PAR-25-446
Development of Interventions to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional)
Summary
PAR-25-446: Development of Interventions to Prevent and Treat Substance Use Disorders and Overdose
Research Focus
This funding opportunity supports preclinical and clinical research to develop and advance interventions for substance use disorders (SUDs) and overdose toward FDA approval or clinical adoption. With over 40 million Americans living with SUDs and 105,000 overdose deaths in 2023—driven largely by synthetic opioids (fentanyl), methamphetamine, and cocaine, plus polysubstance combinations—NIDA seeks high-impact studies that rapidly de-risk candidate interventions. Research priorities include pharmacotherapies (new chemical entities, repurposed medications, biologics), device-based neuromodulatory treatments (transcranial magnetic stimulation, deep-brain stimulation, vagal stimulation), and digital therapeutics (software-based diagnostic or therapeutic platforms). Studies may target prevention of SUD initiation or progression, treatment adherence, withdrawal management, neonatal opioid withdrawal, comorbid SUDs, overdose lethality reduction, and substance-induced respiratory depression. Applications must include clear, quantitative go/no-go milestones for the exploratory (UG3) phase.
At a Glance
- Who can apply: Not stated (see institution eligibility in full FOA)
- Funding & project length: Not stated; UG3/UH3 phased cooperative agreement structure
- Award mechanism: UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement
- Key dates: Applications due October 20, 2025 (earliest cycle); earliest start December 22, 2025; FOA expires August 22, 2028
- Best fit for: Addiction medicine, neuroscience, pharmacology, psychiatry researchers developing medications, neuromodulatory devices, or digital therapeutics for opioid use disorder, stimulant use disorder, and polysubstance overdose in diverse populations
Key Facts
Deadline
Mon, August 21, 2028
Posted
Wed, September 10, 2025
Award Range
— – $3,000,000
Keywords
Research Areas
Gotchas (2)
UG3/UH3 applications must provide clear milestones at the end of the UG3 phase with objective success criteria and go/no-go rules for medications development that include quantitative criteria—this is
95%
Source Text
“Because the development of SUD interventions is likely to be high risk, UG3/UH3 grant applications must provide clear milestones to be accomplished at the end of the UG3 phase. Objective milestones of success and go/no-go rules for medications development progression are required, and both must have quantitative criteria associated with them.”
For device-based studies using sham/placebo comparators, applicants must demonstrate not only adequate masking but also lack of biological action that would exert CNS effects—this is a specific method
88%
Source Text
“Sham/placebo stimulus comparators should be included when appropriate. If a sham is used, demonstration must be provided not only of adequate masking procedures but also lack of biological action that would exert central nervous system effects.”