Effects of repeated voluntary oral consumption of synthetic delta-9-tetrahydrocannabinol on locomotor activity and cannabinoid receptor 1 expression

Abstract

As cannabis legalization expands, preclinical studies continue to investigate the impact of repeated exposure to delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in the plant. With the increasing popularity of cannabis infused foods, the rise of THC in medicinal applications have also expanded. The present study addresses a critical gap in existing literature by investigating the behavioral and neurobiological effects of low-dose edible THC in a preclinical rodent model. Adult male rats were administered synthetic-THC (Dronabinol) (0.0625 mg/kg, 0.125 mg/kg, and 0.25 mg/kg) or vehicle (sesame oil) through edible cookies, 90 min prior to eight locomotor sessions. Locomotor activity significantly increased in both 0.0625 mg/kg and 0.25 mg/kg THC groups, indicating a dose-dependent relationship. Repeated 0.25 mg/kg THC administration dose-dependently reduced cannabinoid receptor 1 expression in the hippocampus. The observed neurobiological change from low dose oral THC advances our understanding of repeated cannabis use. These findings also emphasize the importance of refining rodent models for translational relevance.