Xylazine: Data Update for HHS Region 8
Abstract
Xylazine, a veterinary sedative developed in 1962, has emerged as a significant public health concern due to its increasing presence in the illicit drug supply. Although approved only for animal use, xylazine is frequently combined with fentanyl and other substances, creating a dangerous polysubstance mix that complicates overdose treatment. Its effects on humans include severe central nervous system depression, hypotension, and life-threatening wounds such as necrosis, often requiring amputation. Naloxone does not reverse xylazine’s toxic effects, and routine toxicology screens fail to detect it, contributing to underdiagnosis. DEA data show that in 2022, xylazine was found in nearly a quarter of fentanyl powder samples and in pills seized across 48 states. The Biden-Harris Administration recently designated fentanyl-xylazine combinations as an emerging threat, and legislation is underway to classify xylazine as a Schedule III controlled substance. This trend underscores the urgent need for improved detection, clinical preparedness, and coordinated policy responses to address the escalating overdose crisis.
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Region 8 Substance Use Disorder (SUD) Data Workgroup Data Snack July 2023: Xylazine BACKGROUND Xylazine was developed in 1962 as an analgesic, sleeping aid, and anesthetic, but human clinical trials found it to have severe hypotension and central nervous system (CNS) depressant effects. Currently, the FDA has approved its use ONLY in veterinary medicine as a tranquilizer, sedative, or pain reliever - it has no FDA-approved uses for humans. In veterinary medicine, xylazine is used as a component of diagnostic and surgical procedures in animals ranging from cats and dogs to horses and cattle. It is not currently a controlled substance under the U.S. Controlled Substances Act (see timeline below for proposed changes). In humans, xylazine is a central nervous system depressant that can cause drowsiness and amnesia; and slow breathing, heart rate and blood pressure to dangerously low levels. Repeated use is associated with skin ulcers and abscesses, some of which require amputation if not treated. Other names: “tranq,” “tranq dope,” and “zombie drug.” ROUTES FOR ADMINISTRATION Include injecting, snorting, swallowing, or inhaling. The DEA reports that it is commonly combined with fentanyl,l but has also been detected in mixtures containing cocaine, heroin, and a variety of other drugs. Xylazine is most frequently reported in combinations with two or more substances present. This combination makes it more difficult to treat: Fentanyl suppresses the respiratory system, slowing breathing sometimes to the point of unconsciousness, and xylazine acts to slow the nervous system. People who inject drug mixtures containing xylazine also can develop severe wounds, including necrosis—the rotting of human tissue—that may lead to amputation. Xylazine is an adulterant, meaning it is added to drugs like heroin or cocaine to manipulate or change the way they make users feel when taking them. People report using xylazine-containing fentanyl to extend its euphoric effects. A 2023 study of nine emergency departments found 90 out of 321 patients tested positive for xylazine. Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier. The DEA has seized xylazine and fentanyl mixtures in 48 of 50 States. The DEA Laboratory System is reporting that in 2022 approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine. – Anne Milgram, DEA Administrator
Naloxone will not reverse the effects of xylazine; but the CDC recommends its use in response to any suspected drug overdose to reverse any possible opioid effects because xylazine is often used with opioids like fentanyl. Xylazine withdrawal has unique clinical considerations that many providers are not yet prepared to address. DETECTION AND TESTING Xylazine is rapidly eliminated from the body, with a half-life of 23-50 minutes, which could contribute to its use being undiagnosed. Routine toxicology screens do not detect xylazine. Chemically xylazine is not an opioid, so naloxone is not known to be effective in reversing its toxic effects, though the CDC recommends its use. Biotech company BTNX developed test strips for forensic use that detect the presence of xylazine. Data reviews revealed instances where xylazine presence was noted at the scene of the overdose but not detected on postmortem toxicology. Current testing protocols for xylazine are not standard, which could result in missed detection. Only sporadic reporting in HHS Region 8 states. Source: DEA 346 198 110 77 556 580 118 163 0 100 200 300 400 500 600 700 Northeast South Midwest West DEA Forensic Laboratory Identifications of Xylazine by Region 2020 2021 Percent Increase According to the CDC, 107,735 Americans died between August 2021 and August 2022 from drug poisonings, with 66 percent of those deaths involving synthetic opioids like fentanyl. The Sinaloa Cartel and Jalisco Cartel in Mexico, using chemicals largely sourced from China, are primarily responsible for the vast majority of the fentanyl that is being trafficked in communities across the United States.
TIMELINE Early 2000 Becomes a popular drug of abuse in the United States and Puerto Rico. 2006 Involved in seven overdose deaths in the Philadelphia area. 2014 A study found 43 intoxication cases from xylazine alone (not mixed) in humans were identified from the years 1966 to 2013. 2017 Case report of its use in a drug related crime. 2019 Routinely shows up in illicit drug supply. First electroanalytical method for xylazine quantification is reported. 2020 The pandemic brings with it a surge of use. Identified in the unregulated drug supply in British Columbia, Canada. 2023 Biden-Harris Administration designates fentanyl combined with xylazine as an emerging threat. Bipartisan legislation was introduced in March of 2023 to classify xylazine as a Schedule III controlled substance. The FDA announces they will take action to restrict unlawful import of xylazine. BIBLIOGRAPHY 1. Gupta R, Holtgrave DR, Ashburn MA. Xylazine — Medical and Public Health Imperatives. The New England Journal of Medicine. Published online April 26, 2023. doi:https://doi.org/10.1056/nejmp2303120 2. Alexander RS, Canver BR, Sue KL, Morford KL. Xylazine and Overdoses: Trends, Concerns, and Recommendations. American Journal of Public Health. 2022;112(8):1212-1216. doi:https://doi.org/10.2105/ajph.2022.306881 3. Friedman J, Montero F, Bourgois P, et al. Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis. Drug and Alcohol Dependence. 2022;233:109380. doi:https://doi.org/10.1016/j.drugalcdep.2022.109380 4. Kariisa M, Patel P, Smith H, Bitting J. Notes from the Field: Xylazine Detection and Involvement in Drug Overdose Deaths — United States, 2019. MMWR Morbidity and Mortality Weekly Report. 2021;70(37):1300-1302. doi:https://doi.org/10.15585/mmwr.mm7037a4 5. Love JS, Levine M, Aldy K, et al. Opioid overdoses involving xylazine in emergency department patients: a multicenter study. Clinical Toxicology. 2023;61(3):173-180. doi:https://doi.org/10.1080/15563650.2022.2159427 6. Swanson S, Ranade R. Xylazine: What Health Agencies Need to Know. www.astho.org. Published February 21, 2023. Accessed May 26, 2023. https://www.astho.org/communications/blog/xylazine-what-health-agencies-need-to-know/