Evaluation of reinforcing and aversive effects of voluntary Δ9-tetrahydrocannabinol ingestion in rats

Edible cannabis-infused products are an increasingly popular method of using cannabis in the United States. Yet, preclinical research to determine mechanisms underlying abuse of Δ9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, has focused primarily on the effects of parenteral administration. The purpose of this study was to examine the rewarding and aversive effects of oral THC in a novel rodent voluntary ingestion model. Adult male and female Sprague Dawley rats were given access to sucrose-sweetened solutions during daily sessions. A range of THC concentrations, each paired with a unique flavor previously tested alone, was introduced into these solutions for four-session exposure periods and drinking volumes were measured. Injected (i.p.) THC doses were also paired with unique flavors to compare the effects of route of THC administration on drinking. Introduction of THC into sucrose solutions dose-dependently decreased drinking upon initial exposure, though drinking generally increased in subsequent sessions. By contrast, i.p. THC produced sustained dose-dependent decreases in drinking in rats of both sexes. Subsequent exposure to paired flavors in the absence of THC resulted in further decreases in drinking, suggesting route-specific aversion. Additional testing using saccharin-sweetened solutions in a two-bottle choice paradigm was also conducted, with THC producing sustained dose-dependent decreases in drinking after initial exposure in rats of both sexes. Though self-administration of ingested THC was not demonstrated, evidence of route-specific THC aversion was observed, which suggests that certain routes and/or rates of THC administration may mitigate some of its aversive effects.