Opinion | Xylazine: New Drug, Same Old Mistakes

Reports of the drug xylazine being detected in overdoses across the U.S. have been making news lately and present a new challenge in addressing our ongoing overdose crisis.

Xylazine, sometimes referred to as “tranq,” is not an opioid; it is a member of the class of medicines that agonize alpha adrenergic (α-2) receptors, which in humans are primarily used for blood pressure control but can also be used for sedation. Xylazine is not approved for human use in the U.S., and is only approved for use in veterinary medicine, where it is of significant importance.

Many medical, public health, and media reports refer to xylazine as a “zombie” or “flesh-eating” drug because it causes significant sedation and has been associated with wounds in some users. This language is not only unhelpful, but also unscientific and inaccurate, and derails honest and accurate discussions about xylazine.

What to Know About Xylazine

Despite recent attention, xylazine is not a new drug, and is not even new to the illicit drug supply. In overdose, symptoms can mimic overdoses of opioids like fentanyl, with symptoms of unconsciousness, respiratory depression, and decreased heart rate and blood pressure. While reports of “naloxone-resistant opioids” have previously been debunked, xylazine does not respond to the opioid overdose reversal agent, naloxone (Narcan), because it is not an opioid, making it challenging to treat even in medical settings. There is no current approved — or even proven — antidote for xylazine overdose.

Even though naloxone — and other opioid reversal agents — will not reverse xylazine, naloxone should still be used in overdose situations because it is most commonly found with fentanyl. As a result, reversal of the opioid component will still be helpful and potentially lifesaving. It is just as critical as ever to increase naloxone access and availability.

The majority of opioids sold on the street (usually sold as “heroin” although fentanyl has predominated for years now with heroin being a rarity) are contaminated with other compounds. These are often described as “cutting agents” because they are used to potentiate the opioid effect or reduce the amount needed to get an effect, if not simply replaced with other drugs. This has been the case with fentanyl, and now seems to be happening at times with xylazine as well. Xylazine, however, seems to be primarily found mixed with fentanyl. Outside of the Caribbean, it is almost never used on its own, and also does not seem to be sought out by users.

Many of these features are reminiscent of the emergence of fentanyl in the heroin supply, which not only created new challenges but was not even a desired drug for most users. The response to xylazine in street drugs is also reminiscent of the many knee-jerk responses to fentanyl and synthetic opioids that have not proven to be helpful in reducing overdoses. We have an opportunity to learn from past mistakes instead of repeating them.

A Fresh Chance to Address a Fresh Drug Crisis

So far, primary political efforts have focused on drug scheduling and blanket bans at the federal and state level, with some already passed in certain states. Because xylazine is not approved for any human use and is not even being diverted from the legal veterinary supply, it is already considered illegal and it is unclear what these blanket bans will accomplish. In all likelihood, they will simply add additional criminal charges to already marginalized people who use drugs, and impose significant extra burdens on use of the drug in veterinary medicine. This will also make scientific research into its effects and potential treatments much more difficult.

A Smarter Response

An evidence-based, public health response makes more sense than doubling down on failed policies. The primary reason fentanyl took over the drug supply was the focus on supply-side-only interventions like drug bans, seizures, and even destruction of the opium (heroin) supply, without addressing the demand for drugs at home. While it is unclear why xylazine is increasing in prevalence, targeted criminalization efforts toward fentanyl could certainly be a contributing factor.

To better address demand, we still need to expand treatment resources, but we cannot forget to focus on reducing the harms of these already-prevalent drugs. In addition to naloxone, other critical interventions like test strips for xylazine as well as ensuring nobody uses alone — which is a significant risk factor for fatal overdose — remain woefully underutilized. The best way to prevent overdose deaths would be through widespread implementation of overdose prevention centers (e.g., supervised consumption sites).

The single greatest reason our drug supply has become so toxic is because criminalization drives distributors and dealers and users towards more potent, more discrete, and more dangerous drugs. Xylazine is only one of many drugs to emerge in recent years (the synthetic opioids known as nitazenes being another example), presenting additional problems and being met with nearly identical, unhelpful responses. We have almost a century of data on criminalization policies of the street opioid supply and results showing consistently negative outcomes, including record breaking overdose deaths year after year, including another record breaking 109,680 deaths in 2022.

Instead of doubling down on failed policies and accepting hundreds of thousands of dead Americans, it is time to seriously consider a paradigm shift in our response. This includes not only decriminalization to allow for more harm reduction approaches and research, but also legalization, which is the only way to ensure that drugs can be regulated for safety against such adulterants. If we do not learn from our past mistakes — and start listening to the science — then we are doomed to continue repeating them and to continue failing our fellow citizens.

Ryan Marino, MD, is a medical toxicologist, addiction medicine specialist, emergency physician, and assistant professor at Case Western Reserve University School of Medicine.