The Effect of Orally Administered Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) on Obesity Parameters in Mice

Adi Eitan, Ofer Gover, Liron Sulimani, David Meiri, Betty Schwartz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Prolonged cannabis users show a lower prevalence of obesity and associated comorbidities. In rodent models, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) from the plant Cannabis sativa L. have shown anti-obesity properties, suggesting a link between the endocannabinoid system (ECS) and obesity. However, the oral administration route has rarely been studied in this context. The aim of this study was to investigate the effect of prolonged oral administration of pure THC and CBD on obesity-related parameters and peripheral endocannabinoids. C57BL/6 male mice were fed with either a high-fat or standard diet and then received oral treatment in ramping doses, namely 10 mg/kg of THC or CBD for 5 weeks followed by 30 mg/kg for an additional 5 weeks. Mice treated with THC had attenuated weight gain and improved glucose tolerance, followed by improvement in steatosis markers and decreased hypertrophic cells in adipose epididymal tissue. Mice treated with CBD had improved glucose tolerance and increased markers of lipid metabolism in adipose and liver tissues, but in contrast to THC, CBD had no effect on weight gain and steatosis markers. CBD exclusively decreased the level of the endocannabinoid 2-arachidonoylglycerol in the liver. These data suggest that the prolonged oral consumption of THC, but not of CBD, ameliorates diet-induced obesity and metabolic parameters, possibly through a mechanism of adipose tissue adaptation.

Original languageAmerican English
Article number13797
JournalInternational Journal of Molecular Sciences
Volume24
Issue number18
DOIs
StatePublished - Sep 2023

Bibliographical note

Funding Information:
This research was funded by the Israeli Ministry of Agriculture and Rural Development, grant number 12-05-0025.

Publisher Copyright:
© 2023 by the authors.

Keywords

  • CBD
  • endocannabinoids
  • HFD
  • obesity
  • THC

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