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What are Orphines?

Overview of Orphines

Orphines are a new class of synthetic opioids that are chemically distinct from fentanyl and nitazenes. First found in the US in 2020, detections of orphines in the illicit drug supply have been steadily rising in the US, Canada, and internationally since late 2025.1   

Orphine analogues have been found as a contaminant in counterfeit prescription drugs, fentanyl, medetomidine, nitazenes and designer benzodiazepines.1 Like other opioids, orphines can cause respiratory depression and fatal overdose. Although current potency is still being studied, preliminary findings indicate that orphines are significantly more potent than morphine and can range from comparable to fentanyl to significantly more potent depending on the analogue. 2 3 

Analogues

Within the class of orphines there are several compounds that share a similar chemical structure. These are known as orphine analogues. In the US, Canada, and Europe the following analogues have been found in the illicit drug supply: 

  • Chlorphine 

  • N-Propionitrile Chlorphine (Cychlorphine) 

  • 5,6-Dichloro Desmethylchlorphine 

  • Spirochlorphine  

  • Spirobrorphine 

  • 5,6-Dicholoro Brorphine1 

How do Orphines compare to Fentanyl and Nitazenes?

Fentanyl, Nitazenes, and Orphines are all synthetic opioids, but each has a unique chemical base that makes it distinct. When taken, all three drugs can have similar effects, including severe respiratory depression, which can cause drug poisoning (overdose), however their potencies vary significantly. 

 

Fentanyl  

Nitazene  

Orphines 

Type 

Synthetic Opioid 

Synthetic Opioid 

Synthetic Opioid 

Analogue Examples 

Acetylfentanyl, furanylfentanyl and carfentanil.5 

Isotonitazene, 
metodesnitazene. 4 

Chlorphine, N-Propionitrile Chlorphine (Cychlorphine), 5,6-Dichloro Desmethylchlorphine, Spirochlorphine, Spirobrorphine, and 5,6-Dichloro Brorphine.2 

Potency 

50–100x more potent than morphine  (carfentanil is estimated to be significantly more potent).5 

 

Potency varies according to the analogue. 

Etonitazene is roughly 70x more potent than morphine, while isotonitazene is roughly 500x more potent than morphine and 10–20x more potent than fentanyl.4 6 

Potency varies according to the analogue. 

Cychlorphine is 10x more potent than fentanyl.7 

Potency varies according to the analogue. 
How BTNX Inc. is Responding to the Emergence of Orphines including Cychlorphine

As a pioneer and world leader in drug checking strips, BTNX works diligently to stay abreast of changes in the illicit drug supply. When developing a new test strip, such as an Orphine Test Strip, we work closely with our industry partners to understand the drug supply and assess the need for novel testing capabilities.  

When a need is identified, our R&D team develops a prototype that undergoes rigorous internal testing, across multiple analogues and potential cross-reacting substances. Once our internal testing criteria are met, the strip is then independently tested by a network of third-party research institutes with access to street samples and compared against LC-MS results.  

Our team is currently undertaking this process to develop an Orphine Test Strip for drug checking purposes. 

Additional Facts about Orphines

What is the difference between Orphine and Cychlorphine?  

Cychlorphine (N-Propionitrile Chlorphine) is an orphine analogue, meaning it belongs to the broader orphine class of synthetic opioids. Orphine analogues share a similar core chemical structure but have variations that distinguish one analogue from another. These differences in chemical structure may influence characteristics such as potency and effects on the body.2 

Why is Cychlorphine Significant?  

Cychlorphine (N-Propionitrile Chlorphine), an orphine analogue, was first detected in mid-2024. Research from the Center for Forensic Science Research and Education (CFSRE) found that the number of fatal overdoses linked to cychlorphine rose significantly at the end of 2025.7   

Preliminary evidence has shown that cychlorphine is a highly potent opioid that is approximately 10 times stronger than fentanyl.7 This high potency has the potential to increase the risk of an overdose. The Toronto Drug Checking Service has found cychlorphine in counterfeit pharmaceutical pills as well as in fentanyl.3 

What are Illicit Synthetic Opioids?  

Illicit synthetic opioids are a class of opioid drugs that are chemically manufactured, rather than found in nature, for the illicit drug market. These drugs are often mixed with traditional opioids or other drugs in the illicit drug market. Some synthetic opioids are highly potent, and their unpredictable concentrations and unexpected presence can create a potentially dangerous combination that increases the risk of drug poisonings, or overdoses.7

References
  1. Browne T, Logan BK, Krotulski AJ, Mohr ALA, Kacinko S, Schackmuth M. Emerging global synthetic opioid threats: benzimidazol-2-ones—the orphines. The Colombo Plan; Center for Forensic Science Research and Education. Published February 2026. Accessed September 28, 2026. https://www.cfsre.org/images/content/reports/public_alerts/Colombo_Plan_Orphine_Alert_Feb_2026_v3.pdf 
  2. United Nations Office on Drugs and Crime. Orphine analogues. UNODC Early Warning Advisory on New Psychoactive Substances. Accessed September 28, 2026. https://www.unodc.org/LSS/SubstanceGroup/Details/09f4734d-aadb-44a0-aa76-2e8816b1cc02 
  3. Toronto’s Drug Checking Service. Drug dictionary. Accessed September 28, 2026. https://drugchecking.community/drug-dictionary/#noteworthy 
  4. United Nations Office on Drugs and Crime. Nitazenes. UNODC Early Warning Advisory on New Psychoactive Substances. Accessed September 28, 2026. https://www.unodc.org/LSS/substancegroup/Details/6aefe0ca-aafd-452c-a534-c16aa3a2e507 
  5. O’Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM. Deaths involving fentanyl, fentanyl analogs, and U-47700—10 states, July–December 2016. MMWR Morb Mortal Wkly Rep. 2017;66(43):1197-1202. doi:10.15585/mmwr.mm6643e1. https://www.cdc.gov/mmwr/volumes/66/wr/mm6643e1.htm 
  6. Advisory Council on the Misuse of Drugs. ACMD advice on 2-benzyl benzimidazole and piperidine benzimidazolone opioids. GOV.UK. Updated June 10, 2026. Accessed September 28, 2026. https://www.gov.uk/government/publications/acmd-advice-on-2-benzyl-benzimidazole-and-piperidine-benzimidazolone-opioids/acmd-advice-on-2-benzyl-benzimidazole-and-piperidine-benzimidazolone-opioids-accessible-version 
  7. Krotulski AJ, Papsun DM, Stang BN, Walton SE, Logan BK. Increase in fatal overdoses linked to novel synthetic opioid N-propionitrile chlorphine (cychlorphine). Center for Forensic Science Research and Education. Published January 30, 2026. Accessed September 28, 2026. https://www.cfsre.org/images/content/reports/public_alerts/Public_Alert_N-Propionitrile_Chlorphine_013026.pdf