PROVIDENCE, R.I. [Brown University] — A new analysis revealed the frequency of potentially lethal substances, such as fentanyl and xylazine, in counterfeit pills that had been circulating in Rhode Island’s illicit drug supply.

Study author Dr. Rachel Wightman, an associate professor of epidemiology and emergency medicine at Brown University, said the analysis provides important information about the composition of counterfeit pills, which are designed to replicate legitimate pharmaceutical pills but often lead to adverse health effects.

“The level of detail found in our analysis can help inform treatment conversations and improve patient care,” said Wightman, a physician who cares for patients seeking help for opioid use disorder.

The analysis was published in the Journal of the American Medical Association.

Wightman said that most knowledge of counterfeit pills comes from community drug-checking initiatives or broad government reports with limited data. Comprehensive lab testing is an important complement to identify the range of substances found in counterfeit pills, she said.

Data for the analysis was obtained from law enforcement drug seizures reported by the Rhode Island Department of Health from 2017 to 2022. A total of 1,176 counterfeit pills were tested and classified into five categories: oxycodone, alprazolam, amphetamine/dextroamphetamine, clonazepam and unknown. The researchers found that in 2022, 99.3% of counterfeit oxycodone prescription pills contained fentanyl, a powerful synthetic opioid that is a major contributor to overdoses in the U.S., and 67% contained para-fluorofentanyl, an illicit fentanyl analog.

“Any pill not from a pharmacy may contain fentanyl,” Wightman said.

Even if fentanyl is not present, Wightman said, it is important for health professionals treating patients to understand the contents of counterfeit prescription pills, as the effects of active ingredients may be different than the prescription pills they mimic, thus requiring different treatment approaches.

In 2022, the active substance xylazine, a powerful sedative that has been implicated in the national overdose crisis, was detected in almost 40% of counterfeit oxycodone pills, always alongside fentanyl, the study found. According to the analysis, counterfeit pills often contained methamphetamine or novel benzodiazepines, such as bromazolam, which, like xylazine, are not approved for human use.

“Novel substances can be challenging in overdoses as results from biological testing will not be available in time to guide acute management,” Wightman said. “Furthermore, withdrawal management and substance use treatment are complicated by irregular doses and contents. So having a baseline knowledge of what is in the unregulated drug supply can be very helpful.”

Testing of the seized counterfeit pills was performed via comprehensive gas chromatography and mass spectrometry screening at the Rhode Island Department of Health Laboratories in Providence.

“This retrospective is a nice proof of concept on how impactful the findings can be,” said study author Glen Gallagher, the director of the state health laboratories. “We are taking steps to make the data more readily available so that community partners can be aware of what’s on the street in real time and can help communicate that information to people who use drugs as well as those who treat them, to hopefully mitigate risks.”

This report is one of the first times a comprehensive analysis of counterfeit pills in the unregulated drug supply has been widely shared, the researchers said.

“Part of our goal with this report is to encourage other states as well as the federal government to release this type of data and information to the public,” Wightman said.

Study contributors included Leslie Nolan and Ben Hallowell at the Rhode Island Department of Health; Bryan Volpe of the HIDTA New England Overdose Task Force; and Thomas Chadronnet of the CDC Foundation. The research was supported in part by the U.S. Centers for Disease Control and Prevention.