High Cannabigerol Hemp Extract Moderates Colitis and Modulates the Microbiome in an Inflammatory Bowel Disease Model

Abstract

Cannabis sativa L. has a long history of medicinal use, particularly for gastrointestinal diseases. Patients with inflammatory bowel disease (IBD) report using cannabis to manage their symptoms, despite little data to support the use of cannabis or cannabis products to treat the disease. In this study, we use the well-described dextran sodium sulfate (DSS) model of colitis in mice to assess the impact of commercially available, noneuphorigenic, high cannabigerol (CBG) hemp extract (20 mg/mL cannabigerol, 20.7 mg/mL cannabidiol, 1 mg/mL cannabichromene) on IBD activity and the colonic microbiome. Mice were given 2% DSS in drinking water for 5 days, followed by 2 days of regular drinking water. Over the 7 days, mice were dosed daily with either high CBG hemp extract or matched vehicle control. Daily treatment with high CBG hemp extract dramatically reduces the severity of disease at the histological and organismal levels as measured by decreased disease activity index, increased colon length, and decreases in percent colon tissue damage. 16S rRNA gene sequencing of the fecal microbiota reveals high CBG hemp extract treatment results in alterations in the microbiota that may be beneficial for colitis. Finally, using metabolomic analysis of fecal pellets, we find that mice treated with high CBG hemp extract have a normalization of several metabolic pathways, including those involved in inflammation. Taken together, these data suggest that high CBG hemp extracts may offer a novel treatment option for patients. SIGNIFICANCE STATEMENT: Using the dextran sodium sulfate model of colitis, the authors show that treatment with high cannabigerol hemp extract reduces the severity of symptoms associated with colitis. Additionally, they show that treatment modulates both the fecal microbiota and metabolome with potential functional significance.