Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice

Gernot Riedel, Paola Fadda, Susan McKillop-Smith, Roger G Pertwee, Bettina Platt, Lianne Robinson

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

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.

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 Delta(9)-tetrahydrocannabivarin (Delta(9)-THCV), which behaves like a CB1 antagonist, were also determined in free-feeding animals.

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 Delta(9)-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 Delta(9)-THCV-rich cannabis-extract failed to suppress food intake and weight gain, possibly due to residual Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in the extract. This Delta(9)-THC effect was overcome by the co-administration of cannabidiol.

The data strongly suggest (i) the long-term home-cage observation system is a sensitive and obesity-relevant tool, and (ii) the phytocannabinoid Delta(9)-THCV is a novel compound with hypophagic properties and a potential treatment for obesity.

Original languageEnglish
Pages (from-to)1154-1166
Number of pages13
JournalBritish Journal of Pharmacology
Volume156
Issue number7
Early online date17 Feb 2009
DOIs
Publication statusPublished - Apr 2009

Keywords

  • obesity
  • hypophagia
  • phytocannabinoids
  • delta(9)-THCV
  • AM251
  • home cage
  • mice
  • CB1 receptor
  • inverse agonist AM251
  • stimulates food-intake
  • taste reactivity test
  • body-weight
  • 2-arachidonoyl glycerol
  • endocannabinoid system
  • energy-balance
  • SR 141716
  • high-fat
  • rats
  • obesity
  • hypophagia
  • phytocannabinoids

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