It was first suggested in 2000 that ketamine may have antidepressant effects in humans. The suggestion was based on animal studies of depression showing that a neurotransmitter called glutamate was dysfunctional in depression. Other studies showed that NMDA, a drug that binds to glutamate receptors, relieved depression in humans. This led to the “glutamate hypothesis” about the origins of depression. Ketamine was known to bind to glutamate receptors.