Old opioids, new concerns: the case of acetylfentanyl

Acetylfentanyl is a potent synthetic opioid analgesic that has been increasingly available in America, Europe, Japan, China, and Australia during the last years. It has no approved medical or veterinary use, but it is used illicitly around the world as a substitute of its controlled precursor, fentanyl, as well as of heroin or other related substances in opioid dependent individuals. It is available in retail or “head shops” or over the Internet by companies based mainly in China. Acetylfentanyl is available in the form of powder, tablets, and blotters, while liquid and injectable formulations have been also reported. Acetylfentanyl seizures have dramatically increased during the last 4 years, and its abuse has already caused a number of deaths in the United States, the United Kingdom, Sweden, and Japan, thus leading to its scheduling under the 1961 Single Convention on Narcotic Drugs in the United States, and some European Countries, China, and Japan since 2015. The aim of this review is to summarize the current knowledge about this drug concerning its chemistry, synthesis, prevalence, metabolism, pharmacology, and toxicology, as well as its legal status. Analytical methodologies developed for the determination of acetylfentanyl in biological specimens, as well as published or reported acetylfentanyl related cases, fatal or not, and self reports from drug users are presented.