Federal Grant Award Summary

The University of California, San Diego received a $1.39 million Project Grant award from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) to investigate mitochondrial dysfunction as a therapeutic target in HIV-associated neurocognitive disorders and opioid use disorder. The award, obligated on March 1, 2026 with a completion date of December 31, 2030, funds research examining dysregulated oxidative phosphorylation pathways in individuals living with HIV who also have opioid use disorder, particularly in the context of fentanyl addiction. The research will deliver scientific knowledge and preclinical evidence supporting NAD+ (nicotinamide adenine dinucleotide) as a novel therapeutic strategy to restore mitochondrial function and reduce neuroinflammation.

The grant deliverables include development of a three-dimensional human brain assembloid model incorporating induced pluripotent stem cell-derived neurons, astrocytes, microglia, and blood-brain barrier cells to model HIV and fentanyl exposure effects, along with single-cell transcriptomics analyses and functional assays assessing mitochondrial function and neuronal damage. Additionally, the award funds creation of an integrated HIV transgenic rat model of extended fentanyl self-administration with comprehensive behavioral testing and single-nucleus transcriptomics of the nucleus accumbens across multiple addiction stages. These integrated in vitro and in vivo model systems will generate molecular and functional data to evaluate NAD+ treatment efficacy in mitigating neurotoxicity and cognitive deficits associated with the comorbid conditions of HIV and opioid addiction.