Xylazine a New Potentially Fatal Addition to Other Drugs of Abuse

April 09, 2013

By Lorraine L. Janeczko

NEW YORK (Reuters Health) Apr 09 - Users of illicit drugs are now combining xylazine with other drugs of abuse and may be increasing their risk of death, according to new research.

"Xylazine is a veterinary anesthetic known as 'horse anesthesia' that is dangerous in humans. Over the last couple of years xylazine has been seen as an adulterant in heroin, and more recently cocaine, sold particularly in Puerto Rico," said Dr. Timothy J. Wiegand, a medical toxicologist and emergency medicine physician at the University of Rochester Medical Center (URMC) and Strong Memorial Hospital in Rochester, New York, in an email to Reuters Health.

"The fact that it is now being found in a large number of patients who die due to heroin and/or cocaine indicates that xylazine has become a very common adulterant," he added. Dr. Wiegand was not involved in the study.

Xylazine has no known antidote. Current treatment options include only supportive efforts to maintaining respiratory function and blood pressure, said study author Kazandra Ruiz-Col�n, forensic chemist at the Medico-Legal and Toxicology Investigation Division of the Puerto Rico Institute of Forensic Sciences in San Juan, in an email.

She added that while adulteration of illicit drugs has become an epidemic health concern, "No publication exists about the prevalence of xylazine in postmortem cases, aside from references that related xylazine with speedball (heroin and cocaine mixture) users."

In a poster March 16 at the American College of Medical Toxicology Annual Scientific Meeting in San Juan, Puerto Rico, she and her colleagues reported on the prevalence of xylazine in postmortem cases related to heroin and cocaine intoxication.

The researchers retrospectively studied 75 cases submitted to their laboratory from 2008 to 2010, re-analyzing them for xylazine. They selected cases based on positive immunoassay results for cocaine and opiates and the circumstances of death.

They analyzed blood samples for xylazine, free morphine, 6-acetylmorphine (6-AM), codeine, cocaine and benzoylecgonine (BE) by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Free morphine, 6-AM, codeine, cocaine and BE were initially confirmed by gas chromatography-mass spectrometry (GC-MS) as a routine in the toxicology laboratory.

In 36 out of 75 postmortem cases (48%), xylazine was found in combination with heroin metabolites and/or cocaine metabolites. The 36 subjects ranged in age from 22 to 67; 32 (89%) were male.

Xylazine concentration in postmortem blood ranged from 0.01 mg/L to 0.97 mg/L.

According to the literature, the authors wrote, xylazine dosages known to produce human toxicity and fatality vary from 40 to 2,400 mg, with postmortem xylazine blood concentrations ranging from trace to 16 mg/L and non-fatal blood or plasma concentrations ranging from 0.54 to 4.6 mg/L. This overlap of postmortem concentrations between fatal cases and the non-fatal cases means there is no defined safe, toxic or fatal concentration.

Of the 37 known cases of xylazine toxicity in humans, consumption was accidental, suicidal, homicidal, or intentional, and over 50% of uses resulted in death, the authors wrote in their poster.

Chronic users of xylazine as an adulterant deteriorate physically, and the literature shows some similar pharmacologic effects between xylazine and heroin in humans. These similar pharmacologic effects may create synergistic effects in humans, the authors observed.

Ruiz-Col�n said she would like to see pharmacokinetic studies of xylazine in humans, to understand the onset, duration, and intensity of its action.

"Knowing the pharmacokinetics of xylazine in humans, the drug interaction between xylazine and heroin, cocaine, methadone, buprenorphine and other drugs would be particularly important so we can understand how to treat patients during desintoxication," Ms. Ruiz-Col�n said.

"Xylazine, a powerful veterinary anesthetic similar to anesthetics used in intensive care units on the United States mainland, can potentially intensify the withdrawal syndrome in users who abstain from heroin. We think it makes the drug mixture more toxic or more lethal in overdose. Injection of xylazine has been associated with more ulcers, wound infections and other complications of IV drug use, Dr. Wiegand said.

He observed that in Puerto Rico, the heroin is 'cut' (adulterated) with xylazine, intensifying the intoxication and contributing to more severe drug addiction and dependence because regular use of both heroin and xylazine will make the body withdraw from both.

"Xylazine causes profound sedation and dissociation and intensifies the intoxication and sedation already caused by heroin, with bradycardia, hypotension, increased sedation and coma, etc. Cocaine users combine it as well to give balance to the stimulant effect of cocaine in a 'poor-man's speedball.' It also contributes to more severe physical symptoms of dependence and withdrawal if the drug is not available or is suddenly stopped," he added.

"We don't know whether xylazine contributes to death or makes the use of cocaine/heroin more toxic," he said.

"I've recently seen three patients in my clinic in Rochester, New York, who have come from Puerto Rico with drug dependence (heroin and cocaine primarily) who were also using xylazine. It may become an issue on the U.S. mainland as xylazine is used as an agent to 'intensify' the effects of heroin or cocaine and it increases in prevalence," he commented.

In a related study presented at the meeting, Luz A. Silva-Torres and her colleagues reported finding xylazine in seized drug and biological fluids, indicating that it is sold as a drug of abuse to the addicts of Puerto Rico.

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