By Peter Galvin, MD
As if the epidemic of illicit drug overdoses from fentanyl weren’t enough, a new drug has emerged recently that is adding to the problem, especially here in the Northeast – xylazine. It is an alpha2-agonist, originally developed as an antihypertensive medication in the same class as clonidine. During its clinical trials, xylazine was deemed to have too many side effects and was never approved for use in humans. The FDA, in 1972, did approve it for use in veterinary medicine as a sedative. Centrally acting alpha2-agonist medications inhibit the release of epinephrine and norepinephrine. The effects on the central nervous system include sedation, analgesia, and euphoria, and the effects on the vascular system include reduced heart rate and blood pressure. They are sometimes used to lessen the symptoms of opioid withdrawal. Regular use of xylazine can cause physiological dependence, and the withdrawal symptoms may be severe and include irritability, anxiety, and dysphoria. The withdrawal symptoms are not alleviated by opioids, and the severity of these symptoms may compel people to continue using it as discontinuation without assistance isn’t feasible.
Xylazine has entered the illicit drug supply as an additive to fentanyl. It can be used orally, by smoking, snorting, or intramuscular, subcutaneous, or intravenous injection. Its duration of effect is longer than fentanyl, therefore the addition of xylazine to fentanyl probably enhances the euphoria and analgesia induced by fentanyl, thereby reducing the frequency of use. The first reported illicit use of xylazine occurred in Puerto Rico around 2001. Initially, it was used in polydrug combinations, commonly known as speedball, containing a stimulant (cocaine or amphetamine) and an opiate (heroin, morphine, or fentanyl). Its use with fentanyl has been spreading rapidly throughout the country and is known as “tranq” in Philadelphia. In 2021, xylazine was found in 90% of illicit drug samples in Philadelphia. According to CDC data, the number of drug-poisoning deaths in the US involving xylazine grew from 260 in 2018 to 3480 in 2021.
One problem is that clinicians may not recognize the signs of xylazine intoxication (central nervous system depression, low blood pressure and low heart rate) because they are not aware of its growing use. Another problem is that while naloxone may reverse opioid respiratory depression, it has no effect on xylazine overdosage. In fact, there is no xylazine-reversal agent approved for use in humans. In addition to its acute effects, xylazine is also associated with severe necrotic skin ulcerations. These ulcerations are different from the wounds people who inject drugs may get. Skin injury may occur at or remote from the site of skin injection and may occur irrespective of the mode of drug use. These ulcerations can be severe, causing a person to seek medical care and often require extended hospital stays including skin grafting. But these patients may leave the hospital prematurely due to the severity of xylazine withdrawal symptoms.
The White House Office of National Drug Control Policy declared xylazine, particularly the use of fentanyl adulterated or associated with xylazine (FAAX), an emerging threat on April 12 of this year. The goal is to recognize the threat of xylazine to the public health and take action before it worsens and undermines the efforts to reduce illicit fentanyl use.
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