A therapeutic role for cannabinoid CB1 receptor antagonists in major depressive disorders.

Cannabinoid receptors in the CNS have been implicated in the control of appetite, cognition, mood and drug dependence. Recent findings support the hypothesis that cannabinoid CB1 receptor blockade might be associated with antidepressant and anti-stress effects. A novel potential antidepressant drug class based on this mechanism is supported by the neuroanatomical localization of CB1 receptors and signal transduction pathways that are involved in emotional responses, together with the antidepressant-like neurochemical and behavioral effects induced by CB1 receptor antagonists. Selective CB1 receptor antagonists are in development for the treatment of obesity and tobacco smoking, and could be tested for antidepressant efficacy because recent results of clinical studies suggest that they would also treat comorbid symptoms of depression such as cognitive deficiencies, weight gain, impulsivity and dependence disorders. Thus, CB1 receptor antagonism might constitute an integrated pharmacotherapeutic approach that impacts the affective, cognitive, appetitive and motivational neuronal networks involved in mood disorders.