Novel Synthetic Opioid Cychlorphine: What Doctors Should Know

The emergence of the synthetic opioid cychlorphine (N-propionitrile chlorphine) in recent years has physicians and public health experts worried.

The street drug has been linked to at least 55 deaths nationally from 2025 to 2026, according to a “drug threat notice” issued by the Office of National Drug Control Policy (ONDCP) in April. Prevalence of the drug is highest in Ohio, Tennessee, and Texas.

Cychlorphine belongs to a subclass of opioids known as orphines and is structurally similar to other benzimidazolones, such as brorphine and chlorphine.

Jon E. Sprague, PhD, of Bowling Green State University in Ohio, told MedPage Today that there are a number of unknowns when it comes to orphines. “What’s the human potency? We don’t know. How long does it last? We don’t know. How is it metabolized? We don’t know,” he said. “How well does it cross into the brain? We don’t know.”

Cychlorphine surfaced on the streets between mid-2024 and late 2025, experts said. Sprague noted that when China placed restrictions on nitazenes in July 2025, cychlorphine emerged on the market as traffickers shifted course.

“They’re making these chemical modifications so fast and furious that we don’t know a lot about the compounds before they hit the streets,” he said.

However, the drugs aren’t new. Certain orphines were synthesized and studied for use as potential pain relievers in the 1960s. They were never marketed, “presumably because of the enhanced mu-opioid receptor activity,” Sprague explained.

In one of the few documented cases of a nonfatal overdose involving cychlorphine, authored by Sprague, a 36-year-old man was found unconscious and revived with two doses of naloxone after reportedly snorting what he believed to be alprazolam. While the patient refused urine and blood tests, a small bag “with a tan, crystallized powder” in it was recovered from the scene. Testing detected fentanyl, xylazine, and cychlorphine in the powder. Sprague noted that it took the crime lab in Ohio several weeks to identify the compound.

Another case study published this year focused on a woman in her 20s who was found unresponsive after ingesting what she believed was alprazolam. She was given naloxone by paramedics and taken to the emergency department. Toxicology testing identified cychlorphine, as well as bromazolam, carboxy-THC, acetaminophen, caffeine, citalopram, cotinine, naloxone, naproxen, nicotine, and trazodone and its metabolite.

Rebecca Kusko, MD, an author of the case study, stressed that while standard drug screens may not pick up novel opioid substances, “it still is appropriate to treat with naloxone if someone is presenting in a way that makes you suspicious for opiates.”

Cychlorphine has been found mainly in powders and tablets, including counterfeit pills. Snorting and inhaling are common, but oral exposure and injection are also possible, Shravani Durbhakula, MD, MPH, of Vanderbilt University School of Medicine in Nashville, Tennessee, told MedPage Today.

In her state, the Knox County Regional Forensic Center reported 41 overdose deaths between July 2025 and February 2026. Durbhakula said the center also tracked as many as 63 cychlorphine-associated deaths through June 30, making the drug the fourth most common tied to fatalities this year. “That is an extraordinary signal for a drug that was essentially unknown here a year ago,” she noted.

Chris Thomas, the center’s chief administrative officer, confirmed the 63 deaths, and said cychlorphine was found to be the cause in 58 of those cases. It was the sole drug detected in a handful of the cases, he pointed out, adding that it is “extremely fatal in small doses.”

The ONDCP said the drug may be “up to 10 times more potent than fentanyl” and that “an overdose may require multiple doses of naloxone.” However, Durbhakula noted that such metrics are based on laboratory pharmacology and not human dose-equivalence studies.

“You’ll hear a lot of people say ‘naloxone doesn’t work,’ but that is not a true statement,” said Lewis Nelson, MD, a medical toxicologist at the Charles E. Schmidt College of Medicine at Florida Atlantic University in Boca Raton. He cautioned that the opioid overdose antidote needs to be given before brain swelling occurs, and that those administering naloxone should not expect patients to “respond the way they do in Hollywood movies.”

“The end point for success of naloxone is not waking up, it’s breathing,” he told MedPage Today.

Nelson said it’s difficult to know where cychlorphine is concentrated “because most places, whether they’re public health departments or hospitals or medical examiners, don’t really test for this drug.”

Durbhakula said she worries about “the combination of extreme potency and invisibility,” and warned clinicians that even if an opioid screen is negative for fentanyl or “conventional opioids,” that does not exclude exposure to a possible synthetic opioid.