Produced in conjunction with the Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV

The lethal mixture of xylazine and fentanyl, also known as Tranq dope, may sound unfamiliar to many, but its impact is harming people who use drugs nationwide. Xylazine, approved by the U.S. Food and Drug Administration for veterinary use as a sedative, has become a major component in the illicit drug trade. When consumed by humans, xylazine causes sedation, leading to profound health risks ranging from difficulty breathing to dangerously low blood pressure and even death, according to the Centers for Disease Control and Prevention (CDC). 

Xylazine has earned the ominous nickname of “Frankenstein Opioid” because of the deep wounds and ulcers it inflicts on users. As of March 2023, the additive had been found in drug seizures in 48 states. Drug-poisoning deaths involving xylazine soared 1,238% in the U.S. from 2018 to 2021, according to the CDC, but it is unclear whether xylazine was responsible for increasing deaths or is simply found as a contaminant along with synthetic opioids. 

LDI Senior Fellow Michael Ashburn, along with Rahul Gupta, the Director of the White House Office of National Drug Control Policy (ONDCP), and David R. Holtgrave of ONDCP and Johns Hopkins University, provided insight to the White House on the emerging threat of xylazine. 

“We need much more robust epidemiological data” to give public health officials timely and robust information to guide decisions, Ashburn and Holtgrave wrote. Health officials also need to share best practices to reduce harm, treat withdrawal symptoms and the wounds, and reduce the xylazine supply. 

Building on this work, the White House released the “Fentanyl Adulterated or Associated With Xylazine Response Plan”, which lays out six action areas, including testing, data collection, evidence-based prevention, harm reduction, treatment, supply reduction, scheduling, and research.

To learn more about xylazine and the federal government’s plan to end its harmful impacts, I spoke with LDI Senior Fellows Michael Ashburn and Margaret Lowenstein, along with David Holtgrave.

Can you tell us more about the response plan?

Ashburn and Holtgrave: The White House Office of National Drug Control Policy (ONDCP) published the response plan following the formal designation of xylazine-laced fentanyl as an emerging threat. The plan includes an overview of federal efforts related to epidemiology, testing, evidence–based care, interdiction of illicit supply, possible regulatory action, and support for xylazine-related research.  Many local, state, and federal governmental organizations have already taken significant steps related to xylazine. However, there is much more work to do.

What changes should we make to restructure the health system and remove barriers for patients dealing with xylazine addiction at the federal, state, and local levels?

Ashburn and Holtgrave: There is an urgent need to develop and implement evidence-based guidelines for the treatment of xylazine withdrawal.  While several institutions have published their own organizational guidelines, they need to be rapidly shared and outcome data collected and used to update the guidelines.  Likewise, we need to learn much more about the xylazine–associated skin injuries and improve the care provided to individuals with these wounds. Finally, we need to know more about how to treat patients with presumed xylazine substance use disorder.

There are many challenges to caring for individuals using xylazine.  This starts with supporting harm reduction efforts in providing first–line, community-based care for individuals who are using drugs, including xylazine. The resource needs for persons using fentanyl adulterated with xylazine may include safe housing, adequate food, and basic care, including access to showers, bathrooms, and clean clothes. These organizations can also provide effective wound care, but may not be able to meet all of the real needs of the individuals they serve.  Such efforts will require sustained efforts from local, state, and federal governments to bolster health systems and community organizations efforts.

What is driving the proliferation of xylazine in opioids?

Ashburn and Holtgrave:  We are seeing a shift to illicit synthetic drugs, which are manufactured and produced in laboratories. As part of this shift, the drug supply has become more dynamic, introducing new illicit synthetic drugs into the supply. Xylazine appears to have strong addictive properties, making withdrawal difficult, especially when combined with opioid addiction due to fentanyl. We believe that xylazine is coming from online vendors overseas, including those in China, and is mixed into drugs in the U.S. To a lesser extent, some drug traffickers are also mixing xylazine into fentanyl in Mexico and then importing it to the U.S. Therefore, the recent national response plan to fentanyl adulterated with xylazine calls for further specifying the illicit supply chain and developing strategies for preventing illicit xylazine.

What are the positives of the Fentanyl Adulterated or Associated With Xylazine Response Plan?

Lowenstein: This report helps bring attention to this new challenge we’ve been seeing for several years in Philadelphia, which is often the bellwether for trends in the drug supply nationally. And it’s important that we understand and rapidly respond to the impacts we’re seeing from xylazine as it spreads across the country.  

The report highlights some significant challenges, including the need for research and rapid dissemination about the effects and evolving treatment of xylazine exposure. It also highlights the need to bolster  care delivery models to address xylazine complications, and I applaud the recognition that community organizations will likely be the first to interface with patients exposed to xylazine and are key partners in this effort.

Building on the theme of community partners, what is your best advice for local public health organizations in dealing with xylazine?

Ashburn and Holtgrave: Local public health organizations are doing critically important work addressing xylazine-related issues. It is important to note that the ongoing fentanyl crisis and the growing issues related to xylazine, are coming on the heels of the COVID-19 pandemic. Public health resources are limited, and people are tired. Nonetheless, local public health organizations are starting to refocus again on fentanyl and now toward xylazine. This effort begins with enhanced monitoring and data collection so that public health decisions are data-driven. Partnering with community organizations and health care providers is critical.  Further, naloxone (Narcan) still has a key role in addressing the fentanyl epidemic even if xylazine is adulterating the fentanyl; naloxone is not a reversing agent for xylazine which is not an opioid, but naloxone is still critically important to address opioid overdoses.

What are important next steps? 

Lowenstein: Xylazine is the latest in a series of evolving threats that have emerged in our drug supply. We need to think holistically, integrating surveillance and rapid dissemination about harm reduction and treatment as new substances emerge. Efforts to address xylazine cannot be divorced from challenges involving fentanyl and other synthetic drugs. In Philadelphia, most fentanyl is contaminated with xylazine, and many people who use drugs know that, but there is little they can do to control it. We need to better understand strategies to reduce xylazine’s harms as well as couple xylazine strategies with those for opioid use and substance use in general. Also, since law enforcement strategies have been largely unsuccessful in curtailing drug use or impacting public health, it seems unlikely that policing will have a significant impact. 

We also need better care delivery models for xylazine complications – especially wounds – along with substance use. Currently, many addiction treatment facilities aren’t equipped for wound care and many places that provide wound care do not treat substance use. This leaves patients with few options and makes it hard to recover from either addiction or its medical complications. We need care delivery models that are equipped to address both simultaneously, especially in low-barrier, non-stigmatizing settings. 

Finally, we must have effective public health messaging about xylazine. One of my biggest worries is the messaging out there that naloxone (Narcan) doesn’t work for overdoses involving xylazine. Naloxone does not reverse the effects of xylazine, but xylazine-involved overdoses also involve opioids, which we treat with naloxone. We need to double down on efforts to educate communities that naloxone can and should be used for any suspected overdose.

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