Integrative Research on Polysubstance Abuse and Addiction (R21/R33 Clinical Trial Optional) | PAR 18 084

Opportunity Information: Apply for PAR 18 084

The Integrative Research on Polysubstance Abuse and Addiction (R21/R33 Clinical Trial Optional) funding opportunity (PAR-18-084) is a National Institutes of Health grant supported through the Collaborative Research on Addiction (CRAN), a partnership across NIAAA, NIDA, and NCI. It is aimed at improving how the field understands and responds to polysubstance use, meaning the use of more than one substance, by encouraging projects that connect biological mechanisms to real-world behavioral and public health outcomes. A central idea behind the announcement is that polysubstance use is not simply "single-substance addiction plus another drug," and that combinations of substances can create distinct brain changes, patterns of behavior, and health consequences that need focused, integrative study.

The opportunity has two main scientific goals. First, it seeks research that can characterize how neurobiological alterations, related behaviors, and public health impacts associated with polysubstance use differ from (or resemble) those seen in single-drug use. That includes work that teases apart whether certain drug combinations amplify reward, craving, withdrawal, stress responsivity, pain processing, cognitive impairment, impulsivity, or psychiatric symptoms beyond what would be expected from one substance alone. It also includes clarifying whether harms such as overdose risk, infectious disease transmission, cancer-related risks, accidents and injuries, or progression to more severe substance use disorder trajectories differ when multiple substances are involved. Second, it prioritizes truly integrative polysubstance research that deliberately spans a translational pipeline, linking basic science models, human laboratory research, and population-level epidemiology rather than treating these as separate silos.

The mechanism is a phased innovation award using the R21/R33 structure, designed to push promising early work quickly into a more confirmatory or expanded phase. In practice, the R21 phase supports exploratory or developmental studies that can occur at any point along the translational spectrum, including animal studies, controlled human laboratory paradigms, or epidemiological analyses. The defining feature is what comes next: results generated during the R21 are expected to be rapidly back-integrated or forward-integrated into a different translational stage during the R33 phase. For example, a project might start with an animal model to identify neural circuitry changes linked to combined alcohol and nicotine exposure (R21), then move into a human lab study to test whether related biomarkers or behavioral signatures are observable in people (R33). Alternatively, an epidemiological signal suggesting a high-risk pattern of co-use might motivate a human laboratory study first (R21), followed by mechanistic work in animals or more targeted population analyses (R33). This two-way exchange is meant to speed up translation and ensure that findings inform each other rather than remaining disconnected.

Clinical trials are listed as optional, meaning applicants may propose clinical trials if they are scientifically justified, but the FOA is not limited to clinical trial work and can support non-trial mechanistic, behavioral, and observational designs as well. The emphasis is on the integration across levels of analysis and on generating knowledge that clarifies what is unique (or not) about polysubstance use relative to single-substance use, with the longer-term aim of informing prevention strategies, interventions, and public health responses.

In terms of who can apply, eligibility is broad and includes state, county, city, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other organizations. The announcement also explicitly highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, U.S. territories or possessions, regional organizations, eligible federal agencies, and non-U.S. entities (foreign organizations). This breadth signals an interest in diverse research settings and populations, including communities that may experience disproportionate burdens of substance use harms.

Key administrative details in the source data include that the sponsoring agency is NIH, the funding instrument is a grant, and the activity category is listed under education and health. The CFDA numbers associated with the opportunity are 93.273, 93.279, and 93.399. The record shows a creation date of 2017-11-17 and an original closing date of 2020-01-07. The listed award ceiling is 200000, indicating an upper limit for at least one budget component in the opportunity details as provided.

Overall, the FOA is structured to motivate projects that do more than document co-use patterns. It is designed for teams that can connect mechanisms to outcomes by moving deliberately across animal, human, and population research, and by using the phased R21/R33 structure to turn early discoveries into a more integrated and actionable body of evidence about polysubstance abuse and addiction.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Integrative Research on Polysubstance Abuse and Addiction (R21/R33 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.273, 93.279, 93.399.
• This funding opportunity was created on 2017-11-17.
• Applicants must submit their applications by 2020-01-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $200,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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