Cannabinol and cannabidiol exert opposing effects on rat feeding patterns
Increased food consumption following ∆9-tetrahydrocannabinol-induced cannabinoid type 1 receptor agonism is well documented. However, possible non-∆9-tetrahydrocannabinol phytocannabinoid-induced feeding effects have yet to be fully investigated. Therefore, we have assessed the effects of the individual phytocannabinoids, cannabigerol, cannabidiol and cannabinol, upon feeding behaviors.
Adult male rats were treated (p.o.) with cannabigerol, cannabidiol, cannabinol or cannabinol plus the CB1R antagonist, SR141716A. Prior to treatment, rats were satiated and food intake recorded following drug administration. Data were analyzed for hourly intake and meal microstructure.
Cannabinol induced a CB1R-mediated increase in appetitive behaviors via significant reductions in the latency to feed and increases in consummatory behaviors via increases in meal 1 size and duration. Cannabinol also significantly increased the intake during hour 1 and total chow consumed during the test. Conversely, cannabidiol significantly reduced total chow consumption over the test period. Cannabigerol administration induced no changes to feeding behavior.
This is the first time cannabinol has been shown to increase feeding. Therefore, cannabinol could, in the future, provide an alternative to the currently used and psychotropic ∆9-tetrahydrocannabinol-based medicines since cannabinol is currently considered to be non-psychotropic. Furthermore, cannabidiol reduced food intake in line with some existing reports, supporting the need for further mechanistic and behavioral work examining possible anti-obesity effects of cannabidiol.
KeywordsCannabis Cannabigerol Cannabidiol Cannabinol Phytocannabinoids Feeding Appetite Behavio(u)r
Analysis of variance
Botanical drug substance
Cannabinoid type 1 receptor
Cannabinoid type 2 receptor
Central nervous system
This research was supported in part by the University of Reading Research Endowment Trust Fund (to JAF). The authors thank Ms. Pam Rummings and her team for technical assistance and GW Pharmaceuticals for the kind gift of purified phytocannabinoids.
All procedures were performed in compliance with the requirements of the United Kingdom Animals (Scientific Procedures) Act 1986 and all other applicable laws and standards in the UK.
- BNF (2006) British National Formulary. BMJ Publishing Group, LondonGoogle Scholar
- Clark RT (2009) Annual Report Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 For the Fiscal Year Ended December 31, 2008 United States Securities and Exchange Commission. Merck & Co., Inc., WashingtonGoogle Scholar
- Deiana S, Watanabe A, Yamasaki Y, Amada N, Arthur M, Fleming S, Woodcock H, Dorward P, Pigliacampo B, Close S, Platt B, Riedel G (2012) Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), ∆9-tetrahydrocannabivaron (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive–compulsive behaviour. Psychopharmacol 219:859-873Google Scholar
- EMA (2009) Procedural steps taken and scientific information after the authorisation Acomplia. In: Agency EM (ed) EMEA/H/C/000666/A20/0012. European Union, BrusselsGoogle Scholar
- Farrimond JA, Mercier MS, Whalley BJ, Williams CM (2011) Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation. Phytother Res 25:18Google Scholar
- Farrimond JA, Whalley BJ, Williams CM (2012) Non-∆9tetrahydrocannabinol phytocannabinoids are effective modulators of rat feeding patterns in vivo. Behav Pharmacol 23:113--117Google Scholar
- Gauson L, Stevenson L, Thomas A, Baillie G, Ross R, Pertwee R (2007) Cannabigerol behaves as a partial agonist at both CB1 and CB2 receptors. Symposium on the Cannabinoids. International Cannabinoid Research Society, Burlington, Vermont, USA, 206 ppGoogle Scholar
- O'Shaughnessey WB (1843) On the Preparations of the Indian hemp, or gunjah (Cannabis indica): their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Provincial Medical Journal 5Google Scholar
- Rinaldi-Carmona M, Barth F, Héaulme M, Shire D, Calandra B, Congy C et al (1999) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350(2–3):240–244Google Scholar