"Tranq-dope": The first fatal intoxication due to xylazine-adulterated heroin in Italy.

BACKGROUND AND AIMS: The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids with the sedative to reduce drug manufacturing costs and enhance their effects. In this study, we report the first fatality involving xylazine-adulterated heroin in the EU. MATERIALS AND METHODS: The subject was a 33-year-old Caucasian male with a documented history of drug abuse who was found dead in a public area with puncture marks at the elbow. Peripheral blood and urine were collected at the autopsy and analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) after protein precipitation. RESULTS: 6-Monoacetylmorphine, total/free morphine, and codeine blood concentrations of 20.3, 236/105, and 38.3 ng/mL, respectively, indicated recent heroin consumption. Methadone blood concentration was below 10 ng/mL. Alprazolam, nordiazepam, and flurazepam blood concentrations were 23.9, 61.4, and 55.0 ng/mL, respectively. Benzoylecgonine blood concentration was below 5 ng/mL. Xylazine blood and urine concentrations were 105 and 72.6 ng/mL, respectively. CONCLUSION: The combination of central nervous system depressants, i.e., opioids, benzodiazepines, and xylazine, was the principal cause of death by cardiorespiratory failure. The case was promptly reported to the UE Early Warning System on drugs.

Classics in Chemical Neuroscience: Xylazine.

Xylazine (also known as "tranq") is a potent nonopioid veterinary sedative that has recently experienced a surge in use as a drug adulterant, most often combined with illicitly manufactured fentanyl. This combination may heighten the risk of fatal overdose. Xylazine has no known antidote approved for use in humans, and age-adjusted overdose deaths involving xylazine were 35 times higher in 2021 than 2018. In April 2023, the Biden Administration declared xylazine-laced fentanyl an emerging drug threat in the United States. In 2022, the Drug Enforcement Agency (DEA) reported nearly a quarter of seized fentanyl powder contained xylazine. This dramatic increase in prevalence has solidified the status of xylazine as an emerging drug of abuse and an evolving threat to public health. The following narrative review outlines the synthesis, pharmacokinetics, pharmacodynamics, and adverse effects of xylazine, as well as the role it may play in the ongoing opioid epidemic.

Media framing xylazine as a "zombie drug" is amplifying stigma onto people who use drugs.

Amid increasing efforts to understand xylazine-associated harms, examining the potentially catastrophic role of stigma resulting from media outlets framing xylazine as the "zombie drug" is imperative. Zombies are cinematically depicted as soulless, dangerous, and required to be killed off entirely for public safety, making the "zombie" analogy especially grave amid the fatal overdose crisis. Xylazine is called the "zombie drug" due to its heavy sedative effect and associated-severely infected skin ulcers. We surmise that wide-scale media framing of xylazine as the "zombie drug" has increased stigmas onto people who use drugs as their likening to zombies reifies subhuman status. The present commentary highlights many media headlines and quotes that use "zombie" terminology when writing about xylazine, and examine how this expansive media framing amplifies stigmas. Xylazine's proliferation in the illicit drug market will likely increase infected ulcers needing medical attention. People who use drugs are often reluctant to seek medical care due to experiences of medically-institutionalized stigma. Based on the media's extensive depiction of xylazine as the "zombie drug," it is plausible that medical practitioners have been exposed to this stigmatizing framing, which could unknowingly detrimentally impact provision of medical care. Strategies to offset harms of xylazine-associated stigmas are proposed, including that medical practitioners undergo evidence-based training to reduce stigmatizing responses to severe xylazine-associated ulcers as any indication of enacted stigma can be internalized by the person seeking treatment, which in turn can perpetuate harms like sepsis or overdose. Author ethnographic observations of xylazine presence are included, which encompass three distinct urban settings that span North America. Finally, we suggest approaches media outlets could adopt to reflect on how referring to xylazine as the "zombie" drug amplifies stigmas onto people already surviving under structural conditions heightening physical and mental trauma, and use language instead that could aid in lessening these harms.

The New Stealth Drug on the Street: A Narrative Review of Xylazine as a Street Drug.

Xylazine is an alpha-adrenergic receptor agonist approved for use only in animals with a prescription from a veterinarian. It is a powerful sedative that is slowly infiltrating the recreational street drug scene and is often used by polysubstance abusers. Known as "tranq," it can be fatal, and xylazine-induced toxicity cannot be reversed with naloxone or nalmefene. Due to its vasoconstrictive effects, chronic use of xylazine is associated with necrotic skin lesions and general deterioration of health. Since xylazine is not approved for human use and is not scheduled as a controlled substance, there are no human studies to provide evidence of drug-drug interactions, lethal doses, or reversal protocols. Xylazine is available online without a prescription. Street drug users may take xylazine knowingly or unknowingly, as it is often combined with other illicit substances such as fentanyl. There are no rapid tests for xylazine, although there are specialty tests that can be ordered. Xylazine represents a major threat to street drug users and another challenge to emergency healthcare workers, first responders, and others who care for those who have taken this "new" street drug.

Potency-Enhancing Synthetics in the Drug Overdose Epidemic: Xylazine ("Tranq"), Fentanyl, Methamphetamine, and the Displacement of Heroin in Philadelphia and Tijuana.

Multiple transformations-referred to as "waves" in a panoply of recent public health and law enforcement publications-have rendered North American drug markets increasingly toxic since the early 2010s. The introduction of exceptionally potent synthetic sedatives and stimulants is initiating a new generation of drug injectors into co-use of opioids and methamphetamine, catapulting rates of deadly overdoses and infectious diseases. Drawing on extensive participant-observation research in Philadelphia (2007-present) and Tijuana (2018-present), we document the experience of street-based drug users across these two North American cities to focus on regional shifts in narcotics supplies and endpoint user preferences. We link the dramatic proliferation of fentanyl, methamphetamine, xylazine, and Mexican white powder heroin to: 1) pre-existing drug supply networks on the western and eastern coasts of the North American subcontinent; 2) material characteristics of local heroin supplies in pre-fentanyl opiate markets (Mexican black tar vs. Colombian off-white powder heroin); and 3) racialized repression/incarceration of drug sellers and users on both sides of the Mexico-US border. The article combines economic and medical anthropology to develop an ethnographically-informed political economy approach to an urgent public health challenge among street-based drug users with the highest overdose mortality rates in the US Northeastern Rust Belt and the Northwestern Mexican borderland metroplex anchored by Tijuana. It foregrounds street users' experiences in real time amidst rapidly shifting narcotics supply chains, linking market-driven logics of profit-seeking to the war on drugs' prohibitionist policy context, highlighting increasing toxic impacts on vulnerable sectors across regions.