatment with CB2 agonist had no effect on epithelial apoptosis, but increased epithelial Ki67 expression (25%), and reduced secretome MMP9 and IL-8 levels in inflamed biopsies. Secretomes of CB2-treated biopsies increased Caco-2 number, migration, proliferating cell nuclear antigen and LC3IIB expression (all, p < 0.05), but had no effect on ZO-1. CONCLUSION: Using ex vivo and in vitro human models, we demonstrated that manipulating the cannabinoid system affects colon cells and secretome characteristics that facilitate MH in IBD.

Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption and assessment of side-effects.

OBJECTIVE: Use of medical cannabis for improving symptoms of inflammatory bowel disease is increasing. However, reports on long-term outcomes are lacking. This prospective, observational study assessed the effects of licensed cannabis use among patients with inflammatory bowel disease. METHODS: Dose and mode of consumption, adverse events, use of other medications, and long-term effects were evaluated among 127 patients with inflammatory bowel disease using legalized medical cannabis. Blood count, albumin, and C-reactive protein were assessed before, 1 month, and at least 1 year after medical cannabis therapy was initiated. Questionnaires on disease activity, patient function, and signs of addiction were completed by patients and by a significant family member to assess its effects. RESULTS: The average dose used was 31 ± 15 g/month. The average Harvey-Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P < 0.001) during a median follow-up of 44 months (interquartile range, 24-56 months). There was a slight, but statistically significant, average weight gain of 2 kg within 1 year of cannabis use. The need for other medications was significantly reduced. Employment among patients increased from 65 to 74% (P < 0.05). We conclude that the majority of inflammatory bowel disease patients using cannabis are satisfied with a dose of 30 g/month. We did not observe negative effects of cannabis use on the patients' social or occupational status. CONCLUSIONS: Cannabis use by inflammatory bowel disease patients can induce clinical improvement and is associated with reduced use of medication and slight weight gain. Most patients respond well to a dose of 30 g/month, or 21 mg Δ9-tetra- hydrocannabinol (THC) and 170 mg Cannabidiol (CBD) per day.

Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial.

OBJECTIVES: Ginger is one of the most commonly used herbal medicines for irritable bowel syndrome (IBS) but no data exists about its effectiveness. DESIGN: Double blind randomized controlled trial. SETTING: University of North Carolina, Chapel Hill, North Carolina, USA. INTERVENTION: Forty-five IBS patients were randomly assigned to three groups: placebo, 1g of ginger, and 2g of ginger daily for 28 days. MAIN OUTCOME MEASURES: The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment. RESULTS: There were 57.1% responders to placebo, 46.7% to 1g and 33.3% to 2g of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups. CONCLUSIONS: This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn.

Recommendations for probiotic use-2011 update.

This study describes the consensus opinion of the participants of the third Yale Workshop on probiotic use. There were 10 experts participating. The recommendations update those of the first 2 meetings that were published in 2005 and 2008. The workshop presentations and papers in this supplement relate to the involvement of normal microbiota involved in intestinal microecology, how the microbes interact with the intestine to affect our immunologic responses, the stability and natural history of probiotic organisms, and the role of the intestinal microbatome with regard to affecting cardiac risk factors and obesity. Recommendations for the use of probiotics in necrotizing enterocolitis, childhood diarrhea, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile diarrhea are reviewed. As in previous publications, the recommendations are given as A, B, or C ratings. The recent positive experiences with bacteriotherapy (fecal microbiome transplant) are also discussed in detail and a positive recommendation is made for use in severe resistant C. difficile diarrhea.

Rifaximin therapy for patients with irritable bowel syndrome without constipation.

BACKGROUND: Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS. METHODS: In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study. RESULTS: Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools. (Funded by Salix Pharmaceuticals; ClinicalTrials.gov numbers, NCT00731679 and NCT00724126.).

Randomized controlled trial shows biofeedback to be superior to pelvic floor exercises for fecal incontinence.

PURPOSE: This study aimed to compare manometric biofeedback with pelvic floor exercises for the treatment of fecal incontinence in a randomized controlled trial controlling for nonspecific treatment effects. METHODS: After excluding patients who were adequately treated with medication, education, and behavioral strategies (21%), 108 patients (83 females; average age, 59.6 years) underwent either pelvic floor exercises alone (n = 63) or manometric biofeedback plus pelvic floor exercises (n = 45). Patients in both groups were taught behavioral strategies to avoid incontinence. RESULTS: At three-month follow-up, biofeedback patients had significantly greater reductions on the Fecal Incontinence Severity Index (P = 0.01) and fewer days with fecal incontinence (P = 0.083). Biofeedback training increased anal canal squeeze pressure more than pelvic floor exercises did (P = 0.014) and with less abdominal tension during squeeze (P = 0.001). Three months after training 76% of patients treated with biofeedback vs. 41% patients treated with pelvic floor exercises (chi-squared = 12.5, P < 0.001) reported adequate relief. Before treatment, the groups did not differ on demographic, physiologic, or psychologic variables, symptom severity, duration of illness, quality-of-life impact, or expectation of benefit. At 12-month follow-up, biofeedback patients continued to show significantly greater reduction in Fecal Incontinence Severity Index scores (F = 4.83, P = 0.03), and more patients continued to report adequate relief (chi-squared = 3.64, P = 0.056). CONCLUSION: This investigation provides definitive support for the efficacy of biofeedback. Biofeedback training resulted in greater reductions in fecal incontinence severity and days with fecal incontinence. Biofeedback was also more effective than pelvic floor exercises alone in producing adequate relief of fecal incontinence symptoms in patients for whom conservative medical management had failed.

Randomized, controlled trial shows biofeedback to be superior to alternative treatments for patients with pelvic floor dyssynergia-type constipation.

PURPOSE: This study was designed to determine whether biofeedback is more effective than diazepam or placebo in a randomized, controlled trial for patients with pelvic floor dyssynergia-type constipation, and whether instrumented biofeedback is necessary for successful training. METHODS: A total of 117 patients participated in a four-week run-in (education and medical management). The 84 who remained constipated were randomized to biofeedback (n=30), diazepam (n=30), or placebo (n=24). All patients were trained to do pelvic floor muscle exercises to correct pelvic floor dyssynergia during six biweekly one-hour sessions, but only biofeedback patients received electromyography feedback. All other patients received pills one to two hours before attempting defecation. Diary data on cathartic use, straining, incomplete bowel movements, Bristol stool scores, and compliance with homework were reviewed biweekly. RESULTS: Before treatment, the groups did not differ on demographic (average age, 50 years; 85 percent females), physiologic or psychologic characteristics, severity of constipation, or expectation of benefit. Biofeedback was superior to diazepam by intention-to-treat analysis (70 vs. 23 percent reported adequate relief of constipation 3 months after treatment, chi-squared=13.1, P<0.001), and also superior to placebo (38 percent successful, chi-squared=5.7, P=0.017). Biofeedback patients had significantly more unassisted bowel movements at follow-up compared with placebo (P=0.005), with a trend favoring biofeedback over diazepam (P=0.067). Biofeedback patients reduced pelvic floor electromyography during straining significantly more than diazepam patients (P<0.001). CONCLUSIONS: This investigation provides definitive support for the efficacy of biofeedback for pelvic floor dyssynergia and shows that instrumented biofeedback is essential to successful treatment.