Ketamine is a non-competitive NMDA glutamate receptor antagonist with additional effects on dopamine and mu-opioid receptors. While it does stimulate opiate receptors, much like morphine, its NMDA receptor antagonism at subanesthetic doses is thought to be much more important in the treatment of chronic pain and psychiatric disorders. It is this low dose of intravenous ketamine that has been found to cause a glutamate surge, which appears to play a critical role in the rapid and robust effects of ketamine.
Ketamine is largely different from that of typical FDA-approved antidepressants and pain medications because it works more broadly by reducing NMDA receptor function, therefore, modulating or preventing the brain’s glutamate transmission. This leads to a rapid increase in glutamatergic activity causing regeneration of synaptic connections between brain cells that have been chronically damaged by stress, anxiety, depression, and pain. It is a sort of “rebooting” for the communication system between areas of the brain and body that have previously been damaged by these chronic conditions.
Recently performed and published studies have shown that a very low dose of ketamine infused over one hour has had a dramatic positive effect on clinical depression, especially towards suicidal feelings and in cases that don’t respond to standard treatment. The results indicate an immediate resolution of depression and the relief from a single infusion can last for as little as a few hours to as much as a few weeks.