[Fecal Microbiota Transfer (FMT) in Germany - Status and Perspective]. / Fäkaler Mikrobiota-Transfer (FMT) in Deutschland ­ Status und Perspektive.

INTRODUCTION: Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far. MATERIAL AND METHODOLOGY: Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation. RESULTS: Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%. DISCUSSION: In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.

Menthacarin for long-term treatment of functional dyspepsia - Results from a clinical trial follow-up.

BACKGROUND: Menthacarin was shown to be effective and safe in clinical trials in patients with functional dyspepsia (FD). Long-term treatment results have not been reported yet. METHODS: An open-label, 11-month follow-up (FU) was offered to FD patients who had undergone treatment with Menthacarin (1 gastro-resistant capsule b.i.d. vs. placebo (PL)) in a 4-week, double-blind, clinical trial. During FU, all patients (former verum and PL) were treated with 1 gastro-resistant capsule Menthacarin b.i.d. Main outcomes were the changes in pain intensity and severity of sensation of pressure, heaviness, and fullness from original baseline and global improvement. RESULTS: 70 patients were included in the analyses (former Menthacarin group: 36, former PL group: 34). At the end of the PL-controlled study phase, all 3 main efficacy variables were statistically significantly improved in the Menthacarin group compared to PL. In the FU phase, former PL patients started to improve under Menthacarin treatment towards the outcomes seen in the former Menthacarin group (alignment at approximately 6 months), while former Menthacarin patients showed sustained or even continuously improved outcomes by month 12. At study end, more than 90% of patients were "much or very much improved" in both groups. Menthacarin treatment was well tolerated. CONCLUSIONS: The favorable effects seen in the FU period suggest that Menthacarin is a valuable treatment option in FD patients who require symptomatic treatment also in the longer term for up to 12 months.

[Treatment of IBS with Lactobacillus plantarum 299v: Therapeutic success increases with length of treatment - real-life data of a non-interventional study in Germany]. / Reizdarmbehandlung mit Lactobacillus plantarum 299v: Längere Einnahme verstärkt Behandlungserfolg ­ Ergebnisse einer nichtinterventionellen Studie.

INTRODUCTION: The treatment of irritable bowel syndrome (IBS) in clinical practice is frequently challenging. Modulation of the intestinal microbiome as a treatment option is becoming more and more important. The effectiveness of a bacterial strain, Lactobacillus plantarum 299v (LP299V), was previously investigated in placebo-controlled clinical trials in patients with IBS over 4 weeks. The aims of the present non-interventional study were therefore to investigate tolerability and effectiveness of LP299V under everyday conditions and to gain information on long-term treatment. METHODS: Data on tolerability and effectiveness of LP299V (1 capsule/day; 1 × 1010 CFU) were prospectively collected in 25 centers in 221 patients with IBS. The maximal treatment duration was 12 weeks. The survey was carried out using symptom diaries and medical assessments. Changes in frequency and severity of symptoms were compared to baseline and defined the primary endpoint. RESULTS: During the 12-week treatment, a significant and continuous reduction of overall symptom score (p < 0.05) was observed. In addition, a significant reduction of severity (S) and frequency (H) of individual symptoms, such as abdominal pain (S: - 67 %, H: - 51 %), flatulence (S: - 61 %, H: - 63 %), diarrhea (S: - 70 %, H: - 32 %) and constipation (S: - 79 %, H: - 6 %) was observed. Urgency and feeling of incomplete evacuation were significantly decreased (p < 0.001). Additionally, quality of life increased significantly (mental well-being: + 110 %, influence on everyday life: -67 %, p < 0.01). Self-assessment identified that long-term treatment with LP299V was tolerated well by 94 % of patients. CONCLUSION: In real life, LP299V significantly alleviates the global symptoms of IBS in patients. In order to achieve the maximum effect, long-term use of LP299V (as here 12 weeks) appears to be indicated and is well tolerated.

[Bile acid diarrhea, stepchild of chronic diarrhea - prevalence, diagnosis and treatment. Update 2021]. / Chologene Diarrhö, Stiefkind der chronischen Diarrhö ­ Prävalenz, Diagnostik und Therapie. Update 2021.

Bile acid diarrhea is one of the most frequently undiagnosed causes of chronic diarrhea. A variety of different pathophysiologic causes can underlie chronic diarrhea. Even after exclusion of the more frequent causes, up to 5 % of the population remains affected by unexplained chronic diarrhea. In up to 50 % within this cohort, bile acid diarrhea is the underlying cause.The various pathophysiologies leading to bile acid diarrhea are well characterized. In this way, bile acid diarrhea can be divided into primary, secondary and tertiary subtypes. Common to all causes is the increased amount of bile acids in the colon and in the faeces and the resulting secretory-osmotic diarrhea, in more severe forms in combination with steatorrhea. The diagnosis of bile acid diarrhea follows a clear algorithm which, in addition to the search for the cause and possibly a therapeutic trial, recognizes the 75SeHCAT test as the reference method for the detection of an increased loss of bile acids. In view of the chronic nature of the symptoms and the need for permanent, lifelong therapy, the use of a one-time, reliable diagnostic test is justified, though the test is currently only available at a few centers. In addition to the treatment of identifiable underlying diseases, the current treatment includes the use of drugs that bind bile acids, with additional nutritional recommendations and vitamin substitutions.The present review article summarizes the pathophysiology and importance of bile acid diarrhea and discusses the current approach towards diagnosis and treatment.

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis]. / Akzeptanz des fäkalen Mikrobiota-Transfers (Stuhltransplantation) als alternative Therapie bei Patienten mit Colitis ulcerosa.

INTRODUCTION: Fecal microbiota transplantation (FMT) represents a treatment option for recurring Clostridium difficile-associated colitis. However, there is also evidence that FMT can be effective in treating ulcerative colitis. This study examined the approval and willingness of affected patients who underwent FMT. METHODS: A standardized questionnaire containing 27 polar and open questions was dispatched to a cohort of 262 patients suffering from UC. It included questions regarding the FMT process, donors, and possible concerns. Additionally, aspects of social background and disease activity were addressed. RESULTS: The response rate was 31.3 % (n = 82). Forty-eight (58.5 %) patients were already aware of FMT. Forty-six (56.1 %) were willing to undergo FMT if given a respective indication. The effectiveness of the procedure (40.2 %), followed by failure of all other therapies (17.1 %), formed the principal motivation. The transmission of possible infectious agents (26.8 %), and the potential contamination of the stool graft leading to a deterioration of clinical symptoms, raised the most concerns. (20.7 %).The preferred delivery system of FMT was capsules (67.1 %), followed by colonoscopic application (47.6 %). The patients were in favour of a donor proposed by the physician (52,4 %). Willingness to undergo FMT did not differ significantly between genders (56.4 % women vs. 57.1 % men). Smokers (88.9 %), patients who did not watch television at all (77.8 %) and those with private health insurance, showed an increased willingness to undergo FMT. CONCLUSION: For the majority of the UC patients surveyed, FMT represents a feasible treatment option. Approximately half of the respondents would consider FMT as an alternative treatment option, even inspite of a satisfactory disease response to current standard therapies. Unsurprisingly, there are concerns regarding the transmission of possible infectious agents and the hygienic implementation of FMT itself.

[Eosinophilic Esophagitis Update: New Guidelines of the European Study Group EUREOS]. / Eosinophile Ösophagitis Update 2017: Neue Leitlinien der europäischen Studiengruppe EUREOS.

Eosinophilic esophagitis is now considered to be a frequent chronic esophageal disease and is one of the most common causes for dysphagia and bolus obstruction in children and adults. The increasing significance and new scientific insights in this disorder required an update of currently existing guidelines. Therefore, the European Study Group of Eosinophilic Esophagitis (EUREOS) has elaborated new guidelines for the management of eosinophilic esophagitis, based on a systematic literature search and, for the first time, using the GRADE methodology (Grading of Recommendations Assessment, Development, and Evaluation). The aim of the present article is to summarize and comment on new developments and clinical recommendations of this guideline to further increase the awareness for this relevant esophageal disease.

RGS proteins as targets in the treatment of intestinal inflammation and visceral pain: New insights and future perspectives.

Regulators of G protein signaling (RGS) proteins provide timely termination of G protein-coupled receptor (GPCR) responses. Serving as a central control point in GPCR signaling cascades, RGS proteins are promising targets for drug development. In this review, we discuss the involvement of RGS proteins in the pathophysiology of the gastrointestinal inflammation and their potential to become a target for anti-inflammatory drugs. Specifically, we evaluate the emerging evidence for modulation of selected receptor families: opioid, cannabinoid and serotonin by RGS proteins. We discuss how the regulation of RGS protein level and activity may modulate immunological pathways involved in the development of intestinal inflammation. Finally, we propose that RGS proteins may serve as a prognostic factor for survival rate in colorectal cancer. The ideas introduced in this review set a novel conceptual framework for the utilization of RGS proteins in the treatment of gastrointestinal inflammation, a growing major concern worldwide.

[Eosinophilic Esophagitis Update: New Guidelines of the European Study Group EUREOS]. / Eosinophile Ösophagitis Update 2017: Neue Leitlinien der europäischen Studiengruppe EUREOS.

Eosinophilic esophagitis is now considered to be a frequent chronic esophageal disease and is one of the most common causes for dysphagia and bolus obstruction in children and adults. The increasing significance and new scientific insights in this disorder required an update of currently existing guidelines. Therefore, the European Study Group of Eosinophilic Esophagitis (EUREOS) has elaborated new guidelines for the management of eosinophilic esophagitis, based on a systematic literature search and, for the first time, using the GRADE methodology (Grading of Recommendations Assessment, Development, and Evaluation). The aim of the present article is to summarize and comment on new developments and clinical recommendations of this guideline to further increase the awareness for this relevant esophageal disease.

[Psychosomatics in gastroenterology - statement of the Work Group for Psychosomatics in Gastroenterology of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS)]. / Psychosomatik in der Gastroenterologie ­ Stellungnahme der Arbeitsgemeinschaft Psychosomatik in der Gastroenterologie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS).

The Association Psychosomatics in Gastroenterology of the DGVS aims to sharpen the profile of psychosomatic proportions in diagnostics, differential diagnostics and therapy of gastroenterological diseases, increasingly establish psychosomatic aspects in further education and clinical practice guidelines, deepen the cooperation with psychosomatic societies and strengthen the job satisfaction and mental health of gastroenterologists in Germany.

[Interpretation und performance of high-resolution esophageal manometry: Recommendations of the German Association of Neurogastroenterology and Motility (DGNM) and the German Association of Gastroenterology, Digestive and Metabolic Diseases (DGVS)]. / Interpretation und Durchführung der hochauflösenden Ösophagusmanometrie: Empfehlungen der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) sowie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselerkrankungen (DGVS).

Esophageal manometry provides a detailed evaluation of esophageal contractility and, therefore, represents the reference method for diagnosis of esophageal motility disorders. Significance and clinical relevance have been further increased by implementation of high-resolution esophageal manometry (HRM), which reveals the functional anatomy of the esophagus in a visually-intuitive manner. The current 3 rd version of the international Chicago Classification (CC v3.0) gives standardized recommendations on performance and interpretation of HRM and serves as the basis for much of this expert consensus document. However, CC v3.0 gives only limited information with regards to the function of the lower and upper esophageal sphincters, the use of adjunctive tests including solid test meals and long-term ambulatory HRM measurements. In this expert consensus, we describe how to perform and interpret HRM on the basis of the CC v3.0 with additional recommendations based on the results of recent, high-quality clinical studies concerning the use of this technology to assess the causes of esophageal symptoms in a variety of clinical scenarios.

Cannabinoid Receptor Type 1 and mu-Opioid Receptor Polymorphisms Are Associated With Cyclic Vomiting Syndrome.

OBJECTIVES: Cyclic vomiting syndrome (CVS) is a disorder defined by recurrent, unexplained episodes of severe nausea and vomiting. Our aim was to investigate whether CVS and pathophysiological mechanisms underlying this condition are associated with selected variations in genes encoding the components of the endogenous cannabinoid and opioid systems. METHODS: This case-control study included 65 patients with CVS-16 male and 49 female, and 1,092 healthy controls-525 male and 567 female from the 1000 Genomes Project. CVS subjects filled out study-specific questionnaires. Single-nucleotide polymorphisms (SNPs) in genes encoding cannabinoid receptors (CNR1 and CNR2), fatty acid amide hydrolase (FAAH) and mu-opioid receptor (OPRM1) were analyzed using the TaqMan SNP genotyping assay. Correlations between SNP's and clinical characteristics of CVS were ascertained. RESULTS: Our study disclosed an increased risk of CVS among individuals with AG and GG genotypes of CNR1 rs806380 (P<0.01), whereas the CC genotype of CNR1 rs806368 and AG and GG genotypes of OPRM1 rs1799971 were associated with a decreased risk of CVS (P<0.05). In addition, AG and GG genotypes of OPRM1 rs1799971 were correlated with migraine episodes, AG and GG of OPRM1 rs1799971, and CT and CC of CNR1 rs806368 with a family history of migraines (second degree relatives), and CT and CC of CNR1 rs2023239 with a positive response to therapy. CONCLUSIONS: Our results show for the first time that the variations in CNR1 and OPRM1 genes are associated with CVS and that different genotypes may contribute to the risk of CVS.

Evaluating the Multitarget Effects of Combinations through Multistep Clustering of Pharmacological Data: the Example of the Commercial Preparation Iberogast.

Herbal combination preparations are widely used in traditional herbal medicine and are even established as modern evidence-based herbal medicinal products. The rationale behind such combinations is often questioned and assessing the contribution of each of the combination partners to overall activity is challenging. STW 5 (Iberogast) is such a combination with confirmed clinical efficacy in functional gastrointestinal disorders. It consists of nine plant extracts responsible for its multitarget function in these multifactorial diseases with their heterogeneous and overlapping pathomechanisms. This makes the combination an ideal candidate for the use of the newly described method of stepwise cluster analysis, a standardized procedure to transfer heterogeneous pharmacological data, from different models, into effect size categories. This allows for a stepwise cluster formation starting from the level of single tests up to the level of different pathomechanisms involved in the development of a certain disease, in this case functional dyspepsia subtypes and irritable bowel syndrome. In the current article, an overview on the pharmacological data on STW 5 and its single components is provided. The data are further analyzed using stepwise cluster formation, resulting in a summary of the different modes of action of STW 5 along with an evaluation of the contribution of the single constituents to the overall multitarget effects of the herbal combination preparation.

Cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance.

Cannabinoid receptors are fundamentally involved in all aspects of intestinal physiology, such as motility, secretion, and epithelial barrier function. They are part of a broader entity, the so-called endocannabinoid system which also includes their endocannabinoid ligands and the ligands' synthesizing/degrading enzymes. The system has a strong impact on the pathophysiology of the gastrointestinal tract and is believed to maintain homeostasis in the gut by controlling hypercontractility and by promoting regeneration after injury. For instance, genetic knockout of cannabinoid receptor 1 leads to inflammation and cancer of the intestines. Derivatives of Δ9-tetrahydrocannabinol, such as nabilone and dronabinol, activate cannabinoid receptors and have been introduced into the clinic to treat chemotherapy-induced emesis and loss of appetite; however, they may cause many psychotropic side effects. New drugs that interfere with endocannabinoid degradation to raise endocannabinoid levels circumvent this obstacle and could be used in the future to treat emesis, intestinal inflammation, and functional disorders associated with visceral hyperalgesia.

Modulation of gastrointestinal motility beyond metoclopramide and domperidone : Pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders.

The prokinetic cisapride, an important therapeutic option in functional gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due to rare severe side effects. Likewise in 2014, the use of metoclopramide (MCP) and domperidone in functional GI disorders (FGID) was restricted, consequently leaving a therapeutic gap in clinical practice. A systematic review revealed that the herbal medicinal product (HMP) STW 5 presents a therapeutic option equivalent to MCP and cisapride. STW 5 is the only HMP for which efficacy has been shown in randomized controlled clinical trials (RCTs) in functional dyspepsia and irritable bowel syndrome, based on its multitarget effect on numerous etiological factors. Due to an outstanding favorable safety profile, STW 5 allows an effective and safe use in FGID without a limitation of the duration of the treatment.

Potential Causes and Present Pharmacotherapy of Irritable Bowel Syndrome: An Overview.

BACKGROUND: Irritable bowel syndrome (IBS) is currently one of the most common disorders of the digestive system in the Western society. Almost 2 out of 10 people suffer from IBS with women being more affected than men. IBS is associated with abdominal pain, bloating and altered stool consistency and imposes a heavy burden for the affected patients. SUMMARY: The pathophysiology of IBS remains elusive although potential causes have been suggested, such as a deranged brain-gut signaling, hypersensitivity of visceral sensory afferent fibers, bacterial gastroenteritis, small intestinal bacterial overgrowth (SIBO), genetic alterations and food sensitivity. Targets for the pharmacotherapy of IBS include the serotonergic and opioidergic system, and the microbial population of the gut. Alternative therapies like traditional Chinese medicine have shown some success in the combat against IBS. Key Messages: Many therapeutics for the treatment of IBS have emerged in the past; however, only a few have met up with the expectations in larger clinical trials. Additionally, the multifactorial etiology of IBS and its variety of cardinal symptoms requires an individual set of therapeutics. This review provides a short overview of potential causes and current pharmacological therapeutics and of additional and alternative therapies for IBS.

Anti-inflammatory and antinociceptive action of an orally available nociceptin receptor agonist SCH 221510 in a mouse model of inflammatory bowel diseases.

The nociceptin receptors (NOPs) are expressed in the gastrointestinal (GI) tract on muscle cell membranes and neurons, as well as the immune cells that infiltrate the mucosa. The involvement of NOPs in the pathophysiology of GI inflammation has been suggested, but due to the lack of selective NOP agonists, it never fully elucidated. Our aim was to characterize the anti-inflammatory and antinociceptive effect of the NOP agonist, SCH 221510 [3-endo-8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo [3.2.1]octan-3-ol], as a potential therapeutic strategy in the treatment of inflammatory bowel diseases (IBD). The anti-inflammatory action of SCH 221510 was determined after intraperitoneal, oral, and intracolonic administration of SCH 221510 (0.1-3.0 mg/kg once or twice daily) in mice treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS). Antinociceptive action of SCH 221510 was evaluated in the mouse model of mustard oil (MO)-induced abdominal pain. Relative NOP mRNA expression was assessed in patients with IBD using real-time reverse transcriptase-polymerase chain reaction. We found that the expression of NOP mRNA was significantly decreased in patients with IBD. The administration (0.1 and 1.0 mg/kg i.p. twice daily and 3 mg/kg p.o. twice daily) of SCH 221510 attenuated TNBS colitis in mice. This effect was blocked by a selective NOP antagonist [J-113397 [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one]]. The intracolonic injections of SCH 221510 did not improve colitis in mice. The antinociceptive effect of SCH 221510 was observed after oral administration of SCH 221510 in MO-induced pain tests in mice with acute colitis. In conclusion, our results show a potent anti-inflammatory and antinociceptive effect upon selective activation of NOP receptors and suggest that the NOP agonist SCH 221510 is a promising drug candidate for future treatment of IBD.

Bladder function in a cannabinoid receptor type 1 knockout mouse.

OBJECTIVE: To evaluate bladder function in an established cannabinoid type 1 (CB1) receptor knockout (KO) mouse model via organ-bath (in vitro) and urodynamic (cystometric; in vivo) experiments. MATERIALS AND METHODS: In all, 20 8-week-old female wildtype (WT) mice (C57BL/6) and 20 age-matched CB1 KO mice were used. Six mice from each group were used for the organ-bath experiments, where the contractile responses of bladder tissue strips after carbachol exposure (carbachol concentration response curve [CCRC]; myogenic contraction) and during electrical field stimulation (EFS; neurogenic contraction) were assessed. In all, 14 mice per group were used for cystometric experiments without any anaesthesia, in which standard urodynamic variables were assessed 3 days after bladder catheterisation. RESULTS: The CCRCs of bladder strips from CB1 KO mice were similar to those of WT mice. However, during EFS the bladder strips from the CB1 KO mice had significantly lower contractile responses than WT preparations, indicating that in CB1 KO mice the neuronal component of bladder contraction was different. In cystometric experiments the CB1 KO mice had a higher micturition frequency (shorter mean [sem] inter-micturition interval of 3.24 [0.29] vs 7.32 [0.5] min), a lower bladder capacity (0.09 [0.01] vs 0.18 [0.01] mL) and micturition volume (0.07 [0.01] vs 0.14 [0.01] mL), a lower bladder compliance (0.007 [0.001] vs 0.02 [0.002] mL/cmH2 O), and higher spontaneous bladder activity (5.1 [0.5] vs 2.6 [0.6] cmH2 O) than WT mice (all P < 0.05, Student's t-test). In WT mice, systemic administration of rimonabant (SR141716), a CB1 receptor antagonist, resulted in urodynamic changes similar to those seen in the CB1 KO mice. CONCLUSIONS: In vitro, bladder strips from CB1 KO mice responded to muscarinic receptor stimulation similarly as the WT controls, but were less responsive to electrical stimulation of nerves. In vivo, CB1 KO mice had a higher micturition frequency and more spontaneous activity than WT mice. The present findings suggest that CB1 receptors are involved in peripheral and central nervous control of micturition.

An Internet survey of marijuana and hot shower use in adults with cyclic vomiting syndrome (CVS).

Cyclic vomiting syndrome (CVS) is a chronic disorder characterized by episodic nausea and vomiting. A large proportion of patients use marijuana to control their symptoms. Several case reports implicate marijuana as a cause of intractable vomiting with compulsive hot water bathing considered pathognomonic of "cannabinoid hyperemesis." We sought to examine the relationship between marijuana use and CVS. Patients >18 years of age diagnosed by a health care provider were invited to participate in an anonymous internet-based survey. A total of 514 patients participated and 437 completed questions about marijuana use. Mean age was 34 ± 12 years with patients being predominantly female (63%), Caucasian (92%) and from the USA (82%). Nineteen percent never used marijuana and 81% did. Fifty-four percent used marijuana for health issues and 43% for recreational purposes. Users stated that it improved nausea, appetite, general well-being, stress levels and vomiting. Users were more likely to be male and have an associated anxiety disorder. Sixty-seven percent of patients reported taking hot showers/baths for symptom relief, and this was associated with marijuana use. (OR 2.54, CI 1.50-4.31, P = 0.0006). Eighty-one percent of patients with CVS who completed an internet survey reported frequent use of marijuana. With marijuana use, patients noted the greatest improvement with stress levels, appetite and nausea. Marijuana users were more likely to be male and have associated anxiety. Hot showers were not pathognomonic of marijuana use though they were more likely to be associated with its use.

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.