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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

This is the primary outcomes paper for Aim 2 of CTN-0129.

Purpose: Addressing substance use disorders remains a high priority for many Indigenous communities. Opioid misuse and deaths related to overdose have been increasing sharply in American Indian/Alaska Native populations. Medications for opioid use disorder (MOUD) remain difficult to access in Great Plains Tribal Communities due to the paucity of treatment providers, among other factors. The present study explores the perceived barriers and facilitators to using telehealth to promote access to MOUD and recovery resources in Great Plains Tribal Communities.

Methods: This study employed qualitative methods to review policy considerations for using telemedicine to provide buprenorphine. We obtained qualitative data from 5 interviews with 8 total key informants (62.5% women, 25% with tribal affiliations) with local administrators, health care providers, and policymakers. Their responses were transcribed and coded with NVivo software.

Findings: After coding and analysis, 6 themes emerged: current access, acceptability in Tribal Communities, facilitators, barriers, payment considerations, and policies that support tele-MOUD. Participant responses—though specific to Great Plains Tribal Communities—mirrored other recommendations on telemedicine and substance use disorder services such as federal support of reciprocity of state licenses, permanent codification of the regulatory changes enacted during the COVID-19 public health emergency, increased funding for innovative delivery of services, and considerations of privacy; the need for culture- and trauma-informed providers was also noted.

Conclusions: Telemedicine for the provision of MOUD appears, from this qualitative analysis, to be a feasible way to expand access to care for opioid use disorder in Great Plains Tribal Communities.

Related protocols: CTN-0129

This is the primary outcomes article for Aim 1 of CTN-0129.

Substance use, specifically opioid and methamphetamine use, is of increasing concern among American Indian (AI) populations in the Great Plains. This community-driven participatory study investigated the impacts of substance use and community-defined needs in treating addiction. It determined the priorities for future research on behavioral health and substance misuse in the Great Plains region. Behavioral health and social services professionals and community stakeholders were identified from eight Great Plains communities and invited to attend eight focus groups (N=47). Conversations were audio-recorded, transcribed, and coded by the research team.

The qualitative data analysis identified four themes: (1) Challenges with Treatment and Recovery, (2) Impact of Substance Use, (3) Reasons for Substance Use, (4) Solutions and Research Priorities.

The findings highlight barriers to substance use disorder (SUD) treatment ranging from policy issues to lack of funding. The most significant finding centered on integrating cultural strengths into treatment and recovery programs, including Ceremony Assisted Treatment (CAT). Data reports for each participating organization were provided to disseminate outcomes in their respective communities. Other key findings suggest that addressing the root causes of substance use disorder, along with early intervention and comprehensive counseling services, are essential for long-term success.

Related protocols: CTN-0129