Levamisole in opioid overdose patients: An evolving adulterant landscape

Levamisole is an adulterant commonly associated with cocaine and has remained in the United States illicit drug supply despite a national decline in cocaine use. Levamisole has recently been detected in seized illicit opioid samples, but limited research exists on this drug combination. This study examined the prevalence of laboratory confirmed levamisole exposures among patients with opioid overdose and assessed its association with sociodemographic characteristics along with patterns of co-occurring substance use.

This secondary data analysis of the Toxicology Investigators Consortium (ToxIC) Fentalog Study examined patients presenting to any of ten participating emergency departments throughout the United States with a suspected opioid overdose between 2020-2024. Chart reviews were conducted, and waste serum samples underwent liquid chromatography quadrupole time-of-flight mass spectroscopy for comprehensive toxicology analysis. This secondary analysis only included patients who had confirmed opioid exposure at the time of overdose.

Of 1,678 patients with confirmed opioid use, 225 (13.4%) were levamisole positive. Levamisole was more commonly detected in females (34.2%) compared to males (25.5%, p < 0.01), and there were significant age-related and racial/ethnic differences. Levamisole exposure was associated with a significantly higher number of confirmed co-exposures (levamisole: median = 9 substances, no levamisole: median = 6 substances, p < 0.01). It was also more frequently detected with stimulants (p < 0.01), fentanyl, and fentanyl analogues such as butyrylfentanyl, N-methyl-norfentanyl, ortho-fluorofentanyl, and para-flurorofentanyl (p < 0.05).

More than one in eight patients presenting with an opioid overdose were exposed to levamisole. These findings provide potential new evidence for levamisole adulteration alongside fentanyl and its analogues.