Tuning the endocannabinoid system: allosteric modulators of the CB 1 receptor

Cannabinoid CB 1 receptor antagonists are novel therapeutics with potential for the treatment of a number of conditions including obesity, nicotine addition and metabolic syndrome. In 2005, Price et al . demonstrated that the cannabinoid CB 1 receptor contains an allosteric‐binding site which binds synthetic small molecules. In this issue of the British Journal of Pharmacology , Horswill et al . have extended these observations. They demonstrate that a structurally similar small molecule allosterically modulates the cannabinoid CB 1 receptor and reduces body weight and food intake in an acute feeding model. Allosteric modulation now contends as a new strategy in the therapeutic exploitation of cannabinoid receptors that may offer certain advantages over the more familiar small molecules targeting the orthosteric site. British Journal of Pharmacology (2007) 152 , 565–566; doi: 10.1038/sj.bjp.0707349 ; published online 25 June 2007