Researchers Dr. Robyn Jordan (UNC Psychiatry, Addiction Medicine), Dr. Zoe McElligott (UNC Psychiatry, Bowles Center for Alcohol Studies) and Dr. Nabarun Dasgupta (Gillings School of Global Public Health) partner to take on the evolving drug supply issues, recognizing that the addition of xylazine to fentanyl is likely what’s creating provider challenges with suboxone inductions.
CHAPEL HILL, NC – Our country is facing an opioid overdose epidemic. A recorded 105,452 overdose deaths occurred in the United States in December of 2022, according to the Centers for Disease Control and Prevention (1).
The facts:
(2). From 2019-2020 Opioid-involved death rates increased by 38%.
(3). The Centers for Disease Control and Prevention estimates that 187 people die every day from an opioid overdose.
(4). The U.S. Food and Drug Administration is warning healthcare professionals of the risks to patients exposed to xylazine in illicit drugs.
(5). Xylazine is a powerful sedative principally targeting the α2-adrenergic receptor that has veterinary use.
Clinicians at the UNC Addiction Medicine Program are seeing more and more patients exposed to xylazine, which gives the opiates “legs”. Because fentanyl is a short-acting opioid as compared to heroin, it has been hypothesized that xylazine was added to fentanyl to mimic some of the qualities of heroin. The significance of xylazine is that it seemingly creates more challenges for withdrawals, worsens symptoms, and makes it even more difficult to treat addiction. Xylazine and fentanyl drug mixtures place users at a higher risk of suffering fatal drug poisoning.
Treating addiction with evidence-based medications is the most powerful way to prevent overdose deaths, HIV and hepatitis infection, and drug-related crime. The problem is, we currently lack a full understanding of how xylazine and fentanyl interact in the body and brain. Dr. Robyn Jordan, Director of UNC Addiction Medicine Program and NCSAM Chapter President, says “We think xylazine is here to stay.” Dr. Jordan, partnered with Dr. Zoe McElligott, a pre-clinical researcher and Associate Professor at UNC Department of Psychiatry and Bowles Center for Alcohol Studies, and Dr. Nabarun Dasgupta, an epidemiologist and harm reduction specialist, Innovation Fellow at Gillings School of Global Public Health, with the aim to learn how xylazine works on its own, how it works combined with fentanyl and if it works the way we suspect it does.
Drs. Jordan, McElligott, and Dasgupta are a translational research team aiming to use information gleaned from street drug analysis and rodent models to inform clinical decisions. Dr. Dasgupta provides a detailed chemical analysis of street drugs currently used in the community, Dr. Jordan is providing the clinical perspective, and Dr. McElligott is able to use their information to direct experiments with mouse models. They anticipate they will be able to use Dr. McElligott’s pre-clinical models to help direct clinical practice.
In discussing the evolving drug supply, they recognized that the addition of xylazine to fentanyl is likely what is creating the challenges with suboxone inductions in treatment clinics. The team collaborated on a presentation for the Governor’s Institute’s Annual Addiction Medicine Conference to highlight this translational collaboration (pictured).
“Buprenorphine/naloxone (Suboxone) is an evidence-based medication known to save lives of people with Opioid Use Disorder. Initiation of buprenorphine/naloxone (Suboxone) requires a person to first enter opioid withdrawal. Once the person is in mild/moderate withdrawal, they can take a dose of buprenorphine/naloxone (Suboxone) and their withdrawal symptoms will improve”, says Dr. Jordan. “Beginning Spring of 2021, we noticed that initiating the first dose of buprenorphine/naloxone (Suboxone) resulted in extreme worsening of withdrawal symptoms, a process known as precipitated withdrawal, which is incredibly uncomfortable and can result in the person no longer wanting this life-saving medication. This meant that our traditional protocols for initiating buprenorphine/naloxone (Suboxone) were much less reliable.” In addition to managing fentanyl withdrawal, the current situation requires also contending with xylazine withdrawal.
“Our street drug analysis lab analyzes samples from 110 harm reduction programs and health departments. With this frontline view, we are able to identify emerging illicit drugs very rapidly” Dr. Dasgupta says. “As we identify new substances, we bring them to the attention of Dr. McElligott’s team. Their experimental methods allow us to rapidly understand the pharmacology of the latest drug trends, allowing us to provide information back to public health authorities and community groups in real time. Completing the circle, our collaboration with Dr. Jordan dovetails to allow clinical translation. This efficient and collaborative cycle allows us to prevent health harms among the citizens of North Carolina.”
Dr. McElligott adds, “For several years I have studied how opioids can regulate the α2-adrenergic receptor system, the addition of xylazine to the drug supply complicates this picture in our models, because these two receptor systems are now engaged at the same time, and indeed there are neurons in the brain that express both α2-adrenergic receptors and opioid receptors. My team is already obtaining results with our investigations of xylazine that are surprising and providing novel insights into how these substances may interact with neural systems to alter the clinical landscape. We are continuing to collect data, and hope to share our findings very soon.”
The UNC Addiction Medicine Program is expanding access to Suboxone in rural areas of North Carolina through the Addiction Mobile Unit in partnership with local stakeholders. This grassroots effort is backed by community support and several local agencies supporting the mobile unit in areas where drug use is stigmatized and support for addiction is harder to find.
If you or someone you know is struggling with addiction please visit the Substance Treatment and Recovery (STAR) website. Those interested in learning more about this research can contact Dr. Jordan at her email, robyn_jordan@med.unc.edu.
Sources
- https://blogs.cdc.gov/nchs/2023/05/18/7365/
- https://www.cdc.gov/opioids/basics/epidemic.html
- https://files.asprtracie.hhs.gov/documents/aspr-tracie-opioids-faq.pdf
- https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-risks-patients-exposed-xylazine-illicit-drugs
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361038/