Addressing Methodological Challenges with Clinical Trials of Rapid-Acting Psychotropic Interventional Drugs (RAPIDs)

The National Institutes of Health (NIH), specifically the National Institute of Mental Health (NIMH), has forecasted a funding opportunity focused on addressing methodological challenges associated with clinical trials of rapid-acting psychotropic interventional drugs (RAPIDs). These include psychotomimetic agents (PMAs) such as classic psychedelics (e.g., psilocybin), dissociative anesthetics (e.g., ketamine), and entactogens (e.g., MDMA). This funding opportunity aims to improve the rigor and interpretability of trials evaluating these substances, which have shown significant promise in treating mental health disorders including depression and anxiety. By advancing understanding of the mechanisms and therapeutic effects of PMAs, the initiative seeks to strengthen the validity of emerging evidence and support regulatory and clinical decisions. This Notice of Funding Opportunity (NOFO), with the identifier RFA-MH-27-135, is forecasted and currently not open for applications. The anticipated opening date for submissions is September 3, 2025, with a due date of November 3, 2025. Awards are projected to be made by July 1, 2026, which will also serve as the earliest start date for funded projects. The NIH expects to fund approximately five awards under this program, with total available program funding estimated at $5,000,000. The opportunity is categorized as discretionary and falls under the Assistance Listing 93.242 – Mental Health Research Grants. It is designed for projects that use the R01 grant mechanism, which supports discrete, specified, and circumscribed research projects. Eligibility for this opportunity is broad and inclusive, encompassing a wide range of public and private institutions. Eligible applicants include state governments, county governments, independent school districts, Native American tribal governments (both federally recognized and other tribal organizations), public and state-controlled institutions of higher education, private institutions of higher education, nonprofits with 501(c)(3) status, public housing authorities/Indian housing authorities, small businesses, and for-profit organizations other than small businesses. No cost sharing or matching is required, making the opportunity accessible to entities with varying levels of financial capacity. The primary focus of the research funded through this NOFO is to refine methodologies for clinical trials involving PMAs, ensuring the reproducibility and reliability of their outcomes. This includes addressing unique challenges posed by the subjective and experiential effects of PMAs, the need for innovative trial designs, and the complexity of regulatory requirements for trials involving controlled substances. Applicants are strongly encouraged to engage in early consultation with the U.S. Food and Drug Administration (FDA) to ensure that proposed protocols align with regulatory expectations and standards. Although applications are not yet being solicited, the early publication of this notice is intended to give researchers sufficient lead time to build collaborations, design responsive projects, and ensure compliance with relevant clinical and regulatory requirements. Investigators with expertise in psychotropic drug research, clinical trial methodology, or neuropsychiatric disorders are especially encouraged to prepare for submission. Collaborative applications that combine strengths across disciplines—particularly those bridging psychedelic research and advanced trial design—are welcomed. For further information about the program and application guidance, potential applicants may contact Dr. Jonathan Sabbagh at the National Institute of Mental Health via email at [email protected] or by phone at 301-793-3534. The NOFO does not currently link to a downloadable PDF, and applicants are advised to monitor Grants.gov and the NIH funding website for updates, including the formal release of the application package and further guidance. The forecasted timeline allows for early planning, and applicants are encouraged to act promptly when the opportunity officially opens in September 2025.