Cannabidiol Decreases Intestinal Inflammation in the Ovariectomized Murine Model of Postmenopause

Abstract

Cannabidiol (CBD) (25 mg/kg peroral) treatment was shown to improve metabolic outcomes in ovariectomized (OVX) mice deficient in 17β-estradiol (E2). Herein, CBD effects on intestinal and hepatic bile acids (BAs) and inflammation were investigated. Following RNA sequencing of colon tissues from vehicle (VEH)- or CBD-treated sham surgery (SS) or OVX mice (n = 4 per group), differentially expressed genes (DEGs) were sorted in ShinyGO. Inflammatory response and bile secretion pathways were further analyzed. Colon content and hepatic BAs were quantified by LC-MS (n = 8–10 samples/group). Gut organoids were treated with CBD (100, 250, 500 µM) with or without TNFα and lipopolysaccharide (LPS) followed by mRNA extraction and qPCR to assess CBD-induced changes to inflammatory markers. The expression of 78 out of 114 inflammatory response pathway genes were reduced in CBD-treated OVX mice relative to vehicle (VEH)-treated OVX mice. In contrast, 63 of 111 inflammatory response pathway genes were increased in CBD-treated sham surgery (SS) mice compared to VEH-treated SS group and 71 of 121 genes were increased due to ovariectomy. CBD did not alter BA profiles in colon content or liver. CBD repressed Tnf and Nos2 expression in intestinal organoids in a dose-dependent manner. In conclusion, CBD suppressed colonic inflammatory gene expression in E2-deficient mice but was pro-inflammatory in E2-sufficient mice suggesting CBD activity in the intestine is E2-dependent.

Therapeutic Effects of Cannabinoids on Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Both Doeve et al and Vinci et al concluded similarly, reporting little to no impact of cannabinoids on remission or inflammatory biomarkers 29,30 . In contrast, recent studies in animal models of intestinal inflammation have shown a reduction in colonic inflammation, with degrading enzymes for endocannabinoids; such as fatty acid amide hydrolase inhibitors and cannabidiol 37,38 . Another recent study by Moniruzzaman et al reported that the efficacy of cannabidiol could be increased by using protein nanoparticles to treat inflammatory bowel disease 39 .…”

Special Issue: Therapeutic Potential for Cannabis and Cannabinoids

“…Bacalia et al examined the impact of CBD on intestinal inflammation, and they found that in female mice, CBD suppresses inflammation in the absence of estradiol, but it enhances inflammation in animals with estradiol [ 10 ]. Yekhtin and colleagues found that both THC and CBD reduced nitric oxide production by lipopolysaccharide (LPS)-stimulated peritoneal macrophages [ 11 ].…”