The National Institute on Drug Abuse (NIDA) is inviting applications under the R21 Exploratory/Developmental Research Grant mechanism for research on inflammasome activation in relation to neurocognitive disorders and immune function in people with HIV and substance use disorders (SUDs). This funding opportunity, titled “Targeting Inflammasomes in HIV and Substance Use,” seeks to advance understanding of the mechanisms of inflammasome activation within the central nervous system (CNS) and its impact on inflammation, disease progression, and neurocognitive outcomes in HIV-affected individuals who also use addictive substances. Research areas of interest include examining inflammasome pathways, assessing inflammasome activation in various CNS cell types, and developing potential therapeutic approaches to improve clinical outcomes.

Applicants are encouraged to pursue studies that explore the interplay of substance use and HIV infection on inflammasome activation, especially in myeloid cells, which are critical in both CNS immune function and neuroinflammation. NIDA highlights the importance of understanding how these mechanisms contribute to HIV progression and neuroinflammatory responses, specifically under the influence of opioids, nicotine, cocaine, methamphetamine, stimulants, psychedelics, addictive prescription drugs, cannabinoids, or combinations thereof. The NOFO seeks exploratory studies that investigate cellular pathways, biomarkers of neuroinflammation, and the effect of antiretroviral therapies on inflammasome dynamics, with the ultimate goal of translating findings into clinical applications.

This opportunity provides up to $275,000 in direct costs over a maximum project period of two years. Funding is expected to support approximately four awards across this NOFO (RFA-DA-25-068) and its companion R01 Research Project Grant (RFA-DA-25-069). Applications are restricted to non-clinical trials and must clearly detail the computational or preclinical focus of the proposed work, with a prohibition on projects that study either substance use or HIV in isolation, or on the combination of alcohol exposure with HIV.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, and various government and tribal entities. Both domestic and foreign organizations may apply, and foreign components are permitted. Applicants must ensure all necessary registrations, including SAM, eRA Commons, and Grants.gov, are completed before submission. Key submission dates include a letter of intent due by February 13, 2025, and a final application due by March 13, 2025. Applications must be submitted through ASSIST, Grants.gov Workspace, or an institutional system-to-system solution, using the required NIH application forms.

Review criteria include the significance of the research problem, innovation of the proposed approach, scientific rigor, feasibility of achieving meaningful results, and the qualifications of the research team. Proposals should detail specific curation and data sharing plans in compliance with NIH’s data management policies. Successful applications will exhibit strong relevance to the NIH mission, scientific merit, and alignment with NIDA’s program priorities, and will be subject to the NIH peer review process for scoring on overall impact.

Contact information for programmatic, peer review, and grants management queries is available, with Scientific/Research contacts including Dr. Shang-Yi Anne Tsai and Dr. Yu Lin, both from NIDA. Applications must conform to all NIH and NOFO-specific guidelines, and successful awardees must adhere to relevant data sharing and post-award reporting requirements in alignment with NIH policies.