Stanford Psychiatry’s Carolyn Rodriguez Awarded Grant Examining Mu Opioid Mechanisms of Ketamine's Rapid Effects in OCD

November 1, 2023

Carolyn Rodriguez, MD, PhD

We are excited to announce that Stanford Psychiatry’s Carolyn Rodriguez, professor of psychiatry and behavioral sciences, has received a grant from the National Institute of Mental Health to research the role of ketamine’s opioid properties in modulating fronto-striatal circuitry and bringing about anti-obsessional effects in obsessive-compulsive disorder (OCD).

OCD typically starts in childhood, has lifelong morbidity, and annually costs the economy $2.1 billion in direct costs and $6.2 billion in indirect costs (such as lost productivity). OCD responds inadequately to first-line treatments such as serotonin reuptake inhibitors (SRIs). Moreover, if there is a response to SRIs, it can be only partial as well as delayed by two to three months.

“Given the morbidity and dysfunction OCD imposes on millions of adults in the United States,” writes Dr. Rodriguez, “exploring whether SRI non-responders are helped by adding drugs with different mechanisms of action is urgently needed.”

This project focuses on ketamine’s action on the mu-opioid system and OCD neural circuits. Prior work has found that the mu-opioid receptor antagonist, naltrexone, blocks ketamine’s acute, dramatic antidepressant effects. Naltrexone also worsens OCD symptoms, while morphine (a mu-opioid receptor agonist) diminishes OCD symptoms. To assess the neural targets modulated by mu-opioid receptor antagonism, this study will focus on fronto-striatal cognitive control circuits, which neuroimaging studies show are directly influenced by the mu-opioid system.

The research team will test whether opioid receptor antagonism blocks ketamine’s effects on control and reward circuits and circuit connectivity by combining experimental medication and neuroimaging approaches with the goal of identifying a new avenue for therapeutics to transform psychiatric treatments.

The overarching goal of Dr. Rodriguez’s team in the Translational Therapeutics Lab is to study new pathways for targeted, rapid-acting treatments and to drive insights into the brain basis of OCD and related disorders. Recent publications related to this work include “Rapid and novel treatments in psychiatry: the future is now” in the journal Neuropsychopharmacology and “Cognitive Control Predicts Alleviation of OCD Symptoms by Ketamine,” published in the journal Biological Psychiatry.

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