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I. Executive Summary
This report analyzes recent trends in U.S. drug-related mortality, focusing on the reported decline in drug overdose deaths between 2023 and 2024 and investigating whether this trend is offset by increases in other forms of drug-related harm, such as severe wounds and infections, particularly those associated with fentanyl and xylazine. Provisional data from the Centers for Disease Control and Prevention (CDC) indicate a substantial, historically significant decrease of approximately 26.9% in drug overdose deaths in 2024 compared to 2023, primarily driven by a large reduction in fatalities involving synthetic opioids like fentanyl. While this decline is a positive development, the data are provisional and subject to revision. Furthermore, overdose deaths remain significantly higher than pre-pandemic levels, and the U.S. continues to have the highest overdose mortality rate globally.
Concurrently, there is mounting evidence of severe non-overdose drug-related harms. The emergence of xylazine as an adulterant in the illicit drug supply has been linked to a novel and alarming increase in severe, necrotic skin and soft tissue wounds, which can lead to serious complications, including amputation and life-threatening infections. Hospitalizations for other injection drug use-associated infections, such as endocarditis and sepsis, have also shown increasing trends in recent years, incurring substantial healthcare costs and contributing to morbidity and mortality.
A critical challenge in assessing the true trajectory of overall drug-related mortality lies in the methodologies of data collection and classification. Surveillance systems are primarily geared towards capturing acute overdose deaths. Deaths resulting from chronic complications of drug use, such as infections or organ failure, are often not systematically attributed to underlying substance use on death certificates. This leads to a likely underestimation of the total drug-attributable mortality burden. Variations in death investigation practices, particularly between medical examiner and coroner systems, and challenges in identifying novel substances further complicate the accurate assessment of trends.
In conclusion, while the significant provisional decrease in drug overdose deaths offers a measure of encouragement, it is premature to declare a comprehensive improvement in overall drug-related mortality. The rise in severe wound complications associated with xylazine and the ongoing burden of infectious diseases linked to injection drug use suggest a potential shift in the nature of drug-related harm rather than a straightforward reduction. The limitations in current surveillance systems mean that the full extent of non-overdose drug-related mortality remains inadequately quantified. Addressing the evolving drug crisis requires a multifaceted public health response that not only sustains efforts to reduce overdoses but also enhances surveillance and intervention strategies for the full spectrum of drug-related complications.
II. U.S. Drug Overdose Deaths: Analyzing the 2023-2024 Decline
A. Confirmation and Quantification of the Decrease
Recent provisional data from the Centers for Disease Control and Prevention’s (CDC) National Center for Health Statistics (NCHS) confirm a significant downturn in drug overdose fatalities in the United States. For the 12-month period concluding in December 2024, estimates indicate approximately 80,391 drug overdose deaths. This figure represents a marked decrease of 26.9% from the 110,037 deaths estimated for the comparable period in 2023.1 This projected annual total for 2024 would be the lowest recorded since 2019.1
Earlier provisional figures for the 12-month span ending in September 2024 had already signaled this downward trend, predicting a nearly 24% decline, with an estimated 87,000 drug overdose deaths compared to approximately 114,000 in the preceding year.3 The anticipated reduction of over 27,000 overdose deaths within a single year was characterized by public health officials as "unprecedented".3 Media reports, referencing CDC data, similarly highlighted a 27% decrease in 2024, translating to an estimated 80,000 deaths, and described this as the most substantial single-year decline ever documented.4
This encouraging trend is reflected across several major drug categories. Overdose deaths involving any opioids were estimated at 54,743 in 2024, a substantial drop from 83,140 in 2023. Fatalities specifically involving synthetic opioids (excluding methadone, primarily illicitly manufactured fentanyl and its analogs) saw a particularly sharp decrease, from an estimated 76,282 in 2023 to 48,422 in 2024. Deaths associated with psychostimulants, such as methamphetamine, also declined from 37,096 in 2023 to 29,456 in 2024. Cocaine-involved deaths fell from 30,833 to 22,174, and deaths involving natural and semi-synthetic opioids decreased from 10,511 to 8,006 over the same period.1
Table 1: Provisional Drug Overdose Deaths in the U.S., 2023 vs. 2024 (Overall and by Major Drug Category)
Source: Adapted from CDC, National Center for Health Statistics, Provisional Data.1 Note: Deaths may involve multiple drugs; sum of deaths by specific drug may not equal total.
The detailed breakdown of these figures reveals crucial nuances. The overall decrease in overdose deaths amounts to approximately 29,646 fatalities (from 110,037 to 80,391). The reduction in deaths attributed to synthetic opioids, predominantly fentanyl, accounts for 27,860 of these (from 76,282 to 48,422). This means that the decline in fentanyl-related deaths constitutes roughly 94% of the total decrease in overdose fatalities. Such a significant contribution underscores that factors specifically influencing fentanyl availability, patterns of use, or the lethality of the fentanyl supply have been particularly impactful during this period.
Furthermore, while all major drug categories experienced a decline in associated deaths, the relative magnitude of this decrease varies. Synthetic opioids (fentanyl) saw the most pronounced percentage drop at approximately 36.5%. In comparison, psychostimulants decreased by 20.6%, cocaine by 28.1%, and natural/semi-synthetic opioids by 23.8%.1 This disparity suggests that public health interventions or shifts in the drug market specifically related to fentanyl may have had a disproportionately large effect, or that the extremely high baseline of fentanyl-related deaths allowed for a more substantial absolute and relative reduction.
B. Geographic Variations and Contributing Factors
The national trend of decreasing overdose deaths was widespread, with almost all states reporting reductions. Notably, states such as Louisiana, Michigan, New Hampshire, Ohio, Virginia, West Virginia, and Wisconsin, along with the District of Columbia, experienced particularly steep declines of 35% or more for the 12-month period ending in December 2024.1 Similar significant drops were observed in Ohio and West Virginia, states historically hard-hit by the overdose epidemic.4
However, this positive national picture is not entirely uniform. A few states, including South Dakota and Nevada, registered slight increases in overdose deaths compared to the same period in 2023.1 Earlier provisional data for the 12 months ending September 2024 also indicated increases in Alaska, Montana, Nevada, South Dakota, and Utah.3 This heterogeneity at the state level highlights that national successes are not universally mirrored, and local factors—such as the specific characteristics of regional drug markets, the extent of penetration and uptake of harm reduction services, the robustness of public health infrastructure, and prevailing socioeconomic conditions—play a critical role in shaping overdose outcomes. If national interventions were uniformly effective or if broad national trends were the sole drivers, a more consistent pattern of decrease across all states would be expected. The observed divergence implies that state-specific and community-specific dynamics are powerful modulators of the national trend.
Experts and public health agencies have cited multiple factors potentially contributing to the overall national decline in overdose deaths. These include:
Enhanced Naloxone Availability: Widespread, data-driven distribution of naloxone, the opioid overdose reversal medication, is frequently mentioned as a key intervention.3
Improved Access to Treatment: Better access to evidence-based treatment for substance use disorders (SUDs), particularly Medications for Opioid Use Disorder (MOUD) such as buprenorphine and methadone, is considered crucial.3
Shifts in Illicit Drug Supply and Use Patterns: Changes in the illegal drug supply are noted as a possible factor.3 This could encompass alterations in drug purity or composition. Some suggest that a shift towards smoking fentanyl instead of injecting it, or the presence of xylazine in the fentanyl supply leading some individuals to use drugs less frequently, might contribute to reduced overdose events, although these shifts carry their own distinct risks.5
Strengthened Prevention and Data Systems: The resumption and enhancement of prevention efforts, alongside programs like the CDC's Overdose Data to Action (OD2A) initiative, which improves state and local data systems and supports tailored response activities, are also credited.3
Public Health and Safety Collaboration: Increased public health investments and strengthened partnerships between public health agencies and public safety organizations have improved the capacity to identify emerging drug threats and implement community-based prevention and response.3
Opioid Litigation Funds: The growing financial impact of settlements from opioid-related lawsuits is suggested as a potential contributor to funding for prevention and treatment.4
Demographic Shifts: Some experts theorize that the number of at-risk Americans may be shrinking due to the tragic toll of past mortality waves among older adults and a discernible shift in drug use patterns among teens and younger adults away from the substances causing most overdose deaths.4
Harm Reduction Expansion: Broader availability of harm reduction services, such as fentanyl test strips, allows individuals to make more informed decisions and reduce risks.5
The Drug Policy Alliance emphasizes the pivotal role of public health interventions—naloxone, expanded harm reduction, MOUD, and fact-based drug education—in saving lives, arguing that these efforts must be expanded. Conversely, this organization contends that law enforcement efforts and drug seizures are not the primary drivers of the observed decrease in overdose deaths.5 The multi-causal explanations offered by various sources suggest that a synergistic effect of these diverse interventions, potentially combined with shifts in drug supply dynamics or user behaviors, is more likely responsible for the decline than any single factor. The complexity of the overdose crisis itself, driven by numerous interwoven social, economic, and health-related issues, makes it logical that its amelioration would necessitate a multi-pronged approach. Consequently, sustaining this positive trend will likely require continued investment and effort across all these domains, and attributing the success to one area alone would be an oversimplification of a complex public health achievement.
C. Important Caveats: Provisional Data and Historical Context
While the reported 2023-2024 decline in drug overdose deaths is substantial, several important caveats must be considered. Primarily, the 2024 data are provisional, meaning they are incomplete and subject to change as more death records are submitted to and processed by the National Vital Statistics System (NVSS).1 The CDC routinely releases both reported and predicted provisional overdose death counts on a monthly basis.1 For instance, for December 2024, the initially reported count of overdose deaths was 79,526, while the statistically predicted value, accounting for reporting lags, was 80,391.2 This inherent characteristic of provisional data necessitates caution in drawing final conclusions until definitive numbers are available.
Historically, the U.S. has witnessed temporary plateaus or even declines in overdose deaths, only for the numbers to surge again. A notable example is the 4% drop in overdose deaths observed in 2018, which was followed by a resurgence in subsequent years.4 Data from the NCHS indeed shows a dip in the age-adjusted rate of drug overdose deaths in 2018 (20.7 per 100,000) compared to 2017 (21.7 per 100,000), followed by an increase in 2019 (21.6 per 100,000) and a dramatic rise in 2020 (28.3 per 100,000).6 The provisional nature of the current 2024 data, combined with these historical precedents, calls for cautious optimism. While the "unprecedented" magnitude of the 2024 decline 3 might suggest a more robust and sustainable shift, confirmation with final, verified data will be critical to ascertain the true extent and stability of this trend.
It is also crucial to place the recent decline in a broader context. Despite this improvement, drug overdose remains a leading cause of death for Americans aged 18-44.3 Moreover, even with the significant reduction in 2024, the annual number of overdose deaths remains higher than pre-COVID-19 pandemic levels.4 The estimated 80,000 to 87,000 deaths in 2024 are still considerably above the 70,630 deaths recorded in 2019.6 For context, NCHS data brief DB522, analyzing final data for 2022-2023, reported 105,007 overdose deaths in 2023, which itself was a 4.0% decrease from 107,941 deaths in 2022.8 This earlier, more modest decline preceded the much larger provisional decrease now being reported for the 2023-2024 comparison.
Furthermore, the United States continues to bear the grim distinction of having the highest rate of overdose deaths in the world by a substantial margin.9 In 2022, the U.S. overdose death rate was 324 deaths per 1 million people.9 The fact that overdose deaths, even after a notable decline, remain elevated compared to pre-pandemic figures and that the U.S. still leads globally in this tragic metric indicates that the crisis is far from resolved. The "improvement" is relative to an extremely severe peak, and the nation continues to face a persistent and severe public health challenge.
III. The Hidden Toll: Non-Overdose Drug-Related Mortality and Severe Morbidity
While the decline in acute drug overdose deaths is a significant development, it is imperative to investigate whether this trend is being offset by an increase in other forms of drug-related mortality and severe morbidity that may not be captured under the "overdose" classification. Emerging threats, particularly the adulteration of the illicit drug supply with substances like xylazine, and the persistent scourge of infections related to injection drug use, present complex challenges.
A. Severe Wounds and Tissue Damage: The Xylazine Factor and Beyond
A particularly concerning development is the proliferation of xylazine, a veterinary tranquilizer not approved for human use, as an adulterant in the illicit drug supply, most commonly found with fentanyl.10 Known on the street as "tranq," xylazine is not an opioid, and critically, its sedative and respiratory depressant effects are not reversed by naloxone, the standard opioid overdose antagonist.13
The co-administration of xylazine with illicit fentanyl has been directly linked to severe and often gruesome soft tissue injuries. These wounds can range from superficial skin irritation to profound, deep tissue necrosis, frequently involving underlying muscle and bone.10 The pathogenesis of these xylazine-associated wounds is understood to be multifactorial. Key mechanisms include potent vasoconstriction, which severely reduces blood flow and oxygenation to affected tissues, and direct tissue toxicity potentially exacerbated by the acidic nature of illicitly prepared xylazine solutions.10 These debilitating wounds can manifest not only at direct injection sites but also in areas distant from them, suggesting systemic effects or broader tissue vulnerability.11 Clinically, the wounds often present initially as blackened, necrotic eschars, which can progress to a characteristic "cribriform" or sieve-like appearance. They frequently extrude malodorous pus and are commonly infected with multiple types of bacteria.11 The nature of these injuries has been likened to severe chemical burns.10
The prevalence of these severe wounds among individuals exposed to xylazine-adulterated drugs is alarmingly high. Some reports indicate that skin ulcerations are up to six times more common when fentanyl is contaminated with xylazine compared to fentanyl used alone.10 Xylazine's presence in the drug supply, and consequently xylazine-involved overdose deaths, have been reported to be spreading westward across the U.S., with the most significant initial impact observed in Northeastern regions.11 In Philadelphia, a city heavily affected by xylazine, the substance was detected in nearly one-third of all opioid overdose deaths as early as 2019 16, and more recent reports suggest its presence in as much as 90% of the local illicit opioid supply.10 While one coroner in a xylazine-affected area estimated that only about 10% of decedents in xylazine-involved deaths presented with these characteristic ulcers 12, numerous other clinical reports and public health alerts underscore a high prevalence of severe wounds necessitating aggressive medical interventions, including hospitalization, intravenous antibiotics, surgical debridement, and, in some cases, limb amputation.11
Xylazine contributes to mortality through multiple pathways. It directly contributes to fatal overdoses by causing profound central nervous system depression, leading to respiratory failure, bradycardia (slowed heart rate), and severe hypotension (low blood pressure).11 When combined with fentanyl, xylazine is reported to prolong the euphoric effects, which may increase its appeal but also significantly heightens the risk of a complex and difficult-to-reverse overdose.10 Fatal drug poisonings where xylazine is identified as a contributing factor have increased dramatically in affected regions. For example, in Pennsylvania, the proportion of all overdose deaths involving xylazine rose from 2% to 26% between 2015 and 2020.13
The direct mortality attributable specifically to xylazine-associated wounds (e.g., death from sepsis originating from an infected wound, or complications following amputation) is less clearly quantified in national statistics as a distinct category compared to mortality from xylazine-involved overdoses. However, the inherent severity of these necrotic wounds, their high propensity for life-threatening infections, and the potential for systemic complications strongly imply a considerable, though perhaps under-documented, mortality risk.11 One retrospective study focusing on 55 patients hospitalized with xylazine-associated upper-extremity wounds reported a 0% in-hospital mortality rate. However, this study also documented a very high surgical complication rate of 59% and an alarming 49% rate of patients leaving the hospital against medical advice (AMA), with many of these individuals demonstrating continued drug use.20 This high AMA rate, often driven by the severe and difficult-to-manage xylazine withdrawal syndrome 11, poses a major barrier to effective treatment. It suggests a strong potential for adverse outcomes, including progressive infections and unrecorded mortality occurring outside the hospital setting, which would not be captured in studies limited to in-hospital deaths. The exact lethal concentration of xylazine in humans has not yet been definitively established, and its role in causing death is frequently complicated by the presence of fentanyl and other substances in poly-drug use scenarios.19
While xylazine is the most prominently featured contaminant linked to these unique and severe necrotic wound patterns, the broader question of other fentanyl contaminants causing similar issues remains. The available evidence heavily focuses on xylazine as the primary agent responsible for this specific type of severe tissue damage.14 General non-sterile injection practices inherently carry risks of more common complications like localized abscesses and cellulitis 17, but the widespread, aggressive, and often distant necrotic ulcerations are strongly and specifically associated with xylazine exposure in the current literature.
Table 2: Summary of Xylazine-Associated Wound Characteristics, Complications, and Documented Outcomes
The emergence of xylazine-induced severe wounds signifies a qualitative shift in the landscape of drug-related harm. This pathology extends beyond the acute respiratory and central nervous system depression characteristic of traditional opioid overdoses 22 to include progressive, debilitating, and potentially fatal tissue destruction. This new dimension of harm requires complex and often prolonged medical management, including specialized wound care, infectious disease consultation, and surgical interventions.10 Consequently, even if overdose deaths are declining, the rise of xylazine-related morbidity could impose new and significant strains on healthcare systems, leading to long-term disability and mortality that may not be readily captured by existing overdose-focused surveillance statistics.
The difficulty in reversing xylazine's effects with naloxone 13, coupled with the fact that routine toxicology screening often failed to detect xylazine until relatively recently 10, suggests that xylazine's contribution to both overdose fatalities and deaths from related complications may have been historically underestimated. While increased testing undoubtedly contributes to the rising detection of xylazine, multiple sources affirm an actual increase in its presence within the illicit drug supply.10 This historical under-detection could apply to deaths from wound complications if the crucial link to xylazine—and thereby to drug use—was not established due to a lack of specific testing or awareness of its clinical manifestations.
B. Infectious Complications of Drug Use
Injection drug use (IDU) remains a significant vector for a wide array of serious infectious diseases. These include viral infections such as Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV), as well as severe invasive bacterial and fungal infections that can lead to conditions like infective endocarditis (infection of the heart valves), osteomyelitis (bone infection), and extensive skin and soft tissue infections (SSTIs), including cellulitis and abscesses.24 Such infections typically arise from breaches in sterile technique during the preparation and injection of drugs, allowing pathogens to enter the bloodstream or tissues.25
Recent data indicate concerning trends in the burden of these infections. A study in Oregon revealed a dramatic increase in hospitalizations for serious bacterial infections associated with injection drug use between 2008 and 2018. During this period, hospitalizations for bacteremia (bloodstream infections) and sepsis (a life-threatening response to infection causing organ damage) linked to IDU saw an 18-fold increase. The total healthcare costs for these IDU-related serious bacterial infection hospitalizations in Oregon surged from $16.3 million in 2008 to $150.8 million in 2018.26 Similarly, a study in Michigan focusing on hospitalized individuals aged 18-64 with a substance use diagnosis found substantial increases in hospitalizations for endocarditis (33% increase), osteomyelitis (35% increase), sepsis (24% increase), and SSTIs (12% increase) between 2016 and 2018. These hospitalizations in Michigan alone resulted in over $1.3 billion in healthcare costs during that three-year timeframe.25
Furthermore, individuals who inject drugs (PWID) face a disproportionately high risk of certain infections. For example, PWID were estimated to be 16.3 times more likely to develop invasive Methicillin-resistant Staphylococcus aureus (MRSA) infections compared to non-injecting individuals. The proportion of all invasive MRSA cases that occurred among PWID rose from 4.1% in 2011 to 9.2% in 2016.21 Common clinical manifestations of invasive MRSA in this population included septic embolism, endocarditis, abscesses, cellulitis, and osteomyelitis.21
These infections carry significant mortality risks. For Drug Use-Associated Infective Endocarditis (DUA-IE), the mortality risk during the initial hospitalization can be as high as 10% in some regions.27 Even for those who survive the initial DUA-IE episode, the long-term prognosis can be grim. One cohort study found that among survivors of DUA-IE hospitalization, the 3-year risk of death (specifically, death occurring before a subsequent infection) was 16%. The composite risk of either death or another hospitalization for a selected serious infection within three years was 38%.27 While comprehensive CDC data on sepsis-related mortality in older adults do not specifically delineate drug use as a direct causal factor 28, sepsis is widely recognized as a severe and potentially fatal complication arising from IDU-related infections 14, and the Oregon study specifically noted a dramatic rise in sepsis hospitalizations linked to IDU.26 A broader systematic review encompassing 67 cohorts of PWID calculated a pooled crude mortality rate (CMR) of 2.35 deaths per 100 person-years, with drug overdose and Acquired Immunodeficiency Syndrome (AIDS) identified as the primary causes of death across these diverse cohorts.29
The observed shift in drug administration routes, with some evidence suggesting an increase in smoking fentanyl as opposed to injecting it 5, could theoretically influence the rates of injection-specific infections. Data from 28 jurisdictions between January 2020 and December 2022 showed that the percentage of overdose deaths with evidence of injection decreased by 29.1% (from 22.7% to 16.1%), while the percentage with evidence of smoking increased by 73.7% (from 13.3% to 23.1%).30 While this shift might reduce certain risks, it is not explicitly quantified in the available information as a direct cause for a widespread decline in IDU-related infections nationally, and smoking illicit substances carries its own set of health risks.
Table 3: Trends in Hospitalizations and Mortality for Selected Drug Use-Associated Infections
The substantial and escalating healthcare costs and hospitalization rates associated with these IDU-related infections 25 represent a significant economic and public health burden. This burden may be increasing independently of, or even in contrast to, trends in acute overdose deaths. This points towards a potential shift in the economic impact of drug use, where a reduction in acute overdose events might be paralleled by a rise in costly, long-term infectious complications, thereby transforming rather than necessarily diminishing the overall strain on the healthcare system. Furthermore, the high rates of long-term mortality and re-hospitalization following severe infections like DUA-IE 27 indicate that even when an initial infection is survived, the prognosis for affected individuals often remains poor. This contributes to a sustained, albeit potentially delayed, form of drug-attributable mortality, where the eventual death certificate might list sepsis or heart failure as the cause, obscuring the foundational link to prior drug use if not meticulously tracked and documented.
C. Other Potential Non-Overdose Complications
Beyond acute overdoses and infectious complications, chronic drug use can lead to a range of other non-overdose health problems, including organ failure. However, direct, systematically collected data on trends in organ failure deaths explicitly and separately attributed to chronic illicit drug use (excluding those secondary to infections like sepsis or endocarditis, or acute overdose events) for the 2023-2024 period are limited in the provided information.
Some evidence points to the potential for newer adulterants to cause direct organ damage. Xylazine, for instance, has been associated with adverse cardiovascular effects, including reports of biventricular systolic failure, valvular dysfunction, cardiac fibrosis, and cardiac necrosis. A rare case of xylazine-induced cardiomyopathy has also been described in the literature.19 These findings suggest that xylazine exposure may lead to significant organ damage that is distinct from its role in acute overdose.
Broader historical data on substance-related mortality illustrate that overdoses are but one facet of a larger problem. Between 1990 and 2018, in addition to 756,160 drug poisoning (overdose) deaths, there were 374,197 alcohol-induced deaths and 198,318 deaths attributed to mental and behavioral disorders resulting from the use of psychoactive substances (which includes both drugs and alcohol).31 These figures highlight the substantial burden of non-overdose substance-related mortality, though they do not provide specific trends for illicit drug-induced organ failure for the most recent period.
Fentanyl itself, while primarily known for its potent respiratory depression leading to overdose, can also induce adverse effects such as severe muscle stiffness and slow or irregular heartbeat.22 However, these effects are typically described within the context of acute exposure or overdose, rather than as causes of chronic organ failure leading to death independently of an overdose event.
The focus on xylazine's impact, not only on local tissue (causing severe wounds) but also on systemic functions including the cardiovascular and central nervous systems 19, suggests that emerging adulterants in the drug supply can introduce novel pathways to organ damage and non-overdose mortality. These pathways may not be fully captured or correctly attributed to drug use by current surveillance and death certification practices. Traditional understanding of non-overdose drug-related organ damage often centers on the long-term effects of substances like alcohol on the liver or cocaine on the cardiovascular system. The potential for xylazine to cause conditions like cardiac necrosis or cardiomyopathy 19 introduces a new dimension. If such conditions develop and ultimately lead to a fatality, and if the individual's history of xylazine exposure is unknown or its chronic effects are not well recognized by the certifying physician, these deaths could be misclassified as generic heart disease, severing the crucial link to underlying drug use in official mortality statistics. This highlights a potential new stream of drug-attributable mortality that is neither a direct overdose nor a typical infection secondary to injection.
IV. Deciphering the Data: Collection and Classification of Drug-Related Deaths
Understanding trends in drug-related mortality, whether from overdose or other complications, is fundamentally dependent on the systems used for data collection and the methodologies applied for classifying causes of death. Significant limitations and challenges exist within these systems, impacting the accuracy and completeness of the available data.
A. Surveillance Systems for Drug Overdose Deaths
The primary source for national drug overdose death statistics in the U.S. is the National Vital Statistics System (NVSS), which compiles data from official death certificates filed in states and U.S. territories.1 When a death occurs, a medical certifier (often a physician, medical examiner, or coroner) determines the cause(s) of death, which are then recorded on the death certificate. These causes are subsequently translated into standardized codes from the International Classification of Diseases, 10th Revision (ICD-10). Drug overdose deaths are typically identified using underlying cause-of-death codes X40–X44 (accidental poisoning by drugs), X60–X64 (intentional self-poisoning by drugs/suicide), X85 (assault by drugs/homicide), and Y10–Y14 (poisoning by drugs, undetermined intent).6 To identify the specific types of drugs involved, additional ICD-10 "T-codes" (e.g., T40.1 for heroin, T40.2 for other opioids like morphine, T40.3 for methadone, T40.4 for synthetic opioids like fentanyl, T40.5 for cocaine, T40.7 for cannabis) are used based on the information provided on the death certificate.8
To supplement death certificate data, the CDC also utilizes systems like the State Unintentional Drug Overdose Reporting System (SUDORS). SUDORS aims to collect more comprehensive information from coroner and medical examiner reports, including details about toxicology results and the circumstances surrounding unintentional and undetermined-intent drug overdose deaths. This richer dataset helps public health officials better understand the nuances of the overdose epidemic and inform targeted interventions.3
Despite these systems, several limitations affect the accuracy and utility of overdose data:
Timeliness: The process of collecting, coding, and finalizing death certificate data can be lengthy. This inherent delay means that the most current national figures are often provisional and subject to revision as more data become available.36 This reliance on provisional data is evident in the monthly updates provided by the NCHS.1
Underreporting and Misclassification of Specific Substances: A persistent and significant challenge is the lack of specificity regarding the drugs involved in an overdose on many death certificates. Studies have shown that a substantial percentage of drug overdose death certificates do not list any specific drugs, or list them in vague terms.34 For example, in 2013 and 2014, approximately 19% to 22% of overdose death certificates lacked information on the specific types of drugs involved.37 This lack of detail can lead to a national underestimation of the involvement of specific opioids by as much as 20-35%.38
Specific Drug Misclassifications: Certain drugs pose particular classification challenges. For instance, because heroin is rapidly metabolized to morphine in the body, some heroin-related deaths might be misclassified as morphine-related deaths if toxicological testing or death certificate wording is not precise, leading to an undercount of heroin's true toll.37
Systemic Variations: The structure and resources of medicolegal death investigation systems vary across the U.S. States or counties that utilize a coroner system (where coroners may be elected officials without mandatory medical training) may be more likely to report unspecified overdose deaths compared to those with a centralized medical examiner system (typically staffed by forensic pathologists).34 This variability can impact the quality and consistency of data.
Coding Practices: The way information is recorded by certifiers directly impacts ICD-10 coding. If a certifier writes "opioid" without further specification, the death is coded to T40.6 ("other and unspecified narcotics"). If only "drug overdose" is listed, with no drugs specified, the code T50.9 ("Poisoning by other and unspecified drugs, medicaments and biological substances") is used. Both scenarios obscure the specific substances responsible and contribute to undercounting the involvement of particular drugs like fentanyl or prescription opioids.34 The inconsistent specification of fentanyl on death certificates has also been noted as a problem.39
The known issues of underreporting and misclassification of specific drugs in overdose deaths mean that even the "verified" decline in overall and specific drug overdose deaths, as reported provisionally for 2023-2024, should be interpreted as an imperfect measure. The true magnitude of the change, or the precise substances driving it, could be obscured by these data limitations. For example, if fentanyl involvement was previously under-recorded due to testing limitations or certifier practices and is now being more accurately recorded due to heightened awareness, a reported decline might appear less steep in reality, or conversely, improvements in specificity could make a decline seem larger if previously unspecified deaths are now correctly attributed. This inherent uncertainty affects the precision of our understanding of the overdose crisis and the effectiveness of responses to it.
Furthermore, the variation in data quality between different types of medicolegal death investigation systems (medical examiner versus coroner systems) 34 suggests that national statistics are an amalgamation of data of differing reliability. This can potentially mask regional hotspots or understate the severity of the problem in areas served by less rigorous death investigation systems, which could in turn affect resource allocation and the targeting of public health interventions.
B. Tracking Non-Overdose Drug-Related Mortality
Tracking deaths that result from non-overdose complications of drug use—such as severe infections, wound complications, or chronic organ failure—presents even greater challenges than tracking acute overdose deaths.
A primary hurdle is the difficulty in attribution. When a death occurs due to a complication like sepsis, endocarditis, or organ failure, drug use may be an underlying or contributing cause, but it might not be listed as such on the death certificate. This is particularly true if the death occurs a significant time after the acute drug use episode or the onset of the initial drug-related infection.33 The immediate cause of death (e.g., "septic shock" or "cardiac arrest") is often prioritized on the certificate, potentially obscuring the crucial role of past or ongoing substance use.
The role of coroners and medical examiners (C/MEs) is central to death certification. These officials are responsible for determining both the cause and the manner of death (e.g., natural, accident, suicide, homicide, undetermined).34 However, practices and legal mandates vary significantly by jurisdiction. Some jurisdictions may classify deaths related to the chronic effects of illicit drug use or excessive medication use as "accident" if the circumstances do not clearly point to suicide or homicide.41 Rhode Island law, for example, mandates C/ME investigation for all deaths where there is reasonable suspicion of an unnatural process, including those due to the "use of addictive or unidentifiable chemical substances".33 However, the focus of C/ME investigations is often on establishing the proximate cause of death. If an individual dies from sepsis that originated from an infected injection site, "sepsis" might be listed as the official cause of death, but the underlying injection drug use that led to the infection might not be documented on the certificate, especially if this history is unknown to the certifier or not actively investigated.
The impact of limited or delayed toxicological testing for emerging substances further complicates the picture. For new threats like xylazine, if specific testing is not readily available, not routinely performed in all death investigations, or if certifiers are unaware of its potential involvement, its role in contributing to both overdoses and deaths from complications (such as those arising from severe xylazine-induced wounds) can be entirely missed.10 The Substance Abuse and Mental Health Services Administration (SAMHSA) has explicitly noted that routine toxicology panels often do not include xylazine, potentially leading to its significant under-detection in mortality cases.15
While ICD-10 codes exist for conditions like sepsis (e.g., A41.9 for "Sepsis, unspecified organism"; R65.20 for "Severe sepsis without septic shock") 42 and for various types of organ failure, linking these conditions back to drug use as the underlying cause of death requires that connection to be explicitly stated on the death certificate by the certifier. This crucial linkage is often absent. An experimental "deep dive" study into coroners' records conducted in the UK by the Office for National Statistics (ONS) found that, in many cases, more detailed information about drug involvement and circumstances was held by the coroner than was ultimately transmitted to the ONS through the formal death registration process, suggesting a loss of crucial detail that could link deaths to substance use.40
The current death certification and coding system is primarily designed to capture the proximate cause of death—the immediate physiological derangement or disease process that led directly to death. It is often ill-equipped to systematically track deaths where drug use is a distal but critical underlying cause. For example, if an individual acquires Hepatitis C through injection drug use, develops cirrhosis over many years, and eventually dies from liver failure, the death certificate might list "liver failure" as the cause without explicitly linking it back to the initial drug use that occurred decades prior. This means a substantial portion of true drug-attributable mortality is likely "hidden" within other broad disease categories, leading to a significant underestimation of the total impact of drug use on mortality.
The variability in C/ME practices, resources, and statutory requirements across different jurisdictions 34 creates further inconsistencies in how non-overdose drug-related deaths are investigated and certified. A death that might be certified as "natural" (e.g., from cardiac disease) in one jurisdiction could potentially be recognized as linked to chronic drug use in another jurisdiction that has more extensive investigative resources, different protocols for exploring substance use history, or a lower threshold for including such information on the death certificate. This geographical inconsistency further complicates efforts to obtain a clear and uniform national picture of non-overdose drug-related mortality.
C. Gaps in Achieving a Comprehensive View of Total Drug-Attributable Mortality
Current public health surveillance efforts related to drug use are overwhelmingly focused on acute drug poisoning, commonly referred to as overdose deaths.25 While critical, this focus means that deaths resulting from the chronic health consequences of drug use, or those indirectly caused by it, are not systematically tracked or aggregated in the same way. There is no single, unified national system in the U.S. designed to capture the totality of drug-attributable deaths, encompassing acute poisoning, chronic disease sequelae, and indirect effects.
Estimating the full burden of drug-attributable mortality often requires complex epidemiological modeling or resource-intensive data linkage projects, such as connecting death records with hospital admission data, substance use disorder treatment records, or other health registries.40 These approaches are typically employed in specific research studies rather than being part of routine, ongoing national mortality surveillance.
Data from broader analyses of "substance-related deaths" underscore that overdoses are only one component of a much larger mortality landscape. For example, a study examining working-age mortality between 1990 and 2018 found that, in addition to 756,160 drug poisoning deaths, there were 374,197 alcohol-induced deaths and 198,318 deaths due to mental and behavioral disorders stemming from psychoactive substance use (including both drugs and alcohol).31 These figures clearly demonstrate that non-overdose substance-related deaths constitute a substantial public health problem, although they do not isolate the specific contribution of illicit drugs to non-overdose chronic organ failure in the most recent 2023-2024 period. Even within systems designed to track organ donation, such as the Organ Procurement and Transplantation Network (OPTN), there are acknowledged challenges in definitively attributing donor deaths to drug overdose due to limitations in the data collected, which is primarily tailored for organ matching and allocation rather than detailed cause-of-death investigation.44
Table 4: Challenges in Data Collection and Classification for Different Types of Drug-Related Deaths
Sources: Synthesized from.10
The current public health surveillance infrastructure in the U.S. is predominantly reactive, designed to capture and respond to acute public health events such as drug overdoses. It generally lacks the proactive, integrated, and longitudinal approach necessary to capture the full spectrum of drug-attributable mortality, particularly deaths resulting from chronic conditions or indirect consequences of drug use. Tracking deaths from conditions like complications of DUA-IE or organ failure stemming from years of substance use requires robust data linkage across disparate health and vital records systems 27, a capability not standard in routine U.S. mortality surveillance. This systemic gap means that public health strategies and resource allocation decisions are often guided by an incomplete picture of drug-related harm, potentially underestimating the long-term societal impact of substance use.
The increasing complexity of the illicit drug supply further strains the capabilities of existing death classification systems. The rise of polysubstance use, the continuous emergence of new psychoactive substances, and the proliferation of potent adulterants like xylazine 9 make it progressively more challenging to accurately attribute deaths to specific substances or even to clearly distinguish between a direct overdose and a death resulting from complications exacerbated by these novel agents. Death investigation relies heavily on identifying the substances involved through toxicology.34 However, toxicology panels may not routinely cover all novel psychoactive substances or adulterants, or C/MEs may not always know which specific tests to request, as was initially the case with xylazine.15 Determining which specific substance(s) in a complex mixture was primarily responsible for a death, or for a non-overdose complication that ultimately proved fatal, becomes an exceedingly difficult task. This escalating complexity challenges the already limited surveillance systems, increasing the likelihood of misclassification, unspecified causes of death, and an overall undercount of the true burden of drug-related mortality.
V. Synthesizing the Evidence: Has Overall Drug-Related Mortality Genuinely Improved?
Assessing whether overall drug-related mortality in the United States has genuinely improved requires a careful balancing of the recent, significant decline in provisional overdose death numbers against evidence of other persistent or emerging drug-related harms, all viewed through the lens of data collection limitations.
A. Balancing Overdose Decline Against Other Harms
The provisional data indicating a substantial decrease in drug overdose deaths in the U.S. during 2023-2024 is, without question, a positive and noteworthy development.1 This decline, primarily driven by a reduction in fatalities involving fentanyl, represents the most significant single-year improvement in decades.
However, this encouraging trend in acute overdose mortality must be juxtaposed with evidence suggesting ongoing, and in some cases potentially increasing, harms from non-overdose complications of drug use.
Severe Wounds: The emergence and spread of xylazine as an adulterant in the illicit drug supply have introduced a new and highly morbid category of drug-related injury: severe, necrotic skin and soft tissue wounds.10 These wounds are difficult to treat, often require extensive medical and surgical intervention, and can lead to severe infections, amputations, and long-term disability. While direct mortality from these wounds is not yet clearly quantified at a national level as a distinct cause-of-death category, the severity of the injuries, the high risk of associated systemic infection, and their link to a highly dangerous and unpredictable drug supply are causes for major public health concern.
Infectious Complications: Hospitalizations for serious bacterial infections related to injection drug use—including sepsis, endocarditis, osteomyelitis, and severe skin and soft tissue infections—have shown increasing trends in various regional studies leading up to or overlapping with the 2023-2024 period.25 These infections are associated with significant morbidity, high healthcare costs, and considerable mortality risk.25 It remains unclear from the currently available national data whether this trend in infection-related hospitalizations and deaths has reversed in concert with the decline in overdose deaths during 2023-2024.
On a more positive note concerning non-fatal outcomes, the CDC has observed that alongside the large provisional drop in fatal overdoses, there have also been smaller decreases in nonfatal overdoses, as measured by emergency department visits for overdose.3 This suggests some broader reduction in acute drug poisoning events, but it does not directly address the burden of chronic complications or mortality stemming from them.
A "genuine improvement" in overall drug-related mortality implies a reduction in the total number of deaths attributable to drug use, irrespective of the specific mechanism of death. Overdose deaths are one major, and historically the most visible, mechanism.1 However, severe wounds leading to fatal infections, and chronic infections like DUA-IE leading to delayed mortality, represent other pathways by which drug use can be fatal.10 Data on these latter mechanisms are far less complete and, where available for morbidity (such as hospitalizations), have indicated rising trends in the years preceding the recent overdose decline.25 Therefore, without comprehensive and accurate data on these non-overdose drug-related deaths, a decline in overdose fatalities alone is insufficient to conclude that overall drug-related mortality has genuinely improved. The observed "improvement" might be partial, or it could represent a shift in how drug use is leading to death, rather than an absolute reduction in all drug-caused fatalities.
B. Assessing a Potential Shift in the Nature of Drug-Related Deaths
The confluence of declining overdose deaths and the concurrent rise of novel harms like xylazine-associated wounds, alongside the persistent burden of IDU-related infections, may indicate a shift in the primary nature of drug-related deaths and morbidity. Instead of, or in addition to, acute overdose deaths (particularly those involving fentanyl), the public health crisis may be evolving to encompass an increased burden of severe chronic morbidity. This includes conditions like xylazine-induced wounds requiring long-term, complex care, and recurrent or chronic infections following DUA-IE, which can lead to slower, harder-to-classify deaths resulting from these chronic conditions.
The proliferation of xylazine is a key exemplar of the evolving illicit drug supply and its capacity to introduce new and unexpected forms of harm.10 Its presence complicates overdose response (due to naloxone insensitivity) and creates a novel spectrum of severe physical damage.
Changes in drug use patterns, such as a reported shift from injecting to smoking fentanyl by some individuals 5, could also contribute to this evolving landscape. While smoking may reduce the immediate risk of fatal overdose for some and could theoretically lessen the incidence of injection-specific infections, it does not eliminate the risks of substance use disorder, exposure to toxic contaminants in the drug supply, or other health consequences associated with inhaling illicit substances. Notably, CDC data from 2020-2022 indicated that smoking had become the most commonly identified route of use in overdose deaths in the Midwest and West regions by late 2022 30, suggesting that this route is not without significant danger.
C. Impact of Data Limitations on Definitive Conclusions
The ability to definitively determine whether overall drug-related mortality has genuinely improved is profoundly hampered by the significant limitations in the collection and classification of non-overdose drug-related deaths, as detailed in Section IV. If deaths resulting from complications like xylazine-induced sepsis or endocarditis secondary to IDU are increasing but are not being accurately and consistently attributed to underlying drug use on death certificates, then a decline in recorded overdose deaths could mask a static or even worsening overall drug-attributable mortality. In such a scenario, the nature of drug-related death would have shifted, rather than the overall toll having genuinely diminished.
The absence of a comprehensive, integrated national surveillance system that prospectively and retrospectively tracks all forms of drug-attributable mortality—acute, chronic, direct, and indirect—is a fundamental barrier to answering this critical question with certainty. Without such a system, assessments of overall trends rely on piecing together data from disparate sources, each with its own limitations and biases.
The narrative of a "decreasing crisis" based predominantly on overdose numbers, if not carefully contextualized with information about other drug-related harms and data limitations, could inadvertently lead to a reduction in public health urgency or a misdirection of funding. Such a narrative might fail to address the multifaceted and evolving nature of drug-related harm, including the pressing need for resources dedicated to wound care for xylazine-exposed individuals, treatment for complex IDU-associated infections, and long-term management of substance use disorders and their myriad complications. A decline in one major indicator (overdose deaths) is a positive sign, but it does not necessarily signal the end of the broader public health emergency related to drug use, especially if other serious harms persist or are potentially worsening under the surface of readily available statistics.
VI. Conclusions and Public Health Imperatives
A. Recapitulation of Key Findings
The analysis of recent data on drug-related mortality in the United States presents a complex picture. There is confirmed, albeit provisional, evidence of a significant and historically unprecedented decline in drug overdose deaths during 2023-2024, a trend largely propelled by a substantial reduction in fatalities involving synthetic opioids such as fentanyl. This development offers a crucial window of opportunity and a sign that concerted public health efforts may be yielding positive results in one critical dimension of the drug crisis.
However, this encouraging news is tempered by the serious, ongoing, and potentially escalating burden of non-overdose drug-related harms. The emergence of xylazine as an adulterant in the illicit drug supply has been linked to a new epidemic of severe, necrotic wounds that cause profound morbidity and carry a risk of life-threatening complications. Concurrently, high rates of hospitalizations and mortality associated with injection drug use-related infections, including endocarditis and sepsis, continue to impose a heavy toll on individuals and the healthcare system.
A definitive assessment of whether overall drug-related mortality has genuinely improved or merely shifted in its primary manifestations is profoundly challenging due to systemic limitations in how drug-related deaths, particularly non-overdose fatalities, are tracked and attributed. Current surveillance mechanisms are often inadequate for capturing the full spectrum of mortality where drug use is an underlying or contributing factor, especially for deaths resulting from chronic complications.
B. Implications for Public Health Surveillance, Prevention, and Intervention
The evolving nature of the drug crisis, characterized by a dynamic illicit market and the emergence of novel threats, demands a similarly adaptive and comprehensive public health response.
Surveillance: There is an urgent need to enhance public health surveillance systems to capture a broader spectrum of drug-related harms beyond acute overdose deaths. This requires developing and implementing better methodologies for identifying and recording drug involvement in deaths resulting from infections, organ failure, severe wounds, and other chronic conditions.36 Improving the training for coroners and medical examiners on the nuanced certification of drug-related deaths, and promoting more consistent, detailed reporting of all substances involved, are crucial steps.34 Routine and comprehensive toxicological testing for emerging substances, such as xylazine, in all relevant death investigations and clinical encounters is necessary to understand their true prevalence and impact.
Prevention: Sustained and expanded efforts are essential to prevent substance use disorders from developing and to reduce the myriad harms associated with all forms of drug use. This includes ensuring widespread, low-barrier access to evidence-based interventions such as Medications for Opioid Use Disorder (MOUD) 3, naloxone for overdose reversal 3, fentanyl test strips for drug checking, and comprehensive harm reduction services, including sterile syringe access and safe consumption sites where legally permissible.5 Public awareness and education campaigns must be agile, addressing new threats like xylazine, the dangers of polysubstance use, and the unpredictable nature of the illicit drug supply.45
Intervention: Healthcare systems must be adequately prepared and resourced to manage the complex and often severe medical needs arising from drug use complications. This includes developing expertise and protocols for specialized wound care for xylazine-induced lesions 10, and aggressive, evidence-based treatment for severe infections like DUA-IE.27 Integrating substance use disorder treatment seamlessly with medical care for physical complications is vital to address the root cause of these health issues and improve long-term outcomes.26 Addressing the alarmingly high rates of patients leaving against medical advice (AMA), particularly those with xylazine-associated wounds and withdrawal, is a critical challenge that requires innovative engagement strategies and compassionate, non-punitive care models.20
C. Recommendations for Enhancing Data Collection, Research Priorities, and Clinical Awareness
To effectively navigate the complexities of the current drug crisis, targeted actions are needed across data systems, research agendas, and clinical practice.
Data Collection:
Advocate for and implement standardized death certification practices that mandate greater detail on all substances involved and the sequence of events leading to death, ensuring that underlying causes related to chronic drug use are captured.
Promote and fund robust data linkage studies that connect vital statistics (death records) with other health datasets, such as hospital discharge records, emergency department visit data, and substance use disorder treatment registries, to better understand long-term health outcomes and calculate a more accurate estimate of total drug-attributable mortality.40
Continue to support and expand programs like the CDC's Overdose Data to Action (OD2A) and the State Unintentional Drug Overdose Reporting System (SUDORS) to enhance the timeliness, completeness, and utility of drug overdose surveillance at state and local levels.3
Research Priorities:
Conduct rigorous epidemiological studies to determine the national incidence, prevalence, and mortality associated with xylazine-induced wounds and other non-overdose complications of contemporary drug use.
Investigate the long-term health trajectories and mortality outcomes for individuals who survive severe drug-related infections (e.g., DUA-IE, sepsis) or significant xylazine exposure.
Evaluate the comparative effectiveness of different public health and clinical interventions in reducing both overdose and non-overdose drug-related harms in the context of a rapidly evolving and increasingly complex illicit drug supply.
Elucidate the specific social, economic, and systemic factors that drive geographic disparities in overdose rates and the prevalence of other drug-related harms to inform targeted, equitable interventions.
Support ongoing research efforts, such as those by the National Institute on Drug Abuse (NIDA), into the fundamental mechanisms of addiction, the interplay of substance use with comorbidities (including HIV and mental health disorders), the development of novel prevention and treatment strategies, and the reduction of health disparities and stigma.24
Clinical Awareness:
Develop and disseminate evidence-based clinical guidelines for healthcare providers on the recognition, diagnosis, and multidisciplinary management of xylazine-associated wounds, IDU-related infections, and the complex withdrawal syndromes associated with polysubstance use, including xylazine.
Promote routine screening for substance use disorders, and the offering or active referral to evidence-based treatment, in all healthcare settings (emergency departments, primary care, hospitals, specialty clinics).
Educate clinicians about the importance of harm reduction counseling and the provision of harm reduction resources to all individuals who use drugs.
The current public health success in achieving a provisional decline in overdose deaths, if it can be sustained and validated with final data, is a testament to the impact of concerted efforts. However, this success must be broadened to address the full spectrum of drug-related harms. A singular focus on overdose metrics risks obscuring the evolving nature of the drug crisis and leaving significant, and potentially growing, sources of morbidity and mortality unaddressed. The dynamic and adaptive nature of the illicit drug market, which constantly introduces new substances, combinations, and associated risks 5, necessitates an equally dynamic, adaptive, and comprehensively resourced public health response system. This system must be capable of rapidly identifying emerging threats, understanding new patterns of harm, and deploying effective, evidence-based strategies to protect the health and save the lives of all individuals affected by substance use.
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