What is fentanyl and why is it driving the deadly spike in drug overdoses in the United States? A medical toxicologist explains


Buying drugs on the street is a game of Russian roulette. From Xanax to cocaine, counterfeit drugs or pills purchased from non-medical settings can contain life-threatening amounts of fentanyl.

Doctors like me have seen an increase in the unintentional use of fentanyl by people who buy prescription opioids and other drugs mixed or adulterated with fentanyl. Heroin users in my community in Massachusetts realized that fentanyl entered the drug supply when overdose numbers have skyrocketed. In 2016, my colleagues and I found that patients presenting to the emergency room reporting a heroin overdose often only had fentanyl present in their drug test results.

As head of medical toxicology at UMass Chan Medical School, I have studied fentanyl and its analogues for years. As fentanyl has become ubiquitous in the United States, it has transformed the illicit drug market and increased the risk of overdose.

Fentanyl and its analogues

Fentanyl is a synthetic opioid that was originally developed as an analgesic – or analgesic – for surgery. It has a specific chemical structure with multiple zones that can be altered, often illicitly, to form related compounds with marked differences in potency.

The chemical skeleton of fentanyl (the structure in the center) has several areas (the colored circles) which can be replaced by different functional groups (the colored boxes on the edges) to modify its potency.
Christopher Ellis et al., CC BY-NC-ND

For example, carfentanil, a fentanyl analog formed by replacing one chemical group with another, is 100 times more potent than its parent structure. Another analogue, acetylfentanylis about three times less potent than fentanyl, but still led to clusters of overdoses in several states.

Despite the number and diversity of its analogues, fentanyl itself continues to dominate the illicit supply of opioids. Milligram for milligram, fentanyl is roughly 50 times stronger than heroin and 100 times stronger than morphine.

Mixing or replacing drugs with fentanyl

Drug dealers have used fentanyl analogues as an adulterant in the illicit drug supply since 1979with fentanyl-related overdoses clustered individual cities.

The modern epidemic of fentanyl tampering is much broader in geographic distribution, production, and death toll. Overdose death roughly quadrupledfrom 8,050 in 1999 to 33,091 in 2015. From May 2020 to April 2021, more than 100,000 Americans died of a drug overdose, with more than 64% of these deaths being due to synthetic opioids like fentanyl and its analogues.

Illicitly manufactured fentanyl is internationally synthesized in China, Mexico and India, then exported to the United States in the form of powder or tablets. Moreover, the emergence of dark canvasan encrypted and anonymous corner of the internet that is a haven for criminal activity, has facilitated the sale of fentanyl and other opioids shipped via traditional delivery servicesincluding the US Postal Service.

Fentanyl is the cause of a growing number of opioid overdose deaths.

Fentanyl is both sold on its own and often used as an adulterant because its high potency allows dealers to traffic in smaller amounts while retaining the effects of the drug that buyers expect. Manufacturers can also add bulking agents, such as flour or baking soda, to fentanyl to increase supply without increasing cost. As a result, it is much more cost effective to cut a kilogram of fentanyl compared to a kilogram of heroin.

Unfortunately, the high potency of fentanyl also means that even a small amount can be deadly. If the end user does not know that the medicine they have purchased has been adulterated, this could easily lead to an overdose.

Preventing Fentanyl Deaths

As an emergency doctor, I give fentanyl as a painkiller, or painkiller, to relieve severe pain in an acute care facility. My colleagues and I choose fentanyl when patients need immediate pain relief or sedation, such as anesthesia for surgery.

But even under the controlled conditions of a hospital, there is always a risk that the use of fentanyl could reduce breathing rates at dangerously low levels, the leading cause of death from opioid overdose. For those taking fentanyl in a non-medical setting, there is no medical team available to monitor a person’s breathing rate in real time to ensure their safety.

One measure to prevent a fentanyl overdose is distribution of naloxone to passers-by. Naloxone can reverse an overdose as it occurs by blocking the effects of opioids.

Another measure is to increase the availability of opioid agonists like methadone and buprenorphine which reduce opioid withdrawal symptoms and cravings, helping people stay in treatment and reduce their illicit drug use. Despite the life-saving history of these drugs, their availability is limited by restrictions on where and how they can be used and insufficient number of prescribers.

Naloxone can quickly reverse an opioid overdose.

Other strategies to prevent overdose deaths include lowering the barrier of entry addiction treatment, fentanyl test strips, supervised consumption sites and even prescription diamorphine (heroin).

Despite the evidence supporting these measures, however, local policies and funding priorities often limit the possibility for communities to try them. Bold strategies are needed to halt the ever-increasing number of fentanyl-related deaths.

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