Since last fall, new synthetic drugs called orphines have begun appearing in the illicit drug supply.

The federal Office of National Drug Control Policy (ONDCP) issued a drug threat notice on cyclorphine last week.

The details:

Orphines are a class of synthetic opioids. They are far more potent than fentanyl. Cyclorphine is the most common orphine, and it is up to 10 times more potent than fentanyl.
Cyclorphine can be found on its own or mixed in with fentanyl or other drugs such as methamphetamine, bromazolam, cocaine, and others. It seems to be circulating in counterfeit pills or as a powder, often bulking fentanyl.
Orphines are not detected by drug test strips, routine hospital opioid urine screens, or standard toxicology tests. Prevalence numbers are therefore likely an undercount.
Numerous doses of naloxone may be required to reverse an orphine overdose.

The numbers: Orphines are still much less common than fentanyl but are proliferating quickly.

As of last month, they have been found in 14 states, mostly in the South and Midwest. Cyclophine has been identified in 10 states, with the greatest prevalence in Ohio, Texas, and Tennessee.
Nationally, 55 deaths have been linked to cyclorphine 2025-2026.

The broader context: Orphines started to appear in the drug supply in the wake of crackdowns on fentanyl and nitazenes.

Researchers believe most orphines originate in Chinese labs. In July, China banned nitazenes, and by fall, orphines arrived in the U.S. Cyclorphine is often being delivered by international mail, as it is new and difficult to seize.