Cannabis constituents modulate a†9-tetrahydrocannabinol-induced hyperphagia in rats

The hyperphagic effect of a dagger(9)-tetrahydrocannabinol (a dagger(THC)-T-9) in humans and rodents is well known. However, no studies have investigated the importance of a dagger(THC)-T-9 composition and any influence other non-a dagger(THC)-T-9 cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified a dagger(THC)-T-9, synthetic a dagger(THC)-T-9 (dronabinol), and a dagger(THC)-T-9 botanical drug substance (a dagger(THC)-T-9-BDS), a a dagger(THC)-T-9-rich standardized extract comparable in composition to recreationally used cannabis. Adult male rats were orally dosed with purified a dagger(THC)-T-9, synthetic a dagger(THC)-T-9, or a dagger(THC)-T-9-BDS, matched for a dagger(THC)-T-9 content (0.34-2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following a dagger(THC)-T-9 administration. Data were then analyzed in terms of hourly intake and meal patterns. All three a dagger(THC)-T-9 substances tested induced significant hyperphagic effects at doses a parts per thousand yen0.67 mg/kg. These effects included increased intake during hour one, a shorter latency to onset of feeding and a greater duration and consumption in the first meal. However, while some differences in vehicle control intakes were observed, there were significant, albeit subtle, differences in pattern of effects between the purified a dagger(THC)-T-9 and a dagger(THC)-T-9-BDS. All a dagger(THC)-T-9 compounds displayed classical a dagger(THC)-T-9 effects on feeding, significantly increasing short-term intake whilst decreasing latency to the first meal. We propose that the subtle adjustment to the meal patterns seen between the purified a dagger(THC)-T-9 and a dagger(THC)-T-9-BDS are due to non-a dagger(THC)-T-9 cannabinoids present in a dagger(THC)-T-9-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate a dagger(THC)-T-9-induced hyperphagia, making them worth further investigation for their therapeutic potential.