The latest adulterant in illicit fentanyl was not a sedative or other psychoactive substance but a plasticizer, and it spread across the U.S. in a relatively short period of time, a review showed.
BTMPS, which has a chemical name of bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate, was first detected in June 2024 by community drug checking programs in Philadelphia and Portland, Oregon, after fentanyl samples tested positive for an unknown adulterant, according to Alex Krotulski, PhD, of Thomas Jefferson University in Philadelphia, and colleagues.
By September 2024 -- 3 months later -- BTMPS had been detected in almost all states that submitted samples to the National Institute of Standards and Technology, the researchers wrote in a viewpoint in JAMA Internal Medicine.
It's not clear why BTMPS is appearing in the illicit fentanyl supply, but it's most likely being used as a bulking agent, said viewpoint co-author David Zhu, BSc, an MD/PhD candidate at the Virginia Commonwealth University School of Medicine in Richmond.
"It has proliferated across the entire U.S. almost simultaneously, and no one really knows why it's in the illicit drug supply all of a sudden," Zhu told MedPage Today. "It really contradicted a lot of our pre-existing notions that we had for novel adulterants like xylazine and medetomidine."
"I don't know of any other circumstance where they've taken these non-pharmacological agents like BTMPS and mixed them in as bulking agents," he added.
Lewis Nelson, MD, dean of health affairs at Florida Atlantic University in Boca Raton, Florida, and a specialist in emergency medicine and medical toxicology who wasn't involved with the paper, told MedPage Today that BTMPS has been on his radar for about a year and agreed that it appears to be a bulking agent.
"Because fentanyl and related opioids are ultra-potent, the amount needed to produce typical opioid effects such as euphoria is less than a milligram, which is smaller than a pinhead in quantity," Lewis said. "This makes it impossible to use it straight and it needs to be diluted in a bulking agent for practical purposes."
Nelson noted that over the past several years, many bulking agents -- like xylazine and medetomidine -- have been pharmacologically active, "and this carries both desirable effects and adverse consequences."
"The switch to an inert ingredient is reminiscent of the 'old days' when starch and mannitol were used to cut heroin and cocaine," Nelson added.
One concerning aspect of tucking BTMPS into the illicit drug supply is that it's not approved for human use, and its potential health impacts on humans haven't been studied, Zhu said, noting that some animal studies have shown neurologic and cardiovascular toxicity.
"Some local health departments describe it as causing skin irritation, eye irritation, as well as a strong chemical order that smells like plastic or bug spray," Zhu told MedPage Today. Anecdotal reports have described symptoms including blurred vision, conjunctivitis, tinnitus, and nausea, according to the paper. Injection has been associated with localized burning and skin irritation, and smoking can cause persistent cough, throat irritation, and hemoptysis, Krotulski and colleagues said.
Nelson noted, however, that if the clinical effects were significant, they would likely have been observed to a greater extent by now, given how pervasive the adulterant is. An earlier report in JAMA this year found that among 284 drug product samples from Los Angeles and Philadelphia, 35% contained BTMPS.
With xylazine, for instance, its presence was made apparent because clinicians began seeing severe wounds that required extensive treatment, and sometimes, amputation.
For their report, Krotulski and colleagues examined data from the U.S. Drug Enforcement Agency's National Forensic Laboratory Information System (NFLIS), which documented 1,969 BTMPS reports in 2024, representing 0.2% of the 1,111,895 total drug samples submitted to the database that year.
Notably, there were only 13 reports from January to June 2024, while there were 1,956 in the latter half of the year, they reported.
BTMPS also has protective properties against ultraviolet (UV) light, which could mean that manufacturers are adding it to fentanyl to extend its shelf life, Zhu said.
"Maybe the manufacturers are trying to exploit this UV-protective role to stabilize fentanyl," he said. "That theory hasn't been evidenced, but it's out there."
He said public health groups need rapid access to point-of-care drug testing, as has been done with xylazine and medetomidine, and that harm reduction organizations need better support, including being equipped with "mass spectrometry to have a more reliable method of detecting BTMPS."
Physicians and other healthcare professionals should "be alert to opioid intoxication with atypical features, including a distinctive chemical odor and skin or eye irritation," Krotulski and co-authors wrote. "Clinical management should incorporate standard overdose treatment alongside supportive care for potential complications specific to BTMPS toxicity."
Disclosures
Krotulski reported receiving grants from the National Institute of Justice. A co-author reported relationships with non-profit groups, government agencies, and educational institutions. Zhu had no disclosures.
Authors reported financial relationships with the National Institute of Justice, the U.S. Department of Justice, the National Institute on Drug Abuse, Washington/Baltimore High Intensity Drug Trafficking Area Program, University of Florida, Rutgers University, University of Southern California, Arizona State University, University of Queensland, the Reagan-Udall Foundation for the FDA, and the American College of Neuropsychopharmacology.
Primary Source
JAMA Internal Medicine
Source Reference: Zhu DT, et al "The rapid spread of a novel adulterant in the U.S. illicit drug supply -- BTMPS" JAMA Intern Med 2025; DOI: 10.1001/jamainternmed.2025.2307.
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