Cannabis finds its way into treatment of Crohn's disease

In ancient medicine, cannabis has been widely used to cure disturbances and inflammation of the bowel. A recent clinical study now shows that the medicinal plant Cannabis sativa has lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases. In a prospective placebo-controlled study, it has been shown what has been largely anticipated from anecdotal reports, i.e. that cannabis produces significant clinical benefits in patients with Crohn's disease. The mechanisms involved are not yet clear but most likely include peripheral actions on cannabinoid receptors 1 and 2, and may also include central actions

Brain-gut interactions in IBS

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with an estimated prevalence of 10-20%. Current understanding of the pathophysiology of IBS is incomplete due to the lack of a clearly identified pathological abnormality and due to the lack of reliable biomarkers. Possible mechanisms believed to contribute to IBS development and IBS like symptoms include physical stressors, such as infection or inflammation, psychological, and environmental factors, like anxiety, depression, and significant negative life events. Some of these mechanisms may involve the brain-gut axis (BGA). In this article we review the current knowledge on the possible involvement of the BGA in IBS and discuss new directions for potential future therapies of IBS

The role of AST-120 and protein-bound uremic toxins in irritable bowel syndrome: a therapeutic perspective

AST-120 (kremezin) exhibits its favourable effects in reducing the levels of renal toxins by selective adsorption of low molecular weight substances from the intestinal lumen. So far, a vast majority of studies were focused on the role of AST-120 in the treatment of chronic kidney diseases and cardiovascular disorders, and positive therapeutic effects of the agent have already been confirmed in clinical conditions. Up to the present, there are only a few studies regarding the role of AST-120 in irritable bowel syndrome (IBS). Compelling data suggest the ability of the compound to adsorb protein-bound uremic toxins and mast cell derived mediators and to modulate the farnesoid X receptor, which is a bile acid sensor indispensable for maintaining homeostasis in the intestine. In this review we focus on the actions of AST-120 on intestinal permeability, reduction of visceral sensitivity and alteration of gut motility. We also discuss whether AST-120 can mitigate common IBS symptoms, such as abdominal pain, bloating and malfunction of the colonic transit and thus improve the quality of life of patients with IBS

Cannabinoids for treating inflammatory bowel diseases: where are we and where do we go?

Introduction: Fifty years after the discovery of Delta(9)-tetrahydrocannabinol (THC) as the psychoactive component of Cannabis, we are assessing the possibility of translating this herb into clinical treatment of inflammatory bowel diseases (IBDs). Here, a discussion on the problems associated with a potential treatment is given. From first surveys and small clinical studies in patients with IBD we have learned that Cannabis is frequently used to alleviate diarrhea, abdominal pain, and loss of appetite. Single ingredients from Cannabis, such as THC and cannabidiol, commonly described as cannabinoids, are responsible for these effects. Synthetic cannabinoid receptor agonists are also termed cannabinoids, some of which, like dronabinol and nabilone, are already available with a narcotic prescription. Areas covered: Recent data on the effects of Cannabis/cannabinoids in experimental models of IBD and in clinical trials with IBD patients have been reviewed using a PubMed database search. A short background on the endocannabinoid system is also provided. Expert commentary: Cannabinoids could be helpful for certain symptoms of IBD, but there is still a lack of clinical studies to prove efficacy, tolerability and safety of cannabinoid-based medication for IBD patients, leaving medical professionals without evidence and guidelines

Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans

Background: Exogenous use of the intestinal hormone glucagon-like peptide 1 (GLP-1) lowers glycaemia by stimulation of insulin, inhibition of glucagon, and delay of gastric emptying.Aims: To assess the effects of endogenous GLP-1 on endocrine pancreatic secretion and antro-pyloro-duodenal motility by utilising the GLP-1 receptor antagonist exendin(9-39)amide (ex(9-39)NH2).Methods: Nine healthy volunteers underwent four experiments each. In two experiments with and without intravenous infusion of ex(9-39)NH2 300 pmol/kg/min, a fasting period was followed by intraduodenal glucose perfusion at 1 and 2.5 kcal/min, with the higher dose stimulating GLP-1 release. Antro-pyloro-duodenal motility was measured by perfusion manometry. To calculate the incretin effect (that is, the proportion of plasma insulin stimulated by intestinal hormones) the glycaemia observed during the luminal glucose experiments was mimicked using intravenous glucose in two further experiments.Results: Ex(9-39)NH2 significantly increased glycaemia during fasting and duodenal glucose. It diminished plasma insulin during duodenal glucose and significantly reduced the incretin effect by approximately 50%. Ex(9-39)NH2 raised plasma glucagon during fasting and abolished the decrease in glucagon at the high duodenal glucose load. Ex(9-39)NH2 markedly stimulated antroduodenal contractility. At low duodenal glucose it reduced the stimulation of tonic and phasic pyloric motility. At the high duodenal glucose load it abolished pyloric stimulation.Conclusions: Endogenous GLP-1 stimulates postprandial insulin release. The pancreatic \textgreeka cell is under the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon. GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial inhibition of antral and stimulation of pyloric motility. We therefore suggest GLP-1 as a true incretin hormone and enterogastrone in humans

Metabolomics: is it useful for inflammatory bowel diseases?

Purpose of Review: The assessment of metabolite profiles in biofluids has become a powerful method for the detection of biomarker molecules and disease mechanisms. This review outlines the recent advances in the use of metabolomic techniques to study inflammatory bowel diseases (IBDs). Recent findingsThe last few years have seen an increase in the studies of experimental and human IBD focusing on the search for small metabolites, such as amino acids, bases, and tricarboxylic acid cycle intermediates. Experimental methods for the screening of metabolites in serum, urine, fecal extracts, and colon tissue include H-1 NMR spectroscopy, gas chromatography-mass spectrometry, and liquid chromatography methods. Several studies demonstrate that IBD patients and healthy individuals, as well as the IBD subtypes, can be distinguished using metabolic profiling. Metabolomic data of fecal extracts and urine have revealed disruptions in bacterial populations, findings that are indicative of a possible involvement of the microbiome in the development of IBDs. SummaryMetabolites from biofluids can be detected in IBDs by different experimental methods that allow successful separation of IBD subtypes from healthy cohorts. Knowledge of a unique metabolomic fingerprint in IBDs could be useful for diagnosis, treatment, and detection of disease mechanisms

Herbal extracts modulate the amplitude and frequency of slow waves in circular smooth muscle of mouse small intestine

Background: Herbal preparations like STW 5 (Iberogast(R)) are widely used drugs in the treatment of dyspepsia and motility-related disorders of the gastrointestinal tract. STW 5 is a phytotherapeutic agent consisting of a fixed mixture of 9 individual plant extracts. The electrophysiological mechanisms of action of STW 5 remain obscure. Aim: The aim of the present study was to investigate whether herbal extracts influence electrophysiological parameters of the small intestine. For this purpose, the resting membrane potential (RMP) and the slow wave rhythmicity of smooth muscle cells of mouse small intestine were observed. Methods: Intracellular recordings of smooth muscle cells of the circular muscle layer of mouse small intestine were performed using standard microelectrode techniques. After dissection of the mucosa, the small intestine was placed in an organ bath and a microelectrode was applied on a circular smooth muscle cell. The RMP and the amplitude of slow waves were measured in millivolts. Results: The RMP of smooth muscle cells was - 59 +/- 1.3 mV. This RMP was significantly depolarized by STW 5 ( 9.6 +/- 1.6 mV); the depolarizing effects can be mainly attributed to the constituents of matricariae flos, angelicae radix and chelidonii herba. The basal frequency of small intestinal slow waves was 39.5 +/- 1.4 min(-1) and the amplitude was 23.1 +/- 0.9 mV. STW 5 significantly reduced the amplitude and frequency of the slow waves ( 11.7 +/- 0.8 mV; 33.5 +/- 3.4 min(-1)). This effect on slow waves represents the sum of the effects of the 9 phytoextracts. Whereas angelicae radix and matricariae flos completely blocked slow wave activity, Iberis amara increased the frequency and amplitude, chelidonii herba reduced the frequency and amplitude of the slow waves, mentae piperitae folium reduced the frequency and left amplitude unchanged and liquiritae radix, carvi fructus and melissae folium had no effects. Conclusion: Herbal extracts cause changes in smooth muscle RMP and slow wave rhythmicity, up to reversible abolition, by blockade of large conductance Ca2+ channels and other not yet identified mechanisms. In herbal preparations like STW 5 these effects add up to a total effect and this study indicates that herbal preparations which are widely used in dyspepsia and motility-related disorders have characteristic, reproducible, reversible effects on small intestinal electrophysiology. Copyright (C) 2005 S. Karger AG, Basel

Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists

There is an unmet need for effective pharmacological therapies for constipation, a symptom that significantly deteriorates patients' quality of life and impacts health care. Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor and has been shown to exert prokinetic effects on gastrointestinal (GI) motility via the vagus and pelvic nerves. The pharmacological potential of ghrelin is hampered by its short half-life. Ghrelin receptor (GRLN-R) agonists with enhanced pharmacokinetics were thus developed. Centrally penetrant GRLN-R agonists stimulate defecation and improve impaired lower GI transit in animals and humans. This review summarizes the current knowledge on relamorelin, a potent ghrelin mimetic, and other GRLN-R analogs which are in preclinical or clinical stages of development for the management of disorders with underlying GI hypomotility, like constipation

Non-specific abdominal pain and air pollution: a novel association.

We studied whether short-term exposure to air pollution was associated with non-specific abdominal pain in epidemiologic and animal studies. Patients visiting the emergency department with non-specific abdominal pain were identified in Edmonton (1992 to 2002, n = 95,173) and Montreal (1997 to 2002, n = 25,852). We calculated the daily concentrations for ozone (O(3)), nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), carbon monoxide (CO), and particles <10 (PM(10)) or <2.5 (PM(2.5)) µm. A case crossover study design was used to estimate the odds ratio (OR) and 95% confidence interval (CI) associated with an increase in the interquartile range of the air pollutants. We investigated differential effects by age and sex. Mice were gavaged with urban particle extracts. In animal models, colonic motility was tested, and visceral abdominal pain was measured using a writhing test, and behavioral response to oil of mustard and neostigmine. Motility and pain was measured acutely (1.5 hours after gavage) and chronically (7-days and 21-days after gavage). Emergency department visits for non-specific abdominal pain were primarily by women between the ages of 15-24 years. Individuals aged 15 to 24 years were at increased risk of non-specific abdominal pain in Edmonton (same day CO: OR = 1.04, 95% CI = 1.02-1.06; and NO(2): OR = 1.06, 95% CI = 1.03-1.09). The risk of air pollution among 15-24 year olds in Montreal was significantly positive (same day CO: OR = 1.11, 95% CI = 1.05-1.17; NO(2): OR = 1.09, 95% CI = 1.01-1.16; SO(2): OR = 1.17, 95% CI = 1.10-1.25; PM(2.5): OR = 1.09, 95% CI = 1.04-1.15). Abdominal pain was increased by an acute gavage of pollution extract but not to chronic exposure to pollutants. Colonic transit was delayed following chronic but not acute exposure with the pollutants. Epidemiological and animal data suggest that short-term exposure to air pollution may trigger non-specific abdominal pain in young individuals

Targeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal

Irritable bowel syndrome is a group of functional gastrointestinal disorders with not yet fully clarified etiology. Recent evidence suggesting that mast cells may play a central role in the pathogenesis of irritable bowel syndrome paves the way for agents targeting histamine receptors as a potential therapeutic option in clinical treatment. In this review, the role of histamine and histamine receptors is debated. Moreover, the clinical evidence of anti-histamine therapeutics in irritable bowel syndrome is discussed