Since last fall, new and deadly synthetic opioids called orphines have begun appearing in street drugs in the United States. They are far more potent than fentanyl but cannot be detected by standard toxicology tests.
Orphines are still much less common than fentanyl, but they are proliferating quickly. As of last month, they have been found in 14 states, mostly in the South and the Midwest. Law enforcement officials and public health officials are trying to assess the gravity and endurance of the threat they pose.
Here are answers to some basic questions.
What are orphines?
They are a class of opioids that was created in the 1960s by Paul Janssen, a Belgian doctor and pharmacologist, whose teams investigated rapid, safe pain relievers for surgery. As part of that effort, they also developed fentanyl.
Dr. Janssen and others discovered that orphines had life-threatening side effects such as acute respiratory depression and were highly addictive. Within a few years, the research on them was halted.
Researchers characterize orphines as 10 times more powerful than fentanyl, even in quantities no greater than a few sand-size grains. They can be lethal with stunning speed, with victims slumping over abruptly, respiration shutting down, chest walls rigid. Sometimes the classic signature of overdose, “the foam cone” — froth from the nostrils and mouth — does not even have time to bubble up.
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Still, it is possible for people overdosing on orphines to be revived with naloxone, the opioid reversal medication. But numerous doses may be required, many more than the one or two doses typically needed for fentanyl.
Why did orphines start showing up in United States?
Orphines are among the synthetic opioids that started to appear in the street drug supply in the wake of global crackdowns on fentanyl.
In 2018, the Drug Enforcement Administration issued a temporary ban on all fentanyl-related substances, called analogs. That same year, an article in The Journal of Medicinal Chemistry addressed the challenge of developing opioids without toxic side effects and offered orphines as cautionary examples. It described them as dangerous, because they are so powerfully addictive and may affect breathing.
Researchers speculate that rogue chemists, seeking illicit drugs that can evade international drug laws, may have been inspired by the article to develop orphines. By 2019, brorphine, an early orphine, was detected in Europe.
Around that time, another class of cheap, synthetic opioids called nitazenes had been circulating in Europe and the United States, alarming law enforcement and public health officials. But in July 2025, China, a key manufacturing source of chemicals for nitazenes, banned them.
Nitazenes began to fade but, within months, orphines popped up in the American illicit drug supply.
In what form are orphines sold?
The most common orphine is an analog called cychlorphine (also known as N-propionitrile chlorphine). It seems to be circulating in counterfeit pills or as a powder, bulking and boosting fentanyl. Overdoses and fatalities may occur because the user did not know that the intended drug — such as the stimulant methamphetamine — had been adulterated with the orphine.
Cychlorphine is so new, so difficult to seize that researchers believe it is often being delivered by international mail. In addition to the United States, it has been detected in Estonia, Latvia and Lithuania, France and Germany, where, cheap and available, it has been nicknamed “poor man’s fentanyl.”
There are indications in Europe that cychlorphine is being used on its own, not just to adulterate other drugs. Medical examiners in the United States are starting to surmise this as well because a few overdose fatalities do not test positive for conventional illicit drugs, like fentanyl and benzodiazepines. When further toxicology tests have been done, cychlorphine shows up as the only deadly drug on board.
