Abstract

With approximately 4% of the worlds population using cannabis, there is need to fully understand how cannabis impacts our health. It is universally known that increased food intake is a side effect of cannabis use, also known as the munchies, and it has been established that delta-9-tetrahydrocannabinol (THC), the major psychoactive cannabinoid in cannabis, drives these feeding effects. These appetitive effects of cannabis or THC have been modeled in humans and rodents but have not been fully explored. Therefore, the aim of this study was to use a translational pre-clinical model to characterise how inhalation of vapour from a THC-dominant cannabis extract alters daily feeding patterns and macronutrient-specific food preferences, with focus on microstructural feeding pattern analysis and potential sex differences. We exposed adult male and female Sprague-Dawley rats to THC-dominant cannabis vapour or vehicle vapour daily, then gave rats access to different foods (chow, high-carbohydrate, and/or high-fat food) and post-vapour feeding patterns measured. To study macronutrient-specific food preferences, rats were given a post-vapour choice between a high-carbohydrate and a high-fat food. To assess satiety, rats were given pre-vapour access to a palatable preload in which they readily consume to become satiated. For some animals, blood and brain samples were collected post-vapour to measure phytocannabinoid and metabolite levels using mass spectrometry. We show that THC vapour inhalation increases food intake in the first hour after vapour exposure, an effect that is not dependent on food type, sex or whether animals are satiated or not. These feeding effects were a result of THC vapour decreasing feeding latency and increasing feeding bout frequency. Consistently, these acute feeding effects were compensated for through reductions in subsequent food intake, and THC vapour did not promote weight gain. THC also altered macronutrient-specific food preferences, increasing high-fat food preference in standard conditions, and increasing high-carbohydrate food preference in satiated conditions so that rats no longer significantly preferred one food over the other. Following vapour exposure, female rats had higher THC and metabolite concentrations in plasma and the hypothalamus than males and showed a stronger high-fat food preference following THC vapour compared to males when given a food choice. Overall, this study complements and builds upon previous clinical and pre-clinical data to fully characterise the effects of THC inhalation on feeding patterns and is the first to directly examine how THC alters macronutrient-specific food preferences and assess if appetitive THC-driven sex differences exist. This research sheds light on whether cannabis use can have energy-balance effects, information which is beneficial for recreational and medical cannabis users.