Cannabis constituents modulate super(9)-tetrahydrocannabinol-induced hyperphagia in rats

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