|Biological half-life||7.7 hrs|
|Chemical and physical data|
|Molar mass||394.514 g/mol|
|3D model (Jmol)|
Carfentanil or carfentanyl (also known as 4-carbomethoxyfentanyl) is an analog of the synthetic opioid analgesic fentanyl. It is 10,000 times more potent than morphine, making it among the most potent commercially used opioids. Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceutica which included Paul Janssen. It is marketed under the trade name Wildnil as a general anaesthetic agent for large animals, such as elephants.
Side effects of carfentanil are similar to those of fentanyl, including itching, nausea and respiratory depression, which can be life-threatening. The post-2000 surge in illicit sale and use of fentanyl analogues in Eastern Europe included seizures of carfentanil in Lithuania and Latvia. As of around 2016, carfentanil and other highly potent derivatives of fentanyl started appearing in heroin and were connected to hundreds of overdoses and several deaths in the United States. The extreme 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.
Method of action and toxicity levels
A study using mice concluded that (±)cis-3-carbomethoxyfentanyl and (±)trans-3-carbomethoxyfentanyl are mediated via opioid receptors, most probably of μ type. Acute toxicities of fentanyl and (±)cis-3-carbomethoxyfentanyl were evaluated in the mice. The animals have been followed up for 14 days. There is no difference between LD50 values obtained after 24 h and 14 days. Signs and symptoms of acute toxicity of all three drugs (fentanyl and both the cis and trans versions of 3-carbomethoxyfentanyl were similar: dyspnea, hypoventilation, cyanosis, convulsion, Straub tail, trunk muscle rigidity, prostration etc. In agreement with opioid activity, respiratory depression was the most prominent sign and probably the main cause of death, as well. This is supported by fact that most death occurred in the first few hours after drug administration. There is no significant difference between the therapeutic indices [median lethal dose (LD50) / median antinociceptive dose (AD50)] between fentanyl and (±)cis-3-carbomethoxy- fentanyl: 858.1 (444.9–1654.7) and 918.5 (392.8–2147.5), respectively. This finding suggested that both substances are equally safe in mice. 
Moscow theater hostage crisis
In 2012, a team of researchers at the British chemical and biological defense laboratories at Porton Down found carfentanil and remifentanil in clothing from two British survivors of the 2002 Moscow theater hostage crisis and 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 (the two most commonly-used opioid antagonists) to counteract the carfentanil and remifentanil and save the lives of many of the victims. 125 people exposed to the gas 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, that the worst danger to the theater victims would have been apnea (loss of breathing), and that mechanical ventilation and/or treatment with opioid antagonists could have saved many lives.
Importation from China
According to an Associated Press article, "Chemical weapon for sale: China's unregulated narcotic", fentanyl, carfentanil and other highly potent derivatives of fentanyl are actively marketed by several Chinese chemical companies. Carfentanil was not a controlled substance in China until March 1, 2017, and until then had been manufactured legally and sold openly over the Internet.
Authorities in Latvia and Lithuania have 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 labelled "printer accessories". According to the Canada Border Services Agency, the shipment contained 50 million lethal doses of the drug, more than enough carfentanil 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."
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 carfentanil overdose 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's less expensive, easier to get (Chinese firms advertise and sell carfentanil over the Internet, offering advice to customers in other countries on how to import it illegally) and easier to make than genuine heroin.
Potential as a chemical weapon
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." Mr. 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." Mr. Weber described various ways carfentanil could be used as a weapon, such as knocking troops out and taking them hostage or killing civilians in closed spaces such as train stations.
- Lofentanil (3-Methylcarfentanyl)
- Opioid comparison
- R-30490 (4-Methoxymethylfentanyl)
- "Fentanyl drug profile". EMCDDA.
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text imported under the CC-by license
- Riches, James R.; Read, Robert W.; Black, Robin M.; Cooper, Nicholas J.; Timperley, Christopher M. (November 2012). "Analysis of Clothing and Urine from Moscow Theatre Siege Casualties Reveals Carfentanil and Remifentanil Use". Journal of Analytical Toxicology. 36 (9): 647–656. doi:10.1093/jat/bks078. ISSN 1945-2403. PMID 23002178.
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