Tolerance to hypophagia induced by prolonged treatment with a CB1 antagonist is related to the reversion of anorexigenic neuropeptide gene expression in the hypothalamus.

It is well established that treatment with rimonabant, a CB1 antagonist, decreases food intake and body weight gain. In part, these responses are mediated by increased activity of hypothalamic neurons related with energy homeostasis. However, food consumption is reversed to basal level during prolonged CB1 antagonist treatment, suggesting tolerance to its anorexigenic effect.