Empirical assessment of wounds among people who use substances.

BACKGROUND: Wounds are a significant source of morbidity among people who use substances (PWUS). This project sought to identify the incidence and severity of wounds among PWUS in the South Bronx, a region of New York City with one of the highest morbidities of substance use disorder. METHODS: This study recruited PWUS within the past 30 days. Research staff were trained to document the presence and severity of wounds. The primary outcome measure was the incidence of wounds. Acceptability of on-the-street wound care was assessed by the number of participants encountered. The association between participant characteristics and wounds was also evaluated. RESULTS: In total, 586 PWUS were assessed (19.4 % female: 69 % Hispanic; 23 % Black; 5 % White). Heroin (65.7 %) and psychostimulants (58.3 %) were the most commonly used drugs. Approximately 23 % of outreach recipients disclosed a wound. Among those with a wound, 60.9 % reported one wound, 27.8 % had two wounds, and 11.3 % had three or more wounds. Small wounds (approximately the size of a cherry) were the most common (78.6 %). Recent use of stimulants or heroin, along with intravenous use of any substance were significantly associated with having a wound. CONCLUSIONS: This study found that drug-related wounds were common among PWUS. Toxicology data from other sources indicate that xylazine was present in the NYC market at the time, though its prevalence among the current sample is difficult to determine. The occurrence and severity of substance-related wounds in NYC should continue to be monitored as a function of changes in the xylazine adulteration.

Fentanyl and xylazine crisis: Crafting coherent strategies for opioid overdose prevention.

The United States is in the throes of a severe opioid overdose epidemic, primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine, a veterinary sedative often mixed with fentanyl. The high potency and long duration of fentanyl is compounded by the added risks from xylazine, heightening the lethal danger faced by opioid users. Measures such as enhanced surveillance, public awareness campaigns, and the distribution of fentanyl-xylazine test kits, and naloxone have been undertaken to mitigate this crisis. Fentanyl-related overdose deaths persist despite these efforts, partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies. A multifaceted approach is imperative in effectively combating the opioid overdose epidemic. This approach should include expansion of treatment access, broadening the availability of medications for opioid use disorder, implementation of harm reduction strategies, and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.

Barriers to, and Facilitators of, Checking Drugs for Adulterants in the Era of Fentanyl and Xylazine: Qualitative Study.

BACKGROUND: Overdose deaths continue to reach new records in New York City and nationwide, largely driven by adulterants such as fentanyl and xylazine in the illicit drug supply. Unknowingly consuming adulterated substances dramatically increases risks of overdose and other health problems, especially when individuals consume multiple adulterants and are exposed to a combination of drugs they did not intend to take. Although test strips and more sophisticated devices enable people to check drugs for adulterants including fentanyl and xylazine prior to consumption and are often available free of charge, many people who use drugs decline to use them. OBJECTIVE: We sought to better understand why people in the New York City area do or do not check drugs before use. We plan to use study findings to inform the development of technology-based interventions to encourage consistent drug checking. METHODS: In summer 2023, team members who have experience working with people who use drugs conducted 22 semistructured qualitative interviews with a convenience sample of people who reported illicit drug use within the past 90 days. An interview guide examined participants' knowledge of and experience with adulterants including fentanyl, xylazine, and benzodiazepines; using drug testing strips; and whether they had ever received harm reduction services. All interviews were audio recorded, transcribed, and analyzed for emerging themes. RESULTS: Most participants lacked knowledge of adulterants, and only a few reported regularly checking drugs. Reasons for not checking included lacking convenient access to test supplies, or a place to check samples out of the public's view, as well as time considerations. Some participants also reported a strong belief that they were not at risk from fentanyl, xylazine, or other adulterants because they exclusively used cocaine or crack, or that they were confident the people they bought drugs from would not sell them adulterated substances. Those who did report testing their drugs described positive interactions with harm reduction agency staff. CONCLUSIONS: New forms of outreach are needed not only to increase people's knowledge of adulterated substances and awareness of the increasing risks they pose but also to encourage people who use drugs to regularly check their substances prior to use. This includes new intervention messages that highlight the importance of drug checking in the context of a rapidly changing and volatile drug supply. This messaging can potentially help normalize drug checking as an easily enacted behavior that benefits public health. To increase effectiveness, messages can be developed with, and outreach can be conducted by, trusted community members including people who use drugs and, potentially, people who sell drugs. Pairing this messaging with access to no-cost drug-checking supplies and equipment may help address the ongoing spiral of increased overdose deaths nationwide.

Wastewater Surveillance for Xylazine in Kentucky.

Introduction: In the U.S., xylazine, the veterinary non-opioid sedative, has emerged as a major threat to people who use illicitly manufactured fentanyl and other drugs. The aim of this study was to compare wastewater detection of xylazine with other public health and safety surveillance data from 2019 to 2023 in Kentucky. Methods: Wastewater samples from 5 rest areas, 2 truck weigh stations, and 4 wastewater treatment plants were tested for xylazine. Wastewater xylazine positivity rates were compared with xylazine-positive submission rates from the National Forensic Laboratory Information System and Kentucky's fatal overdoses in 6-month periods (Period 1=January-June; Period 2=July-December). Results: Xylazine was detected in 61.6% (424 of 688) of daily wastewater samples from roadway sites/wastewater treatment plants. For roadways, detection increased from 55% (Period 1, 2021) to 94% (Period 1, 2023), and wastewater treatment plants had an overall detection of 25.8% (n=66 samples, Periods 1 and 2, 2022). Increasing roadway positivity corresponded to trends in National Forensic Laboratory Information System xylazine-positive submission rates: from 0.19 per 1,000 submissions (Period 1, 2019) to 2.9 per 1,000 (Period 2, 2022, latest available). No deaths from xylazine were reported publicly in Kentucky, although this study's authors identified 1-4 deaths (true count suppressed) in the overdose surveillance system, which, in back-of-the-envelope comparisons with other states, is far fewer than expected. Conclusions: Wastewater signals indicate broad geographic exposure to xylazine in Kentucky, yet health outcomes data suggest otherwise. These findings may inform regional, national, and international efforts to incorporate wastewater-based drug surveillance. Harm-reduction activities along roadways and other suitable locations may be needed.

Opioid-related xylazine toxicity manifesting as myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema.

This article provides a report of a case of organ dysfunction, myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema after a patient's use of xylazine and fentanyl. Within the US opioid epidemic, xylazine is emerging as a troubling national sub-story. The prevalence of xylazine within illicitly manufactured opioids and the proportion of opioid-involved overdose deaths with detected xylazine are rising dramatically, the latter increasing 276% between 2019 and 2022. A 27-year-old woman with opioid use disorder, active intravenous drug use, and prior bacteremia presented to our institution's emergency department (ED) with left lower extremity pain and associated weakness, new acute bilateral hearing loss, multiple electrolyte derangements, and cerebral infarcts followed by cerebral edema, leading to an emergent sub-occipital decompressive craniectomy and placement of an external ventricular drain. A definitive mechanism was not determined; however, we hypothesized that xylazine toxicity played a role in her clinical presentation, which could have future clinical implications, including the possibility to incorporate xylazine as part of toxicology screens.

"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.

A content analysis of legal policy responses to xylazine in the illicit drug supply in the United States.

BACKGROUND: Xylazine is a veterinary sedative that is quickly spreading in the U.S. illicit drug supply and is increasingly associated with fatal overdoses and severe wounds. In response, xylazine has been deemed an emerging public health threat and several policy initiatives have been introduced to combat its spread and negative broad health impact. We aimed to synthesize trends in all-time U.S. policy responses to xylazine in the drug supply. METHODS: In April 2024, we systematically identified and categorized proposed and enacted policy initiatives that related to human xylazine consumption by searching LexisNexis and Thomas Reuters Westlaw legal databases. RESULTS: Of 58 unique policy initiatives, most were introduced in 2023 (n = 37/58, 64 %) and concentrated in Northeastern states. Penalties for xylazine possession, often tied to state drug scheduling changes, were the most common provision (n = 34/58; 59 %) and Schedule III was the most frequently proposed scheduling level (n = 17/30; 57 %). Other provisions included proposals to enhance: test strip access (n = 11/58; 19 %), public awareness and education (n = 3/58; 5 %), xylazine-specific research (n = 4/58; 7 %), and surveillance (n = 8/58; 14 %). CONCLUSION: U.S. state and federal policy responses to xylazine grew rapidly in 2023, were most concentrated in states affected most by xylazine, and scheduling was the most commonly proposed policy approach. Research measuring policy effects should be prioritized as policies are implemented.

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.

Evaluation of the ARK Diagnostics immunoassay for qualitative detection of xylazine in urine.

Xylazine exposure is common in some US cities, but a commercial assay for routine laboratory testing for xylazine is not currently available. We evaluated a pre-release version of the ARK Diagnostics immunoassay for qualitative detection of xylazine/4-hydroxyxylazine in urine. Studies were conducted using either the semi-quantitative assay application (A. Roche Cobas 503 analyzer), or the qualitative assay application (B. Beckman Coulter AU480 analyzer). Study specimens consisted of deidentified patient urine samples submitted for routine drugs-of-abuse testing. Measurements of xylazine (X) were performed by LC-MS/MS, to obtain X-NEGATIVE (X<10 ng/mL) and X-POSITIVE (X≥10 ng/mL). The semi-quantitative ARK assay was calibrated with a 10 ng/mL cutoff for ARK-POSITVE. For (A): among 74 X-POSITIVE samples, there was 1 ARK-NEGATIVE result (false-negative rate=1.4%); among 78 X-NEGATIVE samples by LC-MS/MS, there were 0% ARK-POSITIVE results (false-positive rate = 0%). For (B), among 74 X-POSITIVE samples, there were 0 ARK-NEGATIVE results (false-negative rate=0%); among 78 X-NEGATIVE samples there was 1 ARK-POSITIVE sample (false-positive rate=1.3%). Common sources of interferences were investigated without evidence of interference. The ARK xylazine/4-OH-xylazine immunoassay was found to be suitable for routine use in screening patient urine samples for presence of xylazine >10 ng/mL.

The Management of Xylazine Overdose With Naloxone.

This article discusses a rare case of isolated xylazine overdose in a human, treated successfully with naloxone. Xylazine, typically used as a veterinary tranquilizer, acts as a potent α2 adrenergic agonist, leading to sedation, muscle relaxation, and potential respiratory depression. In this case, a female mistakenly injected herself with xylazine mistaking it for a different medication. The report discusses naloxone's role beyond opioid overdose, especially regarding substances causing central nervous system (CNS) depression via mechanisms similar to those of opioids. While naloxone is traditionally associated with opioid receptor antagonism, its successful application here suggests potential benefits against non-opioid substances such as xylazine. The report emphasizes the need for higher naloxone dosages than those used for opioid toxicity and suggests more research into its use for treating xylazine intoxication, reflecting on the growing trend of xylazine as a recreational drug adulterant and the resulting health risks.

Effects of alfaxalone, medetomidine, and xylazine on intraocular pressure in domestic pigeons (Columba livia domestica).

OBJECTIVE: To evaluate the effects of alfaxalone, medetomidine, and xylazine on intraocular pressure (IOP) in domestic pigeons (Columba livia domestica). ANIMALS STUDIED: Eight 12-month-old pigeons (16 eyes). PROCEDURES: The pigeons were randomly assigned to three treatment groups (10 mg/kg of alfaxalone, 0.2 mg/kg of medetomidine, or 10 mg/kg of xylazine) with a 7-day washout period. The IOP was measured using a rebound tonometer and calibrated using the formula y = 0.439x + 2.059, where y is the tonometric IOP and x is the actual IOP. RESULTS: All three drugs significantly reduced IOP. Alfaxalone led to the least reduction at 5.2 mm Hg, medetomidine reduced IOP to 12.5 mm Hg, whereas xylazine resulted in the greatest reduction at 15.3 mm Hg. Alfaxalone achieved its maximum IOP reduction in 6 min, whereas medetomidine and xylazine required 95 and 115 min, respectively. Both alpha-2 agonists, medetomidine, and xylazine, showed a prolonged duration of effect and a greater reduction in IOP than those of alfaxalone. All three medications provided adequate sedation without any discernible adverse effects. CONCLUSIONS: The findings revealed the varied effects of these drugs on IOP in pigeons, potentially providing valuable insights that could be useful for broader applications in veterinary medicine.

Cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry during continuous intravenous infusion of a combination solution of xylazine, butorphanol, and propofol in calves.

General anesthesia in calves is easier to perform under field conditions, total intravenous anesthesia (TIVA) than using inhalation anesthesia. In the present study, cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry were assessed during continuous infusion of a combination solution of 0.01% xylazine, 0.001% butorphanol, and 0.2% propofol (XBP) at doses of 6 (G6; 10 µg/kg/min xylazine, 1 µg/kg/min butorphanol, 200 µg/kg/min propofol) and 9 mL/kg/h (G9; 15 µg/kg/min xylazine, 1.5 µg/kg/min butorphanol 300 µg/kg/min propofol). For both groups, five castrated Holstein calves received intravenous injections of xylazine (0.2 mg/kg) and propofol (2 mg/kg), followed by a continuous infusion of XBP for 60 min to maintain anesthesia. Respiratory management consisted of tracheal intubation followed by spontaneous inhalation of pure oxygen. Cardiopulmonary, anesthesia, hematology, and blood biochemistry variables were assessed at rest (baseline) and every 5 or 15 min after the start of the XBP infusion. Quality of arousal was assessed based on the swallowing reflex recovery time from the stop of XBP infusion, and the sternal position time and standing time after atipamezole administration. XBP produced adequate sedation, analgesia, and muscle relaxation in all calves and maintained stable anesthesia for 60 min. As XBP infusion time passed, rectal temperature and heart rate became lower, and mean arterial blood pressure increased. In both groups, hematologic and blood biochemical effects were mild. The quality of arousal was not different, and all calves were standing. The results of the present study suggested that XBP is useful for TIVA in calves.

Xylazine does not enhance fentanyl reinforcement in rats: A behavioral economic analysis.

The adulteration of illicit fentanyl with the alpha-2 agonist xylazine has been designated an emerging public health threat. The clinical rationale for combining fentanyl with xylazine is currently unclear, and the inability to study fentanyl/xylazine interactions in humans warrants the need for preclinical research. We studied fentanyl and xylazine pharmacodynamic and pharmacokinetic interactions in male and female rats using drug self-administration behavioral economic methods. Fentanyl, but not xylazine, functioned as a reinforcer under both fixed-ratio and progressive-ratio drug self-administration procedures. Xylazine combined with fentanyl at three fixed dose-proportion mixtures did not significantly alter fentanyl reinforcement as measured using behavioral economic analyses. Xylazine produced a proportion-dependent decrease in the behavioral economic Q0 endpoint compared to fentanyl alone. However, xylazine did not significantly alter fentanyl self-administration at FR1. Fentanyl and xylazine co-administration did not result in changes to pharmacokinetic endpoints. The present results demonstrate that xylazine does not enhance the addictive effects of fentanyl or alter fentanyl plasma concentrations. The premise for why illicitly manufacture fentanyl has been adulterated with xylazine remains to be determined.

Broad evidence of xylazine in the UK illicit drug market beyond heroin supplies: Triangulating from toxicology, drug-testing and law enforcement.

BACKGROUND AND AIMS: Xylazine is a non-opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. METHODS: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co-detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner. Drug-testing cases positive for xylazine were collated from the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) drug-testing postal service with the date, location, purchase intent and co-detected drugs detailed. Drug seizures made by UK law enforcement were communicated by the Office for Health Improvement and Disparities with the date and location detailed. RESULTS: By the end of August 2023, xylazine was detected in 35 cases from throughout toxicology, drug-testing and drug seizure sources covering England, Scotland and Wales. There were no cases reported from Northern Ireland. Xylazine was detected in biological samples from 16 people. In most cases where full toxicology results were provided, xylazine was detected with heroin and/or a strong opioid (n = nine of 11), but this polydrug use pattern was not evident in all cases (n = two of 11), suggesting a wider circulation of xylazine in the UK illicit drug market beyond heroin supplies. Evidence from WEDINOS supports this claim, as all 14 drug samples (100%) submitted from across the UK contained xylazine; however, in none of these cases was heroin the purchase intent but rather counterfeit prescription medication tablets (n = 11 of 14), tetrahydrocannabinol (THC) vapes (n = two of 14) or white powder (n = one of 14). Additional evidence for the spread of illicit xylazine comes from five drug seizures made by law enforcement. CONCLUSIONS: Xylazine has penetrated the UK illicit drug market and is not limited to heroin supplies.

Xylazine: A Drug Adulterant of Clinical Concern.

PURPOSE OF REVIEW: The opioid epidemic has been responsible for significant morbidity and mortality in the USA and worldwide. As a result, it is essential to recognize the threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as a drug adulterant has been shown to impact overdose rates drastically. In this regard, the Drug Enforcement Agency recently released a public safety alert announcing the new threat of a new adulterant called xylazine. Xylazine is a powerful animal sedative with a different mechanism of action when compared to illicit opioids such as heroin and fentanyl. Xylazine is typically injected intravenously via a syringe, often in combination with multiple other drugs. One of the most common drugs, xylazine, is taken in combination with fentanyl, with users of this drug combination describing xylazine as prolonging the euphoric sensation produced by fentanyl. RECENT FINDINGS: Xylazine may cause adverse effects such as bradycardia, brief hypertension followed by hypotension, premature ventricular contractions, ataxia, slurred speech, sedation, and respiratory depression. Much of the recent literature on xylazine use in humans comes from case reports and review articles. Related to widespread use in veterinary medicine and increasing circulation in illicit drug markets, there is a critical need for public awareness and additional clinical-based studies to further increase understanding of mediated or modulated pharmacological effects of xylazine in humans. Further research is urgently needed to more clearly understand the implications of unregulated xylazine in the illicit drug market, to formulate public health interventions, and to implement harm reduction strategies.

A quantitative LC-MS/MS analysis of Xylazine, p-Fluorofentanyl, Fentanyl and Fentanyl-Related compounds in postmortem blood.

The purpose of this study was to develop and validate a method to quantitate the veterinary sedative xylazine as well as 4-anilino-N-phenethylpiperidine (4-ANPP), acetyl fentanyl, fentanyl, norfentanyl, and p-fluorofentanyl in blood utilizing liquid chromatography tandem mass spectrometry. This method also qualitatively monitors for the presence of o-fluorofentanyl and m-fluorofentanyl isomers. UCT Clean Screen® DAU extraction columns were utilized to isolate the analytes in postmortem blood samples. The extracts were eluted, evaporated, reconstituted, and then analyzed using a Waters Acquity™ UPLC coupled a triple quadrupole mass spectrometer. The lower limit of quantitation was determined to be 0.1 ng/mL for all analytes, except for xylazine (0.2 ng/mL). The upper limit of quantitation for all analytes was 100 ng/mL. No interferences from matrix, internal standard, or common drug analytes were observed. Bias (-13.1-4.6 %) and precision (-13.14-10.3 %) fell within the acceptable ± 20 % criteria range. Dilution integrity at x2, x10, and x100 was evaluated and all results were within ± 20 % of the target concentration. Processed extract stability was evaluated after 72 h and all results were within ± 20 % of the analyte initial concentration. Matrix effects were the most prominent with xylazine, but deemed acceptable as the deuterated internal standard also observed comparable enhancement. Analysis of 89 postmortem blood samples by this method resulted in positive results for fentanyl (0.27-66 ng/mL, n = 82), xylazine (0.24-958 ng/mL, n = 21), 4-ANPP (0.10-38 ng/mL, n = 72), acetyl fentanyl (0.18-1.5 ng/mL, n = 3), p-fluorofentanyl (0.11-33 ng/mL, n = 30), and norfentanyl (0.10-98 ng/mL, n = 73).

Adulterants present in the San Diego county fentanyl supply: a laboratory analysis of seized law enforcement samples.

BACKGROUND: The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. METHODS: Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff's Department Regional Crime Laboratory for identification. RESULTS: Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. CONCLUSION: This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public.

Xylazine: An Abused Tranq Dope and its Safety Concern.

A drug called Xylazine has gained notoriety in recent times, earning the nickname "zombie drug" due to reported alarming effects on its users. Although Xylazine is primarily intended for veterinary use as a sedative and muscle relaxant for animals, there have been growing concerns about its misuse among humans, particularly in the context of illicit drug use. However, it is essential to rely on accurate and evidence-based information when discussing the health risks associated with any substance, rather than resorting to sensationalized terms like "zombie drug." The situation involving Xylazine misuse is a matter of concern, and the United States Drug Enforcement Administration has highlighted it as a significant threat to public health.