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

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

• Authors: Gernot Riedel, Paola Fadda, Susan McKillop-Smith, Roger G Pertwee, Bettina Platt, Lianne Robinson
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 156 Issue 7 Pg. 1154-66 (Apr 2009) ISSN: 1476-5381 [Electronic] England
• PMID: 19378378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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