DAY 2: Debates in GI: Diet vs. Pharma in IBS and Cannabis Use vs. Risk in DGBI

In the first debate, Dr. Prashant Singh from the University of Michigan in Ann Arbor, MI, argued for the utility of dietary changes in the treatment of IBS. He listed several common objections and made the case that each is false. A commonly heard objection is that patients don’t want dietary treatment. He cited a study showing that up to 84% of patients with IBS say food triggers their symptoms, and 48% prefer dietary therapy to pharmacologic or psychological therapy. The second objection is that the evidence for the benefit of dietary changes is weak. Dietary therapy for IBS has been studied in 23 randomized controlled trials. In 10 of them, the low-FODMAP diet outperformed active comparators, including National Institute for Health and Care Excellence (NICE) and British Dietetic Association (BDA) dietary advice. Dr. Singh also countered the objection that diet changes are less effective than medication. A primary care trial of 459 patients found similar benefits of a low-FODMAP diet and the antispasmodic otilonium bromide. In a second trial of about 300 patients, dietary therapy did better than optimized medical therapy. He also addressed the claim that there is only one, difficult-to-follow diet recommendation for IBS. He noted that this idea is outdated, as the low-FODMAP diet can be simplified: in one RCT, removing only fructans and galactooligosaccharides (GOS) worked as well as the full low-FODMAP diet on all endpoints. Dr. Singh called for a shift from eliminating all 5 FODMAP groups to a step-up approach that makes the diet easier to follow. The Mediterranean diet is another option. In 3 RCTs in IBS, it outperformed other dietary approaches, including NICE/BDA. Dr. Singh also disputed the view that diet only masks symptoms without treating the underlying disease. He cited a study showing that after just 4 weeks on a low-FODMAP diet, patients showed improvements in underlying pathophysiology, including lower mast cell activation, in addition to symptoms. Finally, Dr. Singh argued that diet can be personalized. An IgG ELISA–based elimination diet can help identify the foods most likely to trigger symptoms. He described the findings of a rigorously designed RCT where this approach worked well, including in patients with IBS-C. Other personalized approaches include diets guided by confocal laser endomicroscopy (CLE), which measures mucosal “leakiness” after exposure to food antigens such as gluten. Leukocyte activation testing and disaccharidase deficiency testing can also guide individualized diets. His central message was to think beyond the low-FODMAP diet for patients with IBS.

Dr. Satish S.C. Rao, from the Medical College of Georgia at Augusta University, in Augusta, GA, argued for the role of pharmacotherapy in IBS. He began by describing how host, luminal, and environmental factors all contribute to IBS. Mast cell activation and increased intestinal permeability play a role, but he identified visceral hypersensitivity as the key abnormality. Drug therapy can address all of these mechanisms. Dr. Rao noted that AGA guidelines for both IBS-D and IBS-C recommend several pharmacotherapies, supported by randomized controlled trials, though he acknowledged that the recommendations are conditional, with moderate or low certainty of evidence. Two trials have been published since the 2022 guidelines were published. The ATLANTIS study, a large community-based primary care trial of 463 patients, found that up-titration of amitriptyline significantly improved IBS symptoms compared with placebo. It also showed that dose titration can improve efficacy. The DOMINO trial that compared the low-FODMAP diet with the antispasmodic otilonium bromide found that both improved IBS Symptom Severity Scale (IBS-SSS) scores by more than 50 points. Dr. Rao then described the weaknesses in the dietary evidence. Diet trials cannot be properly double-blinded, so they carry a high risk of bias and may overestimate efficacy. Dietary therapy usually requires dietitian oversight, which limits access. Most diet studies in IBS were conducted in tertiary rather than primary care, and no recommendations support long-term dietary restriction. Dr. Rao closed with several recommendations. Make a positive diagnosis and build rapport with the patient. Recognize abdominal pain and visceral hypersensitivity as key features of IBS, and target treatment to address hypersensitivity. Consider a multipronged approach, and aim to restore patients’ diets rather than restrict them.

In the second debate, Dr. David J. Levinthal of the University of Pittsburgh Medical Center in Pittsburgh, PA, made the case for using cannabis in disorders of gut-brain interaction (DGBI). His first argument was biological plausibility. The endocannabinoid system is a well-mapped therapeutic target. While the cannabis plant contains a mix of cannabinoids, the CB1 and CB2 receptors are found in the brain, immune cells, and gut. Effects of activating these receptors include lower colonic tone and motility, reduced gastric motility and contractility, appetite stimulation, reduced lower esophageal sphincter relaxation, reduction of nausea, and lower visceral pain perception. He acknowledged that cannabinoids may promote fibrosis in the liver and pancreas; however, the evidence is mostly preclinical and is not a reason to dismiss the whole drug class. His second argument was evidence of real-world clinical benefit. Patients with chronic GI symptoms already use cannabis widely and often rate it as more effective than other neuromodulators and antiemetics. About one-third of patients with gastroparesis or gastroparesis-like symptoms have reported current cannabis use and legal access is growing across the US. Because patients are already using these products, he felt that clinicians need to engage with them thoughtfully. He also pointed out that cannabinoids are already part of the neuromodulator toolkit, with dronabinol used for nausea and pain. His third argument was that risk of cannabinoid hyperemesis syndrome (CHS) is real, but it gets outsized attention, and its thresholds have been poorly defined. CHS may be a subset of cyclic vomiting syndrome (CVS), with cannabis acting as a trigger in susceptible people, but the same treatments work for both. Emergency department visits for nausea and vomiting have risen since legalization, but he cautioned that this association does not prove causation. Reporting bias, coding changes, and over-attribution to CHS may all contribute. Of the millions of people who use cannabis, only a small number develop CHS. Dr. Levinthal concluded that a pragmatic, harm-reduction approach works best. He supports permissive, moderate use in adult patients with refractory illness, while steering them away from high-potency concentrates. Cannabis should be avoided in adolescent patients. Judicious, guided use, not reflexive prohibition, is the evidence-based path.

In the counterpoint presentation, Dr. Thangam Venkatesan from The Ohio State University in Columbus, OH, described the real risk of CHS as well as other risks of cannabis use. In 2021, about 52 million people used cannabis at least once, and 16.2 million met the diagnostic criteria for cannabis use disorder. Use spans all age groups, and people now see it as less risky than before. Notably, 45% of new users are 12 to 17 years of age, and they are not necessarily using it for medical reasons. The most common medical uses are pain, anxiety, and insomnia. Potency is also rising sharply. Smoked cannabis contains about 15% THC, while solvent-based concentrates usually contain 40% to 60% and can reach 80%. Known harms include intoxication, delirium, psychosis, sleep disorders, withdrawal, and cannabis use disorder, as well as dose-related cortical thinning and more impulsive behavior. CHS was first reported in Australia in 2004; since then, the literature has consisted mostly of case reports, and there was no uniform definition until the Rome V criteria. She agreed that CHS is considered a subset of CVS. It moves through distinct phases and can be very debilitating, with vomiting, sweating, photosensitivity, and diarrhea. Compulsive hot-water bathing is common but not diagnostic; one study documented a risk of burns. CHS prevalence is estimated at about 2%, but good-quality data are lacking. Dr. Venkatesan also cited ER use data from Colorado. Out-of-state visitors ended up in the ED, and all were under 25 years of age. Edibles sold as gummies have also led to accidental ingestion by children. Hemp-derived products are unregulated. Proposed causes of CHS include genetic predisposition, endocannabinoid deficiency, and use of higher-potency products with a higher THC:CBD ratio. The leading hypothesis is that a subset of people are hypersensitive to cannabis, and these people need to be better identified. Chronic daily use downregulates CB1 receptors, which leads to neuroadaptation and a need for more potent products. This downregulation generally recovers after about four weeks of abstinence, but it may persist in the hippocampus. For lower-risk use, Dr. Venkatesan said abstinence is the most effective strategy. Other advice was to avoid starting use at an early age, choose low-potency products and non-smoked forms, and avoid daily or near-daily use. Dr. Venkatesan recommended advising patients who have CHS to reduce cannabis use rather than requiring complete abstinence, and then treating the underlying CVS. Clinicians should also explain the risks of rising potency and the possibility of hypersensitivity, and address the psychosocial reasons the patient uses cannabis.