Xylazine is a non-opioid sedative medication that is used as a veterinary tranquilizer. [1] Also known as ‘tranq’, xylazine has become increasingly used as an illicit drug of abuse. [1] Xylazine can result in life-threatening reactions, including fatal overdose. Recognizing potential xylazine overdose signs and quickly initiating treatment is important for improving outcomes.Â
- Xylazine, a non-opioid sedative and tranquilizer, has become increasingly used as an illicit drug, often in combination with other illicit substances.
- There is no approved human antidote for xylazine; however, naloxone is often used in xylazine overdoses involving other opioids.Â
- Supportive medical treatment, withdrawal symptom management, wound care, and harm reduction strategies are the key components of xylazine addiction treatment.
Xylazine reversal: What works and what doesn't
Xyazline can cause a variety of potentially dangerous symptoms, which can even be fatal. These include: [3][4]
- Slow breathing
- Reduced consciousness
- Low heart rate and blood pressure
- Severe wounds
There is currently no FDA-approved xylazine reversal agent for humans; however, there are still several treatment options. [2] Naloxone, the opioid reversal medication, is always recommended to be given for a suspected xylazine overdose. [3] While naloxone does not reverse the effects of xylazine, as many overdoses also involve opioids, it will help reverse these effects, which often prevents a fatal overdose. [2] As the effects of opioid and xylazine overdose are similar, it can be difficult to distinguish between the two.Â
If you suspect someone has had a xylazine overdose or symptoms are persisting despite naloxone, it’s vital to call 911 for immediate medical assistance. [3] Severe xylazine overdose will require supportive management of symptoms, often in the ICU. [2] This can include maintaining the airway, artificial respiration, and IV fluids. [2]
There are several reversal agents for xylazine in animals, including atipamezole and tolazoline; however, these treatments are not approved in humans. [5] Further research is required to assess whether these could be used for the treatment of overdose in humans. [5]
Does naloxone reverse xylazine?
The naloxone dose for opioid withdrawal does not reverse xylazine. However, it’s thought that much higher doses of naloxone might help to reverse xylazine; however, more research is needed for this. [5] Naloxone is often used as a standard in suspected xylazine overdoses because many involve the use of another opioid drug.
Why xylazine overdoses look different
Xylazine is a sedative drug that was initially developed as a veterinary tranquilizer. [1] The first illicit use of xylazine was reported in 2001, and it’s often mixed with other substances, including fentanyl and amphetamines. [2] It has rapidly increased in prevalence, with over 90% of illicit drug samples tested in Philadelphia in 2021 containing xylazine. [2] This is especially dangerous because xylazine can prolong and intensify the effects of other opioid drugs, increasing the risk for overdose.
Often, individuals are not aware that their drugs have been adulterated with xylazine, making overdose more likely and dangerous. This polydrug use makes reversing an overdose challenging due to the variety of symptoms it can produce and the combination of reversal strategies required. This, compounded by there being no current human antidote for xylazine, is why these overdoses are different and dangerous.
When to suspect xylazine involvement
Xylazine involvement should be suspected in anyone exhibiting signs of drug overdose, due to how commonly it’s present as an adulterant. If an individual has signs of severe overdose, including reduced consciousness and slow breathing, that do not respond to naloxone, this is even more suspicious for xylazine involvement. The presence of severe skin wounds and ulcers could also indicate prior xylazine use, as these are common adverse effects linked to xylazine abuse.Â
Is there a human antidote?
As mentioned, there is no specific human antidote for xylazine. However, several reversal agents are used in animals, which could hold the key to future human treatment. [5] Atipamezole is the most studied of these drugs and is effective at rapidly reversing xylazine effects in a variety of different mammals. [5] One study from 1990 found atipamezole to be safe in humans, but further research is needed to confirm its safety and effectiveness for xylazine reversal. [5]Â
Alongside current veterinary reversal medications, it has been theorised that a higher dose of naloxone, up to 100 times higher than the standard opioid reversal dose, could also reverse xylazine. [5] Below is a summary table of the current research: [5]
| Drug | Mechanism | Research/approval status |
|---|---|---|
| Atipamezole | Alpha-2 antagonist | Veterinary approval.Research suggests safe in humans. |
| Tolazoline | Alpha-2 antagonist | Veterinary approval.Limited human data. |
| Yohimbine | Alpha-2 antagonist | Veterinary approval.Limited human data. |
| Naloxone | Opioid antagonist | Effective in reversing opioids.Should be given first line for suspected xylazine overdose.High doses might be effective in reversing xylazine. |
While not much human data is currently available, this is a promising field for future research. [5] With further data, some of the veterinary reversal medications could be approved for human use.Â
Emergency or clinic management
Seeing someone who might have had a xylazine overdose can be scary, but it’s important to stay calm. Without putting yourself in danger, try to assess the person’s consciousness and breathing. If either of these is reduced, the following steps should be taken: [1]
- Administer naloxone.
- Put the individual in the recovery position.
- Call 911 for immediate medical support.
While waiting for the ambulance to arrive, it’s important to continue monitoring the individual and not leave them alone. If they stop breathing, CPR should be started immediately. Once in the hands of medical professionals, they will monitor vital signs and provide supportive treatment as needed. This includes: [1]
- Maintaining the airway. This could involve intubation if required.
- Giving rescue breaths.
- Providing supplementary oxygen.
- IV fluids and vasopressor medications to help correct low blood pressure and heart rate.
Xylazine withdrawal and wound care
Xylazine is associated with necrotic wounds, which can occur both at injection sites and elsewhere on the body. Necrotic wounds often have a black, brown, or yellowish appearance and may show signs of active infection. [4] These wounds can be extremely painful and have difficulty healing. [4] Xylazine wound care includes: [1][4]
- Wound cleaning
- Durable dressings
- Treatment for any secondary infection
- Surgical debridement, if required
Xylazine withdrawal is poorly studied, and more research is needed to identify the most common withdrawal symptoms. Body aches, mood changes, and cravings have been reported in chronic users. [6] Although there is limited data about xylazine withdrawal management, several medications are being used for this, including clonidine and dexmedetomidine. [1]
Harm reduction and treatment support
The surest way to prevent xylazine health risks is to avoid using illicit drugs like opioids, which often contain xylazine. Multiple treatment options are available for those needing help with minimizing withdrawals, cravings, and establishing sobriety. For individuals who use xylazine, harm reduction strategies can help minimize health risks. These include: [3]
- Drug testing. Test strips can be used to check if xylazine is present in a drug.
- Never take drugs alone. This ensures someone is available to give medical care and call 911 in the event of an overdose.Â
- Always carry naloxone. This ensures it can be given as quickly as possible. It’s also important to know how to administer naloxone effectively.Â
- Avoid injecting. If possible, using alternative methods to administer the drug helps reduce the risks associated with needles, such as wounds and infections.
- Get medical attention for wounds. This ensures they heal as best as possible, reducing the risk of infection.Â
Xylazine addiction treatment is comprehensive, often comprising medication-assisted treatment, behavioral therapy, and peer support groups. Many services are available that can help support those with xylazine addiction and the associated adverse health issues.
Final thoughts
Xylazine represents an evolving challenge with overdoses in the U.S. While there is currently no FDA-approved human antidote, prompt recognition of overdose and supportive care can be life-saving. With future studies, there is hope that researchers can find a safe and effective human antidote for xylazine.Â
For individuals who use drugs, harm reduction education, access to naloxone, and medical care can help reduce poor outcomes. If you, or someone you know, is struggling with xylazine use, please reach out to a healthcare professional who can help support your recovery.
