Device Based Treatments for Substance Use Disorders (UG3/UH3 Clinical Trial Optional)

The National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), has announced the funding opportunity titled *Device-Based Treatments for Substance Use Disorders (UG3/UH3 Clinical Trial Optional)* under funding opportunity number PAR-25-023. This opportunity aims to accelerate the development of neuromodulatory and neurophysiological devices for the treatment of Substance Use Disorders (SUDs). The goal is to advance these devices through pre-clinical and clinical development stages, ultimately facilitating their progression toward FDA approval for SUD treatment. Applications may focus on developing new devices or repurposing existing FDA-approved devices for other medical indications, with an emphasis on evaluating the devices’ mechanisms of action, safety, and efficacy. The UG3/UH3 funding mechanism follows a phased approach. The UG3 phase supports up to two years of early-stage development and validation, with clearly defined milestones that must be achieved for progression to the UH3 phase. The UH3 phase, contingent upon successful completion of UG3 milestones, provides up to three years of additional funding to support further development, larger-scale testing, and validation of the device-based intervention. The transition between UG3 and UH3 phases is administratively reviewed and prioritized by NIDA, ensuring alignment with program goals and regulatory milestones. The program seeks research into a variety of technologies, including transcranial magnetic stimulation, transcranial direct current stimulation, vagal nerve stimulation, deep-brain stimulation, focused ultrasound, and other related interventions. Applications should include objective measures of target engagement, dose-response relationships, and detailed evaluations of the intervention's effects on brain circuits and behavioral outcomes. The research must incorporate well-defined milestones and a go/no-go decision tree, ensuring clarity in project progression. Investigators are encouraged to address safety, side effects, and contextual aspects of device administration, and to explore integration with existing pharmacological or behavioral therapies. Eligible applicants include higher education institutions, non-profit and for-profit organizations, local and state governments, tribal governments, and foreign entities. Collaborative, interdisciplinary teams are highly encouraged, as the complexity of device-based interventions often requires expertise across clinical, regulatory, and technical domains. Proposals must follow NIH’s standard application guidelines, including instructions from the *SF424 (R&R) Application Guide*, and must demonstrate compliance with data management and sharing requirements. Letters of intent, while not mandatory, are encouraged and should be submitted 30 days before the application due date. Applications will undergo scientific merit review, with evaluation criteria focusing on the significance, innovation, rigor, feasibility, and expertise of the investigative team. Reviewers will assess whether the project adequately addresses regulatory requirements, such as Investigational Device Exemption (IDE) filings, and whether UG3 milestones are clearly defined, quantifiable, and achievable. Successful applications will demonstrate a strong rationale for both UG3 and UH3 phases, clear endpoints for device development, and a robust regulatory and scientific plan for FDA approval. The submission window opens on July 14, 2025, with application due dates on August 13, 2025, December 18, 2025, and August 13, 2026. Scientific merit reviews will follow in November 2025, March 2026, and November 2026, with advisory council reviews in January 2026, May 2026, and January 2027. The earliest anticipated start dates are April 2026, July 2026, and April 2027. The UG3 phase budgets are limited to $500,000 in direct costs per year, while UH3 budgets are not capped but must align with project needs. Prospective applicants are encouraged to consult with NIDA program staff during the planning stages to ensure alignment with program priorities and regulatory requirements. For further assistance, key contacts include Dr. Will M. Aklin and Dr. Katrina Foster for scientific inquiries, Dr. Dharmendar Rathore for peer review questions, and Amy Connolly for financial and grants management.