Veterinary Drugs as Toxic Adulterating Substances in the Street Drug Supply

Street drugs, particularly potent ones like opioids, are commonly mixed with various substances. These additions serve to increase the quantity and reduce the strength of the drugs. However, they can also contain harmful compounds with their own pharmacological effects. Traditionally, these additives have included levamisole/tetramisole, phenacetin, acetaminophen, quinine, lidocaine, tramadol, metamizole/dipyrone, and more recently the veterinary drugs xylazine, acepromazine, pentobarbital, and phenylbutazone. 
This presentation delves into these drugs, their effects, and recent trends concering their appearance in toxicology positivity. A list of concerning adulterants was compiled from literature reviews and data from an international laboratory director's consortium. These substances were then analyzed in forensic toxicology samples using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), which covers over 1,200 therapeutic and abused drugs and adulterants.
The presentation will focus on key adulterants specifically levamisole, phenacetin, and xylazine, examining their positivity rates between 2018 and 2023, alongside major drugs of abuse such as fentanyl, cocaine, heroin, and methamphetamine. Levamisole positivity ranged from 5% to 14% between 2018 and 2021 but spiked to 17% in 2022. It was frequently found in combination with cocaine (8% to 28% of cases), raising concerns due to its adverse side effects.
Phenacetin, which was removed from the US pharmacopeia in 1983 due to serious health risks, reappeared in illicit drug supplies in the US around 2020, appearing in approximately 8% of cases, mainly with fentanyl and other opioids in the Northeastern United States.
Another concerning adulterant is the veterinary tranquilizer and alpha-2-adrenergic agonist xylazine, associated with hypotension and bradycardia. Reports also include disorientation, drowsiness, respiratory depression, and injection-related ulcers and lesions. While historically found in 1-4% of cases, xylazine's positivity has been steadily increasing since early 2020, reaching around 18% in the second quarter of 2022, and at rates as high as 90% in the street drug supply, almost always in combination with fentanyl.  A related veterinary drug, medetomidine began emerging in fentanyl cases in 2023.
Additional emerging veterinary adulterants like acepromazine and phenylbutazone will be discussed. These drugs, not approved for human therapeutic use due to their adverse effects, pose additional risks to drug users when used as adulterants in the recreational drug supply. These findings should be considered when interpreting drug-related deaths or outbreaks of toxic events, and incorporated into drug user education.