Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice
Article first published online: 17 FEB 2009
© 2009 The Authors. Journal compilation © 2009 The British Pharmacological Society
British Journal of Pharmacology
Volume 156, Issue 7, pages 1154–1166, April 2009
How to Cite
Riedel, G., Fadda, P., McKillop-Smith, S., Pertwee, R. G., Platt, B. and Robinson, L. (2009), Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. British Journal of Pharmacology, 156: 1154–1166. doi: 10.1111/j.1476-5381.2008.00107.x
- Issue published online: 31 MAR 2009
- Article first published online: 17 FEB 2009
- Received 6 October 2008; accepted 11 November 2008
- home cage;
- CB1 receptor
Background and purpose: Obesity is a severe health problem in the modernized world and understanding the central nervous mechanisms underlying food-seeking behaviour and reward are at the forefront of medical research. Cannabinoid receptors have proven an efficient target to suppress hunger and weight gain by their pharmacological inactivation.
Experimental approach: A standard fasted protocol and a novel long-term home-cage observation system with free-feeding animals were used to assess the feeding behaviour of mice treated with the CB1 antagonist AM251. Similarly, the effects of the phytocannabinoid Δ9-tetrahydrocannabivarin (Δ9-THCV), which behaves like a CB1 antagonist, were also determined in free-feeding animals.
Key results: AM251 suppressed food intake and weight gain in fasted and non-fasted animals. The suppression of food intake by AM251 (10 mg·kg−1) endured for a period of 6–8 h when administered acutely, and was continuous when injected for four consecutive days. Pure Δ9-THCV also induced hypophagia and weight reduction at doses as low as 3 mg·kg−1. No rebound was observed on the following day with all drug groups returning to normal activity and feeding regimes. However, a Δ9-THCV-rich cannabis-extract failed to suppress food intake and weight gain, possibly due to residual Δ9-tetrahydrocannabinol (Δ9-THC) in the extract. This Δ9-THC effect was overcome by the co-administration of cannabidiol.
Conclusions and implications: The data strongly suggest (i) the long-term home-cage observation system is a sensitive and obesity-relevant tool, and (ii) the phytocannabinoid Δ9-THCV is a novel compound with hypophagic properties and a potential treatment for obesity.