In response to the rapid escalation in the detection of xylazine in the unregulated drug supply, in April 2023, the White House designated fentanyl contaminated with xylazine an "emerging threat" and ONDCP released a National Response Plan in July to coordinate a government-wide response. NIDA’s Division of Therapeutics and Medical Consequences released a Notice of Special Interest (NOSI): Xylazine—Understanding Its Use and the Consequences (NOT-DA-24-012). This funding opportunity encourages research on the prevalence and consequences of xylazine co-use with opioids or opioid/stimulant combinations and research into how xylazine impacts treatment of opioid use disorders and overdose. On June 14, 2023, the National Institute on Drug Abuse (NIDA) Center for the Clinical Trials Network (CCTN) convened health care professionals and federal partners to review current practices in xylazine-related testing, treatment, and wound care to inform evolving best-practices in the field and a xylazine-opioid research agenda. A recording and summary of the meeting, “Managing Patients Taking Xylazine-Adulterated Opioids in Emergency, Hospital, and Addiction Care Settings,” is available. On September 26, 2023, the CCTN convened the “Xylazine Discussion Forum” (the Forum) to provide a venue for CTN researchers and community members to discuss research needs to address this emerging threat. After presentations from experts, there is a Question-and-Answer session.
The meeting is opened by CTN Steering Committee Chair Lisa Marsch, Ph.D., who moderates the Forum. CCTN Director Betty Tai, Ph.D., welcomes participants and thanks the experts and NIDA staff members who organized the Forum. CCTN Associate Director Kristen Huntley, Ph.D., provided introductory remarks, summarized the June 14 meeting to set the stage for the Forum, and introduced the speakers.
Jeanmarie Perrone, M.D., University of Pennsylvania, and Rachel Haroz, M.D., Cooper Medical School of Rowan University
Dr. Perrone reviews the main lessons learned and highlights the research questions that emerged from the June 14 meeting. Little research is available to describe the clinical effects of xylazine, either alone or when mixed with fentanyl and other drugs. She highlights that assessing the xylazine landscape is difficult because the amount of xylazine in the illicit drug supply varies greatly by geographic location.
Dr. Haroz discusses xylazine-related wounds and describes emerging practices for wound care for patients exposed to xylazine and opioids, noting that it is possible for wounds to heal with the appropriate treatment. Routine testing of patients for xylazine exposure is not yet standard practice in emergency departments (EDs). Xylazine test strips with good sensitivity and specificity are now available, but there are many questions about the best way to use them.
Dr. Perrone and Dr. Haroz list selected resources on xylazine.
Presentation 2: An Update on the Toxicology Investigators Consortium (ToxIC) Research Program on Xylazine
Paul M. Wax, M.D., FACMT, Executive Director, American College of Medical Toxicology
Dr. Wax discusses ToxIC—a multi-center research consortium of medical toxicologists, which has a core registry of about 100,000 cases—and three of its relevant projects: (1) the Fentanyl Analog (Fentalog) Study, (2) the Drug Overdose Toxico-Surveillance Reporting Program, and (3) the Real-World Examination of Naloxone for Drug Overdose Reversal (RENDOR). Current ToxIC data indicates that about a quarter of blood samples from people presenting to EDs with nonfatal suspected opioid-involved overdoses have been exposed to xylazine. He highlights the complexity of the xylazine-exposure landscape—as blood tests show the presence of multiple drugs in virtually all cases and the time of drug use is typically not known.
The discussion period features questions about the experiences of individuals using xylazine, recent findings on xylazine from the animal research literature, the profile of intentional veterinary xylazine overdose from case reports in the 1980s, and xylazine withdrawal symptoms. The discussion also covers the paucity of data on the effects of xylazine on pregnant women and neonates, as well as some key areas of future research. The experts emphasize that the focus should be on fentanyl—as this drug rather than xylazine currently drives overdose deaths—particularly ensuring naloxone use for overdose reversal and appropriate care of patients.
Dr. Marsch and Dr. Huntley thank speakers and participants for their contributions and discussion.
Link to Full video: https://youtu.be/KIo2kOUpUJo