The Department of Health and Human Services (HHS), through the National Institute on Drug Abuse (NIDA) at NIH, has reissued a funding opportunity (PAR-25-446) for research into interventions preventing and treating substance use disorders (SUDs) and overdose. This UG3/UH3 cooperative agreement supports preclinical and clinical studies focusing on pharmacotherapies, device-based treatments, digital therapeutics (DTx), and behavioral interventions (Stages I-III). The goal is to advance candidate interventions towards regulatory approval or clinical adoption, addressing the urgent need for effective SUD treatments. Applications are due by 5:00 PM local time, with multiple cycles from October 2025 to August 2028. Eligibility extends to various organizations, including foreign entities, but excludes applications with foreign subawards/subcontracts. Substantial NIH involvement is expected, with clear milestones required for UG3/UH3 phase transitions. Applications that don't focus on novel target identification, mechanistic studies of addiction neurobiology, alcohol as the sole substance, or behavioral interventions beyond Stage III are not responsive.