1. Typical use

2. Modern history
    Increase in illicit use  Importation from China  Moscow theater hostage crisis  Potential as a chemical weapon 

3. Pharmacology

4. Legal status
    China  United States  United Kingdom 

5. See also

6. References

Carfentanil or carfentanyl is a structural analog of the synthetic opioid analgesic fentanyl.^[1] Short acting and with fast onset it has, weight for weight, around hundred times stronger effects than fentanyl and thousands of times stronger than heroin. It is more effective at reducing pain response in rats than any other opioid.{{Citation needed|date=November 2018}}

Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceutica which included Paul Janssen.^[2]

The effects of carfentanil, including overdose, can be reversed by naloxone.^[3]

Carfentanil is legally controlled in most jurisdictions, but has veterinary uses for anaesthetising large animals.

Typical use

Carfentanil has been sold since 1986 under the brand name "Wildnil" for use in tranquilizer darts in combination with an α2-adrenoreceptor agonist^[4] for large mammals including elk and elephants.^[2][5] It is chosen for its high safety margin as the fatal dose of carfentanil is approximately the same as that of fentanyl despite much higher opioid activity.^[6]

Radiolabelled [¹¹C]carfentanil is widely used as a selective radiotracer in animal and human positron emission tomography (PET) imaging studies of the μ-opioid system due to its high affinity for receptors.^[7]

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.^[8] In 2017, a Milwaukee, Wisconsin man died from a carfentanil overdose, likely taken unknowingly with another illegal drug such as heroin or cocaine.^[9] 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.^[11] Health professionals are increasingly concerned about the potential escalation of public health consequences of its recreational use.^[10]

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 are actively marketed by several Chinese chemical companies.^[11] Carfentanil was not a controlled substance in China until 1 March 2017,^[11] 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.^[11][12] 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."^[13]

Moscow theater hostage crisis

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.^[14]

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, 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.^[15]

Potential as a chemical weapon

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.^[13]

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 train stations.^[13]

Pharmacology

Carfentanil is a lipophilic chemical, and hence can much more easily cross the blood-brain barrier.^[16]{{rp|pg 9}} It thus has very rapid onset of effects, but is also shorter acting.

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.^[4][17] It is important to note that lethality and potency are not the same, and carfentanil is less fatal than fentanyl in rats.^[18]

Legal status

China

Carfentanil has been controlled in China since 1 March 2017.^[19]

United States

Carfentanil is classified as Schedule II under the Controlled Substances Act in the United States with a DEA ACSCN of 9743 and a 2016 annual aggregate manufacturing quota of 19 grams (less than 0.7 oz.).^[20]

United Kingdom

Carfentanil has been specifically controlled as a Class A drug since 1986^[21]

See also

• 4-Phenylfentanyl
• Lofentanil (3-methylcarfentanyl)
• N-Methylcarfentanil
• Sufentanil
• Thiafentanil
• Opioid comparison
• R-30490 (4-methoxymethylfentanyl)

References

• Collin Seedorf
• Collinsella intestinalis
• Collinsella massiliensis
• Collinsella stercoris
• Collinsella tanakaei
• Collins' Epitola
• Collins' epitola
• Collins' epitolina
• Collins' Epitolina
• Collin Sexton
• Collins Foods
• Collins Foods International
• Collins Foods Limited
• Collin's Ford Bridge
• Collins Foundation
• Collins, Gary
• Collins Gem Encyclopedia
• Collins GEM series
• Collins, George
• Collins, Gerry
• Collins, Harold
• Collins, Harry
• Collins House (building)
• Collins House (Melbourne)
• Collinsia alba