Despite the strong evidence indicating a beneficial effect of CB1 receptor antagonists in depression, the data obtained so far do not completely support this assumption since, while we and others [19–21] have demonstrated that SR141716A might be effective to reduce depressive-like symptoms in animal models, this CB1 antagonist was withdrawn from the market as an antiobesity drug because of its prodepressant effects. The gene discussed is CNR1; the disease is major depressive disorder.