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

Abstract

Rationale

The hyperphagic effect of ∆⁹-tetrahydrocannabinol (∆⁹THC) in humans and rodents is well known. However, no studies have investigated the importance of ∆⁹THC composition and any influence other non-∆⁹THC cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified ∆⁹THC, synthetic ∆⁹THC (dronabinol), and ∆⁹THC botanical drug substance (∆⁹THC-BDS), a ∆⁹THC-rich standardized extract comparable in composition to recreationally used cannabis.

Methods

Adult male rats were orally dosed with purified ∆⁹THC, synthetic ∆⁹THC, or ∆⁹THC-BDS, matched for ∆⁹THC content (0.34–2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following ∆⁹THC administration. Data were then analyzed in terms of hourly intake and meal patterns.

Results

All three ∆⁹THC 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 ∆⁹THC and ∆⁹THC-BDS.

Conclusion

All ∆⁹THC compounds displayed classical ∆⁹THC 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 ∆⁹THC and ∆⁹THC-BDS are due to non-∆⁹THC cannabinoids present in ∆⁹THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate ∆⁹THC-induced hyperphagia, making them worth further investigation for their therapeutic potential.