It examined toxicology data from a national drug early warning system. It found that orphine analogues have become more common in toxicology samples since appearing in 2020.
What the Study Found
Led by David T. Zhu, the study examined samples tested through the Center for Forensic Science Research and Education’s NPS Discovery program between the third quarter of 2020 and the second quarter of 2026.
Researchers found that orphine detections increased over that period with patterns in location and drug combinations resembling the spread of nitazenes about five years earlier.
Zhu called the findings timely evidence of orphine analogues as an emerging drug threat in the United States. The study lands weeks after CFSRE issued a public alert on the orphine most often seen in fatal casework, N-propionitrile chlorphine, also called cychlorphine.
That alert documents 25 blood specimens from confirmed fatal overdoses at CFSRE, most submitted in late 2025 and early 2026.
Plus more than 100 tentative identifications at partner laboratory NMS Labs. Specimens came from at least eight states and three Canadian provinces.
Why Orphines Worry Toxicologists
Orphines were first studied in the 1960s as potential painkillers. Research on the compounds was abandoned because of concerns about severe breathing problems and their potential for misuse.
Brorphine brought the drug class back into the recreational market in 2020. Since then other related compounds have emerged. Laboratory research suggests cychlorphine is about ten times as potent as fentanyl.
Detecting these drugs can be difficult. Standard opioid screening tests do not reliably identify orphines. Test strips commonly used by harm reduction programs cannot detect them either.
Cychlorphine was the only opioid found in 11 of the 25 confirmed cases reported by CFSRE. Other cases involved substances such as fentanyl oxycodone methamphetamine cocaine novel benzodiazepines and additional orphine analogues.
This creates a challenge for medical providers because routine drug screens may come back negative even when an orphine is responsible for an overdose.
The Substitution Pattern Behind the Surge
Monitoring groups have seen nitazene detections decline while orphine detections have increased since China introduced broader controls on nitazene analogues in July 2025.
A similar shift followed fentanyl controls in 2018 as nitazenes emerged as another concern. These changes suggest that restricting one group of synthetic opioids may lead to the spread of other compounds.
Naloxone remains an important treatment for overdoses involving orphines, although multiple doses may be necessary.
Doctors may need to look for newer synthetic opioids when a patient has overdose symptoms but standard tests fail to detect opioids. Specialized testing is available through the NPS Discovery program.
What This Means for People in Recovery
For people with opioid use disorder and their families, the orphine wave reinforces two realities. The changing drug supply increases the risk of overdose for people who return to opioid use after a period of treatment.
And medications for opioid use disorder, naloxone access and fentanyl test strips remain essential tools, even as the strips’ blind spots widen.
Treatment that considers all aspects of a person’s substance use is important, as new synthetic opioids continue to emerge faster than researchers can track them. Search Rehab.com’s directory to find treatment centers near you or call
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