Since the beginning of the COVID-19 pandemic, a disruption in access to opioid use disorder (OUD) treatment and recovery services, as well as increased social isolation and stress, contributed to a new surge of overdose deaths.  The emergence of illicit falsified prescriptions containing synthetic opioids, notably fentanyl, has contributed to this crisis

Amid these continued challenges, a new concern has emerged – xylazine. This veterinary drug, sometimes called “tranq,” has been increasingly combined with illicit opioids, complicating the already dangerous opioid crisis at a time when overdose deaths have reached all-time highs.  

Xylazine is not approved for human use and poses grave health risks when taken by humans. Adverse effects include respiratory issues, low blood pressure, slow heart rate, and tissue death. Furthermore, xylazine is also associated with physical dependence, withdrawal symptoms, and a general substance use disorder (SUD). While federal law does not classify the drug as a controlled substance (CS), some states have enacted laws or temporary orders to regulate its possession, distribution, and use. In addition, proposed legislation at both the federal and state levels is being considered to reclassify xylazine. 

Veterinarians use xylazine to sedate and relieve pain for cattle, horses, and other large animals. Xylazine is a non-opiate sedative, and although it’s similar to drugs like clonidine and dexmedetomidine which are approved for human use, xylazine lasts longer and is associated with more severe side effects.  

Understanding Xylazine

Xylazine can be combined with fentanyl or other opioids to enhance their effects and reduce the frequency of doses required to retain the desired effects. However, xylazine’s severe side effects in humans increase the risk of overdose and death when combined with opioids. Identifying xylazine-related overdoses in clinical settings has proved challenging, as symptoms appear similar to those of opioid overdoses and may not register in routine drug screenings. Furthermore, because it is not an opioid, naloxone does not reverse xylazine’s effects. In fact, the presence of xylazine may actually make naloxone less effective in reversing opioid overdoses, according to the CDC

Data from Drug Enforcement Administration’s laboratories reveal a concerning surge in xylazine-related overdose deaths across the US in 2020 and 2021 by region: 

  • Northeast: 61% increase 
  • South: 193% increase 
  • Midwest: 7% increase 
  • West: 112% increase 

The tissue damage xylazine can cause at injection sites and throughout the body is another point of concern. Injection wounds may become infected, leading to amputations or sepsis. Additionally, the drug is addictive and can create  different withdrawal symptoms from opioids that cannot be alleviated using medications commonly used to treat patients with OUD.

How the Government is Addressing Xylazine Regulation 

In spring 2023, Congress introduced the Combating Illicit Xylazine Act (S 993/HR 1839). The proposed bill would make xylazine subject to regulation as a Schedule III substance under the Controlled Substance Act. Illicit use would include any use or intended use in people and would address any diversion of xylazine from veterinary sources. Veterinary uses would remain under their current status. Statements of support for the legislation were announced by organizations such as the National Association of Attorneys General and the American Veterinary Medical Association

Other organizations, such as the National Harm Reduction Coalition, have stated that the bill would be a move in the wrong direction by further criminalizing people who use drugs. “Drug users are not seeking xylazine. It’s often mixed into drugs that they’re taking,” the director of overdose prevention policy at the organization told CNN. “So we have concerns that we’d be punishing drug users for a substance that they may not even know is found in their drug.” 

At time, the Combating Illicit Xylazine Act had been referred to committees in both the House of Representatives and the Senate. 

In addition, FDA has issued an alert for US Customs and Border Protection (CBP) to detain shipments of xylazine that appear to be adulterated or misbranded. Further, FDA’s Center for Veterinary Medicine and CBP are working to identify xylazine shipments that are packaged and declared other products. 

The ongoing opioid crisis in the US continues to evolve. According to CDC, nearly 500,000 people died from opioid-involved overdoses from 1999-2019. Xylazine’s inclusion in illicit opioids will create additional risk for those with OUD. Amid the opioid crisis, NABP will continue to monitor and report on trends and regulatory efforts to mitigate harm. 

This blog was adapted from an article that originally appeared in the November/December 2023 issue of Innovations.