History of Fentanyl in Timeline

Fentanyl is a potent synthetic opioid analgesic, significantly stronger than heroin and morphine. Clinically, it's used for severe pain management, particularly in cancer patients and post-surgery. It acts on μ-opioid receptors. Sold under brand names like Actiq, Duragesic, and Sublimaze, fentanyl is fast-acting, but a small amount can cause overdose due to its high potency.

1959: First Synthesis by Paul Janssen

Fentanyl was first synthesized in Belgium by Paul Janssen under the label of his relatively newly formed Janssen Pharmaceutica in 1959.

1959: Fentanyl Synthesis

In 1959, Paul Janssen first synthesized fentanyl.

1964: Patent of original synthesis by Paul Janssen

In 1964, the original synthesis as patented by Paul Janssen involves the synthesis of benzylfentanyl from N-benzyl-4-Piperidone.

1968: Medical use as a general anaesthetic

Fentanyl citrate entered medical use as a general anaesthetic in 1968, manufactured by McNeil Laboratories under the brand name Sublimaze.

1968: Medical Approval in the US

In 1968, Fentanyl was approved for medical use in the United States.

1971: Classification in the UK

In the UK, fentanyl is classified as a controlled Class A drug under the Misuse of Drugs Act 1971.

1978: Siegfried Method

In 1978, the Siegfried method was initially described. This method involves the initial synthesis of N-phenethyl-4-piperidone (NPP).

1998: Introduction of Actiq

In 1998, a flavored lollipop of fentanyl citrate mixed with inert fillers was introduced under the brand name Actiq, becoming the first quick-acting formation of fentanyl for use with chronic breakthrough pain.

1999: Pediatric cases related to fentanyl

In a report published in JAMA Pediatrics, 37.5% of all fatal pediatric cases between 1999 and 2021 were related to fentanyl; most of the deaths were among adolescents (89.6%) and children aged 0 to 4 years (6.6%).

2002: Moscow theater hostage crisis

Russian Spetsnaz security forces are suspected to have used a fentanyl analogue, or derivative, to rapidly incapacitate people in the Moscow theater hostage crisis in 2002. The siege was ended, but many hostages died from the gas.

February 2004: Janssen Pharmaceutica Products recalls Duragesic patches

In February 2004, Janssen Pharmaceutica Products recalled one lot of fentanyl (brand name: Duragesic) patches because of seal breaches that might have allowed the medication to leak from the patch.

March 2004: Series of class II recalls of Duragesic patches initiated

In March 2004, a series of class II recalls was initiated for fentanyl (brand name: Duragesic) patches due to seal breaches.

2004: Experiment on patient-controlled transdermal system (PCTS)

In a 2004 experiment including 189 patients with moderate to severe postoperative pain up to 24 hours after major surgery, 25% of patients withdrew due to inadequate analgesia. However, the PCTS method proved superior to the placebo, showing lower mean VAS pain scores and having no significant respiratory depression effects.

2006: Fentanyl-related overdose outbreak in the United States and Canada

In 2006, illegally manufactured, non-pharmaceutical fentanyl, often mixed with cocaine or heroin, caused an outbreak of overdose deaths in the United States and Canada, heavily concentrated in the cities of Dayton, Ohio; Chicago, Illinois; Detroit, Michigan; and Philadelphia, Pennsylvania.

2006: FDA Investigation into Respiratory Deaths

In 2006, the United States Food and Drug Administration (FDA) began investigating several respiratory deaths related to fentanyl use.

February 2008: ALZA Corporation recalls Duragesic patches

In February 2008, the ALZA Corporation recalled their 25 μg/h Duragesic patches due to a concern that small cuts in the gel reservoir could result in accidental exposure of patients or health care providers to the fentanyl gel.

September 2008: Doctors in the United Kingdom Warned of Risks

Doctors in the United Kingdom were not warned of the risks with fentanyl until September 2008.

2009: FDA Approval of Onsolis

In 2009, the US Food and Drug Administration (FDA) approved Onsolis (fentanyl buccal soluble film) for cancer pain management in opioid-tolerant subjects.

2011: Increase in synthetic opioid deaths

From 2011 to 2021, deaths from prescription opioids remained stable, while synthetic opioid (primarily fentanyl) deaths increased from 2,600 overdoses to 70,601 per year.

April 2012: FDA Report on Accidental Exposure Deaths

In April 2012, the FDA reported that twelve young children had died and twelve more had become seriously ill from separate accidental exposures to fentanyl skin patches.

2012: Recuvyra transdermal solution approved for dogs

In 2012, a highly concentrated (50 mg/mL) transdermal solution, brand name Recuvyra, became commercially available for dogs only. It is approved by the Food and Drug Administration to provide four days of analgesia after a single application before surgery.

June 2013: CDC issues health advisory on acetylfentanyl overdose deaths

In June 2013, the United States Centers for Disease Control and Prevention (CDC) issued a health advisory to emergency departments alerting to 14 overdose deaths among intravenous drug users in Rhode Island associated with acetylfentanyl, a synthetic opioid analog of fentanyl that has never been licensed for medical use.

July 2014: MHRA Issues Warning on Transdermal Fentanyl Patches

In July 2014, the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK issued a warning about the potential for life-threatening harm from accidental exposure to transdermal fentanyl patches, particularly in children.

2014: Increase in fentanyl reports

The United States National Forensic Laboratory estimates fentanyl reports by federal, state, and local forensic laboratories increased from 4,697 reports in 2014 to 117,045 reports in 2020.

September 2015: Public Health Issue in Canada

Death from fentanyl overdose has been a public health issue of national concern in Canada since September 2015.

October 2015: CDC Issues Initial HAN Advisory

In October 2015, the U.S. Centers for Disease Control (CDC) issued an initial HAN (Health Alert Network) Advisory to prevent fentanyl misuse and fatal overdose.

2015: Fentanyl overdoses begin to rise in Canada

Beginning in 2015, Canada has seen several fentanyl overdoses. Authorities suspected that the drug was being imported from Asia to the western coast by organized crime groups in powder form and being pressed into pseudo-OxyContin tablets.

2015: Global Healthcare Usage

In 2015, 1,600 kilograms (3,500 pounds) of fentanyl were used in healthcare globally.

2015: Annual Aggregate Manufacturing Quota

In 2015, the annual aggregate manufacturing quota for Fentanyl was 2,300,000 kg.

November 2016: DEA uncovers counterfeit oxycodone and Xanax operation

In November 2016, the DEA uncovered an operation in Cottonwood Heights, Utah, making counterfeit oxycodone and Xanax from a home. They found about 70,000 pills in the appearance of oxycodone and more than 25,000 in the appearance of Xanax. The accused owned a tablet press and ordered fentanyl in powder form from China.

2016: Fentanyl Overdose Deaths in British Columbia

In 2016, deaths from fentanyl overdoses in the province of British Columbia averaged two persons per day.

2016: Annual Aggregate Manufacturing Quota

In 2016, the annual aggregate manufacturing quota for Fentanyl was 2,300,000 kg.

April 2017: Increase in Death Rate in British Columbia

In April 2017 the death rate increased by more than 100% with 368 overdose-related deaths in British Columbia between January and April 2017.

2017: Most Widely Used Synthetic Opioid

As of 2017, fentanyl was the most widely used synthetic opioid in medicine.

2017: Report on Transdermal Exposure Risk

In 2017, The American College of Medical Toxicology and the American Academy of Clinical Toxicology issued a joint report asserting the risk of fentanyl overdose via incidental transdermal exposure is very low.

2017: Study on Fentanyl Lozenges for Children

In 2017, a study suggested the efficacy of fentanyl lozenges in children as young as five, weighing as little as 13 kg, for pain management.

2017: Fentanyl discovered for sale in illicit markets in Australia

In 2017, fentanyl was discovered for sale in illicit markets in Australia.

2017: Increase in Fentanyl-Related Deaths in the US

In the US, fentanyl and fentanyl analogs caused over 29,000 deaths in 2017, a large increase over the previous four years.

February 2018: DEA classifies illicit fentanyl analogs as Schedule I drugs

In February 2018, the U.S. Drug Enforcement Administration (DEA) indicated that illicit fentanyl analogs have no medically valid use, and thus applied a "Schedule I" classification to them.

July 2018: CDC Issues HAN Alert on Rising Deaths

In July 2018, a subsequent HAN Alert was issued, warning of rising numbers of deaths due to fentanyl abuse and mixing with non-opioids.

August 2018: Nebraska uses fentanyl in execution

In August 2018, Nebraska became the first American state to use fentanyl to execute a prisoner. Carey Dean Moore was executed using a lethal injection with a drug cocktail that included fentanyl citrate to inhibit breathing and render the subject unconscious. The execution caused controversy.

2018: Dark Web Ban on Fentanyl Trafficking

A 2018 report by The Guardian indicated that many major drug suppliers on the dark web have voluntarily banned the trafficking of fentanyl.

2018: Allegations of hindered cooperation between Canada and China to seize fentanyl imports

In 2018, Global News reported allegations that diplomatic tensions between Canada and China hindered cooperation to seize imports, with Beijing being accused of inaction.

2018: Fentanyl discovered for sale in illicit markets in New Zealand

In 2018, fentanyl was discovered for sale in illicit markets in New Zealand. In response, New Zealand experts called for wider availability of naloxone.

2018: Fentanyl overtakes heroin

Since 2018, fentanyl constitutes the majority of all drug overdose deaths in the United States, overtaking heroin.

February 2019: Record fentanyl seizure by U.S. Customs and Border Protection

On February 2, 2019, U.S. Customs and Border Protection in Nogales, Arizona, seized a record amount of fentanyl. The 254 pounds (115 kg) of fentanyl, which was estimated to be worth US$3.5M, was concealed in a compartment under a false floor of a truck transporting cucumbers.

May 1, 2019: China Classifies Fentanyl as Controlled Narcotic

Effective from May 1, 2019, China officially classified all forms of fentanyl as controlled narcotics.

May 2019: Drug overdose deaths

From May 2019 to May 2020, 81,230 drug overdose deaths occurred, the largest number of drug overdoses for a 12-month interval ever recorded for the U.S.

May 2019: China regulates fentanyl-type drugs and precursors

In May 2019, China regulated the entire class of fentanyl-type drugs and two fentanyl precursors.

2019: Commonly Prescribed Medication

In 2019, fentanyl was the 278th most commonly prescribed medication in the United States, with over a million prescriptions.

2019: Overdose deaths surge

Overdose deaths by fentanyl and other illegally imported opioids were surging since 2019 and are presently a major cause of death in all U.S. states.

March 2020: Increase in Overdose Deaths

From March 2020 to May 2020, there was a concerning acceleration of the increase in drug overdose deaths, coinciding with the implementation of widespread mitigation measures for the COVID-19 pandemic.

May 2020: Increase in Overdose Deaths

December 2020: CDC Issues HAN Advisory on Overdose Deaths

In December 2020, a HAN Advisory from the CDC warned of substantial increases in drug overdose deaths across the United States, primarily driven by rapid increases in overdose deaths involving illicitly manufactured fentanyl.

2020: Journal of Medical Toxicology Article

A 2020 article from the Journal of Medical Toxicology stated that the scientific consensus remains that illness from unintentional fentanyl exposures is extremely unlikely.

2020: Survey of First Responders in New York

A 2020 survey of first responders in New York found that 80% believed “briefly touching fentanyl could be deadly.”

2020: British Columbia reports 1,716 fentanyl-related deaths

In 2020, British Columbia reported 1,716 deaths related to fentanyl overdoses, which prompted Health Canada to expedite the review of naloxone's prescription-only status in an effort to combat overdoses of the drug.

2020: Pricing comparison of fentanyl formulations in the United States and Australia

In 2020, in the United States, the 800 mcg tablet was 6.75 times more expensive than the lozenge. In a 2020 report by the Australian Institute of Criminology, a 100-microgram transdermal patch was valued from between AU$75 and AU$450 on illicit markets. Furthermore, in another 2020 study, the average price per gram of non-pharmaceutical fentanyl on various cryptomarkets was US$1,470.40 for offerings of less than five grams; the average for offers over five grams was US$139.50.

2020: Myanmar military confiscates methyl fentanyl and precursors

In 2020, the Myanmar military and police confiscated 990 gallons of "methyl fentanyl" [sic], as well as precursors for the illicit synthesis of the drug.

2020: Increase in fentanyl reports

The United States National Forensic Laboratory estimates fentanyl reports by federal, state, and local forensic laboratories increased from 4,697 reports in 2014 to 117,045 reports in 2020.

October 2021: British Columbia reports 1,782 fentanyl-related deaths from January to October

From January to October 2021, British Columbia reported 1,782 deaths related to fentanyl overdoses. Because of the rising deaths across the country, Health Canada is putting a rush on a review of the prescription-only status of naloxone in an effort to combat overdoses of the drug.

2021: Paper on physical fears over Fentanyl

A 2021 paper expressed concern that physical fears over fentanyl may inhibit effective emergency response to overdoses.

2021: Gupta Method

For the first half of 2021, the U.S. Drug Enforcement Administration found the Gupta method was the predominant synthesis route in their samples of seized fentanyl.

2021: Overdose deaths caused by Fentanyl

In 2021, fentanyl and its analogues were responsible for over 71,238 drug overdose deaths in the United States.

2021: UNODC reports decline in opium poppy cultivation in Burma

In 2021, the United Nations Office on Drugs and Crime reported a further drop in opium poppy cultivation in Burma, as the region's synthetic drug market continues to expand and diversify.

2021: Reduction in Manufacturing Quota

In 2021, the annual aggregate manufacturing quota for fentanyl significantly reduced to 731,452 kg, a nearly 68.2% decrease from previous years.

2021: Percentage of overdoses involving Fentanyl

While overdoses involving fentanyl in the United States have decreased in 2024, the overall percentage of overdoses involving fentanyl has remained stable between 70% and 80% from 2021-2024.

2022: Direct fentanyl shipments from China stopped

According to the national archives and the DEA, direct fentanyl shipments from China have stopped since 2022.

2022: China halts cooperation with the United States on combatting drug trafficking

Following the 2022 visit by Nancy Pelosi to Taiwan, China halted cooperation with the United States on combatting drug trafficking.

2022: Fentanyl synthesis by Braga and coworkers

In 2022, Braga and coworkers described a synthesis of fentanyl involving continuous flow that uses reagents similar to the ones described for the Gupta procedure.

April 2023: Teva Pharmaceuticals USA recalls Fentanyl Buccal Tablets

In April 2023, Teva Pharmaceuticals USA recalled 13 lots of their Fentanyl Buccal Tablets CII due to missing safety information sheets on how to properly administer their product.

2023: Average cost for an injectable fentanyl solution

As of 2023, the average cost for an injectable fentanyl solution (50 mcg/mL) is around US$17 for a supply of 20 milliliters, depending on the pharmacy.

2023: California police union director charged with importing synthetic opioids

In 2023, a California police union director was charged with importing synthetic opioids, including fentanyl and tapentadol disguised as chocolate.

2023: Record Overdose Deaths in the U.S. and Canada

In 2023, overdose deaths in the U.S. and Canada again reached record numbers. Also according to a 2023 report, the increased numbers of deaths are not related to an increased number of users but to the lethal effects of fentanyl itself.

2024: Bilateral talks between US and China on fentanyl resume

In 2024, bilateral talks on fentanyl resumed in San Francisco when then U.S. President Joe Biden and Chinese President Xi Jinping met.

2024: Fentanyl overdoses

While overdoses involving fentanyl in the United States have decreased in 2024, the overall percentage of overdoses involving fentanyl has remained stable between 70% and 80% from 2021-2024.

February 2025: President Trump imposes tariffs on Chinese imports

In February 2025, US president Trump imposed a 10% tariff on Chinese imports, claiming the move as a way "to pressure China into taking action on fentanyl". But experts have expressed concern that these tariffs could reverse the progress made under the Biden administration and weaken the international cooperation necessary to combat global drug trafficking.