receptor over the μ2-opioid receptor. Carfentanil has approximately 10,000 times the analgesic potency of morphine, 4,000 times the potency of heroin, and 20 to 100 times the potency of fentanyl in animal studies. The effects of carfentanil are reversed by μ-opioid receptor antagonists like naloxone and naltrexone, though higher than normal doses of these agents may be necessary in humans due to the extremely high potency of carfentanil. Pharmacokinetics A lipophilic chemical that can easily cross the blood–brain barrier, carfentanil has a very rapid onset of action and is longer acting than fentanyl. Its elimination half-life in humans was 42 to 51 minutes following an intravenous bolus at an average dose of 1.34 μg (19 ng/kg). However, in a case study of recreational exposure, the half-lives of carfentanil and its metabolite norcarfentanil were estimated to be 5.7 hours and 11.8 hours, respectively. Chemistry Carfentanil is an analogue of fentanyl and is also known as (4-methoxycarbonyl)fentanyl. Related analogues of fentanyl include 4-phenylfentanyl, lofentanil (3-methylcarfentanyl), N-methylcarfentanil, R-30490 (4-methoxymethylfentanyl), sufentanil, and thiafentanil. History Increase in illicit use Over three hundred cases of overdose related to fentanyl and fentanyl analogues were reported between August and November 2016 in several of the United States, including Ohio, West Virginia, Indiana, Kentucky and Florida. In 2017, a Milwaukee, Wisconsin, man died from a carfentanil overdose, likely taken unknowingly with another illegal drug such as heroin or cocaine. Carfentanil is most often taken with heroin or by users who believe they are taking heroin. Carfentanil is added to or sold as heroin because it is less expensive, easier to obtain, and easier to manufacture than heroin. Health professionals are concerned about the potential escalation of public health consequences of its recreational use. Importation from China Authorities in Latvia and Lithuania reported seizing carfentanil as an illicit drug in the early 2000s. Around 2016, the United States and Canada reported a dramatic increase in shipment of carfentanil and other strong opioid drugs to customers in North America from Chinese chemical supply firms. In June 2016, the Royal Canadian Mounted Police seized one kilogram of carfentanil shipped from China in a box labeled "printer accessories". According to the Canada Border Services Agency, the shipment contained 50 million potentially lethal doses of the drug, in containers labeled as toner cartridges for HP LaserJet printers. Carfentanil was not a controlled substance in China until 1 March 2017, and until then was manufactured