Departments of Biochemistry and Molecular Biology (B.D.A., A.B.) and Veterinary and Biomedical Sciences (J.J.K.), and One Health Microbiome Center, Huck Life Sciences Institute (J.E.B.), Pennsylvania State University, University Park, Pennsylvania; and Departments of Pharmacology (D.E.S., R.N., A.C.-R., M.D.C., W.M.R.-K.) and Anesthesiology & Perioperative Medicine (D.E.S.), Center for Cannabis & Natural Product Pharmaceutics (D.E.S., R.N., A.C.-R., M.D.C., J.E.B., J.J.K., W.M.R.-K.), and Divison of Gastroenterology & Hepatology, Department of Medicine (M.D.C., J.J.K.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
Departments of Biochemistry and Molecular Biology (B.D.A., A.B.) and Veterinary and Biomedical Sciences (J.J.K.), and One Health Microbiome Center, Huck Life Sciences Institute (J.E.B.), Pennsylvania State University, University Park, Pennsylvania; and Departments of Pharmacology (D.E.S., R.N., A.C.-R., M.D.C., W.M.R.-K.) and Anesthesiology & Perioperative Medicine (D.E.S.), Center for Cannabis & Natural Product Pharmaceutics (D.E.S., R.N., A.C.-R., M.D.C., J.E.B., J.J.K., W.M.R.-K.), and Divison of Gastroenterology & Hepatology, Department of Medicine (M.D.C., J.J.K.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania
J Pharmacol Exp Ther. 2024 Aug 19;390(3):331-341. doi: 10.1124/jpet.124.002204.
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.
大麻素有悠久的药用历史，尤其在胃肠道疾病方面。炎症性肠病（IBD）患者报告使用大麻来控制其症状，尽管几乎没有数据支持使用大麻或大麻制品来治疗该疾病。在这项研究中，我们使用了已被充分描述的葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型，以评估市售的、无致幻作用的、高含量大麻萜酚（CBG）的大麻素 Hemp Extract（20mg/ml 大麻萜酚，20.7mg/ml 大麻二酚，1mg/ml 大麻环萜酚）对 IBD 活性和结肠微生物组的影响。将小鼠用 2%的 DSS 饮用水处理 5 天，随后用普通饮用水处理 2 天。在 7 天的时间里，小鼠每天给予高 CBG 大麻素 Hemp Extract 或匹配的载体对照物进行处理。每日给予高 CBG 大麻素 Hemp Extract 治疗可显著降低疾病的严重程度，从组织学和机体水平上衡量，表现为疾病活动指数降低、结肠长度增加和结肠组织损伤百分比降低。粪便微生物组的 16S rRNA 基因测序表明，高 CBG 大麻素 Hemp Extract 治疗可导致微生物群的改变，这可能对结肠炎有益。最后，通过对粪便样本的代谢组学分析，我们发现用高 CBG 大麻素 Hemp Extract 治疗的小鼠有几种代谢途径得到了正常化，包括涉及炎症的途径。总的来说，这些数据表明高 CBG 大麻素 Hemp Extract 可能为患者提供一种新的治疗选择。
使用葡聚糖硫酸钠诱导的结肠炎模型，作者表明高大麻萜酚大麻素 Hemp Extract 治疗可减轻与结肠炎相关的症状严重程度。此外，他们还表明，治疗可调节粪便微生物群和代谢组，具有潜在的功能意义。
