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American Indian and Alaska Native (AI/AN) communities experience a disproportionate burden of substance use disorders (SUDs) alongside persistent barriers to culturally responsive care and research participation. Despite this need, AI/AN populations remain underrepresented in substance use research, in part due to historical and ongoing systemic inequities, including research practices that have not adequately respected Tribal sovereignty or incorporated Indigenous knowledge systems. This commentary synthesizes research conducted within the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) focused on AI/AN communities, identifies key lessons learned from this body of work, and offers recommendations for future research.

First, we provide an overview of CTN-supported studies involving AI/AN populations, highlighting both the diversity of substance use patterns across communities and the feasibility of conducting rigorous, culturally responsive research. Second, we synthesize lessons learned from these studies and related literature, including the importance of long-term relationship building, the need for culturally responsive research frameworks, structural barriers to implementation, and workforce and infrastructure challenges. Third, we present recommendations for the field, emphasizing the central role of community-based participatory research (CBPR) and Tribal participatory research (TPR), the integration of Indigenous knowledge systems, and the importance of Tribal data sovereignty and community-led dissemination.

Collectively, this commentary argues that sustainable progress in addressing SUDs among AI/AN populations requires a fundamental shift toward community-engaged, culturally responsive, and equity-focused research partnerships. The experiences of the CTN AI/AN Special Interest Group demonstrate that such approaches are not only feasible but essential for advancing both scientific knowledge and community health.

Related protocols: CTN-0020-A-1, CTN-0033-Ot-1, CTN-0033-Ot-2, CTN-0033-Ot-3, CTN-0033-Ot-4, CTN-0033-Ot-5, CTN-0044-A2, CTN-0078-Ot, CTN-0096, CTN-0096-A-1, CTN-0118, CTN-0123, CTN-0129

Employment difficulties are common among American Indian individuals in substance abuse treatment. To address this problem, the Southwest Node of the National Drug Abuse Treatment Clinical Trials Network conducted a single-site adaptation of its national Job Seekers Workshop (protocol CTN-0020) in an American Indian treatment program, Na’Nihoozhi Center (NCI). One hundred and two (80% men, 100% American Indian) participants who were in residential treatment and currently unemployed were randomized to (1) a three-session, manualized program (Job Seekers Workshop: JSW) or (2) a 40-minute video on how to interview for a job (Job Interviewing Video: JIV). Outcomes were assessed at 3-month follow-up: 1) number of days to a new taxed job or enrollment in a job-training program, and 2) total hours working or enrolled in a job-training program. No significant differences were found between the two groups for time to a new taxed job or enrollment in a job-training program. There were no significant differences between groups in substance use frequency at 3-month follow-up.

These results do not support the use of the costly and time-consuming JSW intervention in this population and setting. Despite of the lack of a demonstrable treatment effect, this study established the feasibility of including a rural American Indian site in a rigorous CTN trial through a community-based participatory research approach.

Related protocols: CTN-0020-A-1