The United States is in the midst of an opioid epidemic. Approved treatments for opioid use disorder (OUD) show only moderate efficacy, and most patients relapse early in treatment. There has been increased interest in the role of the immune system in OUD in terms of both pathophysiology and treatment. Opioids are known to activate microglia ? the brains' innate immune cells ? which leads to an immediate immune response; however, with chronic opioid use, the peripheral immune system becomes suppressed. Persistent, chronic immune activation becomes pathological, and can lead to long-standing, widespread alterations in reward and neurocognitive processes, which negatively impact treatment outcome. Further, while studies have consistently shown that chronic opioid abuse leads to suppressed peripheral immune function, it is not known whether chronic opioid abuse impacts the neuroimmune system. We have developed and validated the tools to measure a marker of microglia in living humans, specifically positron emission tomography (PET) imaging with the radiotracer [11C]PBR28. The overall goal of the proposed project is to use these tools to measure microglia levels in living individuals with OUD compared to healthy controls (Aim 1), and to determine relationships between microglia levels and objective measures of reward processing and neurocognitive function (Aim 2). Findings from this high-risk exploratory R21 proposal will improve our understanding of the neuroimmune mechanisms underlying OUD and its associated clinical correlates. These results have the potential to uncover a novel and treatable neuroimmune mechanism of OUD, and may guide the use of immunomodulatory agents in the clinical treatment of OUD.

Public Health Relevance

The United States is in the midst of an opioid epidemic, and more treatments are desperately needed. The brains' immune system has recently become a potential target for treatment development to help individuals suffering from opioid use disorder; and, in the proposed grant we will use state-of-the-art brain imaging tools to explore the brains immune system in living individuals with opioid use disorder, which will inform clinical treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DA047621-01
Application #
9650758
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Pariyadath, Vani
Project Start
2019-02-01
Project End
2021-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520