As mentioned in prior pearls, xylazine (aka “Tranq”) is alpha-2 adrenergic agonist that has been used as an adulterant of various substances including cocaine, heroin and fentanyl.
Intoxication/Overdose
- Usually unintentional: patient’s not knowing the presence of adulterant 
- Symptoms: CNS depression, bradycardia, hypotension, miosis, anticholinergic effects 
Overdose Treatment
- Naloxone ineffective against xylazine, but still recommended to use as most overdoses are combination of xylazine and opioid. 
- Several medications in veterinary medicine are available as alpha-adrenergic antagonists, but not approved for use in humans (atipamezole, tolazoline, yohimbine). 
- Treatment is largely supportive. 
Withdrawal
- Symptoms: Anxiety, Restlessness, Depressed mood, Body aches 
- Withdrawal Treatment (based on case studies): - Alpha-agonists (to decrease noradrenergic activity) including clonidine 0.1-0.3mg q6-8hr (monitor for hypotension), tizanidine 2-8mg q8hr, dexmedetomidine IV infusion in ICU 
- Benzodiazepines 
- Gabapentin/Pregabalin 
- Phenobarbital 
- Olanzapine 
 
- MOUD treatment/withdrawal management: MOUD (suboxone/methadone) + adjunctive medication (Ondansetron, Acetaminophen, NSAIDS, etc.)