LH 21 is a 1,2,4-triazole that acts as a cannabimimetic. It has a relatively low-affinity for the central cannabinoid (CB) receptor (K = 855 nM). However, it interferes, at low nanomolar concentrations, with the action of the potent CB agonist WIN 55,212-2 on murine vas deferens, suggesting that LH 21 acts as a silent CB antagonist. Consistent with this interpretation, LH 21 diminishes the in vivo effects of WIN 55,212-2 on standard CB tetrad responses in mice and reduces food intake and body weight gain in obese Zucker rats. However, in CHO cells overexpressing CB, LH 21 is able to elevate cAMP, suggesting that, in this model, it acts as an inverse agonist of CB Furthermore, LH 21 suppresses food intake and body weight gain in both wild-type and CB receptor knockout mice, indicating that this receptor is not necessary for these effects.