Depression is one of the most common mood disorders, affecting over 320 million people worldwide; however, an effective medication for this condition is still elusive. Because the pathogenesis of depression involves multiple pathways of the nervous system, recent attempts to develop therapeutic strategies with high effectiveness and minimal side effects focus on the combined administration of drugs that mediate diverse neurotransmissions. In particular, scientists have reported that therapeutic compounds acting on the cannabinoid receptors, CB1 and CB2, are promising enhancers of conventional antidepressant drugs.
Two conventional antidepressant medications tested were Bupropion and Moclobemide. Surprisingly, both the pharmaceutical activator and inhibitor of the CB1 receptor could improve Bupropion potency. Meanwhile, only the pharmaceutical inhibitor of the CB1 receptor could potentiate Moclobemid. The mechanisms underlying these complicated, seemingly paradoxical effects remain to be explored. Drugs that activate or inhibit the CB2 receptor appeared to have no significant antidepressant-enhancing impacts, possibly because this receptor is far less abundant in the brain. Nonetheless, that regulations of CB1 receptor function influenced the activities of antidepressant drugs confirmed the major roles of the endocannabinoid system in depression pathogenesis.