Ketamine’s Antidepressive Effects Tied to Opioid System in Brain; Stanford Findings Overturn Beliefs That Drug’s Antidepressive Effects Stem Solely from Impact on Glutamate System

Scientists at the Stanford University School of Medicine have discovered that ketamine works as an antidepressant, at least in part, by activating the brain's opioid system. The finding overturns previously held beliefs that the drug's antidepressant effects stemmed solely from its impact on the glutamate system. These beliefs led to the widespread use of ketamine to treat depression and spurred the development of glutamate-blocking drugs for use as antidepressants. The new finding also highlights the interaction between depression, pain, and opioid addiction and presents an opportunity for clinicians to reframe treatment approaches for three of the most important public health crises today. The research is believed to be the first to address how ketamine works in the human brain to provide relief from depression. A paper describing the work was published online on August 29, 2018 in The American Journal of Psychiatry. The article is titled “Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.” The article is accompanied by an editorial titled “Is There Really Nothing New Under the Sun? Is Low-Dose Ketamine a Fast-Acting Antidepressant Simply Because It Is an Opioid?" "Before we did the study, I wasn't sure that ketamine really worked to treat depression. Now I know the drug works, but it doesn't work like everyone thought it was working," said Alan Schatzberg, MD, the Kenneth T. Norris Jr. Professor of Psychiatry and Behavioral Sciences, who shares senior authorship of the paper with Carolyn Rodriguez, MD, PhD, Assistant Professor of Psychiatry and Behavioral Sciences. Ketamine was developed in the 1960s and has been used for decades as an anesthetic during surgery.
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