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Associated Press
07-05-2025
- Health
- Associated Press
New Study Links Intestinal Cannabinoid Receptors to Alcohol-Induced Leaky Gut
A new study reveals that gut cannabinoid receptor 1 (CB1R) plays a key role in alcohol binge-induced intestinal permeability, commonly known as 'leaky gut.' BETHESDA, MD, UNITED STATES, May 7, 2025 / / -- Heavy alcohol consumption is a leading cause of gastrointestinal diseases, with binge drinking linked to increased intestinal permeability—a condition commonly known as 'leaky gut.' Despite the significant health impact of alcohol-associated gastrointestinal disorders, effective pharmacological treatments remain limited. A new study published in eGastroenterology explores the role of gut cannabinoid receptor 1 (CB1R) in alcohol binge-induced intestinal permeability and reveals how its inhibition can help protect the gut barrier. The research, conducted by scientists from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) at the National Institutes of Health (NIH), demonstrates that alcohol bingeing increases endocannabinoid levels in the proximal small intestine, triggering CB1R activation in intestinal epithelial cells. This activation disrupts tight junction proteins, which generally maintain the integrity of the gut lining, leading to increased intestinal permeability. This process can allow harmful substances, such as bacteria and toxins, to enter the bloodstream, contributing to inflammation and other health complications. To investigate the role of CB1R, the researchers developed genetically modified mice with intestinal epithelial-specific CB1R deletion (CB1IEC−/− mice). They found that alcohol bingeing significantly increased gut permeability in normal mice, but this effect was absent in CB1IEC−/− mice, indicating that CB1R is a key mediator of alcohol-induced leaky gut. Additionally, the study examined the effects of pharmacological CB1R inhibition using a peripherally restricted CB1R antagonist (S)-MRI-1891. When administered to normal mice before alcohol bingeing, this compound successfully prevented the increase in intestinal permeability. However, the drug had no effect in CB1IEC−/− mice, further confirming that CB1R in the intestinal epithelium is responsible for alcohol-induced gut barrier disruption. Mechanistic studies revealed that CB1R activation in the gut epithelium triggers the ERK1/2 signalling pathway, which leads to the downregulation of tight junction proteins and a reduction in villus length—key factors contributing to a leaky gut. By inhibiting CB1R, researchers could reverse these changes, restoring gut barrier function and improving overall gut health. These findings hold significant implications for the treatment of alcohol-related digestive disorders. Currently, there are no FDA-approved drugs specifically designed to treat alcohol-induced intestinal permeability. The study suggests that targeting CB1R with peripherally restricted antagonists could provide a novel therapeutic approach, potentially preventing systemic inflammation and other complications associated with alcohol-induced gut barrier dysfunction. These insights could have broader applications in gastrointestinal health beyond alcohol-related gut disorders. The endocannabinoid system is known to influence gut motility, immune function, and microbiota composition, and its role in intestinal permeability suggests that CB1R inhibition may be beneficial in other conditions characterized by increased gut permeability, such as inflammatory bowel disease and metabolic disorders. However, the study also highlights some limitations. While CB1R inhibition effectively prevented alcohol-induced leaky gut, it did not significantly impact metabolic parameters or liver disease progression. This suggests that although a leaky gut contributes to alcohol-related health issues, other mechanisms are also at play in the development of liver disease and metabolic dysfunction. Future research will explore whether combining CB1R inhibitors with other therapeutic strategies could offer more comprehensive protection against alcohol-induced organ damage. Additionally, further studies are needed to assess the long-term safety and efficacy of CB1R antagonists in clinical settings. This groundbreaking study advances our understanding of the gut's response to alcohol and opens new avenues for targeted therapies. By identifying CB1R as a crucial mediator of alcohol-induced intestinal permeability, researchers have paved the way for potential pharmacological interventions that could help mitigate the harmful effects of binge drinking on gut health. Funder The authors received financial support from the Intramural Program of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), NIH (Grant Nos. AA00350, AA000369, AA000368), the National Research, Development and Innovation Office (Grant No. PD-139012) and the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. See the article: Maccioni L, Dvorácskó S, Godlewski G, et al. Gut cannabinoid receptor 1 regulates alcohol binge-induced intestinal permeability. eGastroenterology 2025;3:e100173. doi:10.1136/egastro-2024-100173 eGastroenterology is a new, open-access, and open peer-reviewed BMJ Journal, which focuses on basic, clinical, translational, and evidence-based medicine research in all areas of gastroenterology (including hepatology, pancreatology, esophagology, and gastrointestinal surgery). For more information, please visit: and follow us on Twitter (@eGastro_BMJ). Contact: Dr. Bin Gao National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Bethesda, Maryland, USA Email: [email protected] Dr. George Kunos National Institute on Alcohol Abuse and Alcoholism [email protected] Legal Disclaimer: EIN Presswire provides this news content 'as is' without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.
Business Upturn
30-04-2025
- Health
- Business Upturn
NeuroSigma Announces New Clinical Trial of Monarch eTNS System for Treatment of ADHD in Children with Fetal Alcohol Syndrome at UCLA
By GlobeNewswire Published on April 30, 2025, 20:00 IST Trial to be conducted at UCLA and funded by a grant from National Institute on Alcohol Abuse and Alcoholism (NIAAA) First phase of trial will enroll up to 30 children ages 8 – 12 with exposure to alcohol during gestation to receive treatment with the Monarch Upon successful completion of Phase I, investigators will proceed with a larger, double-blind randomized crossover trial LOS ANGELES, April 30, 2025 (GLOBE NEWSWIRE) — NeuroSigma, Inc. , a Los Angeles-based bioelectronics company commercializing the Monarch external Trigeminal Nerve Stimulation (eTNS) device for treating ADHD , today announced a new clinical trial of the Monarch for treating symptoms of ADHD in children with fetal alcohol syndrome (FAS). The 2-year trial will be led by Professor Joseph O'Neill , Adjunct Professor of Psychiatry at UCLA, and is being funded by an initial $350,000 grant from the National Institute of Alcohol Abuse and Alcoholism (NIAAA) . Monarch devices and supplies for the trial will be provided by NeuroSigma. Repeated exposure to alcohol during gestation is associated with a significantly increased risk of learning and behavioral problems during childhood. These children tend to develop symptoms similar to ADHD such as hyperactivity, impulsivity, and executive function deficits. Children with FAS also tend to be less responsive to conventional ADHD therapies, such as stimulant medications, which can lead to worse outcomes, and increases the need for new approaches to treating this vulnerable population. In its first phase, the trial will enroll up to 30 children ages 8 – 12 with exposure to alcohol during gestation and exhibiting symptoms of ADHD. The children will receive nightly therapy with the Monarch for 4 weeks, and parents will keep track of their children's ADHD symptoms, sleep habits, adverse events, and tolerability of the therapy during the 4-week treatment period. The primary goal of Phase I is to demonstrate feasibility. If successful, investigators will proceed with a larger, double-blind randomized crossover trial. 'NeuroSigma is thrilled to work with leading medical professionals and scholars in the field of child psychiatry to expand the indications for our proprietary Monarch eTNS therapy. We are grateful to Professor O'Neil and his colleagues for commencing this innovative and important clinical trial,' commented Colin Kealey, M.D., President and CEO of NeuroSigma, adding, 'We would also like to thank the NIAAA for their generous grant that will support this work. According to the CDC, up to 1 in 20 school aged children may suffer from fetal alcohol spectrum disorders, and our goal is that the Monarch will provide patients, caregivers, and healthcare providers with a new option for treating this underserved population.' Families interested in participating in the clinical trial may email the study at [email protected] , call at (310) 267-2710, or fill-out an online screener to determine eligibility . About NeuroSigma NeuroSigma is a Los Angeles, California-based bioelectronic medical device company developing technologies to transform medical practice and patients' lives. The company's lead product is the Monarch eTNS System, which is the first non-drug treatment for pediatric ADHD cleared by the FDA. Pipeline indications for the Monarch include neurodevelopmental disorders such as Autism Spectrum Disorder (ASD), learning disabilities, and epilepsy. For more information about NeuroSigma, please visit . For more information on the Monarch eTNS System, please visit . Contact: Colin Kealey, M.D., President of NeuroSigma at [email protected] Disclaimer: The above press release comes to you under an arrangement with GlobeNewswire. Business Upturn takes no editorial responsibility for the same. GlobeNewswire provides press release distribution services globally, with substantial operations in North America and Europe.
