Fentanyl, a potent synthetic opioid, is primarily used for pain management and sedation. It is significantly more potent than heroin and morphine. Fentanyl's adverse effects include addiction, respiratory depression, and even death. Naloxone can reverse its effects. Fentanyl was first synthesized in 1959 and approved for medical use in 1968. It is widely used in medicine and is on the WHO's List of Essential Medicines. However, fentanyl has contributed to a significant increase in synthetic opioid overdose deaths in the US, surpassing heroin-related deaths. Its high potency and ease of production have made it a major concern in the ongoing opioid crisis.
In 1957, Eddy NB and Halbach H conducted a study on synthetic substances that have morphine-like effects. The study focused on the potency, side-effects, and addiction liability of these substances.
Fentanyl was first created and developed by Dr. Paul Janssen in 1959 under a patent held by his company Janssen Pharmaceutica. It is a powerful analgesic that is nearly a hundred times more potent than morphine.
In 1960, Dr. Paul Janssen, a Belgian chemist and founder of Janssen Pharmaceutica, synthesised fentanyl. It was a significant breakthrough in pain management as fentanyl was around 100 times more powerful than morphine.
Fentanyl was approved for medical use in the United States in 1968.
In 1971, the UK classified fentanyl as a controlled Class A drug under the Misuse of Drugs Act. This classification signifies the strict regulations and penalties associated with the possession and distribution of fentanyl in the country.
Strauer BE conducted a comparative study in 1972 on the contractile responses of morphine, piritramide, meperidine, and fentanyl on the isolated ventricular myocardium. The research aimed to compare the effects of these substances on cardiac muscle contraction.
In 1974, Freye E examined the cardiovascular effects of administering high dosages of fentanyl, meperidine, and naloxone in dogs. The study aimed to understand the impact of these substances on the cardiovascular system.
In 1975, a study observed the myocardial sparing effect of fentanyl when used during halothane anesthesia in dogs. The research aimed to understand how fentanyl could potentially protect the heart muscle during anesthesia.
A study conducted in 1976 examined the cardiovascular dynamics in dogs after administering large doses of fentanyl and fentanyl plus N2O. The research focused on the effects of these substances on the cardiovascular system.
Stanley TH, Bidwai AV, Lunn JK, and Hodges MR investigated the cardiovascular effects of nitrous oxide when combined with meperidine infusion in dogs in 1977. The study focused on the interaction between nitrous oxide and meperidine on the cardiovascular system.
In 1978, a study investigated the anesthetic requirements and cardiovascular effects of Fentanyl-Oxygen and Fentanyl-Diazepam-Oxygen anesthesia in humans. The findings were published in Anesthesia and Analgesia.
A study in 1979 investigated the use of high dose fentanyl anesthesia for coronary artery surgery. The research focused on the plasma fentanyl concentration and the influence of nitrous oxide on cardiovascular responses during the procedure.
A study conducted in 1980 examined the plasma catecholamine and cortisol responses to fentanyl-oxygen anesthesia for coronary-artery operations. The research focused on the hormonal responses induced by fentanyl anesthesia during the surgical procedure.
In 1981, a study investigated the effects of high dose fentanyl anesthesia on the electroencephalogram. The research aimed to understand the impact of fentanyl anesthesia on brain activity as reflected in the EEG.
A study in 1982 compared the use of sufentanil-O2 and fentanyl-O2 for coronary artery surgery. The research aimed to evaluate the efficacy and safety of these two anesthesia methods for the surgical procedure.
A double-blind study conducted in 1983 evaluated the intraoperative effectiveness of Sufentanil, Fentanyl, Meperidine, or Morphine in balanced anesthesia. The research was published in Anesthesia and Analgesia.
In April 1992, the article 'The history and development of the fentanyl series' was published, discussing the significant role of opioid analgesics like fentanyl, sufentanil, and alfentanil in anesthetic practice.
Actiq was the first pain medicine approved to treat cancer breakthrough pain, but it raised safety concerns due to its resemblance to a lollipop, leading to a restricted distribution program to prevent accidental exposure in children and potential abuse. It later became part of the category of opioids known as transmucosal immediate-release fentanyl products.
During the Moscow theater hostage crisis in 2002, Russian Spetsnaz security forces are suspected to have used a fentanyl derivative to incapacitate individuals. The gas based on fentanyl led to casualties among the hostages.
American professional wrestler Anthony Durante, also known as 'Pitbull #2', died from a fentanyl-induced overdose.
In February 2004, Janssen Pharmaceutica Products initiated recalls of fentanyl patches due to seal breaches that could lead to medication leakage. Subsequent recalls were made in 2004 and 2008 by different pharmaceutical companies.
Between June 2005 and October 2006, more than 80% of patients using Actiq lollipop were prescribed 'off-label', meaning they did not have cancer as the intended condition for the drug.
In 2006, the United States Food and Drug Administration (FDA) initiated an investigation into several respiratory deaths associated with fentanyl use.
In 2007, there were several seizures of illicit fentanyl, including a raid on a lab manufacturing counterfeit OxyContin. This highlighted the presence of illegally manufactured fentanyl in the market.
In September 2008, doctors in the United Kingdom were finally warned of the risks associated with fentanyl, two years after the FDA investigation began in the United States.
Wilco guitarist Jay Bennett died from an accidental overdose of fentanyl.
Slipknot bassist Paul Gray died from an overdose of morphine and fentanyl.
Abstral, a fentanyl product, was approved as the fourth TIRF product with a Risk Evaluation and Mitigation Strategies (REMS) in place.
Lazanda, a fentanyl product, was approved as the fifth TIRF product with a Risk Evaluation and Mitigation Strategies (REMS) in place.
FDA approved a single-shared Risk Evaluation and Mitigation Strategy (REMS) system for all TIRF products, aiming for a unified approach to safety measures.
Subsys, a fentanyl sublingual spray, was approved as the sixth TIRF product and integrated into the single-shared TIRF REMS.
The single-shared Transmucosal Immediate-Release Fentanyl (TIRF) REMS system went live, marking a collaborative effort to address patient access issues.
In April 2012, the FDA reported that twelve young children had died and twelve more had become seriously ill due to separate accidental exposures to fentanyl skin patches.
In June 2013, the CDC issued a health advisory regarding 14 overdose deaths linked to acetylfentanyl among intravenous drug users in Rhode Island. Acetylfentanyl is a synthetic opioid analog of fentanyl that has not been approved for medical use.
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. They advised that the patches should be folded with the adhesive side in before being discarded to prevent harm.
In October 2015, the U.S. Centers for Disease Control issued an initial Health Alert Network Advisory warning about the misuse and fatal overdose risks associated with fentanyl.
Musician Prince accidentally overdosed on fentanyl, among other substances, as concluded by medical examiners.
Canadian video game composer Saki Kaskas died of a fentanyl overdose after battling heroin addiction.
In 2017, there were growing concerns about the abuse of fentanyl, with many attributing it to the drug being highly addictive and causing numerous deaths. The issue of fentanyl abuse raised questions about the ethical implications of its creation.
FDA convened a joint meeting to discuss the risk evaluation and mitigation strategy for TIRF medicines, focusing on safe use, patient access, and healthcare system burden.
American rapper Lil Peep died of an accidental fentanyl overdose.
Musician Tom Petty died from an accidental drug overdose that included fentanyl among other medications.
American rapper Mac Miller died from an accidental overdose of fentanyl, cocaine, and alcohol.
American tech entrepreneur Colin Kroll died from an overdose of fentanyl, heroin, and cocaine.
On 2 February 2019, U.S. Customs and Border Protection seized 254 pounds of fentanyl, valued at US$3.5M, hidden in a truck transporting cucumbers in Nogales, Arizona. This was a significant interception of illicit fentanyl entering the country.
In 2019, fentanyl continues to play a significant role in medical treatment, especially for terminal and chronic pain patients. Despite its benefits, the drug has also been misused and abused, leading to serious consequences.
American baseball player Tyler Skaggs died from pulmonary aspiration under the influence of fentanyl, oxycodone, and alcohol.
American rapper, singer, and songwriter Lexii Alijai died from accidental toxicity due to a combination of alcohol and fentanyl.
During the 12 months-ending January 31, 2020, overdose deaths involving opioids increased by 38.1 percent in the United States.
American singer, songwriter, and musician Justin Townes Earle died from an accidental overdose caused by cocaine laced with fentanyl.
Riley Gale, frontman for the Texas metal band Power Trip, died as a result of the toxic effects of fentanyl in an accidental manner.
In the 12 months-ending January 31, 2021, overdose deaths involving synthetic opioids, primarily illicitly manufactured fentanyl, rose by 55.6 percent, contributing significantly to the overall rise in drug overdose deaths.
American musician Mark Goffeney, known as 'Big Toe', died from an overdose of fentanyl.
Digital Underground frontman Shock G died from an accidental overdose of fentanyl, meth, and alcohol.
Actor Michael K. Williams, known for his role as Omar Little on The Wire, died from an overdose of fentanyl, parafluorofentanyl, heroin, and cocaine.
Rapper Coolio died from an accidental overdose of fentanyl, heroin, and methamphetamine.
Angus Cloud, known for his role as Fezco on Euphoria, died from an accidental overdose of methamphetamine, cocaine, fentanyl, and benzodiazepines.
An infant died at a daycare center in The Bronx, New York City, due to fentanyl contamination, causing sickness in other children.
Mark D'Wit was sentenced to a minimum of 37 years imprisonment for murdering individuals by giving them drinks laced with fentanyl.