Opioid Use in the United States: Fentanyl, Xylazine, and Settlements

The opioid crisis in the United States has killed roughly 806,000 people since 1999 and cost the economy an estimated $2.7 trillion in 2023 alone, but after more than two decades of climbing deaths the country is now in the middle of its first sustained decline. Overdose deaths fell 26.2 percent in 2024 and dropped another 21 percent through much of 2025, driven mostly by a collapse in fentanyl fatalities. The toll is still enormous — about 79,384 Americans died of drug overdoses in 2024, and roughly 4.8 million people live with opioid use disorder — and newer synthetic opioids are already moving into the supply.

How Big the Problem Still Is

In 2023, approximately 105,000 people died from drug overdoses in the United States, with nearly 80,000 of those deaths — about 76 percent — involving opioids.¹ An estimated 5.7 million Americans were living with opioid use disorder that year.²

A March 2025 White House analysis put the total economic cost of the illicit opioid epidemic at $2.7 trillion for 2023, equivalent to 9.7 percent of GDP. Nearly half of that figure reflected the diminished quality of life for people living with opioid use disorder; another 41 percent represented the value of lives lost. Healthcare costs, lost labor productivity, and crime-related expenses accounted for the rest.³

How the Crisis Got Here

The Centers for Disease Control and Prevention describes the opioid crisis as unfolding in three overlapping waves.¹

The first wave began in the 1990s, when a surge in opioid prescribing — encouraged by pharmaceutical marketing that downplayed addiction risk — drove a steady rise in deaths involving prescription painkillers like oxycodone, hydrocodone, and methadone. Overdose deaths involving these drugs started climbing around 1999.

The second wave began in 2010, as deaths involving heroin rose rapidly. Many of the people affected had become dependent on prescription opioids and moved to a cheaper, more accessible supply.

The third wave began in 2013 with illicitly manufactured fentanyl and its chemical cousins. Because fentanyl is far more potent than heroin and is routinely mixed into other drugs, including cocaine, methamphetamine, and counterfeit pills, it has become the dominant killer in the crisis.

Deaths Are Falling Fast

After peaking in 2022, overdose deaths have dropped substantially. An NCHS Data Brief published in January 2026 reported 79,384 drug overdose deaths in 2024 — a 26.2 percent decline in the age-adjusted death rate compared to 2023, the single largest annual decrease observed over the prior decade. Deaths involving synthetic opioids other than methadone (primarily fentanyl) fell 35.6 percent, heroin-related deaths dropped 33.3 percent, and deaths involving prescription opioids declined 20.7 percent.⁴

Provisional data suggests the decline continued into 2025. The 12-month count ending in October 2025 stood at roughly 68,400 reported deaths, with a predicted total around 71,500 after adjusting for reporting delays, well below the roughly 79,200 reported for the period ending January 2025.⁵ CDC estimates cited in January 2026 showed overdose deaths falling about 21 percent as of August 2025 compared to the same period a year earlier, with declines reported in 45 states.⁶

The declines crossed every demographic group. Adults aged 15 to 24 saw the steepest reduction (37 percent), and Black non-Hispanic populations experienced the largest decrease among racial and ethnic groups (30.9 percent).⁴ The CDC cautions, though, that provisional counts are underestimates and that “true declines or plateaus cannot be ascertained until final data become available.”⁵

What’s Driving Deaths Now

Illicit Fentanyl and the Supply Chain

Illicitly manufactured fentanyl remains the primary driver of opioid deaths. The supply chain typically begins with Chinese companies and brokers producing precursor chemicals, which are shipped to Mexico — often mislabeled or routed through third countries — where cartels, principally the Sinaloa Cartel and Jalisco New Generation Cartel, synthesize fentanyl in clandestine laboratories. The finished product crosses the Southwest border into the United States in small, hard-to-detect shipments.⁷⁸ Drug proceeds are laundered through Chinese money laundering organizations using underground banking networks, cryptocurrency, and front companies.

Xylazine

The veterinary sedative xylazine has increasingly been mixed into the fentanyl supply. The DEA has encountered fentanyl-xylazine combinations in 48 of 50 states, with the prevalence of xylazine in seized fentanyl tablets increasing fivefold since 2020.⁹ Because xylazine is not an opioid, naloxone, the standard overdose reversal drug, does not counteract its effects.¹⁰ Xylazine remains unscheduled under federal law, which limits the DEA’s ability to monitor its import and distribution.

Nitazenes

Even as fentanyl deaths decline, a newer class of synthetic opioids called nitazenes is spreading. Developed in the 1950s as experimental painkillers but never approved for medical use, nitazenes can be up to 40 times more potent than fentanyl and 500 times more potent than heroin.¹¹ They are rarely sold on their own; investigations show they are almost always mixed with fentanyl, cocaine, or methamphetamine, often without the user’s knowledge.

Confirmed overdose deaths involving nitazenes rose from 27 in 2020 to 409 in 2024, with expert estimates of actual deaths reaching as high as 2,000 since 2019. DEA forensic laboratory reports of nitazene seizures jumped from 43 in 2019 to nearly 2,000 in 2024, with 48 states reporting seizures.¹¹ The DEA has identified 22 unique nitazene compounds since 2020, of which 21 are classified as Schedule I substances.¹² China placed the majority of nitazenes under national control in July 2025, but manufacturers are already pivoting to newer, unregulated synthetic opioids known as “orphines.” Many toxicology labs do not routinely screen for nitazenes.

Who Is Dying

The 2024 National Survey on Drug Use and Health estimated that about 4.8 million people aged 12 and older had opioid use disorder, down from roughly 5 million the year before. Women slightly outnumbered men (2.48 million versus 2.34 million), and the vast majority of those affected were adults over 26. Among racial groups, white Americans accounted for the largest absolute number (3.1 million), followed by Hispanic or Latino Americans (816,000) and Black Americans (454,000).¹³

Those raw numbers hide sharp disparities in who is actually dying. A 2024 study in the American Journal of Preventive Medicine found that between 1999 and 2022, age-adjusted overdose mortality increased 249 percent among Black Americans, 172 percent among Hispanic and Latino Americans, and 166 percent among Native Americans, all outpacing the rise in white populations.¹⁴ From 2019 to 2020 alone, overdose death rates jumped 44 percent for Black Americans and 39 percent for American Indian and Alaska Native populations. Black men aged 65 and older had an overdose rate nearly seven times that of white men in the same age group by 2020.¹⁵

Systemic barriers compound the problem. Evidence of previous substance use treatment was documented in only 8.3 percent of Black overdose decedents, lower than rates in other groups. Overdose rates were also higher in counties with greater income inequality, and Black and Hispanic patients are less likely than white patients to receive adequate pain treatment or referrals to specialists.¹⁵¹⁶

Treatment and Overdose Reversal Have Gotten Easier to Access

Several policy shifts in recent years have expanded access to medications for opioid use disorder, the evidence-based treatments that research consistently shows reduce overdose deaths.

The Consolidated Appropriations Act of 2023 eliminated the so-called X-waiver, a longstanding requirement that forced physicians to obtain a special federal waiver before prescribing buprenorphine for addiction. Any practitioner with a standard DEA registration and authority to prescribe Schedule III substances can now prescribe buprenorphine without a separate waiver or patient cap. A final DEA rule that took effect in February 2025 further expanded access by allowing practitioners to prescribe buprenorphine via telemedicine, including audio-only encounters, without an initial in-person visit, provided they first check the state prescription drug monitoring program.¹⁷

The FDA approved naloxone for over-the-counter sale in 2023, making the overdose reversal drug available without a prescription for the first time. Pharmacy-dispensed naloxone prescriptions roughly quadrupled between 2018 and 2023, rising from about 555,000 to nearly 2.2 million.¹⁸ High cost and inconsistent retail stocking remain barriers. Total naloxone prescriptions declined to about 1.5 million in 2024 after peaking the year before.¹⁹

Prescribing of opioid painkillers has continued its long decline. In 2024, approximately 120.4 million opioid prescriptions were dispensed through U.S. retail pharmacies, down from 153.6 million in 2019. The national dispensing rate fell from 46.8 prescriptions per 100 people in 2019 to 35.4 in 2024.¹⁹

Congress reauthorized the SUPPORT for Patients and Communities Act in December 2025, extending federal substance use disorder prevention, treatment, and recovery programs through fiscal year 2030. The legislation passed the House 366 to 57 and cleared the Senate by unanimous consent before President Trump signed it on December 1, 2025. The reauthorization covers programs including SAMHSA’s Comprehensive Opioid Recovery Centers grants, the SUD Treatment and Recovery Loan Repayment Program, and grants for treatment of pregnant and postpartum women. Whether the programs receive adequate funding remains an open question, as they depend on annual appropriations.²⁰

Federal Enforcement and International Pressure

The Trump administration has pursued an aggressive enforcement posture against fentanyl trafficking. On January 20, 2025, Executive Order 14157 designated international drug cartels, along with Tren de Aragua and MS-13, as Foreign Terrorist Organizations and Specially Designated Global Terrorists.²¹ In February 2025, tariffs were imposed on goods from China, Mexico, and Canada, explicitly linked to fentanyl flows.⁸

The HALT Fentanyl Act (P.L. 119-26), signed July 16, 2025, permanently placed the entire class of fentanyl-related substances into Schedule I of the Controlled Substances Act, ending years of temporary scheduling extensions that had been renewed since 2018. The law applies existing mandatory minimum sentences for fentanyl analogues to these substances, while including streamlined registration processes for researchers studying Schedule I drugs.²²²³ Fentanyl itself remains a Schedule II substance available for legitimate medical use. In September 2025, the DEA permanently scheduled seven additional specific fentanyl-related substances, including variants of chlorofentanyl and fluorofuranyl fentanyl.²⁴

On December 15, 2025, the administration issued an executive order designating illicit fentanyl and its core precursor chemicals as Weapons of Mass Destruction.²⁵ The designation draws on 18 U.S.C. § 2332a, which carries penalties up to and including the death penalty for use or conspiracy to use a WMD. The order directs the Attorney General to pursue enhanced prosecutions and instructs the Departments of Defense and Homeland Security to incorporate the fentanyl threat into their chemical incident protocols. Critics at the Brookings Institution have questioned whether the designation will function as intended, noting that thousands of DHS investigators have been reassigned to immigration enforcement, potentially undermining counternarcotics capacity.²⁶

Diplomatic pressure has yielded some movement abroad. China committed in 2024 to tighter controls on precursor chemicals and, by mid-2025, had completed scheduling of all internationally listed fentanyl precursors and designated nitazene-class substances for domestic control. In November 2025, Beijing announced export licensing requirements for 13 precursor chemicals shipped to the United States, Mexico, and Canada, with additional chemicals added in 2026.⁷ Congressional testimony in June 2026 noted that China’s actions remained narrow and had not addressed U.S. concerns about tax rebates for precursor exports or systemic domestic enforcement. Mexico, under President Claudia Sheinbaum, stepped up enforcement operations, including what was described as the largest fentanyl seizure in Mexican history in December 2024, and reinforced its northern border with 10,000 National Guard troops. Canada appointed a “fentanyl czar” and unveiled a $1.3 billion border security plan.⁸

The Lawsuits and the Money

Purdue Pharma and the Sacklers

Purdue Pharma, maker of OxyContin, filed for Chapter 11 bankruptcy in September 2019 amid thousands of lawsuits. A reorganization plan that would have shielded the Sackler family, Purdue’s owners who had extracted $11 billion in pre-tax distributions from the company, from civil liability in exchange for a contribution of up to $6 billion was struck down by the U.S. Supreme Court in June 2024. In Harrington v. Purdue Pharma L.P., a five-to-four majority held that bankruptcy law does not authorize nonconsensual releases of claims against parties who have not themselves filed for bankruptcy.²⁷²⁸

A renegotiated deal followed. On November 18, 2025, U.S. Bankruptcy Judge Sean Lane confirmed an entirely consensual plan under which the Sackler family will pay up to $7 billion over 15 years, with potential additional recoveries from insurance and the sale of the family’s international pharmaceutical business bringing the total above $7.4 billion. Unlike the rejected plan, the new agreement allows entities that do not opt in to pursue lawsuits against family members. The Sacklers relinquished ownership of Purdue, which will be dissolved and its assets transferred to Knoa Pharma, a public benefit company operated by an independent foundation. The plan also mandates the release of internal company documents, including material previously shielded by attorney-client privilege. More than 99 percent of voting creditors supported the agreement.²⁹ Approximately $850 million is designated for individual victims, with all individual payouts scheduled for distribution in 2026.³⁰ The plan became effective on May 1, 2026.³¹

Everyone Else

Beyond Purdue, dozens of other companies have settled opioid-related claims. Major defendants include the three largest pharmaceutical distributors — McKesson, Cardinal Health, and AmerisourceBergen (now Cencora) — as well as Johnson & Johnson (through its Janssen subsidiary), Teva, Allergan, and pharmacy chains including CVS, Walgreens, Walmart, and Kroger.³² States, localities, and tribal governments have collectively recovered more than $55 billion.³³ Notable individual amounts include a $4.7 billion Walgreens settlement and a McKinsey & Company resolution totaling hundreds of millions of dollars across state, local, and federal claims.³⁴

Where the Money Is Going

How the money actually reaches communities affected by the crisis has become a significant concern. Most settlement agreements require that a high percentage of funds, typically 85 percent or more, go toward “opioid abatement” such as treatment, overdose prevention, harm reduction, and recovery support. The structure was deliberately designed to avoid a repeat of the 1990s tobacco settlements, where much of the money was funneled into general government budgets.³⁵

That structure has not prevented controversy. In New Jersey, the state legislature in 2025 diverted $45 million of its settlement to four hospital systems without specific conditions tying the funds to addiction treatment, prompting criticism from the state Attorney General. Nevada’s governor proposed using $5 million in settlement money to cover a welfare program with, legislators argued, a tenuous connection to opioid remediation. In Ohio, the state channeled $440 million to its OneOhio Recovery Foundation, which faced criticism for a lack of board diversity and initially blocked public access to meetings about fund distribution. The Ohio Supreme Court eventually ruled that the foundation was the “functional equivalent of a public organization,” requiring it to open its records.³³

Transparency remains uneven. As of February 2026, only ten states had published complete reports detailing their spending plans for settlement funds.³³ Pennsylvania, which stands to receive $2.2 billion through 2038, launched an independent tracking database in August 2025 to monitor spending at the county level; over $80 million had been spent on approved programs by the end of 2024.³⁵ Maryland allocated 70 percent of its funds to local subdivisions, with oversight mechanisms including mandatory annual reporting and a public dashboard, though as of fiscal year 2025, more than half of participating subdivisions had not yet submitted required spending plans.³⁶

Early research suggests the spending is making a difference where it happens. A 2025 study published in AJPM Focus by researchers at RAND, Rutgers, and the University of Pennsylvania found that each additional dollar of settlement funds spent per capita in 2023 was associated with a 2.46 percent decline in opioid-related overdose deaths, and that funds were being directed more heavily toward states with higher baseline death rates.³⁷

What Comes Next

The downward trend in overdose deaths is genuinely encouraging, but dozens of people still die from opioid overdoses in the United States every day. The drug supply continues to evolve: as enforcement tightens around fentanyl, manufacturers are shifting to nitazenes and other novel synthetics that are harder to detect and deadlier per dose. Whether the decline holds will depend in part on whether settlement funds are spent effectively, whether treatment access continues to expand, and whether law enforcement and diplomatic efforts can keep pace with a supply chain that has repeatedly adapted faster than the policies aimed at shutting it down.

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37
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