03. Xylazine (”Tranq Dope”) Overdose: What Clinicians Should Know

Text version

Management of Xylazine Toxicity

Xylazine Emergence And Clinical Relevance

Xylazine is a veterinary medication with a rapidly growing presence on the illicit drug market. Xylazine was first detected in illicit drug samples in Puerto Rico in 2000 and has now spread throughout the United States. It is commonly known on the street as “tranq dope” because it is approved for use as a veterinary tranquilizer.

Helping spread xylazine use is its legal status. Xylazine is legal at the federal level and is not even a controlled substance. The actual prevalence of xylazine use remains unknown because xylazine is not asked about in most drug use surveys.

We do know that xylazine overdose has caused several thousand deaths in the United States over the past several years. The exact number of deaths is unknown because xylazine is not detected by standard toxicology assays and it is also not routinely tested for. About 95% of these overdose deaths involve xylazine combined with another drug, most commonly fentanyl. 

Pharmacology And Overdose Implications

Naloxone is an effective treatment for overdose on fentanyl and other opioid drugs. However, naloxone does not work for xylazine overdose for the simple reason that xylazine is not an opioid. Rather, xylazine activates the alpha-2 adrenergic receptor on neurons.

Thus, xylazine use creates substantial harm for which we currently have no effective treatment. We also know very little about the clinical pharmacology of xylazine because it has never been approved for human use by the Food and Drug Administration (FDA). The little information we do have is based on the few animal studies done to get xylazine approved for veterinary use.

Systematic Review Reports Evidence Quality Is Poor

A recent review by Dr. Owusu-Antwi and colleagues aims to reduce this information gap by conveniently summarizing in one article all that is currently known about the diagnosis and treatment of patients with xylazine intoxication including overdose and withdrawal. The authors used accepted methods following the widely respected PRISMA guidelines for systematic reviews. They conducted an electronic search of the published medical literature from 1957 through 2024, so their article is fairly up to date.

This research identified 34 relevant articles. The quality of the identified evidence was very poor. All of these articles were case reports or case series.

There were no clinical trials of any kind. Almost half the cases did not have toxicology testing to confirm the presence of xylazine. Many cases had no followup after the acute episode resolved in the emergency department.

Clinical Presentation Of Xylazine Intoxication

Based on this review, the typical patient with xylazine intoxication presents with a characteristic cluster of findings. These are important for us to keep in mind at the bedside.

Typical clinical features include:

• Drowsiness
• Impaired level of consciousness
• Autonomic instability
• Sinus tachycardia

Supportive Care Only Clear Consensus

The only consensus on the treatment of patients with xylazine intoxication is the use of supportive and symptomatic care. This includes close monitoring of vital signs and mental status, supplemental oxygen and intravenous fluid as needed.

There is currently no specific antidote for xylazine intoxication. Thus, it is no surprise that a wide variety of medications has been used in reported cases namely:

• Atropine
• Benzodiazepines
• Clonidine
• Dexmedetomidine
• Gabapentin
• Naloxone
• Tizanidine

As each medication was given to only a few patients, it’s hard to know which medications might be broadly effective.

Naloxone Addresses Opioid Co-intoxication

Only the use of naloxone has a clear pharmacological rationale. Most xylazine overdoses are combined with opioids such as fentanyl or heroin. Naloxone as an opioid receptor blocker would be effective in minimizing the opioid contribution to overdose.

A similar broad range of medications was used to treat suspected xylazine withdrawal. These included benzodiazepines, clonidine, gabapentin, phenobarbital, second-generation antipsychotics, pregabalin and ropinirole.

Practical Diagnostic Approach In Clinic

Given the sparse and weak evidence, the authors understandably made no specific diagnostic or treatment recommendations other than what is clinical common sense. The diagnosis of xylazine intoxication is made by history from the patient when possible and from collateral informants and toxicology testing including for xylazine when available. Treatment is supportive and symptomatic including close monitoring of vital signs and mental status.

Knowledge Gaps And Future Directions

To their credit, the authors also highlight the major gaps in our knowledge and provide some leads for future research. For example, in Veterinary Medicine, atipamezole effectively reverses the effects of xylazine. Atipamezole is an alpha-2 adrenergic receptor blocker that is FDA approved for use in animals but atipamezole is not approved for human use.

The bottom line is that we currently have little good quality knowledge of how to treat xylazine intoxication, overdose or withdrawal. There are no available clinical practice guidelines. This article usefully outlines what little is known but clinicians are left largely on their own until research catches up with our clinical reality.

Abstract

Management of xylazine toxicity, overdose, dependence, and withdrawal: A systematic review

Philipa Owusu-Antwi, M.D., MPH, Priya Atodaria M.D., MS, Edmund Appiah-Kubi M.D., Zainab Shah M.D. & Elpidio Marlon García, M.D.

Background and Objectives

Xylazine, an alpha-2-adrenergic agonist, has been increasingly implicated in substance use and overdose crises. However, little is known about its effects on humans. With the growing public health crisis surrounding xylazine, it has become important to recognize and promptly manage symptoms of xylazine toxicity, withdrawal, and overdose. We conducted a systematic review to consolidate the existing literature on the topics, aiming to identify gaps and propose evidence-based actions for managing patients.

Methods

Published literature from 1957 to 2024 was searched to identify studies focusing on the management of xylazine intoxication, withdrawal, overdose, and dependence in humans. PRISMA guidelines and JBI critical appraisal tools were used to ensure the methodological quality of the included studies and reduce bias in study selection. Thirty-four studies were included in this review.

Results

Xylazine misuse was common among men aged 19–45 years and was more likely to be used with other substances than alone. The doses ranged from 40 to 4300 mg, with no established toxic dosing. Supportive care included treatment with naloxone, alpha-2 agonists, and GABAergic medications. There is no antidote or evidence-based treatment recommendations.

Discussion and Conclusions

This systematic review consolidated the outcomes and proposed guidelines from xylazine management trials. It can serve as a reference for providers to promptly manage xylazine toxicity, withdrawal, and overdose symptoms to improve patient outcomes.

Scientific Significance

Although there is currently no standardized treatment or antidote, this review will aid ongoing research to address these gaps in xylazine management.

Reference

Owusu-Antwi, P. M.D., MPH; Atodaria, P. M.D., MS; Appiah-Kubi, E. M.D.; Shah, Z. M.D. & Marlon García, E. M.D. (2025). Management of xylazine toxicity, overdose, dependence, and withdrawal: A systematic review. Am J Addict. 2025; 34: 589-602.