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Background: Amidst a national surge in overdose deaths among racial and ethnic minoritized people and people who use stimulants (cocaine or methamphetamines), our objective was to understand how these groups are adapting to a rapidly changing illicit drug supply., Methods: We conducted semi-structured interviews with 64 people who use drugs and who self-identified as Black, Hispanic, Multiracial, or other Non-White race in three states (Michigan, New Jersey, and Wisconsin). Transcribed interviews were coded thematically., Results: Most respondents used stimulants alone or in combination with opioids. Respondents perceived that the drug supply had become more unpredictable and dangerous but differed in their personal perception of risk and their adaptations. For example, respondents had very mixed perceptions of their own risk of being harmed by fentanyl, and differing opinions about whether fentanyl test strips would be useful. Xylazine, a novel adulterant in the opioid drug supply that has received public health and media attention, was not well known within the sample., Conclusion: Our study highlights the challenges experienced by minoritized people who use drugs in responding to a changing drug supply, underscoring the limits of public health approaches focused solely on individual behavioral change., Competing Interests: Declarations. Ethics approval: This research was reviewed and approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board. Consent for publication: All authors granted consent for publication. The interview guide for this study can be found in the appendix. Drs. Sherman and Saloner serve as expert witnesses on behalf of Baltimore City in its litigation against opioid manufacturers and distributors. The authors received support from the Bloomberg Philanthropies as part of The Bloomberg Overdose Prevention Initiative, a collaborative partnership aimed at combating the nation’s opioid epidemic. Competing interests: Drs. Sherman and Saloner serve as expert witnesses on behalf of Baltimore City in its litigation against opioid manufacturers and distributors., (© 2024. The Author(s).)