The first controlled evidence has been released showing that an intranasal ketamine spray conferred an unusually rapid antidepressant effect –- within 24 hours —- and was well tolerated in patients with treatment-resistant major depressive disorder. One of the most common NMDA receptor antagonists, ketamine is an FDA-approved anesthetic. It has been used in animals and humans for years. Ketamine has also been a drug of abuse and can lead to untoward psychiatric or cognitive problems when misused. In low doses, ketamine shows promise in providing rapid relief of depression, with tolerable side effects.