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

Br J Pharmacol. 2009 Apr;156(7):1154-66. doi: 10.1111/j.1476-5381.2008.00107.x.

Abstract

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 Delta9-tetrahydrocannabivarin (Delta9-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 Delta9-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 Delta9-THCV-rich cannabis-extract failed to suppress food intake and weight gain, possibly due to residual Delta9-tetrahydrocannabinol (Delta9-THC) in the extract. This Delta9-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 Delta9-THCV is a novel compound with hypophagic properties and a potential treatment for obesity

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite Depressants / pharmacology*
  • Cannabinoid Receptor Antagonists*
  • Dronabinol / administration & dosage
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Eating / drug effects
  • Fasting
  • Feeding Behavior / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacology*
  • Solvents
  • Weight Gain / drug effects

Substances

  • Appetite Depressants
  • Cannabinoid Receptor Antagonists
  • Piperidines
  • Pyrazoles
  • Solvents
  • tetrahydrocannabivarin 9
  • AM 251
  • Dronabinol