Increased danger for illicit manufactured fentanyl users: new adulterants

A recent study reports that as many as 7.5% of U.S. adults use illicitly manufactured fentanyl (IMF). The content of this “street fentanyl” is rapidly changing and increasingly complex with multiple dangerous other substances (adulterants) in the mix. Unfortunately the antidote for fentanyl overdose (naloxone) has no effect on the dangerous and possibly life threatening adverse effects of these other adulterants.

The addition of adulterants to illicitly manufactured synthetic opioids such as fentanyl is common practice. Xylazine, a veterinary anesthetic is probably the best known adulterant and until recently was implicated in more than 90% of “fentanyl” overdoses across the country. However, the past 18 months has seen the emergence of other substances mixed with fentanyl creating greater risks for users and challenges for health care providers managing overdoses.

IMF users are not usually aware of the presence of a specific adulterant. Testing for the presence of these newer substances may not be routinely available in many hospital emergency rooms. The adulterant’s adverse effects - sedation, respiratory depression, and hypotension (low blood pressure) among others - are not reversed by naloxone (Narcan), the cornerstone of fentanyl overdose treatment.

The three newest aduterants found in an increasing percentage of fentanyl overdoses include:

• Medetomidine

  This drug, like xylazine, is a veterinary drug used in surgery for sedation, muscle relaxation, and pain relief. It is not approved for human use. It’s at least 20 times more potent than xylazine. It has rapidly replaced xylazine as the most commonly detected adulterant in the illicit fentanyl supply in Philadelphia and other areas of the country. It is not an opioid and doesn’t respond to naloxone. It has been associated with a withdrawal syndrome including rapid heart rate, hypertension, restlessness and disorientation.

• BTMPS (bis2,26,6 tetramethyl-4-piperidyl sebacate)

  This compound is actually a light stabilizer/UV protectant, sometimes considered an industrial solvent, which has not known psychoactive or sedative properties. It’s not intended for human use. Though it only appeared as a fentanyl adulterant in mid-2024, it’s now present in more than one-third of tested illicit fentanyl samples in large cities such as Philadelphia and Los Angeles. Its purpose as an adulterant isn’t clear but most likely it’s used as a bulking agent. Its effects in humans are really unstudied and unknown but animal studies suggest significant cardiotoxic risks.

• Local Anesthetics (the “caine” drugs)

  Since late 2024, local anesthetics such as lidocaine, procaine, benzocaine and bupivicaine have been found as adulterants in up to 30% of fentanyl samples. These drugs, particularly in higher doses, have multiple potential adverse effects including numbness of limbs, bradycardia (slow heart rate), hypotension, acute anxiety, and seizures. Fentanyl overdoses complicated by these drugs may be atypical with numbness of arms and leg, intense anxiety, and hallucinations.

The challenge to health care providers caring for opioid overdoses complicated by one or more of these adulterants is clear. The challenge to employers is to raise an awareness of these emerging new hazards in employees by providing education and help for those struggling with substance use disorders. The need for investment in treatment of substance use disorders cannot be overstated.