Important relation between self-efficacy, sense of coherence, illness perceptions, depression and anxiety in patients with inflammatory bowel disease.

INTRODUCTION: Anxiety and depression are common disturbances in patients with inflammatory bowel diseases (IBD), and were found to impact the disease course. Illness perceptions (IPs), self-efficacy (SE) and sense of coherence (SOC) are important psychological functions, used by the individual to cope with his chronic disease. AIMS: to investigate the association of IP, SE and SOC on anxiety and depression among patients with IBD. PATIENTS AND METHODS: Patients filled questionnaires including: demographic, socioeconomic and clinical features. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. IP, SE and SOC were assessed using the Brief Illness perception Questionnaire, IBD-SE and SOC scales. RESULTS: The study sample consisted of 299 patients with IBD, median age 34.15, 63% females, 70.9% had Crohn's disease, filled the questionnaires. In the multivariate analysis, lower results in IP, SE and SOC were found to be associated with significantly increase anxiety (OR 8.35, p<0.001; OR 4.18, p=0.001; OR 4.67, p<0.001, respectively) and depression (OR 15.8, p=0.001; OR 10.99, p=0.029; OR 6.12, p=0.014. CONCLUSIONS: Anxiety and depression are associated with IP, SE and SOC in patients with IBD. Clinicians should be aware of this impact, recognise their patients' psychological abilities to cope with the disease and improve those abilities, when needed, in order to achieve a better coping with the disease and to prevent the development of anxiety and depression.

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.

Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn's Disease, a Randomized Controlled Trial.

BACKGROUND: Cannabidiol (CBD) is an anti-inflammatory cannabinoid shown to be beneficial in a mouse model of IBD. Lacking any central effect, cannabidiol is an attractive option for treating inflammatory diseases. AIM: To assess the effects of cannabidiol on Crohn's disease in a randomized placebo-controlled trial. PATIENTS AND METHODS: Twenty patients aged 18-75 years with a Crohn's disease activity index (CDAI) >200 were randomized to receive oral (10 mg) CBD or placebo twice daily. Patients did not respond to standard treatment with steroids (11 patients), thiopurines (14), or TNF antagonists (11). Disease activity and laboratory parameters were assessed during 8 weeks of treatment and 2 weeks thereafter. Other medical treatment remained unchanged. RESULTS: Of 20 patients recruited 19 completed the study. Their mean age was 39 ± 15, and 11 were males. The average CDAI before cannabidiol consumption was 337 ± 108 and 308 ± 96 (p = NS) in the CBD and placebo groups, respectively. After 8 weeks of treatment, the index was 220 ± 122 and 216 ± 121 in the CBD and placebo groups, respectively (p = NS). Hemoglobin, albumin, and kidney and liver function tests remained unchanged. No side effects were observed. CONCLUSION: In this study of moderately active Crohn's disease, CBD was safe but had no beneficial effects. This could be due to lack of effect of CBD on Crohn's disease, but could also be due to the small dose of CBD, the small number of patients in the study, or the lack of the necessary synergism with other cannabinoids. Further investigation is warranted. CLINICALTRIALS.GOV: NCT01037322.

Cannabis for inflammatory bowel disease.

The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds. Studies have revealed that the endocannabinoid system is involved in almost all major immune events. Cannabinoids may, therefore, be beneficial in inflammatory disorders. In murine colitis, cannabinoids decrease histologic and microscopic inflammation. In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis. Despite anecdotal reports on medical cannabis in inflammatory bowel disease (IBD), there are few controlled studies. In an observational study in 30 patients with Crohn's disease (CD), we found that medical cannabis was associated with improvement in disease activity and reduction in the use of other medications. In a more recent placebo-controlled study in 21 chronic CD patients, we showed a decrease in the CD activity index >100 in 10 of 11 subjects on cannabis compared to 4 of 10 on placebo. Complete remission was achieved in 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity. In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use.

Treatment of Crohn's disease with cannabis: an observational study.

BACKGROUND: The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn's disease (CD) was ever published. OBJECTIVES: To describe the effects of cannabis use in patients suffering from CD. METHODS: In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn's disease. RESULTS: Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 +/- 6.7 to 7 +/- 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use. CONCLUSIONS: This is the first report of cannabis use in Crohn's disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.

Treatment of preestablished diet-induced fatty liver by oral fatty acid-bile acid conjugates in rodents.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries. It has no accepted medical therapy. Fatty acid-bile acid conjugates (FABACs) were proven to prevent diet-induced NAFLD in rodents. AIM: This study was undertaken to test whether oral FABACs are also effective in reducing liver fat in preestablished diet-induced NAFLD. METHODS: NAFLD was induced in mice and rats by a high-fat diet and maintained by various proportions thereof. The FABACs used were conjugates of cholic acid with either arachidic or stearic acids. RESULTS: FABAC therapy reduced liver fat in all four series of experiments. The rapidity of the effect was inversely proportional to the concentration of fat in the maintenance diet. In mice on a 25% maintenance diet FABACs decreased total liver lipids by about 30% in 4 weeks (P<0.03). Diglycerides (P<0.003) and triglycerides (P<0.01) were the main neutral liver lipids that decreased during FABAC therapy. Both FABACs tested reduced liver fat in NAFLD at doses of 25 and 150 mg/kg/day. High-fat diet increased, whereas FABAC therapy decreased plasma 16 : 1/(16 : 0+16 : 1) fatty acid ratio - a marker of stearoyl CoA desaturase activity. In HepG2 cells FABACs decreased de-novo fatty acid synthesis dose dependently. CONCLUSION: Oral FABAC therapy decreased liver fat in preestablished NAFLD in mice and rats. Inhibition of stearoyl CoA desaturase activity and fatty acid synthesis are mechanisms that may contribute to this decrease. FABACs may be potential therapeutic agents for human NAFLD.

Ziziphus jujuba extract for the treatment of chronic idiopathic constipation: a controlled clinical trial.

PURPOSE: To investigate the safety and efficacy of an extract of Ziziphus jujuba for chronic constipation.Constipated patients received liquid Z. jujuba or placebo for 12 weeks. Subjects completed questionnaires, a visual analog scale and transit time (TT) tests before and after treatment. RESULTS: Of 37 patients with a prolonged TT, 18 received the study drug and 19 a placebo. Two (12%) of the study and 16 (84%) of the control group dropped out due to severe constipation. The TT decreased from 12.2 particles for the study group to 3 particles at week 11. Symptom severity ratings decreased from 6 and 6.2 to 2 and 5, and the quality of life score improved from 1.9 and 2.3 to 1.3 and 1.4 in the study and control groups, respectively. CONCLUSION: Z. jujuba extract is an effective and safe treatment for chronic constipation.

Biliary and systemic effects of fatty acid bile acid conjugates.

BACKGROUND: Fatty acid bile acid conjugates (FABACs) are novel synthetic molecules that solubilize cholesterol, prevent cholesterol crystal and gallstone formation, and dissolve pre-existing gallstones in mice. They are thus potential agents for gallstone prevention and treatment. The available knowledge concerning their biliary, systemic or possible toxic effects is, however, incomplete. AIM: To obtain information regarding biliary and systemic effects of FABACs. METHODS: Hamsters, rats and mice were administered C20-FABAC intragastrically, and serum and bile chemistries, organ histology, animal wellbeing, and survival were monitored. RESULTS: FABAC feeding (150 mg/kg/day) caused no adverse effects in any of the animal species studied. FABAC did not influence biliary cholesterol, phospholipid, or bile-salt concentrations in mice. In hamsters, biliary cholesterol concentration decreased slightly, but effects on phospholipids and bile salts were inconsistent. In some mouse strains, FABAC supplementation increased transaminases slightly. In hamsters and rats, transaminases were mainly unaffected or even decreased. Serum alkaline phosphatase, creatinine, albumin and glucose were generally unaffected by FABAC feeding. No gross or histopathological differences between controls and FABAC-fed animals were noted in any of the organs investigated. CONCLUSIONS: C20-FABAC given at a pharmacological dose is safe and devoid of any significant toxic effects in three different animal species.

Dissolution of cholesterol gallstones in mice by the oral administration of a fatty acid bile acid conjugate.

Gallstones, mostly cholesterol stones, affect some 15% of the population. Oral bile salts dissolve human cholesterol gallstones, but with low efficacy, and surgery remains the main therapeutic option. Fatty acid bile acid conjugates (FABACs) were shown to prevent formation of cholesterol gallstones in experimental animals. The aim of this study was to test whether these compounds could dissolve preexisting cholesterol gallstones via oral administration. Inbred, gallstone-susceptible C57J/L mice were given a lithogenic diet for 2 months, and the presence of gallstones was ascertained. The mice were then switched to a regular diet while part of them were given in addition C20-FABAC, by gavage, at a dose of 0.5 or 3 mg per animal per day. All mice tested had cholesterol gallstones after 2 months on the lithogenic diet. In study I, after 2 months on the regular diet, 3 of 4 (75%) of the controls had gallstones, whereas none of the 6 FABAC-fed animals (3 mg/d) had stones (P =.033). In study II, evaluating 2 FABAC doses, after 2 months on the regular diet, 8 of 8 (100%) of the controls had gallstones, which were found in 2 of 7 (28%) and 1 of 8 (12%) of the mice supplemented with 0.5 mg/d (P =.007) or 3 mg/d (P =.001) FABAC, respectively. On a molar basis, the dose of 0.5 mg FABAC is equivalent to 14 mg/kg/d of a bile acid. In conclusion, FABACs given orally can dissolve preexisting cholesterol gallstones in mice. This was accomplished with a dose of FABAC equivalent to the dose of bile acids used in human gallstone dissolution.