Xylazine
Learn more about xylazine, the drug often associated with polydrug use.
Overview
Common Nicknames
Tranq, zombie drug, sleep cut, tranq dope (mixed with fentanyl)
Drug Class
Sedative
Drug Form
Liquid or powder
Route of Administration
Oral, inhalation, injection
What is the science of Xylazine?
Xylazine is a veterinary medicine, first developed in 1962. It is given to animals prior to surgery for sedative and anaesthetic purposes. However, it has seen a significant rise in human use over the past six years.
It was first reported as a drug contaminant in Puerto Rico in 2001, and has been seen in opioid-related deaths in mainland United States from 2006. it is commonly known on the streets as “tranq.” Xylazine is frequently mixed with fentanyl, as well as heroin and cocaine.
Xylazine can be used via oral ingestion, inhalation (through smoking or vapes) and sniffing, although the most common route of administration is injection. It has a different mechanism of action compared to opioids like fentanyl and heroin, which it is often added to. There have even been anecdotal reports of Xylazie being detected in ketamine and cocaine in the UK. The mechanism of action is only partially known, and more research will have to be done to fully understand the working of xylazine in humans.
Xylazine acts as a potent a2-adrenergic agonist that stimulates central a2-receptors. This stimulation inhibits the release of noradrenaline and dopamine in the central nervous system. Noradrenaline is a neurotransmitter involved in the "fight or flight" response, enhancing alertness, energy, and stress responses by activating the sympathetic nervous system. However, with xylazine's inhibition, there is a decrease in sympathetic activity, resulting in sedation and muscle relaxation. By dampening the excitatory signals in the central nervous system, xylazine induces a state of relaxation and drowsiness.
What are the risks?
The use of xylazine carries certain risks, especially when it is used in combination with other opioids like fentanyl and heroin. Xylazine on its own can cause low blood pressure, low or irregular heart rate, high blood sugar levels, central nervous system depression (drowsiness, confusion and in severe cases, coma) and slow or insufficient breathing.
Using xylazine in combination with other opioids like fentanyl and heroin, which is often the case, is particularly risky. As all three substances have some similar pharmacological effects, like depressing the nervous system and respiratory function, synergistic effects may occur. This can cause a bigger depressant effect on the nervous system and respiratory function, increasing the risk of unconsciousness and death. Naloxone can partially reverse the effects of an opioid overdose, including those involving xylazine. While naloxone does not directly counteract xylazine's sedative effects, it can restore breathing, which is crucial in opioid overdoses, even when xylazine is present.
How might the drug make you feel?
Desired effects of xylazine are opioid-like euphoric effects. Users have also noted secondary effects such as sedation, muscle relaxation, and decreased perception of painful stimuli. These effects are caused by the decreased release of norepinephrine and dopamine in the central nervous system.
Xylazine causes a drop in blood pressure and a depressant effect on the heart rate and respiratory functions as a result of stimulations of the peripheral a2-receptors. Overdoses involving xylazine are characterised by low blood pressure, low or irregular heart rate, high blood sugar levels, central nervous system depression (drowsiness, confusion and in severe cases, coma) and slow or insufficient breathing. Naloxone can be used to restore breathing, but not consciousness.
Is Xylazine addictive, and what are the long-term effects?
Since there has not been a lot of research into xylazine use in humans, it is not entirely clear how addictive xylazine is. Much of what is understood about xylazine dependency comes from anecdotal accounts shared by people who use it illicitly. They note a strong dependency on the substance, mainly due to quick and intense withdrawal effects.
Some people who use xylazine describe an intense withdrawal, sometimes immediately after the drug's effects wear off. This rapid withdrawal can encourage repeated use, leading to a vicious cycle of repeated use to stave off the discomfort of withdrawal. The combination of xylazine and opioids is particularly potent, as it reportedly produces a stronger high than opioids alone. This synergistic effect makes the combination more attractive but also more dangerous, increasing the risk of dependency and overdose.
Withdrawal from xylazine, especially when mixed with fentanyl, is described as exceedingly severe. Users report extreme physical and psychological symptoms, including intense anxiety, muscle cramps, and profound agitation. The extremity of the withdrawal symptoms plays a role in the addictiveness of xylazine, as users want to avoid the extreme discomfort withdrawal gives them.
The long-term effects of xylazine on health and well-being are not well studied.
One known specific aspect of long-term xylazine use is that it can cause open skin ulcers and abscesses. These open wounds are painful, may limit mobility, and can lead to further infections or amputation of the infected skin. This is caused by injection-related soft tissue damage, both at the injection site and at non-injection site parts of the skin, however there has been reports of non-injected skin ulcers as well. While xylazine-associated wounds are extreme in appearance, they often respond well to appropriate wound care consisting of cleaning, treating and dressing the wound.
Harm Reduction and Drug-Drug Interactions
Safe Drug Use: To reduce the risk of disease transmission and other health complications, always use your own sterile needles and syringes for each injection. Sharing or reusing equipment increases the risk of infections like HIV, hepatitis C, and bacterial infections. Clean surfaces and hands before use, and use sterile water to prepare your drugs. If sterile water isn’t available, use water that has been boiled and cooled.
Wound Care: Xylazine use can lead to severe skin ulcers, even when not injected directly into the skin. Proper wound care is crucial to prevent infections. Never inject into an existing wound or ulcer, as this can worsen the damage and increase the risk of serious infection. Before injecting, clean the site thoroughly with an alcohol swab or soap and water. For existing wounds, wash them daily with mild soap and water, apply an antibiotic ointment, and cover them with a clean bandage. If you notice signs of infection such as increased redness, swelling, warmth, pus, or fever, seek medical care.
Safe Environment: Xylazine’s sedative effects, which can cause a trance-like state or even blackouts, leave users vulnerable to robbery, physical assault, or sexual violence. It’s important to use it in a trusted environment with people you know well. Establish safety protocols, like making a plan with friends to check in on each other. If you do use it alone, consider setting up a phone check-in system with someone you trust.
Emergency Response: When someone is suffering from a xylazine overdose, it is important to call medical help. While waiting for emergency services, place the person in the recovery position (on their side) to prevent choking if they’re unconscious. Stay with the person and keep them warm. If you have naloxone available, it can be useful to give this to the person overdosing on xylazine in combination with opioids.
Xylazine is commonly used in combination with other substances. It is frequently mixed with fentanyl and heroin and is increasingly detected in cocaine, methamphetamine, oxycodone, and illicit benzodiazepines. The reasons behind the addition of xylazine to the unregulated drug supply are not fully known.
Some users report that xylazine, when combined with opioids, can extend the effects of the opioid, alleviate withdrawal symptoms, and reduce the risk of respiratory depression by allowing a lower opioid dose. However, combining xylazine with other sedatives like fentanyl and heroin may also intensify the depressant effects on the central nervous and respiratory systems. This potentiation can increase the risk of toxic side effects, including severe respiratory depression, unconsciousness, and death. Others suggest that xylazine may enhance the addictive properties of these drugs and increase their street value by adding weight to each dose.
Medical Uses
Xylazine was originally investigated in humans as a sedative-hypnotic, analgesic and anaesthetic drug, but was rejected because of reports of severe low blood pressure (hypotension) and central nervous system depression. It was then adapted for use as a sedative, analgesic, and muscle relaxant for animals. It is an approved substance for use in animals, but is not approved for use in humans.
Myths and Misconceptions
Naloxone doesn't work on xylazine overdoses
This is partially true but often misunderstood. Naloxone does not reverse xylazine's effects, as xylazine is not an opioid. However, xylazine is almost always found in combination with opioids, meaning naloxone should still be administered in a suspected overdose. It will reverse the opioid component and may be life-saving. Naloxone should never be withheld on the assumption that xylazine is present.
Xylazine wounds are just typical injection site injuries
Xylazine is associated with severe necrotic skin wounds that can appear even at sites away from where the substance was injected, suggesting a systemic mechanism rather than purely local tissue damage. These wounds can progress rapidly and, if untreated, may require surgical intervention. They are distinct from typical injection site injuries and require prompt medical attention.