THC and CBD affect metabolic syndrome parameters including microbiome in mice fed high fat-cholesterol diet

Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes
obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut
microbiome in NAFLD. While cannabis and its phytocannabinoids may potentially be benefcial for treating metabolic
disorders such as NAFLD, their efects on liver diseases and gut microbiota profle have yet to be addressed. In this
study, we evaluated the therapeutic efects of the two major cannabinoids, delta-9-tetrahydrocannabinol (THC) and
cannabidiol (CBD), on NAFLD progression.
Methods: NAFLD was induced by feeding mice a high fat-cholesterol diet (HFCD) for 6 weeks. During this period, the
individual cannabinoids, THC or CBD, were added to the experimental diets at a concentration of 2.5 or 2.39 mg/kg.
Profle of lipids, liver enzymes, glucose tolerance, and gene expression related to carbohydrate lipids metabolism and
liver infammation was analyzed. The efect of THC or CBD on microbiota composition in the gut was evaluated.
Results: While not alleviating hepatic steatosis, THC or CBD treatment infuenced a number of parameters in the
HFCD mouse model. CBD increased food intake, improved glucose tolerance, reduced some of the infammatory
response including TNFa and iNOS, and partially mitigated the microbiome dysbiosis observed in the HFCD fed mice.
THC produced a much weaker response, only slightly reducing infammatory-related gene expression and microbi‑
ome dysbiosis.
Conclusions: The results of this study indicate the potential therapeutic efects of individual phytocannabinoids are
diferent from the efects of the cannabis plant possessing a mixture of compounds. While CBD may help ameliorate
symptoms of NAFLD, THC alone may not be as efective. This disparity can putatively be explained based on changes
in the gut microbiota