Federal Project Grant Award Summary

The National Institute on Drug Abuse (NIDA) awarded the University of Pittsburgh a $700,254 Project Grant under the Drug Use and Addiction Research Programs (CFDA 93.279) to conduct preclinical and human research examining the neurobiological effects of combined nicotine and opioid exposure on the prefrontal cortex in individuals with opioid use disorder (OUD). The research will investigate how nicotine and opioids interact to produce synaptic and molecular adaptations in somatostatin-expressing inhibitory neurons within the prefrontal cortex—a brain region implicated in cravings and anhedonia associated with OUD. The deliverables include controlled preclinical experiments utilizing mouse models and postmortem human brain analysis to test the hypothesis that nicotine primes prefrontal cortex neurons to promote opioid use and social withdrawal during opioid withdrawal, with the ultimate goal of identifying novel treatment targets to address the 60–90% relapse rate in OUD populations.

The five-year project period extends from June 1, 2026 through March 31, 2031 and addresses a significant research gap in understanding nicotine dependence as a confounding factor in OUD treatment translation, given that 80–90% of individuals with OUD smoke. By elucidating the synergistic molecular and synaptic mechanisms underlying polysubstance use involving nicotine and opioids, this research is expected to inform the development of improved treatment strategies that address both cravings and affective symptoms in OUD populations.