xylazine

Xylazine was discovered as an antihypertensive agent in 1962 by Farbenfabriken Bayer in Leverkusen, West Germany.{{cite journal | vauthors = Greene SA, Thurmon JC | title = Xylazine--a review of its pharmacology and use in veterinary medicine | journal = Journal of Veterinary Pharmacology and Therapeutics | volume = 11 | issue = 4 | pages = 295–313 | date = December 1988 | pmid = 3062194 | doi = 10.1111/j.1365-2885.1988.tb00189.x }} {{cite book | vauthors = Lamont LA, Creighton CM | chapter = Sedatives and Tranquilizers | title = Veterinary Anesthesia and Analgesia, The 6th Edition of Lumb and Jones | pages = 338–344 | isbn = 978-1-119-83027-6 | veditors = Lamont L, Grimm K, Robertson S, Love L, Schroeder C | publisher = Wiley Blackwell }} In human trials xylazine was found to depress the central nervous system leading to the discontinuation of further research for its use in human and it was instead marketed as a veterinary sedative. Xylazine was first used for this purpose in the late 1960s. Xylazine proved popular and in the 1970s became one of the most common large animal sedatives. In 1981 a study discovered that the cause sedation was due to xylazine's effect on the α2-adrenergic receptor.{{cite journal | vauthors = Hsu WH | title = Xylazine-induced depression and its antagonism by alpha adrenergic blocking agents | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 218 | issue = 1 | pages = 188–192 | date = July 1981 | pmid = 6113279 | publisher = J Pharmacol Exp Ther }} This lead to the development of other α2-adrenergic receptor agonists such as detomidine, medetomidine, dexmedetomidine, and romifidine.

In the United States, xylazine was approved by the FDA only for veterinary use as a sedative, analgesic, and muscle relaxant in dogs, cats, horses, elk, fallow deer, mule deer, sika deer, and white-tailed deer. The sedative and analgesic effects of xylazine are related to central nervous system depression. Xylazine's muscle relaxant effect inhibits the transmission of neural impulses in the central nervous system.{{cite journal |vauthors = Delehant TM, Denhart JW, Lloyd WE, Powell JD |year = 2003 |title = Pharmacokinetics of xylazine, 2,6-dimethylaniline, and tolazoline in tissues from yearling cattle and milk from mature dairy cows after sedation with xylazine hydrochloride and reversal with tolazoline hydrochloride |journal = Veterinary Therapeutics |volume = 4 |issue = 2 |pages = 128–134 |pmid = 14506588}}

In scientific research using animal experiments, xylazine is a component of the most common anesthetic, ketamine-xylazine {{crossreference|(see: Rodent cocktail)}}, to anesthetize rats, mice, hamsters, and guinea pigs.{{cite journal |vauthors = Veilleux-Lemieux D, Castel A, Carrier D, Beaudry F, Vachon P |date = September 2013 |title = Pharmacokinetics of ketamine and xylazine in young and old Sprague-Dawley rats |journal = Journal of the American Association for Laboratory Animal Science |volume = 52 |issue = 5 |pages = 567–570 |pmid = 24041212 |pmc = 3784662}}

Xylazine has not previously been a controlled substance; however, due to illicit abuse of xylazine legislative restrictions have been proposed in multiple countries. Xylazine was made a class C drug in the UK on 15 January 2025.{{Cite web |title=Britain working at pace to curb rising synthetic drugs threat |url=https://www.gov.uk/government/news/britain-working-at-pace-to-curb-rising-synthetic-drugs-threat |access-date=2025-05-30 |website=GOV.UK |language=en}}{{Cite web |title=The Misuse of Drugs Act 1971 (Amendment) (No. 2) Order 2024 and The Misuse of Drugs and Misuse of Drugs (Designation) (England and Wales and Scotland) (Amendment) (No. 2) Regulations 2024 |url=https://www.gov.uk/government/publications/circular-0022025-the-misuse-of-drugs-act-1971-order-2024/the-misuse-of-drugs-act-1971-amendment-no-2-order-2024-and-the-misuse-of-drugs-and-misuse-of-drugs-designation-england-and-wales-and-scotland |access-date=2025-05-30 |website=GOV.UK |language=en}}

File:Rompun.jpg

Xylazine is widely used in veterinary medicine as a sedative, muscle relaxant, and analgesic. It is frequently used in the treatment of tetanus. It is not used in human medical treatment. Xylazine is similar to drugs such as phenothiazines, tricyclic antidepressants, and clonidine. As an anesthetic, it is typically used in conjunction with ketamine.{{cite journal |vauthors = Xiao YF, Wang B, Wang X, Du F, Benzinou M, Wang YX |date = October 2013 |title = Xylazine-induced reduction of tissue sensitivity to insulin leads to acute hyperglycemia in diabetic and normoglycemic monkeys |journal = BMC Anesthesiology |volume = 13 |issue = 1 |pages = 33 |pmid = 24138083 |pmc = 4016475 |doi = 10.1186/1471-2253-13-33 |doi-access = free }} In animals, xylazine may be administered intramuscularly, intravenously, and intraosseously.{{cite journal | vauthors = Ruiz-Colón K, Chavez-Arias C, Díaz-Alcalá JE, Martínez MA | title = Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: A comprehensive review of the literature | journal = Forensic Science International | volume = 240 | pages = 1–8 | date = July 2014 | pmid = 24769343 | doi = 10.1016/j.forsciint.2014.03.015 }} Subcutaneous, oral transmusocal and intranasal have been investigated but are not standard routes for xylazine administration. As a veterinary anesthetic, xylazine is typically only administered once for the intended effect before or during surgical procedures. α₂-Adrenergic receptor antagonists such as atipamezole and yohimbine may be used to reverse the effects of xylazine in animals.{{cite journal | vauthors = Kollias-Baker CA, Court MH, Williams LL | title = Influence of yohimbine and tolazoline on the cardiovascular, respiratory, and sedative effects of xylazine in the horse | journal = Journal of Veterinary Pharmacology and Therapeutics | volume = 16 | issue = 3 | pages = 350–358 | date = September 1993 | doi = 10.1111/j.1365-2885.1993.tb00182.x | pmid = 8230406 }}{{cite journal | vauthors = Murahata Y, Miki Y, Hikasa Y | title = Antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats | journal = Canadian Journal of Veterinary Research | volume = 78 | issue = 4 | pages = 304–315 | date = October 2014 | pmid = 25356000 | pmc = 4170770 }}{{cite journal | vauthors = Janssen CF, Maiello P, Wright MJ, Kracinovsky KB, Newsome JT | title = Comparison of Atipamezole with Yohimbine for Antagonism of Xylazine in Mice Anesthetized with Ketamine and Xylazine | journal = Journal of the American Association for Laboratory Animal Science | volume = 56 | issue = 2 | pages = 142–147 | date = March 2017 | pmid = 28315642 | pmc = 5361038 }}

Side effects in animals include transient hypertension, hypotension, and respiratory depression. Further, the decrease of tissue sensitivity to insulin leads to xylazine-induced hyperglycemia and a reduction of tissue glucose uptake and utilization. The effects in animals last up to 4{{nbsp}}hours.

In dogs, sheep, horses, and cattle, the half-life is very short: only 1.21–{{hsp}}5.97 minutes. Complete elimination of the drug can take up to 23{{spaces}}minutes in sheep and up to 49{{spaces}}minutes in horses. In young rats the half-life is one hour. Xylazine has a large volume of distribution of {{mvar|V}}{{sub|d}} = {{nowrap|1.9{{hsp}}–}}2.5 for horses, cattle, sheep, and dogs. Though the peak plasma concentrations are reached in {{nowrap|12{{hsp}}–}}14 minutes in all species, the bioavailability varies between species. The half-life depends on the age of the animal, as age is related to prolonged duration of anesthesia and recovery time. Toxicity occurs with repeated administration, given that the metabolic clearance of the drug is usually calculated as 7–{{hsp}}9 times the half-life, which is 4{{spaces}}to 5 days for the clearance of xylazine.

[[File:Xylazine synthesis.png|class=skin-invert-image|thumb|Xylazine synthesis adapted from Elliot & Ruehle (1986).{{cite patent |invent1=Elliott, Richard L. |invent2=Ruehle, Paul H. |number=4614798A |fdate=9 April 1985 |gdate=30 September 1986 |assign1=Vetamix |status=expired |title=Process for the production of xylazine |country=US}} (expired 9 April 2005).

]]

Xylazine is a potent α₂-adrenergic receptor agonist.{{cite journal | vauthors = Hsu WH | title = Xylazine-induced depression and its antagonism by alpha adrenergic blocking agents | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 218 | issue = 1 | pages = 188–192 | date = July 1981 | doi = 10.1016/S0022-3565(25)32650-9 | pmid = 6113279 | url = https://jpet.aspetjournals.org/content/218/1/188 | url-access = subscription }} When xylazine and other α₂-adrenergic receptor agonists are administered, they distribute throughout the body within 30 to 40 minutes. Due to xylazine's highly lipophilic nature, it directly stimulates central α₂-adrenergic receptors as well as peripheral α-adrenergic receptors in a variety of tissues. As an agonist, xylazine reduces release of norepinephrine and dopamine in the central nervous system. It does so by mimicking norepinephrine in binding to the pre-synaptic surface autoreceptors, which leads to feedback inhibition of norepinephrine release.{{cite journal |vauthors = Park JW, Chung HW, Lee EJ, Jung KH, Paik JY, Lee KH |date = April 2013 |title = {{math|α}}{{sub|2}}-Adrenergic agonists including xylazine and dexmedetomidine inhibit norepinephrine transporter function in SK-N-SH cells |journal = Neuroscience Letters |volume = 541 |pages = 184–189 |pmid = 23485735 |doi = 10.1016/j.neulet.2013.02.022 |s2cid = 46338840}}

Xylazine also serves as a transport inhibitor by suppressing norepinephrine transport function through competitive inhibition of substrate transport. Accordingly, xylazine significantly increases K_m and does not affect V_max. This likely occurs by direct interaction on an area that overlaps with the antidepressant binding site. For example, xylazine and clonidine suppress uptake of iobenguane (MIBG), a norepinephrine analogue, in neuroblastoma cells. Xylazine's chemical structure closely resembles clonidine.

It has also been reported that xylazine activates the κ-opioid receptors, with low potency, which may contribute to its effects.{{Cite journal | vauthors = Bedard ML, Huang XP, Murray JG, Nowlan AC, Conley SY, Mott SE, Loyack SJ, Cline CA, Clodfelter CG, Dasgupta N, Krumm B |date=2024-05-03 |title=Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism |journal=Addiction Neuroscience |language=en |volume=11 |pages=100155 |doi=10.1016/j.addicn.2024.100155|doi-access=free |pmid=39086495 |pmc=11290297 }}

Unlike other α₂-adrenergic receptor agonists xylazine does not have any imidazoline receptor activity. Xylazine binds at a ratio of 160:0, the lowest of all α₂-adrenergic receptor agonists and 1/10th of that of medetomidine and dexmedotimidine.

Xylazine is absorbed, metabolized, and eliminated rapidly. Xylazine can be inhaled or administered intravenously, intramuscularly, subcutaneously, or orally either by itself or in conjunction with other anesthetics, such as ketamine, barbiturates, chloral hydrate, and halothane in order to provide reliable anesthesia effects. The most common route of administration is injection.

Xylazine's action can be seen usually 15–30 minutes after administration and the sedative effect may continue for 1–2 hours and last up to 4 hours. Once xylazine gains access to the vascular system, it is distributed within the blood, allowing xylazine to enter the heart, lungs, liver, and kidney.{{cite journal |vauthors = Silva-Torres L, Veléz C, Alvarez L, Zayas B |year = 2014 |title = Xylazine as a drug of abuse and its effects on the generation of reactive species and DNA damage on human umbilical vein endothelial cells |journal = Journal of Toxicology |volume = 2014 |page = 492609 |pmid = 25435874 |pmc = 4243599 |doi = 10.1155/2014/492609 |doi-access = free}} In non-fatal cases, the blood plasma concentrations range from 0.03 to 4.6 mg/L. Xylazine diffuses extensively and penetrates the blood–brain barrier, as might be expected due to the uncharged, lipophilic nature of the compound.

Xylazine is metabolized by the liver's cytochrome P450 enzymes. When it reaches the liver, xylazine is metabolized and proceeds to the kidneys to be excreted in urine.{{cite journal |vauthors = Barroso M, Gallardo E, Margalho C, Devesa N, Pimentel J, Vieira DN |date = April 2007 |title = Solid-phase extraction and gas chromatographic–mass spectrometric determination of the veterinary drug xylazine in human blood |journal = Journal of Analytical Toxicology |volume = 31 |issue = 3 |pages = 165–169 |pmid = 17579964 |doi = 10.1093/jat/31.3.165 |doi-access = free}} Around 70% of a dose is excreted by urine. Thus, urine can be used in detecting xylazine administration because it contains many metabolites, which are the main targets and products in urine. Within a few hours, xylazine decreases to undetectable levels. Other factors can also significantly impact the pharmacokinetics of xylazine, such as sex, nutrition, environmental conditions, and prior diseases.

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In 1979, the first case of xylazine toxicity was reported in a 34-year-old male who had self-medicated for insomnia with an injection of 1g of xylazine.{{cite journal | vauthors = Carruthers SG, Nelson M, Wexler HR, Stiller CR | title = Xylazine hydrochloridine (Rompun) overdose in man | journal = Clinical Toxicology | volume = 15 | issue = 3 | pages = 281–285 | date = October 1979 | pmid = 509891 | doi = 10.3109/15563657908989878 }}

Xylazine is not regulated as a controlled substance under the Controlled Substances Act. It is sold online through distributors often without requiring proof of a veterinary license. As a commonly used veterinary medicine xylazine is probably diverted from veterinary sources. The cost to purchase Xylazine from overseas suppliers is around $6–20 per kilogram. This low price makes it attractive for dealers looking for a cheap additive that is addictive and not treatable with opiate withdrawal medications.{{cite web |title=Xylazine in Minnesota |url=https://www.health.state.mn.us/communities/opioids/documents/2023xylazinebrief.pdf |website=Minnesota Department of Health}}{{cite web |title=The Growing Threat of Xylazine and its Mixture with Illicit Drugs |website=Drug Enforcement Administration |publisher=USDOJ |url=https://www.dea.gov/sites/default/files/2022-12/The%20Growing%20Threat%20of%20Xylazine%20and%20its%20Mixture%20with%20Illicit%20Drugs.pdf}} The withdrawal can last for two weeks and has a quicker onset than fentanyl.{{cite news |title=What is 'tranq' and why do police carry wound care kits because of it? |url=https://www.masslive.com/news/2024/05/what-is-tranq-and-why-do-police-carry-wound-care-kits-because-of-it.html |access-date=11 August 2024 |work=Masslive |date=May 9, 2024}}

Xylazine is most commonly ingested as an additive with fentanyl.{{Cite journal | vauthors=Hoffman GR, Giduturi C, Cordaro NJ, Yoshida CT, Schoffstall AM, Stabio ME, Zuckerman MD | date=May 15, 2024 | title=Classics in Chemical Neuroscience: Xylazine | journal=ACS Chem Neurosci | volume=15 | issue=11 | pages=2091–2098 | doi=10.1021/acschemneuro.4c00172| pmid=38747710 }} Xylazine has also been reported in combination with medetomidine, another potent α₂-adrenergic receptor agonist.{{Cite journal | vauthors=de Andrade Horn P, Berida TI, Parr LC, Bouchard JL, Jayakodiarachchi N, Schultz DC, Lindsley CW, Crowley ML | date=October 2024 | title= Classics in Chemical Neuroscience: Medetomidine | journal=ACS Chem Neurosci | volume=15 | issue=21 | pages=3874–3883 | doi=10.1021/acschemneuro.4c00583| doi-access=free | pmid=39405508 | pmc=11587509 }} It is unknown if drug users are ingesting it knowingly. As of 2024, Seattle police report that some users wrongly believe they are consuming higher-quality fentanyl.{{cite web | vauthors = Rose D |title=Seattle Police warn that base ingredient in 'zombie drug' tranq is being sold as standalone pill |date=April 7, 2024 |work=Fox 13 Seattle |url=https://www.fox13seattle.com/news/tranq-zombie-drug-seattle}}{{cite web |title=Xylazine |url=https://oasas.ny.gov/xylazine |website=Office of Addiction Services and Supports (OASAS) - New York |publisher=OASAS |access-date=11 August 2024}}{{cite journal | vauthors = Meyer GM, Maurer HH | title = Qualitative metabolism assessment and toxicological detection of xylazine, a veterinary tranquilizer and drug of abuse, in rat and human urine using GC-MS, LC-MSn, and LC-HR-MSn | journal = Analytical and Bioanalytical Chemistry | volume = 405 | issue = 30 | pages = 9779–9789 | date = December 2013 | pmid = 24141317 | doi = 10.1007/s00216-013-7419-7 | s2cid = 23164588 }} Xylazine's street name in Puerto Rico is anestesia de caballo, which translates to "horse anesthetic".{{cite journal | vauthors = Torruella RA | title = Xylazine (veterinary sedative) use in Puerto Rico | journal = Substance Abuse Treatment, Prevention, and Policy | volume = 6 | pages = 7 | date = April 2011 | pmid = 21481268 | pmc = 3080818 | doi = 10.1186/1747-597x-6-7 | doi-access = free }} From 2002 to 2008, its use was associated with a high number of inmate deaths at the Guerrero Correctional Institution in Aguadilla, Puerto Rico.{{Cite news | vauthors = Melia M |date=5 August 2010 |title=ACLU probes prisoner deaths in Puerto Rico |publisher=Boston.com |agency=Associated Press |url=http://archive.boston.com/news/world/latinamerica/articles/2010/08/05/aclu_probes_prisoner_deaths_in_puerto_rico/ |access-date=24 August 2016}}

Xylazine's street name in the United States, particularly when it is mixed with fentanyl, is "tranq", "tranq dope" and "zombie drug".{{cite web |title=Opioid Epidemic Updates: "Frankenstein Opioids" and Xylazine-Induced Skin Ulcers |url=https://www.aafp.org/pubs/afp/afp-community-blog/entry/opioid-epidemic-updates-frankenstein-opioids-and-xylazine-induced-skin-ulcers.html#:~:text=Xylazine%2C%20which%20goes%20by%20the,is%20already%20a%20staggering%20epidemic. |website=aafp.org |access-date=23 February 2023}}

As of 2012, xylazine users in Puerto Rico were more likely to be male, under age 30, living in a rural area, and injecting rather than inhaling xylazine. Because xylazine and heroin trigger similar behavioral outcomes, the former is often secretly mixed into illegal doses of heroin.{{Citation needed|date=September 2024}} The combination of heroin and xylazine produces a potentially more deadly high than administration of heroin alone. Xylazine is also frequently found in "speedball", a mixture of a stimulant drug such as cocaine with a depressant drug such as heroin, morphine and/or fentanyl. As of 2012, causal factors underlying xylazine's increasing popularity were still unknown.

As of 2022, more information on the distribution of xylazine in the body, physical symptoms, and factors predictive of chronic use was known: when used, frequency of use depended on social or economic factors, as well as each user's subjective response to the drug's addictive properties.{{cite web |title=Research Topics - Xylazine |url=https://nida.nih.gov/research-topics/xylazine |website=National Institute on Drug Abuse |date=21 April 2022 |publisher=U.S. Department of Health and Human Services |access-date=25 January 2023}} From November 2021 until August 2022, 80% of drug paraphernalia which tested positive for fentanyl at needle exchange programs in Maryland also contained xylazine.{{cite journal | vauthors = Russell E, Sisco E, Thomson A, Lopes J, Rybak M, Burnett M, Heilman D, Appley MG, Gladden RM | title = Rapid Analysis of Drugs: A Pilot Surveillance System To Detect Changes in the Illicit Drug Supply To Guide Timely Harm Reduction Responses - Eight Syringe Services Programs, Maryland, November 2021-August 2022 | language = en-us | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 72 | issue = 17 | pages = 458–462 | date = April 2023 | pmid = 37104171 | doi = 10.15585/mmwr.mm7217a2 | s2cid = 258354168 | doi-access = free }} As of 2022, xylazine was almost invariably combined with opioids when used recreationally, and the drug produced a characteristic withdrawal syndrome which complicates treatment of addicted users.{{cite journal | vauthors = Friedman J, Montero F, Bourgois P, Wahbi R, Dye D, Goodman-Meza D, Shover C | title = Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis | journal = Drug and Alcohol Dependence | volume = 233 | pages = 109380 | date = April 2022 | pmid = 35247724 | pmc = 9128597 | doi = 10.1016/j.drugalcdep.2022.109380 }}{{cite journal | vauthors = Ehrman-Dupre R, Kaigh C, Salzman M, Haroz R, Peterson LK, Schmidt R | title = Management of Xylazine Withdrawal in a Hospitalized Patient: A Case Report | journal = Journal of Addiction Medicine | year = 2022 | volume = 16 | issue = 5 | pages = 595–598 | doi = 10.1097/ADM.0000000000000955 | pmid = 35020700 | s2cid = 245907730 }}

In April 2023, the Biden administration declared xylazine-laced fentanyl an official emerging drug threat to the nation, the first time such a label has been given. Rahul Gupta, director of the Office of National Drug Control Policy (ONDCP), said he was troubled about what he learned "about the devastating impact of the fentanyl-xylazine combination, which is growing in youth across the nation".{{Cite web | vauthors = Weixel N |date=2023-04-12 |title=White House says fentanyl laced with 'tranq' drug is 'emerging threat' |url=https://thehill.com/policy/healthcare/3945198-white-house-says-fentanyl-laced-with-tranq-drug-is-emerging-threat/ |access-date=2023-04-13 |website=The Hill |language=en-US}} According to Gupta, xylazine is the deadliest drug threat the United States has ever faced. The Drug Enforcement Administration (DEA) has seized xylazine and fentanyl mixtures in most states, finding 23% of seized fentanyl powder and 7% of fentanyl pills adulterated with xylazine.

In July 2023, the first death following xylazine use outside of North America was reported to have taken place in Solihull, England in May 22. A 43-year-old male was found dead at home with postmortem toxicology detecting heroin, cocaine, fentanyl and xylazine.{{Cite journal | vauthors = Rock KL, Lawson AJ, Duffy J, Mellor A, Treble R, Copeland CS |date= July 2023 |title=The first drug-related death associated with xylazine use in the UK and Europe |journal=Journal of Forensic and Legal Medicine |language=en |volume=97 |pages=102542 |doi=10.1016/j.jflm.2023.102542 |pmid= 37236142 |s2cid= 258859939 |issn=1752-928X|doi-access=free }} Xylazine is anticipated to make inroads in the European illicit drug market once the most recent Afghanistan opium poppy harvest has been produced and delivered, the Taliban having banned poppy cultivation in 2023.{{Cite web|url=https://www.euronews.com/health/2023/05/26/xylazine-what-to-know-about-the-flesh-eating-zombie-drug-spreading-from-the-us-to-europe|title=Xylazine: Flesh-rotting 'zombie' drug claims first victim in Europe|date=May 26, 2023|website=euronews}}

In April 2024, xylazine was reported to be present in illicit THC e-cigarettes in the UK.{{Cite journal | vauthors = Copeland CS, Rice K, Rock KL, Hudson S, Streete P, Lawson AJ, Couchman L, Holland A, Morley S |date= April 2024 |title=Broad evidence of xylazine in the UK illicit drug market beyond heroin supplies: Triangulating from toxicology, drug-testing and law enforcement |journal=Addiction |volume= 119 |issue= 7 |pages= 1301–1309 |language=en |doi=10.1111/add.16466 |doi-access=free |pmid= 38593992 }}{{Cite web|url=https://www.bbc.co.uk/news/health-68760301|title='Zombie' drug xylazine found in cannabis THC vapes in UK|date=Apr 10, 2024|website=BBC News}}

In April 2024, Seattle police reported that "tranq" was being sold as a standalone narcotic, something they had not seen before. According to Seattle police officials, their patrol officers are now on alert for people collapsing due to tranq consumption. As of May 2024, over 90% of illegally purchased opiates were adulterated with Xylazine in Philadelphia. In Massachusetts, the percentage of samples containing xylazine increased to 42%.

Police departments in 45 US states are preparing for wound care, overdose response, and creating educational materials for communities. There are still surveillance blind spots and, according to one police officer conducting educational outreach with first responders, high school students "[know] more about xylazine than paramedics, nurses, and police officers."

Xylazine overdose is often fatal in humans. Because it is used as a drug adulterant, the symptoms caused by the drugs accompanying xylazine administration vary between individuals.

The most common side-effects in humans associated with xylazine administration include bradycardia, respiratory depression, hypotension, transient hypertension secondary to α₁-adrenergic receptor stimulation, and other central and hemodynamic changes.{{cite journal | vauthors = Ball NS, Knable BM, Relich TA, Smathers AN, Gionfriddo M, Nemecek BD, Montepara CA, Guarascio AJ, Covvey JR, Zimmerman DE | title = Xylazine poisoning: a systematic review | journal = Clinical Toxicology | volume = 60 | issue = 8 | pages = 892–901 | date = August 2022 | pmid = 35442125 | doi = 10.1080/15563650.2022.2063135 | s2cid = 248264717 }} Xylazine significantly decreases heart rate in animals that are not pre-medicated with medications that have anticholinergic effects.

Xylazine administration can lead to diabetes mellitus and hyperglycemia. Other possible side-effects are areflexia, asthenia, ataxia, blurred vision, disorientation, dizziness, drowsiness, dysarthria, dysmetria, fainting, hyporeflexia, slurred speech, somnolence, staggering, coma, apnea, shallow breathing, sleepiness, premature ventricular contraction, tachycardia, miosis and dry mouth. Rarely, hypotonia, urinary incontinence, and nonspecific electrocardiographic ST segment changes occur. Following a human overdose, symptoms can last for 8–72 hours, varying based on xylazine's combined usage with other drugs.

Xylazine use can cause transient hypertension, hypotension, bradycardia, and respiratory depression lower tissue oxygenation in the skin. Thus, chronic use of xylazine can progress the skin oxygenation deficit, leading to severe skin ulceration. Lower skin oxygenation is associated with impaired healing of wounds and a higher chance of infection. The ulcers may ooze pus and have a characteristic odor. In severe cases, surgical amputations must be performed on the affected extremities.

Human tolerance to xylazine varies widely, with toxicity and fatality occurring between doses of {{cvt|40|-|2400|mg}}. Non-fatal blood or plasma concentration ranges from 0.03 to 4.6 mg/L. In fatalities, the blood concentration of xylazine ranges from trace to 16 mg/L. It is reported that there is no defined safe or fatal concentration of xylazine because of the significant overlap between the non-fatal and postmortem blood concentrations of xylazine.

Hemodialysis has been suggested as a form of treatment, but is usually unfavorable due to the large volume of distribution of xylazine.

There are no standardized screenings to determine if an overdose has occurred. Detection of xylazine in humans involves various screening methods, such as urine screenings, thin layer chromatography (TLC), gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS). As of November 2022, detecting xylazine in a drug sample requires spectrophotometry.{{cite web |title=Xylazine Public Health Advisory, November 2022 |url=https://content.boston.gov/sites/default/files/file/2023/01/BPHC%2BXylazine%2BPublic%2BHealth%2BAdvisory_November%2B2022_1.pdf |website=Boston Public Health Commission |publisher=City of Boston |access-date=25 January 2023}}

As of 1998, the α₂-adrenergic receptor antagonist atipamezole was used to reverse the effects of xylazine or the related drug dexmedetomidine in veterinary medicine,{{cite journal | vauthors = Scheinin H, Aantaa R, Anttila M, Hakola P, Helminen A, Karhuvaara S | title = Reversal of the sedative and sympatholytic effects of dexmedetomidine with a specific alpha2-adrenoceptor antagonist atipamezole: a pharmacodynamic and kinetic study in healthy volunteers | journal = Anesthesiology | volume = 89 | issue = 3 | pages = 574–584 | date = September 1998 | doi = 10.1097/00000542-199809000-00005 | pmid = 9743392 | s2cid = 25346350 | doi-access = free }} but this is not an approved medical treatment for humans, despite Phase I clinical trials in 2005.{{cite journal | vauthors = Pertovaara A, Haapalinna A, Sirviö J, Virtanen R | title = Pharmacological properties, central nervous system effects, and potential therapeutic applications of atipamezole, a selective alpha2-adrenoceptor antagonist | journal = CNS Drug Reviews | year = 2005 | volume = 11 | issue = 3 | pages = 273–288 | doi = 10.1111/j.1527-3458.2005.tb00047.x | pmid = 16389294 | pmc = 6741735 }}

As of 2001, the effects of xylazine in animals were also reversed by the analeptics 4-aminopyridine, doxapram, and caffeine, which are physiological antagonists to central nervous system depressants.{{cite journal |vauthors = Ndeereh DR, Mbithi PM, Kihurani DO |date = June 2001 |title = The reversal of xylazine hydrochloride by yohimbine and 4-aminopyridine in goats |journal = Journal of the South African Veterinary Association |volume = 72 |issue = 2 |pages = 64–67 |pmid = 11513261 |doi = 10.4102/jsava.v72i2.618 |doi-access = free}} Further research is needed to accurately identify chronic xylazine usage and standardize effective treatments. As of 2014, multiple drugs have been used for therapeutic intervention, including lidocaine, naloxone, thiamine, lorazepam, vecuronium, etomidate, propofol, tolazoline, yohimbine, atropine, orciprenaline, metoclopramide, ranitidine, metoprolol, enoxaparin, flucloxacillin, insulin, and irrigation of both eyes with saline.

The treatment after a xylazine overdose primarily involves maintaining respiratory function and blood pressure. In cases of intoxication, physicians recommend intravenous fluid infusion, atropine, and hospital observation. Severe cases may require tracheal intubation, mechanical ventilation, gastric lavage, activated charcoal, bladder catheterization, electrocardiographic (ECG) and hyperglycemia monitoring. Physicians typically recommend which detoxification treatment should be used to manage possible dysfunction involving highly perfused organs such as the liver and kidneys.

In 2022, the Food and Drug Administration (FDA) issued an alert to American healthcare providers on the risks patients face if exposed to xylazine in illicit drugs.{{Cite web | work = Center for Drug Evaluation and Research|date=2022-11-08 |title=FDA alerts health care professionals of risks to patients exposed to xylazine in illicit drugs |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-risks-patients-exposed-xylazine-illicit-drugs |archive-url=https://web.archive.org/web/20221108182938/https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-risks-patients-exposed-xylazine-illicit-drugs |url-status=dead |archive-date=November 8, 2022 |publisher = U.S. Food and Drug Administration |language=en}}

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{{refbegin}}

• {{cite book |vauthors = McCurnin DM, Bassert JM |year = 2002 |title = Clinical Textbook for Veterinary Technicians |edition = 5th |publisher = Saunders |location = Philadelphia}}
• {{cite web | publisher = Bayer Healthcare | title = Rompun Homepage | url = http://www.rompun.com:80/ | archive-url = https://web.archive.org/web/20070302155131/http://www.rompun.com:80/ | url-status = dead | archive-date = 2007-03-02 | date = 2005 }}
• {{cite web | vauthors = Wright B |url=https://www.omafra.gov.on.ca/english/livestock/horses/facts/00-063.html|archive-url=https://web.archive.org/web/20060907095904/https://www.omafra.gov.on.ca/english/livestock/horses/facts/00-063.html|archive-date=7 September 2006|url-status=dead|title = Human health concerns when working with medications around horses | work = Agdex# 460 |publisher=Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA) | date = 2000 }}

{{refend}}

• {{cite web | url=https://nida.nih.gov/research-topics/xylazine | publisher=National Institute on Drug Abuse (NIDA) |title=Xylazine| date=21 April 2022 }}

{{Hypnotics and sedatives}}

{{Adrenergic receptor modulators}}

Category:Alpha-2 adrenergic receptor agonists

Category:Analgesics

Category:Anilines

Category:Equine medications

Category:Sedatives

Category:Thiazines