Abstract

In 2018, 67% of all opioid-related deaths in the United States traced back to synthetic opioids, mainly fentanyl.1 Synthetic drugs are made for any number of reasons, including superior pharmacological attributes, but drugs with abuse potential such as opioids may result in synthetic products to appeal specifically to the illicit market. So ubiquitous are illicit fentanyl analogs that they are collectively termed “nonpharmaceutical fentanyl” (NPF) to distinguish them from pharmaceutical-grade fentanyl, a powerful anesthetic and analgesic drug. NPFs were first observed in street drugs from 2005 to 2007, all traced back to a single clandestine laboratory; when the lab was closed in 2007, NPF trade stopped, but not until more than 1,000 NPF-related deaths had occurred.2 Since that time, more clandestine laboratories have opened and NPF reappeared in the street-drug stream in 2010 as an additive to heroin and cocaine, as a product on its own, or as the active ingredient in counterfeit opioid analgesic tablets or counterfeit benzodiazepines. While the first fentanyl analog (AMF) was produced by Janssen Pharmaceutica in the 1960s, today numerous fentanyl products are on the market or being developed. The original analogs of fentanyl were developed for specific uses, such as veterinary medicine for large animals (carfentanil).3

Each novel agent represents a major new challenge to drug enforcement as the specific formulation may not be known to medicine or law enforcement, may not technically be illegal or scheduled as a controlled substance, and may not be testable using available testing options. The purpose of our review was to revisit an important topic relevant to the opioid overdose crisis.