XYLAZINE – A “ZOMBIE STREET DRUG” CRISIS

Viktoria Shihab, M.D., R.D., M.P.H. – Extern and Researcher
Sandy Elsabbagh, M.B.B.Ch.
Steven Lippmann, M.D. – Emeritus Professor, University of Louisville School of Medicine

Following its discovery in 1962, xylazine was trialed as an antihypertensive agent, but determined to be unsafe for human consumption.1-3 Ten years later, this pharmaceutical received approval to enter the market as a non-narcotic veterinary sedative, muscle relaxant, and analgesic.4 Since the early 2000s, xylazine has attracted attention as a dangerous opioid adulterant in Puerto Rico.By 2021, xylazine was detected in 91% of fentanyl and/or heroin samples in Philadelphia.2 Xylazine prevalence continues to rise and contribute to the danger of drug overdoses throughout the U.S.A., especially in the Northeastern states.2

           Xylazine functions as an alpha-2A adrenergic receptor agonist, decreasing norepinephrine and epinephrine via a negative feedback mechanism and increasing the risk of bradycardia and hypotension.It also activates alpha-2B adrenergic receptors, constricting the peripheral skin vasculature.5,6 Its sympatholytic properties combined with vasoconstriction often result in cutaneous pathology with infection. Xylazine is notorious for inducing ulceration, abscesses, and necrosis that may require surgical intervention. This side effect in users has earned xylazine its “zombie street drug” media name.5

The veterinary tranquilizer poses a high risk for treatment-resistant overdose. Naloxone, prescribed to treat opioid overdose, is much less effective in treating opioids mixed with xylazine as xylazine has no known antidote.7 Overdose deaths from fentanyl mixed with xylazine have increased by 276% from 2019 to 2022.This number might be underreported due to coroner inconsistency with testing for and reporting the drug on death certificates.8 Xylazine has an addiction potential. It is often mixed with opioids because it is cheap, poorly regulated, and potentiates the effect of narcotics;  it can be acquired for <$20/kg from Chinese suppliers online. Often, many users are unaware of having ingesting it.4,10 Besides being added to narcotics, xylazine is frequently mixed with other drugs like cocaine, benzodiazepines, and ketamine; this further complicates clinical recognition and treatment of xylazine intoxication.10

For over a decade, xylazine has been identified as a major public health concern.11 In response to the rising fentanyl overdose crisis, in March 2023, the federal government called for an investment of >$46 billion in National Drug Control Programs.12 By April 2023, the government designated fentanyl combined with xylazine as an “Emerging Threat to the United States”.13  In July 2023, the White House Office of National Drug Control Policy released a National Response Plan.14 Under this proposal, various agencies are working to restrict xylazine’s entry into the U.S.A. and only for its intended veterinary purposes. However, online purchases remain difficult to regulate.The strategy also includes expanding xylazine research, standardizing the testing, reporting of cases, establishing an evidence-based treatment protocol, and developing an antidote. It also aims to educate the public, healthcare providers, and researchers about the dangers of this drug.14

References

1.    Greene, S. A., & Thurmon, J. C. (1988). Xylazine–a review of its pharmacology and use in veterinary medicine. Journal of Veterinary Pharmacology and Therapeutics, 11(4), 295–313. https://doi.org/10.1111/j.1365-2885.1988.tb00189.x

2.    Papudesi BN, Malayala SV, Regina AC. Xylazine Toxicity. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK594271/  Accessed November 8, 2023.

3.    Ruiz-Colón, K., Chavez-Arias, C., Díaz-Alcalá, J. E., et al. (2014). Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: A comprehensive review of the literature. Forensic Science International, 240, 1–8. https://doi.org/10.1016/j.forsciint.2014.03.015 Accessed November 8, 2023.

4.    Forfa, T. (2023) What We’re Doing to Stop Illicit Xylazine from Getting into the U.S. U.S. Food and Drug Administration. https://www.fda.gov/animal-veterinary/news-events/what-were-doing-stop-illicit-xylazine-getting-us Accessed November 8, 2023.

5.    Kanagy N. L. (2005). Alpha(2)-adrenergic receptor signalling in hypertension. Clinical Science (London, England): (1979), 109(5), 431–437. https://doi.org/10.1042/CS20050101

6.    Malayala, S. V., Papudesi, B. N., Bobb, R., et al. (2022). Xylazine-Induced Skin Ulcers in a Person Who Injects Drugs in Philadelphia, Pennsylvania, USA. Cureus, 14(8), e28160. https://doi.org/10.7759/cureus.28160 Accessed November 8, 2023.

7.    Alexander RS, Canver BR, Sue KL, et al.(2022).  Xylazine and Overdoses: Trends, Concerns, and Recommendations. American Journal of Public Health 112(8):1212-1216.PMID:35830662 https://doi.org/10.2105/AJPH.2022.306881

8.    Kariisa M, O’Donnell J, Kumar S, et al.(2023) Illicitly Manufactured Fentanyl–Involved Overdose Deaths with Detected Xylazine — United States, January 2019–June 2022. Morbidity and Mortality Weekly Report;72:721–727. DOI: http://dx.doi.org/10.15585/mmwr.mm7226a4 Accessed November 8, 2023.

9.    Drug Enforcement Administration (2022). The Growing Threat of Xylazine and its Mixture with Illicit Drugs. https://www.dea.gov/sites/default/files/2022-12/The%20Growing%20Threat%20of%20Xylazine%20and%20its%20Mixture%20with%20Illicit%20Drugs.pdf Accessed November 8, 2023.

10.  Ayub, S., Parnia, S., Poddar, K., et al. (2023). Xylazine in the Opioid Epidemic: A Systematic Review of Case Reports and Clinical Implications. Cureus, 15(3), e36864. https://doi.org/10.7759/cureus.36864. Accessed November 8, 2023.

11.  Reyes, J. C., Negrón, J. L., Colón, H. M., et al. (2012). The Emerging of Xylazine as a New Drug of Abuse and its Health Consequences  among Drug Users in Puerto Rico. Journal of Urban Health, 89(3), 519–526. https://doi.org/10.1007/s11524-011-9662-6

12.  The White House. (2023). President Biden Calls for Historic Funding to Beat the Overdose Epidemic Being Driven by Fentanyl. https://www.whitehouse.gov/ondcp/briefing-room/2023/03/09/president-biden-calls-for-historic-funding-to-beat-the-overdose-epidemic-being-driven-by-fentanyl/?utm_source=link Accessed November 8, 2023.

13.  The White House. (2023). Biden-⁠Harris Administration Designates Fentanyl Combined with Xylazine as an Emerging Threat to the United States. https://www.whitehouse.gov/ondcp/briefing-room/2023/04/12/biden-harris-administration-designates-fentanyl-combined-with-xylazine-as-an-emerging-threat-to-the-united-states/ Accessed November 8, 2023.

14.  The White House.(2023). Fentanyl-Adulterated-Or-Associated-With-Xylazine-Emerging-Threat-Response-Plan-Report. https://www.whitehouse.gov/wp-content/uploads/2023/07/FENTANYL-ADULTERATED-OR-ASSOCIATED-WITH-XYLAZINE-EMERGING-THREAT-RESPONSE-PLAN-Report-July-2023.pdf Accessed November 8, 2023.

Reflection: 2023 KPMA Annual Meeting

By Ali Farooqui, MD

Chair, Scientific Research Committee

At the conclusion of the KPMA annual meeting on March 10, I was left with a deep feeling of gratitude, accomplishment, and pride. We held the meeting at a new venue to attract psychiatrists from multiple areas of the Commonwealth. The enthusiasm and dedication of our presenters and panelists was palpable. Our presenters volunteered their time to educate our membership on the topics of eating disorders, pharmacology, ADHD, neurodivergence, cannabis, and covid-19. In addition to invaluable knowledge that was shared, we were able to reconnect with our colleagues from across the state and experience camaraderie and fellowship. I am grateful for the selfless service of our presenters and panelists, and for the participation and attendance of our members.

I am particularly grateful for the hard work and dedication of Dr. Mark Wright, the outgoing chairperson of the scientific committee. His leadership and guidance is irreplicable, and I hope to rely on his advice, mentorship, and guidance as the incoming chair.

The landscape of mental health care is rapidly evolving in both press and practice. Psychiatric disorders are becoming a topic of discussion nationwide, and interest in novel psychiatric therapies is gaining momentum. As we look into the future, I hope to humbly follow in the footsteps of my predecessor and provide the psychiatrists of Kentucky an avenue for sharing opinions and ideas, and a platform for education on mental health issues that are relevant and of interest to the practicing psychiatrist.

We could not have held this meeting without the tireless efforts of our executive director, Miranda Sloan, who was the glue that held us together and navigated the schedules of our busy physicians. Thank you to our president Dr. Suleman, the scientific committee, and the executive council, for their leadership and dedication to organized psychiatry. I would also like to personally thank each member of KPMA for trusting us with your time, and for your continued involvement in our meeting. I look forward to being of service to you all as we move toward planning our next scientific meeting in 2024.

Sincerely,

Ali A. Farooqui, MD

KPMA Town Hall Meeting

Please join us Thursday, November 11th, 2021, virtually for a Town Hall beginning at 6:30pm.  Our schedule is as follows:

6:30pm – 7:00pm    Sheila Schuster, Ph.D., will discuss assessment thus far from Severe Mental Illness Task Force and tentative recommendations for improving access and care for this patient population.

7:00pm – 7:30pm     Gagandeep Kaur, M.D, will discuss rising number of young adolescent suicidality/attempts, particularly in young girls.

7:30pm – 8:00pm     Allen Brenzel, M.D, will provide a high level overview of current mental health and SUD/OUD climate in Kentucky.  Discuss what strategies/initiative (if any) are being planned at the state level to mitigate for Kentuckians suffering from mental illness/SUD/OUD, with respect to the pandemic.

Registration is free for this virtual event.  You may register using the link below.  A calendar invite is attached as well.

Register Now