Cannabis constituents modulate ∆9-tetrahydrocannabinol-induced hyperphagia in rats

Rationale The hyperphagic effect of ∆ 9 -tetrahydrocannabinol (∆ 9 THC) in humans and rodents is well known. However, no studies have investigated the importance of ∆ 9 THC composition and any influence other non-∆ 9 THC cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified ∆ 9 THC, synthetic ∆ 9 THC (dronabinol), and ∆ 9 THC botanical drug substance (∆ 9 THC-BDS), a ∆ 9 THC-rich standardized extract comparable in composition to recreationally used cannabis. Methods Adult male rats were orally dosed with purified ∆ 9 THC, synthetic ∆ 9 THC, or ∆ 9 THC-BDS, matched for ∆ 9 THC content (0.34–2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following ∆ 9 THC administration. Data were then analyzed in terms of hourly intake and meal patterns. Results All three ∆ 9 THC substances tested induced significant hyperphagic effects at doses ≥0.67 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 ∆ 9 THC and ∆ 9 THC-BDS. Conclusion All ∆ 9 THC compounds displayed classical ∆ 9 THC 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 ∆ 9 THC and ∆ 9 THC-BDS are due to non-∆ 9 THC cannabinoids present in ∆ 9 THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate ∆ 9 THC-induced hyperphagia, making them worth further investigation for their therapeutic potential.