Orphine Opioids Emerge as Fentanyl Era Shifts in 22 States

Published: 10/16/2026 | Author: Quentin Blount

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A new class of synthetic opioids is spreading through the US illicit drug supply as the fentanyl era shifts, and it’s accelerating. Orphine analogs were detected in 22 states. The first on the list is cychlorphine, first detected in 2024 and is the most common orphine listed in the United Nations Office on Drugs and Crime early-warning system.

“The findings provide timely evidence of orphine analogues as an emerging drug threat in the US illicit drug supply,” wrote the investigative team at Virginia Commonwealth University School of Medicine in Richmond.

Orphines in the Storm

Researchers analyzed biospecimens collected through the Center for Forensic Science Research and Education’s NPS Discovery early-warning program from 2020-2026. Of 14,261 specimens tested, 142 were positive for orphines, about 1%.

The pattern consisted of two waves. The first in 2020 was dominated by brorphine. A second larger wave began in 2025. Cychlorphine accounted for 100 of 102 orphine cases.

Geographically, 53% of positive specimens originated in the South and 37% in the Midwest. Tennessee placed first with 50 specimens, followed by Illinois with 37, Texas with 14 and Minnesota with 10. All detections in Tennessee and Texas involved cychlorphine, while Minnesota’s involved brorphine and Illinois showed a mixture.

Drivers of the Trend

In July 2025, China generically scheduled nitazene analogues, disrupting supply chains. Cychlorphine specimens rose rapidly immediately afterwards and only a minority of orphine specimens contained nitazene-related compounds. Suppliers facing pressure on one class of synthetic opioid appear to have pivoted to another.

Scheduling has slowly followed. Brorphine is permanently on Schedule I. In August 2026, the DEA moved cychlorphine, spirochlorphine and SR-17018 into Schedule I under a temporary order until August 2028. Four of the five analogues analyzed are on the Controlled Substances Act’s Schedule I list.

Orphines Compared to Fentanyl

Orphine analogues are mu-opioid receptor agonists that first arrived in pharmaceutical programs back in the 1960s. Some are up to 10x deadlier than fentanyl and cause respiratory depression. 

Polysubstance exposure was the norm rather than the exception. Benzodiazepine-related compounds appeared in 37% of orphine specimens, fentanyl and methamphetamine or other amphetamines in 36% and cocaine-related compounds in 20%. Nitazenes showed up in 9%, medetomidine in 11% and xylazine in 8%. That mixing raises the risk of fatal overdoses since the depressants compound each other.

Standard Testing Misses Them

The authors called for clinical guidance on managing Cychlorphine and other overdoses, greater access to testing and naloxone and looking out for additional analogues. 

They cautioned that submitted specimens came through random and for-cause testing and weren’t systematically drawn from all jurisdictions. So the findings might not be nationally representative.

Harm Reduction & Treatment

Naloxone remains the recommended first response for any suspected opioid overdose, and people who use any street substance should carry it. High-potency opioids can require repeated naloxone doses and close monitoring for re-sedation and calling 911 remains essential.

Medication-assisted treatment remains one of the most effective care programs to thwart withdrawal.

Peer support through Narcotics Anonymous meetings is free and available in most communities. NA works alongside medical treatment.

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