Fentanyl analogues are synthetic derivatives of the opioid drug that are structurally and chemically similar with slight differences. They are often called “designer” drugs and regularly created on the black market.
Fentanyl is an extremely powerful synthetic opioid that is 50 to 100 times more potent than heroin.1 It is cheap and easily made on the black market, and it is often used to “cut” the more expensive opioids like heroin or prescription painkillers.1
There are a few pharmaceutical fentanyl analogues that do have approved medical uses, such as sufentanil, remifentanil, and alfentanil for humans, and carfentanil for animals.2 These medications, like fentanyl, are classified as Schedule II controlled substances by the Drug Enforcement Administration (DEA).2 This is because they have medical use for controlling extreme pain, but they also have a high potential for abuse and dependence.2
Most fentanyl analogues are created as illicit substances, often called NPS (new psychoactive substances). Some common NPS include the following:
- Furanyl fentanyl
- Acetyl fentanyl
- Cyclopropyl fentanyl
- 4-fluoroisobutyryl fentanyl
Fentanyl analogues are extremely dangerous with a high potential for overdose and addiction.4 Most are listed as Schedule I controlled substances, meaning that they are illegal in the United States with no approved medical use.
Carfentanil is used as an elephant tranquilizer. It is 100 times more potent than fentanyl itself, and 10,000 times more potent than morphine.3
It is highly dangerous and can be lethal in extremely small doses. Like fentanyl, it can be absorbed through the skin on contact or breathed in.
After exposure, overdose can occur within seconds.13 It may include symptoms such as these:3
- Trouble breathing and respiratory distress
- Pinpoint pupils
- Loss of consciousness and/or sedation
- Clammy skin
Carfentanil is one of the most potent opioids on the commercial market. It is commonly found on the black market cut into fentanyl and heroin.4
Users, and often the drug dealers themselves, are not even aware that carfentanil is in the drug being sold or used, which can greatly increase the risk for an unintentional overdose. It is illicitly sold in tablet, powder, blotter paper, and spray form.1
A derivative of fentanyl, furanyl fentanyl binds tighter to opioid receptors than morphine does.5 It has a higher liposolubility than fentanyl itself, which allows it to be absorbed into the bloodstream quicker.5
It has been reported in heroin and also crack cocaine. It is often found in liquid form, such as nasal sprays, and as a powder. It is also found in tablets, green herbal materials, and as an e-liquid for use in a vape pen.
Furanyl fentanyl has an analgesic effect, which means it blocks pain sensations. At the same time, it causes respiratory depression, making it highly dangerous.
Furanyl fentanyl also causes the following:3
- Constricted pupils
- Lowered heart rate
- Reduced body temperature
- Mood changes and euphoria
- Physical dependence
Furanyl fentanyl is about seven times more potent than fentanyl.6
A fentanyl analogue that has been rising in popularity, jumping up on the DEA’s emerging threat report between 2017 and 2018, is acetyl fentanyl.7 It is not quite as strong as fentanyl, but it is still about 5 to 15 times more potent than heroin.8 It is also lethal in small doses.
Acetyl fentanyl does not have as powerful of a painkilling effect, but it still causes respiratory and central nervous system depression along with a euphoric high. It is also commonly found mixed with fentanyl, heroin, and other drugs.
Cyclopropyl fentanyl is most commonly found in powder form, but it has been detected in both tablets and liquids as well.9 It is about three times more potent than fentanyl.
Up until October 2019, it was marketed as a “legal” high. This was until cyclopropyl fentanyl was placed into Schedule I under the Controlled Substances Act (CSA) by the DEA, making it an illegal drug in the United States.10
Cyclopropyl fentanyl is similar in mechanism to fentanyl with its analgesic and euphoric side effects as well as its potential to cause respiratory depression, dependence, and potentially fatal overdose.
Initially sold on the black market as a “designer” and legal fentanyl analogue, 4-fluoroisobutyrly fentanyl was placed into Schedule I in early 2018, as reports on the drug and its hazards were on the rise.11 It has a lower potency than fentanyl, but it is still extremely addictive and has a high risk for deadly overdose.
This NPS designer drug is also called 4-FIBF and p-FIBF. It is regularly mixed with other drugs and substances. 4-FIBF is highly dangerous as an opioid analgesic with a significant risk for respiratory depression and altered consciousness.
The Legal Status of Fentanyl Analogues
Fentanyl analogues jumped onto the scene as the fifth most common type of drug involved in drug poisoning deaths in 2016.7 By 2017, fentanyl analogues leaped to third on this list.
These designer opioids are created illicitly in underground laboratories, as they are often easier and cheaper to make than other more tightly controlled drugs. Fentanyl analogues are continually being altered slightly to get around drug scheduling and legal issues.
Prior to 2018, these drugs would have to become a “threat” to public health, as determined by the DEA, in order to be placed into an emergency Schedule I status through the CSA one at a time. In 2018, under the Federal Analogue Act, the DEA was able to automatically place drugs with “substantial similarity” to fentanyl directly into Schedule I, making them illegal to possess, sell, and use.
Fentanyl analogues are most commonly found on the black market, often ordered online and shipped from China. They are mostly considered to be illegal in the United States.
The legal system has largely been reactive when it comes to NPS and fentanyl analogues. It can be difficult to keep these drugs off the market.12
As fentanyl analogues become known to law enforcement, usually through a spike in overdose deaths or found in seized illegal drugs, the DEA is cracking down on them. They are making them illegal and raising penalties for trafficking them.
As analogues become known, drug manufacturers will slightly alter their chemical makeup to form a new analogue that is unknown and therefore not controlled or scheduled.
The legal status of fentanyl analogues changes frequently, requiring constant and vigilant attention as these drugs are highly dangerous.
1 (February 2019). Fentanyl DrugFacts. National Institute on Drug Abuse (NIDA). https://www.drugabuse.gov/publications/drugfacts/fentanyl
2 Drug Scheduling. United States Drug Enforcement Administration (DEA). Retrieved April 2021 from https://www.dea.gov/drug-scheduling
3 (September 2016). DEA Issues Carfentanil Warning to Police and Public. United States Drug Enforcement Administration (DEA). Retrieved April 2021 from https://www.dea.gov/press-releases/2016/09/22/dea-issues-carfentanil-warning-police-and-public
4 Opioids Fentanyl and Fentanyl Analogues. Minnesota Department of Health. Retrieved April 2021 from https://www.health.state.mn.us/communities/opioids/basics/fentanyl.html
5 (November 2017). Furanyl Fentanyl Critical Review Report. World Health Organization (WHO). Retrieved April 2021 from https://www.who.int/medicines/access/controlled-substances/CriticalReview_FuranylFentanyl.pdf?ua=1
6 (April 2019). Metabolic Pathways and Potencies of New Fentanyl Analogues. Frontiers in Pharmacology. Retrieved April 2021 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461066/
7 (June 2019). Fentanyl and Fentanyl Analogues. Substance Abuse and Mental Health Services Administration (SAMHSA). Retrieved April 2021 from https://www.samhsa.gov/sites/default/files/meeting/documents/fentanyl-analogs-06112019.pdf
8 (October 2016). Lethal High: Acetyl Fentanyl. U.S Pharmacist. Retrieved April 2021 from https://www.uspharmacist.com/article/lethal-high-acetyl-fentanyl
9 (2018). Cyclopropylfentanyl. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Retrieved April 2021 from https://www.emcdda.europa.eu/system/files/publications/7926/20181014_TDAS18001ENN_PDF.pdf
10 (October 2019). Rules 2019. Drug Enforcement Administration (DEA). Retrieved April 2021 from https://www.deadiversion.usdoj.gov/fed_regs/rules/2019/fr1025.htm
11 (November 2018). Rules – 2018. Drug Enforcement Administration (DEA). Retrieved April 2021 from https://www.deadiversion.usdoj.gov/fed_regs/rules/2018/fr1129.htm
12 (June 2017). Fentanyl, Fentanyl Analogues and Novel Synthetic Opioids: A Comprehensive Review. Neuropharmacology. Retrieved April 2021 from https://www.fresno.ucsf.edu/wp-content/uploads/2018/03/2017-Fentanyl-Fentanyl-analogs-and-novel-synthetic.pdf
13 (April 2017). Characteristics of Fentanyl Overdose. Centers for Disease Control and Prevention. Retrieved April 2021 from https://www.cdc.gov/mmwr/volumes/66/wr/mm6614a2.htm
14 (March 2019). DEA Chemists Solved Mystery of Drug Causing Mass Overdoses. WKYT. Retrieved April 2021 from https://www.wkyt.com/content/news/DEA-chemists-solved-mystery-of-drug-causing-mass-overdoses-506601211.html