In this NDEWS Weekly Briefing, we highlight the emergence of a class of synthetic opioids known as benzimidazol-2-ones, or “orphines,” as described in a January 30, 2026 report from CFSRE and The Colombo Plan. Their identification follows regulatory action in July 2025, when China implemented core-structure scheduling of nitazenes and related compounds. Data from late 2025 indicated a decrease in reported nitazenes, alongside the detection of "orphines" in forensic and toxicology findings.

NDEWS has tracked these substances through available data sources and ongoing coordination with its Early Warning Network. Discussions in March and subsequent information sharing with national and international partners contributed to continued monitoring of this class as it appeared in reporting systems. In April 2026, the Office of National Drug Control Policy issued a Drug Threat Notice on cychlorphine, and in May 2026, the United Nations Office on Drugs and Crime also reported on cychlorphine as an emerging synthetic opioid.

In July 2026, the Drug Enforcement Administration temporarily placed several related substances, including 5,6-dichloro brorphine, 5,6-dichloro desmethylchlorphine, N-propionitrile chlorphine, and spirochlorphine, into Schedule I of the Controlled Substances Act. These developments document the identification, monitoring, and regulatory response to "orphines" within the broader synthetic opioid landscape. NDEWS continues to track this class using available surveillance and reporting systems.

As always, we welcome your input.

Nationally, from January 1, 2020 to April 30, 2026, there were 39 EMS encounters for suspected drug-related fatal and nonfatal overdoses related to “Benzimidazol-2-ones”, also referred to as “orphines”. The term “orphine analogs” returned the 39 suspected overdoses; they occurred within 32 counties from 15 states. Due to low raw count, a measure of the monthly detection of at least one orphine-related EMS record is reported.
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Why are we reporting on this? The term “orphines” refers to synthetic opioid research chemicals such as brorphine, spirobrorphine, spirochlorphine, cyclorphine, and cychlorphine, which are increasingly discussed on Reddit as alternatives to other high-potency opioids. Reddit discussions indicate growing interest in these compounds due to their availability through research chemical markets, comparisons with nitazenes and prescription opioids, and conversations surrounding potency, routes of administration, and withdrawal management. Discussants also describe concerns regarding overdose risk, respiratory depression, and uncertainty surrounding the identity and composition of products sold under these names.

What are "Orphines"? Brorphine, spirobrorphine, spirochlorphine, cyclorphine, and cychlorphine are synthetic opioids belonging to a group of research chemicals commonly referred to as "orphines." These compounds are discussed as high potency opioid receptor agonists that are distributed through research chemical markets and are available in powder, liquid, and solution formulations. Reddit discussions frequently compare these compounds with nitazenes, fentanyl analogs, heroin, methadone, and prescription opioid medications.

Public Health Impacts: Reddit discussants report concerns regarding respiratory depression, prolonged sedation, and overdose potential associated with several "orphine" compounds. Multiple commenters describe the need for careful dosing due to the perceived high potency of these substances and discuss carrying or using naloxone because of overdose concerns. Discussants also report prolonged effects, development of opioid tolerance, and withdrawal symptoms following repeated use. Additional discussions highlight uncertainty regarding product identity, with reports of mislabeled research chemicals and concerns that products marketed as opioid analogs may contain other unexpected substances.

How is it Being Discussed? Reddit discussions primarily focus on comparing the potency, duration, and subjective effects of brorphine, spirobrorphine, spirochlorphine, cyclorphine, and cychlorphine with other synthetic opioids and nitazenes. Discussants frequently seek advice regarding routes of administration, solution preparation, solubility, and relative potency when transitioning between different opioid research chemicals. Comparisons between the various orphine compounds are common, with commenters debating differences in euphoria, sedation, duration, and perceived strength.There is frequent discussion surrounding the emergence of newer analogs, particularly spirobrorphine, with commenters sharing information about newly available products and comparing them with earlier compounds such as spirochlorphine and brorphine. Reddit discussions also include conversations about combining "orphines" with other opioids or central nervous system depressants, managing withdrawal with other research chemicals, and using these compounds as alternatives when heroin or pharmaceutical opioids are unavailable. Additional discussions reference regulatory actions involving related compounds, concerns over counterfeit or mislabeled products, and reports from drug checking services identifying unexpected substances in products marketed as opioid research chemicals.

Drug Terms: orphines, brorphine, spirobrorphine, spirochlorphine, cyclorphine, cychlorphine

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Laboratory Director and NDEWS Scientific Advisory Group Member Agnes Winokur has worked for the Drug Enforcement Administration (DEA) for more than 28 years in various roles (e.g., forensic chemist, supervisor, program manager). In this webinar Dr. Winokur will present on "orphines", Benzimidazol-2-ones, a class of potent synthetic opioids and designer drugs that have emerged in the US illicit drug market. Watch the full webinar here.

Recently, the Administrator of the Drug Enforcement Administration issued a notice of intent to publish a temporary order to Schedule I four synthetic opioids. The temporary scheduling order will impose the regulatory controls and administrative, civil, and criminal sanctions applicable to Schedule I controlled substances on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle these four specific substances. Read the full notice here.

A recent public health alert was issued by the New York State Department of Public Health regarding N-propionitrile brorphine in Upstate New York. N-propionitrile brorphine, is a synthetic opioid belonging to the emerging benzimidazole-2-one, or “orphine” class. In New York State, N-propionitrile brorphine was identified through laboratory results received on June 25, 2026; the first sample containing N-propionitrile brorphine was collected in April 2026. 

Read the full advisory here.

A health alert issued earlier this year issued by The Colombo Plan and the Center for Forensic Science Research & Education highlights the emergence of benzimidazol-2-one ("orphine") class. This alert describes the emergence of these potent opioids, and spotlights their detection in US and international drug markets.

Read the full report here.

A recently recorded presentation by the United Nations Office on Drugs and Crime produced for the Australian Prompt Response Network (PRN) national meeting was held on June 16, 2026. It provides a brief overview of the emergence of "orphines", including their chemical characteristics, pharmacological profile, patterns of use, and increasing presence in illicit drug markets. The presentation also highlights challenges related to detection, surveillance, and early warning systems, as well as associated public health risks and implications for forensic and policy responses.

Watch the full presentation here.

📅 Date: Tuesday, July 14, 2026

🕑 Time: 12:00 pm - 1:00 pm ET

📍 Location: Virtual via Zoom

Learning Objectives:
1. To describe the goals and objectives of the National Drug Early Warning System.

2. To describe the methods used and to discuss ways to integrate data from multiple sources to better understand signals and trends of use.

3. To identify the most recent data available on new drug threats with a particular focus on fentanyl adulterants.

Register here.

As gabapentin prescribing has doubled over the past decade, its nonmedical use has risen in parallel, primarily in people with opioid use disorder. Yet the assumptions driving both clinical practice and scheduling policy have largely outpaced the evidence. This webinar presents data from multiple studies spanning national surveillance surveys, Medicaid claims, urine drug testing data, and clinical interviews that together reframe the gabapentin problem and moves us forward toward understanding the role of gabapentin as friend or foe in the ongoing opioid crisis.

📅 Date: Thursday, July 30, 2026

🕑 Time: 1:00 pm - 2:00 pm ET

📍 Location: Virtual via Zoom

Register here.

Are you committed to advancing the science of substance use and public health? The University of Florida’s NIDA-funded T32 Training Program offers predoctoral and postdoctoral scholars an exceptional opportunity to launch impactful research careers focused on NDEWS!

What We Offer:
- Interdisciplinary training at the intersection of addiction science, epidemiology, and surveillance
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- Hands-on research with landmark and important NIH-funded projects and access to rich data
- Career development support, including grant writing, publishing, and professional networking
- A collaborative, inclusive research community committed to reducing the burden of substance use

Eligibility:
- US citizens or permanent residents
- Interested in a PhD in Epidemiology, or early-stage postdoctoral fellows
- Demonstrated interest in substance use, addiction, or public health research

Location: Gainesville, Florida — a dynamic hub for scientific innovation with high quality of life and low cost of living.

The NDEWS Weekly Briefing curates emerging data and findings from across the Early Warning Network, which includes three core components: our Scientific Advisory Group (SAG), comprised of national experts and federal partners; our Sentinel Site Directors (SSDs), who lead local surveillance in key geographic regions; and our Community-Based Health Experts, who provide on-the-ground insights from populations most impacted by drug trends. Together, these contributors generate timely, multidisciplinary and impactful information, ranging from peer-reviewed research findings to local surveillance data. These contributions inform public health and research communities.

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If you miss or want to learn more about NDEWS Original Content, you can find our archived content on the NDEWS website:

     • NDEWS Hotspot Alerts using substance-related EMS data
     • NDEWS Rapid Street Reporting (RSR) survey data reports
     • NDEWS Web Monitoring Team Reddit Alerts
     • NDEWS Sentinel Site Reports
     • Previous issues of the NDEWS Weekly Briefings

The Weekly Briefing is a newsletter published each week by the National Drug Early Warning System (NDEWS) Coordinating Center, which is funded by the National Institute on Drug Abuse (U01DA051126) to the University of Florida (MPI: Cottler (contact), Co-Is: Goldberger, Nixon, Striley), NYU Langone Health (MPI: Palamar), and Florida Atlantic University (Co-I: Barenholtz). Any item may be reproduced provided the source is acknowledged.