Carfentanil or carfentanyl is a structural analog of the synthetic opioidanalgesicfentanyl. Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceutica which included Paul Janssen. The effects of carfentanil, including overdose, can be reversed by naloxone. Carfentanil is legally controlled in most jurisdictions, but has veterinary uses for anaesthetising large animals.
Typical use
Carfentanil was sold starting in 1986 under the brand name "Wildnil" for use in tranquilizer darts in combination with an α2-adrenoreceptor agonist for large mammals including elk and elephants. It was chosen for its high therapeutic index. Commercial production of Wildnil ceased in 2003, and the drug is available only as a compounded dosage form. Radiolabelled carfentanil is widely used as a selective radiotracer in animal and human positron emission tomography imaging studies of the μ-opioid system due to its high affinity for receptors.
Modern history
Increase in illicit use
A November 2016 article in Time, "Heroin Is Being Laced With a Terrifying New Substance: What to Know About Carfentanil", reports over 300 cases of overdose related to fentanyl and fentanyl analogues and several deaths connected to the drug since August 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 make than heroin. Health professionals are increasingly concerned about the potential escalation of public health consequences of its recreational use.
Importation from China
According to an Associated Press article from 2016, "Chemical weapon for sale: China's unregulated narcotic", fentanyl, carfentanil and other highly potent derivatives of fentanyl were actively marketed by several Chinese chemical companies. Carfentanil was not a controlled substance in China until 1 March 2017, and until then was manufactured legally and sold openly over the Internet. Authorities in Latvia and Lithuania reported seizing carfentanil as an illicit drug in the early 2000s. Around 2016, the US and Canada started reporting 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 lethal doses of the drug, more than enough to wipe out the entire population of the country, in containers labeled as toner cartridges for Hewlett-Packard LaserJet printers. Allan Lai, an officer-in-charge at the Royal Canadian Mounted Police in Calgary who helped oversee the criminal investigation said, "With respect to carfentanil, we don't know why a substance of that potency is coming into our country."
In 2012, a team of researchers at the British chemical and biological defence laboratories at Porton Down found carfentanil and remifentanil in clothing from two British survivors of the 2002 Moscow theater hostage crisis and in the urine from a third survivor. The team concluded that the Russian military used an aerosol mist of carfentanil and remifentanil to subdue Chechen hostage takers. Authors of a previous paper in the Annals of Emergency Medicine surmised from the available evidence that the Moscow emergency services had not been informed of the use of the agent, but were instructed to bring opioid antagonists. Not knowing to expect hundreds of patients exposed to high doses of strong opioids, the emergency workers did not bring enough naloxone or naltrexone to counteract the carfentanil and remifentanil and save the lives of many of the victims. 125 people exposed to the aerosol used in the rescue attempt are confirmed to have died from both respiratory failure and aerosol inhalation during the incident. The authors state that, assuming carfentanil and remifentanil were the only active ingredients of the knockout gas, the worst danger to the theater victims would have been apnea, and that mechanical ventilation and/or treatment with opioid antagonists could have saved many lives.
The toxicity of carfentanil in humans and its ready commercial availability has aroused concerns over its potential use as a weapon of mass destruction by rogue nations and terrorist groups. The toxicity of carfentanil has been compared to that of nerve gas, according to the Associated Press' article "Chemical weapon for sale: China's unregulated narcotic". The article quoted Andrew C. Weber, Assistant US Secretary of Defense for Nuclear, Chemical and Biological Defense Programs from 2009 to 2014, as saying "It's a weapon. Companies shouldn't be just sending it to anybody." Weber added "Countries that we are concerned about were interested in using it for offensive purposes... We are also concerned that groups like ISIS could order it commercially." Weber described various ways carfentanil could be used as a weapon, such as knocking troops out and taking them hostage or killing civilians in enclosed spaces such as railway stations.
Pharmacology
Carfentanil is a lipophilic chemical, and can easily cross the blood-brain barrier. It has very rapid onset of effects, but is also shorter acting than fentanyl. For pain relief, a unit of carfentanil is 100 times as potent as the same amount of fentanyl, 5,000 times as potent as a unit of heroin and 10,000 times as potent as a unit of morphine. This is despite only having 14-135 times higher affinity for the μ receptor. Despite its higher potency, carfentanil is less fatal than fentanyl in rats.
Legal status
China
Carfentanil has been controlled in China since 1 March 2017. The trade war between China and the US has included controversy over the effectiveness of this control.
United States
Carfentanil is classified as Schedule II under the Controlled Substances Act in the United States with a DEAACSCN of 9743 and a 2016 annual aggregate manufacturing quota of 19 grams.
United Kingdom
Carfentanil has been specifically controlled as a Class A drug since 1986
