16S rRNA sequencing of fecal samples from ovariectomized mice fed cannabidiol. CBD_16SrRNA

Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, metabolic endotoxemia, and increased risk of cardiometabolic disease and osteoporosis. The risk-benefit profile of hormone replacement therapy (HRT) is not favorable in postmenopausal women therefore better treatment options are needed. Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice. We evaluated the efficacy of CBD (25 mg/kg) administered perorally to OVX and sham surgery (SS) mice for 18 weeks. CBD-treated OVX mice had improved oral glucose tolerance and increased energy expenditure. Dual energy x-ray absorptiometry (DEXA) analysis showed CBD-treated OVX mice had improved whole body bone mineral density (BMD) and bone mineral content (BMC) while microcomputed tomography (microCT) revealed improved femoral BMD, bone volume fraction, and trabecular thickness. In agreement with the improved bone and metabolic phenotypes, CBD-treated OVX mice also had increased Lactobacillus sp. in feces, higher concentration of tauroursodeoxycholic acid (TUDCA) in serum, and gene expression changes in the intestine and femur consistent with reduced inflammation and less bone resorption. These data provide preclinical evidence supporting further investigation of CBD as a therapeutic for postmenopause-related disorders.