Ketamine activates opioid system

A new study appearing online today from the American Journal of Psychiatry finds that ketamine’s acute antidepressant effect requires opioid system activation, the first time that a receptor site has been shown in humans to be necessary for any antidepressant’s mechanism of action. While opioids have been used historically to treat depression, they are known to carry a high risk of dependence. Alan F. Schatzberg, M.D., who led this research at Stanford, cautions against widespread and repeated use of ketamine for depression treatment until more research can be done on both the mechanism of action and the risk of tolerance, abuse and dependence.

Previous research has found ketamine to have rapid-onset antidepressant effects. While the specific mechanism of action for these effects was unknown, it had been generally thought to be due to NMDA receptor antagonism. Since many efforts to develop NMDA antagonists as antidepressants have been unsuccessful, this new study aimed at determining the role of the opioid system in ketamine’s antidepressant and dissociative effects in adults with treatment-resistant depression.

Source: New research: Ketamine activates opioid system to treat depression