Drug overdose deaths in the US have finally begun to abate. Between June 2023 and June 2024, they fell by 14%. However, deaths from a drug used to sedate large animals, called carfentanil, rose by at least 720% between the first half of 2023 and the first half of 2024.
The total number of deaths from carfentanil in the US is still tiny compared with deaths from the related drug fentanyl, but still, the trend is concerning.
Carfentanil was first synthesised in 1974 at Janssen Pharmaceuticals and sold under the brand name Wildnil. It is typically used to dart large animals such as deer, moose, elk, rhinoceros and elephants. A dose of 10mg is enough to knock out or even kill a fully grown African elephant.
Carfentanil is 100 times more potent than fentanyl and 10,000 to 100,000 times more potent than morphine. It is too powerful to use in human medicine as a painkiller.
The first evidence of its use as an illicit drug was in 2016. A dose of as small as one microgram (one-thousandth of a milligram) can cause euphoria and relaxation, but also nausea, constipation, respiratory depression, brain damage and death.
Street dealers are known to cut heroin with it to give it a harder-hitting, longer-lasting high. It is also often found in “polydrug” mixtures, which may contain cannabis, cocaine, methadone, dihydrocodeine, tramadol, benzodiazepines and ketamine. All are extremely potent and dangerous.
Due to the potency of the drug, there is also a risk to paramedics, healthcare workers and laboratory personnel.
With no legitimate medical use and because of the health risks associated with the drug, carfentanil has been controlled internationally under the United Nations Single Convention on Narcotic Drugs, 1961. In the UK it is controlled as a class A drug (in the same class as heroin and cocaine) and in the US is scheduled under the Controlled Substances Act.
Of the many drugs related to fentanyl (so-called “analogues”), carfentanil is the most potent yet synthesised. The reason lies in its chemistry. Of the opioids, carfentanil binds the most strongly to part of the cell membrane called the mu-opioid receptor, which results in pain relief and the effects sought by the recreational drug users.
Also, due to the chemical nature of the drug it can be stored in fatty tissue and subsequently, two to 24 hours later, redistributed in the blood stream resulting in a phenomenon known as “re-narcotisation” where the effects of the drug are observed again in an overdose patient after they have been stabilised.
Although there are legitimate sources of carfentanil for veterinary medicine, illicit sources are often traced to China where it is made to order and then exported to the US through Canada or Mexico. However, it is also reported that there are several vendors with US-based internet addresses that also make carfentanil – suggesting that manufacture also occurs outside of China.
No new fentanyl derivatives – for now
Thankfully, the production of new fentanyl-based compounds seems to have slowed. In Europe, eight new fentanyl derivatives were reported in 2016 and ten in 2017. However, no new fentanyl derivatives were reported in the period 2021 to 2023. In this period, the new compounds have been dominated by another group of opioids called nitazenes.
A changing drug market does not diminish the dangers presented by carfentanil. Although an antidote to the drug called naloxone is available, multiple doses are often needed to revive a person who has overdosed on carfentanil.
Unfortunately, because of carfentanil’s potency, it can be hard for toxicology laboratories to detect traces of the drug in post-mortem blood – which may mask the true extent of the deaths the drug causes. There are also no standard methods for screening street samples for the drug. This is, indeed, a very worrying drug.
Michael Cole receives funding and “in kind” support from the European Union and a number police forces and forensic science organisations around the world to carry out research.
