Medically Reviewed

Polysubstance Use: Xylazine (Tranq) Drug Use in Combination with Other Substances

3 min read · 6 sections
Xylazine, sometimes referred to as “tranq,” has recently been making national headlines because of the role the substance plays in the current surge of overdose deaths nationwide. From January 2019 to June 2022, the monthly percentage of illicitly manufactured fentanyl-involved deaths, where xylazine was detected, increased 276% in 21 jurisdictions, which includes 20 states and the District of Columbia.1 In fact, research indicates that xylazine has been increasingly detected in illicitly manufactured fentanyl products in the U.S.1 Besides contributing to overdose, combining xylazine with opioids can cause painful and dangerous effects.
What you will learn:
What xylazine is
What it's used for
Adverse effects of xylazine use
Using xylazine in combination with other substances
Treatment for polysubstance use involving xylazine

What is Xylazine?

Xylazine, created in 1962 by Bayer Pharmaceuticals, is a nonopioid analgesic used as a tranquilizer and sedative in veterinary medicine.2,3 The U.S. Food and Drug Administration (FDA) approved xylazine for animal use only.3 It is legally sold in vials or in preloaded syringes through pharmaceutical distributors who cater to veterinarians.4 Illicitly, xylazine has been sold inexpensively in liquid or powder form that is increasingly being found mixed into other drugs sold on the street, including fentanyl, heroin, and cocaine.3,4

Why is Xylazine So Dangerous?

While xylazine on its own can be dangerous—it’s not FDA-approved for human use because of its central nervous system (CNS) depressant effects (amnesia, slowed-breathing and drowsiness)—it’s the increasing use (whether intentional or not) with fentanyl that caused the White House’s Office of National Drug Control Policy to declare the xylazine-fentanyl combination an “emerging threat to the United States” in April 2023.2 Xylazine has played a rapidly increasing role in overdose deaths (particularly with fentanyl) in every region of the United States.4  To put it in perspective: Between 2020 and 2021 xylazine-detected overdose deaths increased 1,127% in the southern states, 750% in the west, 516% in the Midwest, and 103% in the northeast.4

What are the Effects of Xylazine Use?

While most of what’s known about xylazine’s effects are anecdotal since standard drug trials have not been conducted on humans, individuals who have used the substance alone report adverse effects, including:4,5

  • Dry mouth.
  • Drowsiness.
  • High blood pressure.
  • Rapid heartbeat followed by dangerously low blood pressure and slowed heart rate.
  • Low body temperature.
  • Elevated blood sugar.
  • Coma.
  • Slowed, ineffective breathing.

Dangers of Mixing Xylazine with Opioids

Again, while not well documented, evidence suggests that the combined use of xylazine with an opioid such as fentanyl may increase the risk of life-threatening overdoses.5 There is also some documentation showing that the combination of xylazine and fentanyl may potentiate all of fentanyl’s effects—including sedation, respiratory depression, slowed heart rate, and slowed breathing.5

Additionally, individuals who repeatedly inject xylazine or fentanyl mixed with xylazine may develop injuries that can lead to necrotic tissue (open skin ulcers), which may lead to amputation.3,4

Because xylazine is not regulated and relatively cheap, it is an attractive “cutting agent” for drug traffickers. While some individuals seek out xylazine-laced fentanyl or xylazine-laced heroin—believing that xylazine prolongs fentanyl or heroin’s effects—others take it unknowingly.6

As of March 2023, fentanyl mixed with xylazine had been found in drug seizures in 48 of 50 states.7 Additionally, in Puerto Rico, xylazine use has been associated with “speedballs,” the combined use of heroin and cocaine.

The Centers for Disease Control and Prevention (CDC) estimated the number of drug poisoning deaths involving xylazine in the United States grew 1,238% between 2018—when there were 260 deaths that involved xylazine—and 2021, when that number rose to 3,480.7

Furthermore, naloxone, a medication that rapidly reverses an opioid overdose, might be rendered less effective when xylazine is also present in the case of an opioid overdose. While naloxone will still effectively reverse opioid-induced respiratory depression—and should be used as a life-saving treatment for any overdose that might involve opioids, as well as calling 911—the drug won’t reverse the effects of xylazine. Thus, xylazine overdose may require additional supportive care, including maintaining an open airway, administering rescue breathing, and remaining with the individual until medical professionals arrive.7

Is Xylazine Addictive?

Since xylazine is not approved for human use, it is difficult to say whether xylazine is addictive as not much research on the addictive potential of this drug has been done. However, addiction may be more likely if xylazine is used in combination with opioids like fentanyl as opioids are known to carry a high addiction potential.9 Opioids, like fentanyl are known to reduce pain and  flood the brain with reward circuit signals, resulting in feelings of euphoria.10,11 With repeated use, the brain adapts to the presence of the fentanyl (or other opioids), which can make it difficult to feel pleasure without them. This may lead to the development of an opioid use disorder, the clinical term for opioid addiction.9,10

Polysubstance Use: Treating Addiction When Xylazine is Involved

Polysubstance use (using multiple drugs at once) may be done intentionally or unintentionally.2 The concurrent use of xylazine and fentanyl (and other opioids) can complicate addiction treatment.7

Currently, the primary approach to treating polysubstance use that involves xylazine is to treat the substance use disorder of the substance combined with the xylazine, such as fentanyl.7 There is a need for more robust evidence on treatment options for acute xylazine intoxication, management of xylazine withdrawal symptoms, and wound care associated with injecting xylazine into the skin and blood vessels.7 More research is needed to understand the motivations and circumstances leading to xylazine use, which is vital to the development of effective psychosocial support and substance use disorder treatment interventions.6

Individuals who struggle with concurrent xylazine and opioid (or other substance) use should seek treatment. Many treatment centers offer individualized treatment plans to address your specific needs regarding the substance or substances you use and any co-occurring mental health disorders as well. Treatment may include a combination of detox, medications, and behavioral therapies that help you address the thoughts, emotions, and behaviors that led to your substance use and teach you coping strategies to identify triggers, manage stressors, and prevent relapse.

If you or a loved one struggles with xylazine and opioid use or any polysubstance use, reach out to American Addiction Centers (AAC) to talk to one of our compassionate and knowledgeable admissions navigators, who can listen to your story, answer your questions, explain your options, and help you get started on the road to recovery.

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