Fentanyl is a potent opioid drug that is used to treat severe pain in patients around the globe, especially after severe surgeries. It was first developed in 1960 by Paul Janssen, and it was the fastest-acting opioid at the time of its discovery (Han et al., 2019). It plays a role like that of morphine and has become more popular over the last few years in both medical and non-medical use. It is believed to be approximately 100 times more potent than morphine and 50 times more potent than heroin (“Fentanyl,” n.d.). However, while it is therapeutic, fentanyl’s properties also make it highly addictive and lethal. Over the last few years, the drug has become a popular item in the drug market because of its properties and poses serious issues to many people with its increasing number of users and high lethality rates. Fentanyl can be reviewed in multiple sections to properly understand the drug and its use as well as its future. This paper reviews fentanyl’s chemical components, pharmacological effects, lethality and overdose, production, and its future.
First of all, fentanyl needs to be reviewed with its chemical components to understand its pharmacological effects. While opioids generally refer to the drugs made from the opium poppy plant, fentanyl is a synthetic opioid that appears in white crystals or powder, meaning it was produced in a lab. Fentanyl has multiple pharmacological effects, such as in vivo potency, rapid onset of action, rapid cessation, induction of muscle rigidity, and euphoria (Kelly et al., 2023). These pharmacological effects are a result of fentanyl’s various chemical properties and cause its addictive and lethal properties.
One chemical property of fentanyl is its high selectivity for mu opioid receptors (MOR) (Eshleman et al., 2020). Mu opioid receptors are considered a primary receptor for opioids and are found in the periaqueductal gray and raphe nuclei, regions of the brain with a role in pain and analgesia (“Opioid Receptors,” n.d.). Fentanyl’s high selectivity for these receptors makes it more likely to bind and, in turn, decrease pain in patients and users. It is one of the main reasons fentanyl is more potent than other drugs. Furthermore, these receptors develop dependence and are ineffective against morphine-resistant interactive pain (Mizoguchi et al., 2012). The in vivo potency of the drug is a reason a lot of people become interested in the excessive use of the drug, which later turns into addiction (Kelly et al., 2023).
Another one of fentanyl’s chemical properties is its solubility in water, which causes a rapid onset of action and cessation (Kelly et al., 2023). Fentanyl’s high lipid solubility, or lipophilic properties, allows it to penetrate the cell membrane and make it through the blood-brain barrier, “a tightly locked layer of cells that protect the brain from outside substances” (“Blood Brain Barrier,” n.d.). This allows fentanyl to both showcase its properties and disappear quickly, relieving patients with severe pain rapidly or causing users to crave the drug, leading to addiction over time.
Furthermore, fentanyl has a pharmacological effect of inducing severe muscle rigidity in the chest wall and diaphragm (Eshleman et al., 2020). This effect of fentanyl is a reason its overdose can be lethal in users.
Additionally, another pharmacological component is euphoria, which is a state of intensive happiness or excitement. The rapid onset and lipophilic properties lead to a rapid euphoria in users (Eshleman et al., 2020). While these are not the only chemical or physiological properties of the drug, they are the main reasons for fentanyl’s success as a drug in the medical field, its increasing use among people and production in the drug market, and its lethality in overdosed users.
Drug poisoning is a leading cause of death among Americans aged 18–45, according to the Centers for Disease Control and Prevention (CDC) (Lewis, 2024). It has been recorded since 2021 that 100,000 people have lost their lives to overdose every year (Lewis, 2024). The CDC estimated over 110,000 people died in the U.S. from drug overdose in 2022, and 70% of these deaths were caused by fentanyl and other synthetic opioids (“Operation Engage Spokane,” n.d.). In 2023, estimated deaths due to fentanyl were 74,702 (CDC, 2024a). Between 2015 and 2017, there was a 55% increase in fentanyl-related overdose deaths in New York City (Han et al., 2019). In other words, fentanyl has been becoming more popular ever since its discovery, with an exponential growth in the overdose rate. However, fentanyl does not just cause death by itself, but with other drugs as well. It has been seen that when taken at the same time, some drugs have more intense effects on the users. For both the drug market and fake pills, fentanyl is mixed with other kinds of drugs like methamphetamine, cocaine, heroin, and more. This causes its pharmacological effects to be more severe and leads to rapid death. For example, fentanyl is a major contributor to cocaine-related overdose deaths in New York City (Han et al., 2019). The Drug Enforcement Administration’s (DEA) lab testing found in 2022 that 6 out of 10 fentanyl-laced fake prescription pills contain a potentially lethal dose of fentanyl (DEA, n.d.). The lethality and increased overdose of the drug make finding a treatment essential.
The primary way of treating fentanyl overdose is giving patients Naloxone, which is an opioid antagonist. Naloxone binds to the opioid receptors and reverses/blocks the opioid overdose (“Opioid Overdose Reversal Medications (OORM),” n.d.). However, Naloxone is only effective when used early. A systematic review was done by Chimbar and Moleta (2018) to determine if take-home naloxone was effective in preventing overdose deaths. The researchers searched multiple databases such as CINHAL, MEDLINE, SocINDEX, etc. with keywords such as “mortality” and “Narcan.” While the study lacked randomized controlled trials due to ethical issues, it concluded that there was overwhelming support for take-home naloxone programs being effective in preventing fatal opioid overdose. The main reason behind this was likely the early administration of Narcan, as the drug does not treat the aftereffects but gives the body time to dispose of the fentanyl or other opioids before they bind to the receptors. In March 2023, the Food and Drug Administration (FDA) approved Naloxone nasal sprays as the first over-the-counter OORM (“Opioid Overdose Reversal Medications (OORM),” n.d.). While take-home programs and the availability of Naloxone help prevent overdose deaths, they are not a solution to increased fentanyl production in illegal foreign labs.
Fentanyl’s production is a political and social problem in addition to a scientific one. According to the DEA, fentanyl is primarily produced in foreign clandestine labs and smuggled into the United States, mainly from Mexico (“Facts About Fentanyl,” n.d.). It is presented in various forms, such as nasal sprays, powders, and pills made to look like prescription pills, which contain potentially lethal doses as mentioned above. Fentanyl, being a synthetic drug, requires chemical research and delicacy in a clean environment. In the illicit labs, there is no research to test the doses or concentration of fentanyl used. Furthermore, its effects are not tested when laced with other drugs. According to DEA analysis, when mixed with other drugs, fentanyl is more lethal, and 42% of pills tested for fentanyl contained at least 2 mg of the drug, a lethal dose (“Facts About Fentanyl,” n.d.). In other words, illegal production, the main source of these pills, increases both fentanyl’s lethality and rapid onset, which makes the Naloxone ineffective in fighting the overdose deaths. This issue raises concerns for the future.
Fentanyl’s popularity is on the rise around the globe, and especially in the United States. Its first production in the 1960s has created a new treatment for patients suffering from pain and has worked to benefit humans. However, its future is not as clear. In illicit labs, the drug is constantly being developed to become more addictive, which leads to increased lethality. Fentanyl is a low-cost drug, and, according to the DEA, drug dealers are mixing fentanyl with heroin, methamphetamine, and cocaine (“Facts About Fentanyl,” n.d.). DEA has also found that illegal drugs have been intentionally contaminated with fentanyl. Currently, the drug plays a major role in the U.S., but it is likely to spread to other parts of the globe over time. Problems in parts of Canada are as severe as in the eastern United States (Pardo et al., 2019). Another topic to think about is the government’s role. Governments need to fund data collection and monitor drug use (Pardo et al., 2019). More government funding to different sectors can help develop better medications against overdose deaths, prevent the smuggling of drugs into the U.S., and raise public awareness against opioids like fentanyl.
In conclusion, drugs, specifically opioids, have been playing a role in humans’ lives for a long time. They have been used for medicinal values where they have contributed to managing pain. Fentanyl is one of these opioids synthesized in labs and has changed the market. Chemical properties and pharmaceutical effects of fentanyl have opened a new and popular market for drug dealers. While the government is working to stop smuggling and increase access to medication, the problem continues to exist. Until the overdose deaths and production are taken under control, there will be a need for a better solution.
