A population‐based study exploring racial and gender inequities in polysubstance‐related deaths across the United States from 2004 to 2022 - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. 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Learn more: PMC Disclaimer | PMC Copyright Notice Addiction . 2026 Apr 15;121(8):2035–2042. doi: 10.1111/add.70409 Search in PMC Search in PubMed View in NLM Catalog Add to search A population‐based study exploring racial and gender inequities in polysubstance‐related deaths across the United States from 2004 to 2022 Kechna Cadet Kechna Cadet 1 Department of Emergency Medicine, Columbia University Irving Medical Center, New York, NY, USA 2 Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA Find articles by Kechna Cadet 1, 2, ✉ , Paige Brinzo Paige Brinzo 3 Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA Find articles by Paige Brinzo 3 , Silvia S Martins Silvia S Martins 1 Department of Emergency Medicine, Columbia University Irving Medical Center, New York, NY, USA Find articles by Silvia S Martins 1 Author information Article notes Copyright and License information 1 Department of Emergency Medicine, Columbia University Irving Medical Center, New York, NY, USA 2 Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA 3 Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA * Correspondence , Kechna Cadet, Department of Emergency Medicine, Columbia University Irving Medical Center, 530 West 166th St, New York, NY 10032, USA. Email: [email protected] ✉ Corresponding author. Received 2025 May 1; Accepted 2026 Feb 24; Issue date 2026 Aug. © 2026 Society for the Study of Addiction. PMC Copyright notice PMCID: PMC13089300 NIHMSID: NIHMS2156831 PMID: 41986927 Abstract Background and aim Recent studies have shown that Black men and women have been disproportionately impacted by overdose deaths within recent years, with their mortality rates rising sharply compared with their White counterparts. As the United States is in the fourth wave of the polysubstance use overdose crisis, it is unclear if polysubstance use is contributing to these disparate patterns of overdose mortality across race and gender. This study aimed to measure gender‐specific racial disparities in opioid related polysubstance use drug mortality in the United States from 2004 to 2022. Design, setting and participants In this population‐level study of all deaths occurring in the United States, we obtained finalized death records of overdose fatalities identified using codes in the International Classification of Diseases , Tenth Revision (ICD‐10) from Centers for Disease Control (CDC) and Prevention's Wide‐Ranging Online Database for Epidemiologic Research (WONDER) Multiple Cause of Death file, from 2004 to 2022. Annual Percent Change (APC) and Annual Average Percent Change (AAPC) in age‐adjusted mortality rates (AAMR) for White men, White women, Black men, Black women, Hispanic men and Hispanic women were determined using joinpoint regression in this cross‐sectional study. Measurements Joinpoint regression was used to examine mortality rates for opioid‐only, opioids with a stimulant, opioids with benzodiazepines, among racial/gender groups to measure temporal trends in age‐adjusted overdose mortality due to polysubstance‐related overdose. Findings The final analytic sample included n = 627 793 opioid‐only deaths, n = 196 001 opioid‐stimulant and n = 117 322 opioid‐benzodiazepine overdose deaths. Opioid‐involved deaths increased across all groups, with the highest absolute rate change experienced by non‐Hispanic Black men (53.55 per 100 000, AAPC: 17.3%) and pronounced increases shown to occur between 2011 and 2022 (APC: 29.0%). Opioid‐stimulant polysubstance use deaths had the largest increases among non‐Hispanic Black men and women, with a 39.5% APC (2011–2022) for men and 36.2% APC (2012–2022) for women. Among Hispanic men, the rates accelerated 33.8% per year (2012–2022). For opioid‐benzodiazepine polysubstance use deaths, non‐Hispanic White men and women experienced the highest absolute rate change of 3.39 and 2.41 per 100 000, respectively. Conclusions In the United States from 2004 to 2022, overdose deaths from polysubstance use escalated sharply across all racial and ethnic groups, with disproportionate increases across non‐Hispanic Black and Hispanic individuals, particularly in opioid‐stimulant and opioid‐only profiles. Keywords: inequities, opioid‐benzodiazepine, opioid‐stimulant, opioid , overdose, polysubstance use INTRODUCTION During the past two decades, the United States (US) has experienced increasing drug related deaths related to shifting patterns of use. In 2023 alone, provisional data from the Centers for Disease Control and Prevention's (CDC) National Center for Health Statistics estimated 107 543 lives were lost because of overdose deaths [ 1 ]. Although this estimate represented a 3% decrease from overdose deaths in 2022 overall, overdose involving cocaine and methamphetamine increased [ 1 ]. Many US states such as Alaska, Washington and Oregon experienced notable increases up to approximately 27% in overdose deaths in 2023 compared to similar periods in the prior year [ 1 ]. This remains a growing public health crisis, with overdose patterns increasingly involving polysubstance use [ 2 , 3 ]. Polysubstance use is currently defined as using two or more drugs intentionally or unintentionally within a specified timeframe (e.g. hourly, daily and monthly) [ 4 ]. Polysubstance use has significant physiological effects, for example, the co‐use of stimulants and opioids can heighten cardiovascular strain and cause respiratory depression, therefore, increasing the risk of overdose‐related morbidity and mortality [ 5 , 6 , 7 ]. Similarly, the concomitant use of opioids and benzodiazepines can lead to synergistic respiratory depression and increases the risk of fatal and non‐fatal overdose [ 7 , 8 , 9 , 10 ]. With opioid‐stimulant overdose deaths increasing from 23% to 53% between 2015 and 2022 [ 11 ], it is pertinent to investigate these trends to implement targeted public health strategies to mitigate further harm. Furthermore, there have been emergent racial disparities across the US overdose crisis with disproportionate mortality rates observed among Black and American Indian or Alaska Native populations compared to White populations [ 12 , 13 , 14 , 15 , 16 ]. Black individuals surpassed their White counterparts in drug‐related mortality in 2019 across 23 US states, with fentanyl, heroin and cocaine largely driving the higher overdose deaths rates [ 12 ]. Showing the differences in the fatal overdose crisis through the lens of race and sex can provide a contemporary depiction of the overdose issue within the framing of polysubstance use [ 17 ]. For example, a recent study by Cadet and colleagues [ 17 ] revealed that age‐adjusted drug poisoning mortality rate for Black men exceeded that of White men in 2016, while Black women surpassed their White women counterparts in 2019. At the US state level, drug poisoning deaths are disproportionately distributed with Maryland experiencing the highest increase in Black men mortality rates (+485.4%), whereas Alaska recorded declines in White women mortality (−23.0%) [ 17 ]. However, it is unclear if these widening racial and sex disparities in drug‐related premature deaths are seen across opioid‐related polysubstance use trends. Although the overdose crisis was once characterized as primarily affecting White communities, many studies have shown that this trend has since shifted [ 17 , 18 ]. By grounding this research in disaggregating by race, ethnicity and gender, this study aims to explore combinations of opioid‐related polysubstance use that are more prevalent among racial/gender subpopulations. Therefore, this study aims to examine racial/sex (non‐Hispanic White men, non‐Hispanic White women, non‐Hispanic Black men, non‐Hispanic Black women, Hispanic men and Hispanic women) differences in opioid and polysubstance use related drug mortality. We aim to identify socio‐demographic subgroups that are experiencing the highest burden of specific combinations of opioid‐related polysubstance overdoses and are in dire need of intervention. METHODS Design and database The data used in this study were de‐identified and sourced from the CDC's Wide‐Ranging Online Database for Epidemiologic Research (WONDER) Multiple Cause of Death file, covering the period from 2004 to 2022 [ 19 ]. This is a population‐level database representing all deaths occurring in the United States, and the death certificates are coded by the National Center for Health Statistics. Overdose deaths are identified using codes in the International Classification of Diseases, tenth revision (ICD‐10). The analysis used the following underlying cause of death codes: X40–45 (unintentional), X60–65 (intentional), X85 (homicide) and Y10–15 (undetermined intent). Opioid‐related deaths were identified using ICD‐10 codes: T40.0 (opium), T40.1 (heroin), T40.2 (other opioids), T40.3 (methadone), T40.4 (fentanyl and other synthetic opioids) and T40.6 (other and unspecified narcotics). To identify opioid polysubstance overdose deaths, ICD‐10 codes for opioids were combined with the following additional codes: T42.4 (benzodiazepines), T40.5 (cocaine) and T43.6 (psychostimulants excluding cocaine). See Table S1 for additional details. Three distinct categories of opioid polysubstance mortality were examined: opioids with stimulants (cocaine and psychostimulants), opioids with benzodiazepines and opioids only. Mortality rates are presented as age‐adjusted rates (AARs) per 100 000 population. This cross‐sectional study conducted a temporal analysis of opioid‐only and opioid‐polysubstance overdose mortality between 2004 and 2022, comparing aggregate age‐adjusted mortality rates per 100 000 by race and sex subgroups across the United States. To enable race‐specific trend comparisons over time, the National Center for Health Statistics developed a race‐bridging method in 2001. The CDC and the US Census Bureau developed a methodology to bridge the multiple‐race categories into single‐race categories and match them to the 1997 OMB racial categories in the mortality data [ 20 ]. The bridged‐race mortality data (available for 2004–2020) were used for the temporal analysis and aggregated age‐adjusted rate comparisons by race‐sex subgroups and shifted to single‐race denominators in 2021, introducing a methodological break [ 21 ]. As per CDC WONDER data use policies, small counts (fewer than 10 deaths per stratum) were suppressed to maintain confidentiality, leading to data unavailability for certain strata. This study was determined exempt from approval by the Columbia University Mailman School of Public Health institutional review board because of the de‐identified and publicly available nature of the data. The research question and analysis plan were not preregistered, therefore, results should be considered exploratory. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross‐sectional studies. Population and exposures Participants span all ages and are from all 50 US states and Washington, District of Columbia, with race classified by the census bridged‐race and filtered to include the following racial/ethnic and gender groups: non‐Hispanic White men, non‐Hispanic White women, non‐Hispanic Black men, non‐Hispanic Black women, Hispanic men and Hispanic women. Statistical analysis Outcomes The annual percent change in age‐adjusted overdose death rates by racial and gender subgroups are calculated using joinpoint regression. The Joinpoint Regression Program (version 5.30), developed by the National Cancer Institute (NCI), was used to apply weighted least‐squares regression models for analyzing mortality trends from 2004 to 2020 [ 22 ]. This software identifies points in time, referred to as joinpoints, where significant changes in trends occur, specifically for aggregated vital statistics data (Ingram et al .) [ 20 ]. The program calculates slope estimates and their variances, conducts trend tests, and is particularly effective in handling abrupt trend changes [ 20 ]. A minimum number of time points from a joinpoint to either end of the data and the minimum number of observations between two joinpoints were set to the default of 2. As the data used contains 17 time points, the maximum number of joinpoints was set to the default of 4. Model selection was completed with the permutation test with an overall significance level of 0.05 (see Table S2 ). Annual percent changes (APCs) and annual average percent changes (AAPCs) were estimated using joinpoint regression. Statistical significance was denoted by P < 0.05 (*) and P < 0.01 (**). Non‐significant APCs and AAPCs were reported without P ‐values. Statistical software Data management and statistical analysis was conducted in RStudio software version 4.4.2 (R Project for Statistical Computing), and the NCI's Joinpoint Regression Program, version 5.3.0. The visualizations were created in RStudio software version 4.4.2 (R Project for Statistical Computing) using the ggplot2 . RESULTS Descriptive analysis The final analytic sample consists of 627 793 opioid‐only deaths, including 196 001 opioid‐stimulant and 117 322 opioid‐benzodiazepine overdose deaths. Baseline characteristics of the study population stratified by substance use classification are shown in Table S3 and trend analysis in age‐adjusted mortality rates with joinpoints are presented in Figure S1(a)–(c) . Trends in opioid‐related overdose mortality: AAPC across drug combinations (2004–2022) Opioid‐only overdose mortality During 2004 to 2022 (Figure 1 , Table 1 ), AARs for opioid‐only involved overdose deaths increased across all race/ethnicity and sex groups, with the highest absolute rate change observed among non‐Hispanic Black men (53.55 per 100 000, increasing from 2.78 to 56.55 per 100 000; AAPC, 17.3; P < 0.005) with notable acceleration in mortality rates after 2011 (APC = 29.0%, P < 0.05). The second largest absolute rate of change occurred among non‐Hispanic White men (31.05 per 100 000), increasing from 6.32 to 37.37 per 100 000 (AAPC, 11.1; P < 0.05). Hispanic men experienced an absolute change of 24.19 per 100 000 (AAPC, 12.5; P < 0.05) with mortality rates increasing gradually from 2004 to 2013 (APC = 2.9%) and surging from 2013 to 2022 (APC = 23.1%, P < 0.05). FIGURE 1. Open in a new tab NH indicates non‐Hispanic. The Lollipop Plot depicts the absolute rate change in overdose deaths in 2004 compared to 2022 across opioid‐benzodiazepine, opioid‐stimulant and opioid‐only groups by racial/ethnic and gender demographics. TABLE 1. Trends in age‐adjusted overdose death rate per 100 000 involving opioid‐only, opioid‐stimulant and opioid‐benzodiazepine polysubstance use by race/sex groups. Joinpoint analyses (2004–2022) Trend 1 Trend 2 Type of overdose Race/ethnicity and gender 2004 observed AAR per 100 000 2022 observed AAR per 100 000 2004–2022 absolute rate change 2004–2022 AAPC AAPC 95% CI Years APC Years APC Opioid‐only Non‐Hispanic White Men 6.32 37.37 31.05 11.1 * (9.9–12.8) 2004–2022 11.1 ** Women 3.44 17.22 13.78 9.5 * (8.7–10.5) 2004–2022 9.5 ** Non‐Hispanic Black Men 2.78 56.33 53.55 17.3 * (15.1–20.4) 2004–2011 0.9 2011–2022 29.0 ** Women 1.5 18.43 16.93 14.9 * (13.7–16.4) 2004–2013 6.3 ** 2013–2022 24.3 ** Hispanic Men 3.16 27.35 24.19 12.5 * (11.4–14.1) 2004–2013 2.9 2013–2022 23.1 ** Women 1.16 6.93 5.77 11.8 * (10.3–13.6) 2004–2018 8.4 ** 2018–2022 24.6 ** Opioid‐stimulant Non‐Hispanic White Men 1.19 18.57 17.38 15.9 * (13.5–19.1) 2004–2011 0.1 2011–2022 27.2 ** Women 0.45 8.51 8.06 17.7 * (15.5–21.7) 2004–2010 1 2010–2022 27.1 ** Non‐Hispanic Black Men 1.11 31.86 30.75 19.1 * (16.8, 22.7) 2004–2011 −7 2011–2022 39.5 ** Women 0.51 10.25 9.74 18.4 * (16.6–21.1) 2004–2012 −0.5 2012–2022 36.2 ** Hispanic Men 0.81 13.92 13.11 16.3 * (15.0–18.6) 2004–2012 −2.3 2012–2022 33.8 * Women 0.18 3.48 3.3 15.8 * (13.3–19.2) 2004–2012 0 2012–2022 30.3 ** Opioid‐benzodiazepine Non‐Hispanic White Men 1.05 4.44 3.39 7.5 * (5.2–11.1) 2004–2017 10.6 ** 2017–2022 −0.2 Women 0.65 3.06 2.41 8.0 * (6.7–9.7) 2004–2016 11.8 ** 2016–2022 0.8 Non‐Hispanic Black Men 0.18 2.34 2.16 18.1 * (16.1–21.8) 2004–2022 18.1 ** Women 0.21 1.7 1.49 14.6 * (13.0–17.5) 2004–2022 14.6 ** Hispanic Men 0.27 2.11 1.84 11.9 * (10.3–14.6) 2004–2022 11.9 ** Women 0.17 0.99 0.82 10.0 * (8.8–11.9) 2004–2022 10.0 ** Open in a new tab Abbreviations: AAPC, annual average percent change; AAR, age‐adjusted rate; APC, annual percent change. * Indicates a significant AAPC. ** Indicates a significant APC. Across racial categories among women, the AAPC during the 2004–2022 time period was highest for non‐Hispanic Black women (14.9%, P < 0.05), with observed AAR of 1.5 to 18.43 per 100 000 and non‐Hispanic Black women seeing a stark increase after 2013 (APC = 24.3, P < 0.05). The second largest absolute rate change occurred for non‐Hispanic White women (13.78 per 100 000), increasing from 3.44 to 17.22 per 100 000 (AAPC, 9.5; P < 0.05). Hispanic women experienced an absolute change of 5.77 per 100 000 (AAPC, 11.8; P < 0.05) with mortality rates increasing gradually from 2004 to 2018 (APC = 8.4%) and surging from 2013 to 2022 (APC = 24.6%, P < 0.05). Opioid‐stimulant polysubstance use overdose mortality The opioid‐stimulant overdose mortality rate (see Figure 1 , Table 1 ) for non‐Hispanic White men increased from 1.19 to 18.57 per 100 000 (AAPC = 15.9%), with notable shift in 2011 where the APC sharply increased from 0.1 in 2004–2011 to 27.2% in 2011–2022. Non‐Hispanic Black men experienced a greater increase in mortality rate from 1.11 to 31.86 per 100 000 (AAPC = 19.1%), with a significant 7% decline per year from 2004 to 2011, followed by an accelerated increase of 39.5% per year from 2011 to 2022. Across Hispanic men, the opioid‐stimulant mortality rate increased from 0.81 to 13.92 per 100 000 (AAPC = 16.3%), with an initial 2.3% decline from 2004 to 2012, followed by a sharp increase by 33.8% from 2012 to 2022. Across racial categories among women, the AAPC during the 2004 to 2022 time period was highest for non‐Hispanic Black women (18.4%, P < 0.05), with observed AAR of 0.51 to 10.25 per 100 000 and non‐Hispanic Black women seeing a stark increase after 2012 (APC = 36.2, P < 0.05). The second largest AAPC occurred for non‐Hispanic White women (17.7%, P < 0.05), increasing from 0.45 to 8.51 per 100 000 (APC, 8.06; P < 0.05). Hispanic women experienced a 15.8% AAPC (AAPC, 15.8; P < 0.05) with mortality rates increasing gradually from 0.18 to 3.48 per 100 000. Opioid‐benzodiazepine polysubstance use overdose mortality For opioid‐benzodiazepine overdose deaths (Figure 1 , Table 1 ), the absolute rate change was highest for non‐Hispanic White men (3.39 per 100 000), followed by non‐Hispanic White women 2.41 per 100 000), non‐Hispanic Black men (2.16 per 100 000), Hispanic men (1.84 per 100 000), non‐Hispanic Black women (1.49 per 100 000) and Hispanic women (0.82 per 100 000). However, the highest AAPC from 2004 to 2022 was among non‐Hispanic Black men (18.1%) followed by non‐Hispanic Black women (14.6%). Non‐Hispanic White men and women showed early increases followed by a slight decline after 2017 and 2016, respectively, but statistically significant. Hispanic men and women experienced steady increases, with AAPCs of 11.9% and 10.0%, respectively. DISCUSSION Our study provides a comprehensive and contemporary assessment of opioid‐only, opioid‐stimulant and opioid‐benzodiazepine deaths across race/ethnic and gender socio‐demographic profiles in the United States. Overall, the findings show that overdose mortality rates among Black and Hispanic populations, particularly among men, have increased dramatically in recent years, with the most pronounced increase in trends seen in opioid‐stimulant overdoses. Although opioid‐benzodiazepine overdose deaths remain relatively lower, race/ethnic and gender disparities continue to widen for non‐Hispanic White men and women. Conversely, Black men are experiencing the most significant increases in opioid‐only and opioid‐stimulant polysubstance use in recent years. Several joinpoint trends shifted around 2011 to 2013, particularly for opioid‐only and opioid‐stimulant polysubstance use. These shifts coincide with the introduction of the second wave of the overdose crisis, characterized by the rise of street‐based heroin use [ 2 , 23 ]. Overall, these findings align with previous studies highlighting the widening racial and ethnic disparities in overdose fatalities in recent years [ 24 , 25 ]. Furthermore, as opioid and opioid‐related polysubstance use deaths increase, evidence suggests that treatment admissions are not increasing in parallel, which may suggest that the current treatment system may not be adequately targeting the ongoing crisis [ 26 ]. Historically, Black and Hispanic people are less likely to receive medication for opioid use disorder compared to their White counterparts, and buprenorphine is generally more accessible for White and higher income people [ 27 ]. A few of the contributing factors to these disparities includes unequal access to healthcare and treatment, poverty and lack of health care insurance, distrust in the medical system and lack of therapeutic alliance and culturally sensitive medical providers to understand the needs of racial and ethnic minority patients [ 27 ]. In addition, a great barrier to overcoming this opioid‐stimulant polysubstance use mortality crisis is the lack of pharmacotherapy for stimulant use disorder to date. To date, the US Food and Drug Administration has not approved any pharmacotherapy for the treatment of stimulant use disorder, which includes cocaine and methamphetamine, therefore, treatment primarily relies on behavioral therapies in the age of polysubstance use [ 28 ]. Contingency management remains an evidence‐based approach for stimulant use disorder that is culturally responsive and acceptable in diverse contexts, and that can be combined with medications for opioid use disorder to address the poly‐use outcomes across these populations [ 29 ]. Historically, the Substance Abuse and Mental Health Services (SAMHSA) capped the contingency management reimbursement at $75 per patient per year, which was significantly lower than the evidence‐based threshold presented in the literature [ 28 ]. In 2025, that cap was increased to $750 for grantees, a policy change anticipated to improve the implementation of contingency management for stimulant use disorder treatment [ 30 ]. Aside from the SAMHSA funding, Medicaid Section 1115 waivers may be another pathway to funding contingency management. However, only five states to date have approved waivers to support these protocols [ 31 ]. White men and women experienced the greatest absolute rate change for opioid‐benzodiazepine overdose deaths, which may partly be explained by racial and rural differences in benzodiazepine prescribing [ 32 , 33 ]. Although factors influencing clinicians' differential prescribing patterns of benzodiazepines are not well understood, there is evidence showing that White individuals are more likely than any other racial/ethnic group to receive benzodiazepine prescriptions after adjusting for patient diagnosis and severity [ 32 , 33 ]. Findings from the National Survey on Drug Use and Health data show women and non‐Hispanic White respondents reported the highest rates of past‐year benzodiazepine use, and prescription opioids were strongly associated with benzodiazepine use and dependence [ 34 ]. Rural areas also exhibit higher rates of benzodiazepine prescribing, especially among older adults, but more research is needed to understand the factors relating to the rural–urban differences in benzodiazepine prescribing [ 35 ]. Given the increased availability of designer benzodiazepines such as etizolam and diazepam in the drug market and the driving demand despite their potent nature [ 36 ], the epidemiology of polydrug profile warrants continued surveillance and active harm reduction strategies such as testing strips and targeted educational messaging to mitigate harms. Combining opioids with benzodiazepines has become increasingly prevalent to increase the potency and prolong the euphoric effect of the opioid [ 37 ]. Initially, fentanyl was combined with heroin to prolong the euphoric rush of the fentanyl, which was originally termed ‘fentanyl with legs’, however, as heroin supply started to decline across many regions, the practice shifted to using benzodiazepine with the fentanyl to prolong the short‐acting effect [ 37 ]. Still, the unregulated drug supply frequently results in the unintentional polysubstance use as well, with additives like xylazine, benzodiazepines and other substances being mixed with the opioid batches to enhance potency and reduce costs [ 38 ]. This contributes to the rapidly shifting drug market, where novel formulations introduce potency variability, further complicating efforts to address the evolving challenge of polysubstance use trends. Additionally, prescription benzodiazepines are also complicit in the increasing opioid‐benzodiazepine overdose deaths, as recent literature linking post‐mortem toxicology and prescription and illicit benzodiazepines has shown that 92.7% of benzodiazepine‐involved deaths involved an opioid [ 39 ]. Although this study, stratified by race and sex, provided an important lens on this evolving overdose crisis, future research should draw on Crenshaw's intersectionality theory, which highlights how overlapping systems of oppression—such as racism and sexism—create unique vulnerabilities for marginalized groups [ 40 ]. The conceptualization of intersectionality theory emerged from sociology, psychology and economics, underscores the importance of collectively considering the joint effects of different social categorizations to reveal the unique experiences and adverse health effects observed across intersectional social categories [ 40 ]. Future research can use quantitative methods outlined in previous literature [ 41 , 42 ] to determine whether the differences observed in this study are not merely additive, but reflect differences across multiple intersecting identities. Altogether, this study has limitations to note. The AARs for 2004 to 2020 are based on the bridged‐race denominators, whereas the 2021 to 2022 years used the single‐race denominators, introducing a methodological break, therefore, the 2021 boundary trends should be interpreted with caution. Another limitation is the lack of temporality in polysubstance use; therefore, it is unclear if individuals engaged in polysubstance use simultaneously (e.g. using opioids and stimulants at the same time) or concurrently (e.g. using opioids and stimulants during the same day but on different occasions). Furthermore, novel psychoactive substances such as nitazenes, xylazine and medetomidine, which are increasingly present in the drug supply, do not have their own standalone ICD‐10 codes, which makes it difficult to track their specific role in the overdose deaths in this study. Additionally, American Indian/Alaska Native populations, who have experienced disproportionately high overdose mortality rates, were not included in this study because of a lack of data availability across all years. This highlights the need for improved data collection to capture the epidemiology of overdose rates across this salient population. Furthermore, adolescents were grouped with adults in this analysis, which limits the ability to examine‐age‐specific differences in opioid‐related polysubstance use mortality. Additionally, the CDC WONDER does not report deaths of non‐residents, including non‐residents and residents of Puerto Rico, Guam and other US territories. Last, toxicology testing in death investigations is often inconsistent across regional jurisdictions, leading to potential underreporting and misclassification as a limitation. CONCLUSION Although non‐Hispanic White individuals had higher initial rates, the burden of opioid‐only and opioid‐stimulant polysubstance use has shifted toward non‐Hispanic Black men and women in recent years. Still, non‐Hispanic White individuals continue to see accelerated mortality rates and a greater burden of overdose deaths for opioid‐benzodiazepine polysubstance use in recent years. Findings can be used by policymakers to better inform the target for harm reduction interventions. Although our findings highlight the need for further epidemiologic and intervention research stratified by race and gender, the current federal directives prohibit the use of federal funding to support this line of research. Now more than ever, it is important to continue equity‐based research to prevent loss of life. Future research should examine the efficacy of racially and gender‐tailored interventions for polysubstance use. AUTHOR CONTRIBUTIONS Kechna Cadet: Conceptualization (equal); investigation (equal); methodology (equal); project administration (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). Paige Brinzo: Data curation (equal); formal analysis (equal); methodology (equal); software (equal); visualization (equal); writing—review and editing (equal). Silvia S. Martins: Funding acquisition (equal); supervision (equal); writing—review and editing (equal). DECLARATION OF INTERESTS None. Supporting information Table S1. Data Download. Table S2. Joinpoint Regressions Settings. Table S3. Descriptive statistics of opioids, opioid‐stimulant, and opioid‐benzodiazepine overdose deaths. Figure S1a. Opioid‐Only Mortality by Race/Ethnicity and Gender, 2004–2022. Figure S1b. Opioid‐Stimulant Mortality by Race/Ethnicity and Gender, 2004–2022. Figure S1c. Opioid‐Benzodiazepine Mortality by Race/Ethnicity and Gender, 2004–2022. ADD-121-2035-s001.docx (600.9KB, docx) Data S1. Supporting Information. ADD-121-2035-s002.docx (32.3KB, docx) ACKNOWLEDGEMENTS We acknowledge the National Institute of Health and the Columbia University Data Science Institute for funding this research study. Cadet K, Brinzo P, Martins SS. A population‐based study exploring racial and gender inequities in polysubstance‐related deaths across the United States from 2004 to 2022. Addiction. 2026;121(8):2035–2042. 10.1111/add.70409 Funding information This study has been supported by the Columbia University Data Science Institute Seed Funding (SF‐169; K.C., Principal Investigator), Substance Abuse Epidemiology Training Grant (T32DA031099; S.S.M. and Hasin, Principal Investigator), R01DA059376 (S.S.M., Principal Investigator) and the National Institutes of Health Loan Repayment Program (L60DA061545; K.C., Principal Investigator) from the National Institute of Drug Abuse (K01DA062726, R01DA059376). The funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. DATA AVAILABILITY STATEMENT The data for this study is publicly available on the CDC website. REFERENCES 1. CDC, National Center for Health Statistics . May 15, 2024. U.S. Overdose Deaths Decrease in 2023, First Time Since 2018. 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Am J Public Health. 2012;102(7):1267–1273. 10.2105/AJPH.2012.300750 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Supplementary Materials Table S1. Data Download. Table S2. Joinpoint Regressions Settings. Table S3. Descriptive statistics of opioids, opioid‐stimulant, and opioid‐benzodiazepine overdose deaths. Figure S1a. Opioid‐Only Mortality by Race/Ethnicity and Gender, 2004–2022. Figure S1b. Opioid‐Stimulant Mortality by Race/Ethnicity and Gender, 2004–2022. Figure S1c. Opioid‐Benzodiazepine Mortality by Race/Ethnicity and Gender, 2004–2022. ADD-121-2035-s001.docx (600.9KB, docx) Data S1. Supporting Information. ADD-121-2035-s002.docx (32.3KB, docx) Data Availability Statement The data for this study is publicly available on the CDC website. 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