1206-P: Effects of Short-Term Administration of Delta-9-tetrahydrocannabinol on Metabolic Parameters of C57bl/6 Mice

Abstract

Cancer and HIV-related cachexias are among the qualifying conditions for medical cannabis use. Although effective to alleviate nausea and vomiting, clinical trials demonstrated little to no impact of cannabinoids on weight gain in patients. Consistent with this, cannabis users have a lower prevalence of obesity in epidemiological studies. Since cannabinoid-1 receptors (CB1R) regulate food intake and adipose tissue thermogenesis, we studied the metabolic effects of a low dose of delta-9-tetrahydrocannabinol (THC), a CB1R agonist and the main bioactive chemical in cannabis, in 8-week old male mice maintained on a 10%-fat-calorie diet. Mice received daily intraperitoneal injections of THC (3 mg/Kg, n = 15) or vehicle (n = 12) just before the dark cycle for 7 days. THC-treated mice gained an average of 1.6 grams compared to 2.6 grams gained by the vehicle-treated mice (p = 0.03). Despite the attenuated weight gain, automated home cage phenotyping revealed an increase in food intake in the 90 minutes after injections in the THC-treated mice (mean = 0.78 vs. 0.53 grams; p = 0.001). No differences, however, were detected in overall light (p = 0.39) or dark-cycle food intake (p = 0.07). THC-treated mice also showed reduced locomotor activity in the dark cycle compared to vehicle-treated mice (p <0.001). There were no robust differences in indirect calorimetry parameters between groups in the dark cycle, whereas the respiratory exchange rates were lower among THC-treated mice during the light cycle (p = 0.01). Gene expression studies revealed reduced CB1R mRNA levels in brown adipose (mean = 0.61; p = 0.02) and liver (mean = 0.30; p = 0.04) of THC-treated mice. In summary, administration of a low dose of THC was associated with attenuated weight gain in male C57BL/6 mice, possibly through downregulation of CB1R in metabolically active tissues. Future studies will elucidate the effects of chronic THC administration on CB1R expression and thermogenesis under high fat feeding and obesity. Disclosure E. Kurjan: n/a. L. K. Olson: None. O. Alshaarawy: None. Funding National Institutes of Health (R00AT009156)