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.

DISMANTLING FAULTY BELIEFS ABOUT EATING DISORDERS 

Jillian Rigert, D.M.D, M.D. 

Oral Medicine Specialist & Patient with Lived Experience 

The University of Texas M.D. Anderson Cancer Center 

To provide high quality care to patients with potentially life-threatening eating disorders, it is imperative to dismantle the faulty beliefs that the conditions are mostly about food, exercise, weight, and body image. From my perspective as a healthcare professional and a patient who has lived with anorexia nervosa, portrayals of people with eating disorders described in medicine, media, and Hollywood are superficial, misguided, and contribute to harm. 

Due to the complex nature of eating disorders, the education provided in medical schools and residencies remains suboptimal.1 From my experience, teachings continue to portray an individual with anorexia in a reductionist manner (i.e., as a young, Caucasian cisgendered woman fixated on calorie control and exercise with intense fear of gaining weight). The reality is that restrictive eating disorders may impact patients of all gender identities, ethnicities, and body sizes. While the clinical manifestations of eating disorders appear to revolve around food, exercise, weight, and body size, these signs warrant a comprehensive evaluation of the patient’s psychosocial-spiritual and physical wellbeing. 

Demystifying eating disorders through improved education will hopefully increase the quality of care provided. Change is urgently needed to reduce patient harm and address unmet needs which include the following: 

  1. Delays in diagnosis: Weight biases in medical practice often contribute to delays or missed diagnoses of eating disorders in normal to higher weight patients. Further, weight loss is often celebrated without identifying if the change was accomplished using harmful methods. It is important to accept that people with restrictive eating behaviors may present overweight or at normal weight, and thus patients of all body sizes must be screened to detect disordered eating. Delays in diagnosis may worsen a patient’s prognosis and invalidate the harm an eating disorder has on their mental and physical health.2,3
  •  Siloed care: Eating disorder education, research, and treatments are often inappropriately separated from other psychiatric conditions and considered a specialty of psychiatry. About 95% of patients with eating disorders have a co-occurring affective illness, thus improved training in medical and psychiatry residencies is needed.4 Up-to-date, research-based knowledge needs to be published in mainstream medical journals rather than specialty-specific journals, and patients need to be provided concurrent treatment for co-occurring conditions.4
  1. Therapeutic gaps: The majority of people with eating disorders never receive any intervention,4 and for those who do receive treatment, many approaches hyperfocus on improving the patient’s energy-balance as the outcome measure for recovery. While an essential part of treatment, a properly fueled body is often able to feel what the eating disorder has numbed. Energy-balance should not be the end point, but rather marks the beginning – a time when further therapeutic healing modalities should be explored. Disordered eating has multifactorial etiologies and thus warrants a multidisciplinary approach. Each patient must be evaluated as an individual and provided personalized care that addresses needs across psychosocial, spiritual, and physical dimensions.

Takeaways

  1. Increase the education about eating disorders in medical training; aim to reduce and/or eliminate biases.
  2. Evaluate personal biases (especially of weight-related issues) which may contribute to harmful delays in access to compassionate, comprehensive eating disorder care.
  3. When screening and treating patients, focus on providing a safe space and listen with compassionate curiosity. 
  4. Consider the role(s) that disordered eating behaviors may have in a person’s life that go deeper than some overt signs imply. Provide holistic, multidisciplinary care according to each patient’s individual needs, fostering psychosocial-spiritual and physical wellbeing. 

References 

  1. Mahr F, Farahmand P, Bixler EO, et al. A national survey of eating disorder training. Int J Eat Disord. 2015;48(4):443-445. doi:10.1002/eat.22335
  1. Lebow J, Sim LA, Kransdorf LN. Prevalence of a history of overweight and obesity in adolescents with restrictive eating disorders. J Adolesc Health. 2015;56(1):19-24. doi:10.1016/j.jadohealth.2014.06.005
  1. Neumark-Sztainer D. Higher weight status and restrictive eating disorders: an overlooked concern. J Adolesc Health. 2015;56(1):1-2. doi:10.1016/j.jadohealth.2014.10.261
  1. Haynos AF, Egbert AH, Fitzsimmons-Craft EE, et al. Not niche: eating disorders as an example in the dangers of overspecialisation. Brit J Psych. 2023:1-4.  doi:10.1192/bjp.2023.160.

Financial Disclosure

J. Rigert receives support from the National Institute of Dental and Craniofacial Research Diversity Supplement 3R01DE028290-02S1 for the project “Utilizing novel advanced imaging techniques with clinical biomarkers to predict and prevent radiation-attributable oro-dental sequelae.” This manuscript was written during time unrelated to my funding support hours. 

Member Highlight

Dr. Zubi Suleman, appointed by Governor Beshear, has been a key figure in the advocation for the well-being of Kentuckians through her membership on the Eating Disorder Advisory Council. 

Through this council, Dr. Suleman has taken on a leadership role as one of the committee chairs dedicated to Health Service Providers education. The core objective of this council is to address existing gaps and barriers in the care of individuals grappling with eating disorders within the state of Kentucky.

Committed to raising awareness about the grave implications of eating disorders and the imposing weight stigma within both the general population and healthcare professionals, Dr. Zubi Suleman undertook the initiative of presenting a resolution on eating disorders and weight stigma in Kentucky to the KMA Reference Committee.

It is with great pleasure to announce that this resolution was recently voted on and passed by KMA House of delegates on August 28, 2023, and is now formally integrated into the KMA’s policy framework. 

We extend our heartfelt congratulations to Dr. Zubi Suleman and her dedicated team for their unwavering efforts and for laying the foundation for advocacy endeavors in this critical area.

2024 Forging the Future in Psychiatry & Mental Health Conference

Please save the date for our annual Spring meeting which will be held Friday, March 8th, at the Shelbyville Convention Center. If you are interested in exhibiting or sponsoring this event please email Miranda at msloan@kypsych.org.

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The Hybrid Model: New Normal or Unstable Transition Phase?

ROBERT CAUDILL, M.D., & PETER YELLOWLEES, M.D., M.B.B.S

Before the world ground to a halt in an effort to contain the COVID-19 virus, the hybrid model of telepsychiatry was envisioned as a means of encouraging greater adoption of telehealth. With hybrid care, psychiatrists could connect in person with patients in the clinic as well as virtually with those at home or in community settings. Most of those practicing telepsychiatry divided their time between seeing patients in person and online, but they did not move their practice out of their clinics. Instead, a portion of the established caseload was strategically offered a virtual care option after some degree of screening and orientation of the patients. While slow at first, the adoption of a hybrid model of telepsychiatry was making gradual inroads among psychiatrists, where it was seen as having little threat to the overturning of more traditional workflows. Read more!