Setting an agenda for adolescent substance use research in the National Drug Abuse Treatment Clinical Trials Network.

Adolescent substance use (SU) presents a distinct public health challenge, as this developmental stage carries heightened vulnerability for progression to problematic use. Early SU-before age 18-is a major risk factor for later Substance Use Disorders (SUD), with long-term neurobiological and psychosocial consequences. National surveillance data show a continued decline in alcohol and cigarette use, yet persistent concerns around cannabis (including synthetic variants) and sharp increases in vaping. The frequent occurrence of polysubstance use further complicates prevention and intervention efforts. The intersection of SU and mental health conditions, such as anxiety and depression, compounds these challenges. The 2024 National Survey on Drug Use and Health data reveal that nearly one-third (27.9%) of adolescents aged 12-17 with both SUD and a Major Depressive Episode receive no treatment for either condition. Despite promising evidence-based interventions, their implementation remains limited, revealing a critical translational gap between research efficacy and real-world effectiveness. To close this gap, the National Drug Abuse Treatment Clinical Trials Network (CTN) is leveraging its multi-site research infrastructure to conduct pragmatic clinical trials that emphasize the inclusion of adolescents from all backgrounds. The CTN's agenda identifies six priorities to advance scalable, impactful solutions: Through this coordinated agenda, the CTN aims to build an equitable, evidence-informed framework that bridges discovery and practice, drives innovation, and informs policies that foster resilient, healthy futures for adolescents nationwide.