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What Clinicians Can Do About the Rise of the “Zombie Drug”

Op-Med is a collection of original articles contributed by Doximity members.

When I was in medical school, fentanyl was a major topic of conversation and training. The recent rise of another drug, xylazine, has reminded me of this time, with an added layer of fear and uncertainty. Xylazine, commonly known as “tranq,” has also been referred to as the “zombie drug” — it has both a sedative effect and is also associated with skin ulcerations, which can lead to more severe health complications if left untreated. Xylazine-positive overdoses have been skyrocketing; a DEA report from 2022 showed increases in all regions of the U.S. from 2020 to 2021, and a CDC report from 2022 showed an increase of 276% in xylazine-positive overdoses from January 2019 to June 2022. Below, I offer an introduction to xylazine and describe the current efforts to combat its rise.

What Is Xylazine?

Xylazine is a non-opioid sedative with analgesic and muscle relaxant effects, approved for use as a veterinary tranquilizer but not for use in humans (studies of its use as an antihypertensive were discontinued due to adverse effects). It is an alpha-2 receptor agonist active both centrally and peripherally, and given its different mechanism of action, does not respond to opioid antagonists such as Naloxone. As a street drug, it is being mixed with other substances such as fentanyl; therefore, its use is often unintentional. Recent mice studies have shown that the combination of xylazine with fentanyl potentiates its lethality, posing significant concerns for the rise in use observed over the past couple years. 

What is the Government Doing to Combat It?

In response to this alarming trend, the White House released a statement in April 2023 designating fentanyl that has been “adulterated or associated with xylazine as an emerging threat to the United States.” There are active efforts underway at the state and federal levels to increase monitoring, to promote harm reduction, and to allow for further regulation. 

Currently, xylazine is not classified as a controlled substance under the Controlled Substances Act (CSA) — in short, this means that the DEA does not have the authority to regulate it. It is, however, regulated via the FDA, and policies may also vary depending on the state. There are several pieces of legislation that have been introduced to change this. Some have proposed classifying xylazine as a Schedule III drug under the CSA; Schedule III drugs are considered to be at intermediate risk of abuse (fentanyl is considered to be a Schedule II drug, with higher abuse potential but some role for medical use, and Schedule I drugs are at the highest risk, with no accepted medical use). The Tranq Research Act was signed into law in 2023, requiring the National Institute of Standards and Technology to support increased research on xylazine, in the hopes of furthering detection and treatment options. 

What Can Clinicians Do About It?

As clinicians, one of the major ways we can make an impact is through advocacy at the state level. In New York City, where I am currently completing my training, 19.1% of opioid overdose deaths in 2021 involved xylazine. As a result, legislation has been proposed in New York State to designate xylazine as a controlled substance, specifically a Schedule III depressant. Another bill proposes its designation as a Schedule I controlled substance. Yet another bill would prohibit the sale of xylazine to minors, and without proof of the purpose of its use. Getting involved in state medical societies can be an effective way for clinicians to get facetime with our local legislators, and to make them aware of what our patients have been experiencing.

In addition, there is currently movement in New York State toward improving testing options. Clinicians — and state residents — are now able to order test strips for free online, which can detect the presence of xylazine in other substances. 

However, clinicians across the country are still facing a number of challenges in managing the consequences of xylazine use. With limited testing options, there may be a delay in treating patients and recognizing the contribution of xylazine to the clinical picture. It is likely that cases are being missed in the hospital setting and therefore being inadequately treated; xylazine is not often included in standard urinary toxicology screens. Additionally, xylazine has a short detection window due to its rapid elimination, further limiting detection. Finally, there is limited clinical data regarding treatment options for acute withdrawal symptoms; current efforts typically utilize a combination of alpha-2 agonists such as clonidine, guanfacine, and dexmedetomidine, in addition to other medications such as benzodiazepines. 

When it comes to harm reduction for xylazine use, making our patients aware of the specific risks associated with the drug is paramount. Chronic xylazine use leads to necrotic skin ulcerations, which can place patients at risk of additional adverse health outcomes. It may also limit patients’ options for outpatient treatment facilities, which are often not equipped to treat these severe wounds. It is important to explain these additional consequences to patients, and to provide basic education on wound stages and recognizing signs of necrosis. 

In addition, providing patients with testing strips (or telling them where to find them) is an excellent harm reduction step. Correcting any misinformation about Naloxone is also key; while Naloxone will not reverse xylazine effects, given the frequent combination of opioids and xylazine, it is still important for patients to know about and to use. Educating our patients in this manner will go a long way toward enhancing their safety.

Across the country, this “zombie drug” threatens to amplify the opioid epidemic we have been responding to for years. As clinicians, we bear a responsibility to educate ourselves and to respond, whether it be at the individual, the local, the state, or the federal level.

Have you seen an uptick in xylazine-positive overdoses in your area? Share in the comments!

Dr. Avneet Soin is a psychiatry resident in New York City. She is interested in consultation liaison psychiatry and advocacy work, and in her free time enjoys reading and exploring the dessert scene in NYC! Dr. Soin is a 2023–2024 Doximity Op-Med Fellow.

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