This Is What Makes Certain Opioids More Deadly Than Others

The opioid crisis has run rampant across the U.S., and synthetic opioids have led to an increase in opioid-involved overdose deaths.

By Mac Stone
Mar 2, 2023 5:00 PM
Opioid overdose
Depiction of opioids, or pain killers, referencing the opioid crisis. (Credit: Victor Moussa/Shutterstock)


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According to the Centers for Disease Control and Prevention, more than 932,000 people have died from a drug overdose in the U.S. since 1999. In 2020 alone, nearly 100,000 people died from an overdose. The main cause? Synthetic opioids — specifically fentanyl.

This sharp rise in opioid-related overdoses in recent years includes almost 69,000 deaths in 2020. Of those deaths, 82.3 percent of them involved synthetic opioids, which are artificially produced. But what makes synthetic opioids so deadly?

Fentanyl and Synthetic Opioids

Fentanyl is a synthetic opioid that is about 100 times more potent than morphine and 50 times more potent than heroin in how it effects the body, according to the Department of Justice/Drug Enforcement Administration.

While it has become a household name in recent years, fentanyl has been around since its creation in 1959 and was introduced in the 1960s as an intravenous anesthetic to relieve pain.

But today, the increase in illegal trafficking of fentanyl and other synthetic opioids has led to a skyrocketing number of drug overdoses in the U.S., and beyond. These drug overdoses often occur when people use a drug, such as heroin, that has been laced with fentanyl.

Because a person is unaware of the presence of fentanyl, they do not know they are taking a potentially deadly dose. Once injected into the body, the drug travels to the brain, where it binds to certain opioid receptors, known as mu-opioid receptors. These receptors are in the part of the brain that manages pain and emotion, which is why these drugs provide extreme pain relief.

Why Are These Synthetic Opioids so Deadly?

Synthetic opioids, specifically fentanyl, are more lethal than more naturally occurring opioids for one main reason: They are more effective at binding to mu-opioid receptors.

When an opioid enters the brain and binds to those opioid receptors, an excess amount of binding can lead to drowsiness, disrupt the body’s breathing process and eventually lead to loss of consciousness.

According to a 2021 study published in Nature, fentanyl can adopt different binding modes in the brain, which may be why fentanyl is so lethal in such small doses. However, researchers admit that more research is needed to understand how fentanyl works in the brain.

“Surprisingly little is known about the signaling mechanism of fentanyl and how it interacts with [mu-opioid receptors] to illicit analgesic response,” researchers write in the study. “It is conceivable that fentanyl and its analogs bind and activate [mu-opioid receptors] in the same manner as morphinan compounds; however, the structural basis remains lacking.”

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