Orphines

Description

Orphines are a general term for a family of potent synthetic opioids, also known as piperidinylbenzimidazolones, benzimidazol-2-ones, piperidine benzimidazolones, or brorphine analogues. These compounds are not derivatives of morphine, and are chemically distinct from fentanyl and nitazenes, but still activate the μ-opioid receptor (MOR). This means the effects are similar to those of morphine, heroin, fentanyl and nitazenes.

Identified analogues include brorphine, chlorphine, cychlorphine (N-propionitrile chlorphine), spirochlorphine (R6890), and 5,6-dichloro desmethylchlorphine (SR-17018). Since 2019, Orphines have been increasingly identified in forensic casework and drug checking services, often being found as counterfeit medications (pills/tablets) or heroin, with WEDINOS reporting multiple instances in a year period (2025-2026) where an orphine analogue is found in combination with medetomidine.

Pharmacology

Orphines are a class of µ opioid receptor (MOR) agonists, similar to morphinans like heroin, fentanyl and nitazenes. Many orphines have only been invented within the past decade, meaning little is known about how they differ in potency, duration, and effects compared to other opioids particularly in humans.

Brorphine acts as a full MOR agonist with a similar potency to fentanyl, and has been associated with several deaths in recent years. Chlorphine, brorphine and iodorphine are more active than flurorphine and orphine. Spirochlorphine is a nociceptin receptor (NOP) agonist as well as a potent MOR agonist. 5,6-dichloro desmethylchlorphine (SR-17018) is an atypical opioid thought to be a partial and/or biased MOR agonist.

Some orphines including SR-17018 are thought to favour (bias) MOR’s G-protein signalling pathway responsible for analgesic effects and disfavour the β-arrestin pathway involved in receptor desensitisation. However, in a recent study, brorphine, chlorphine, and iodorphine didn’t show significant biased agonism compared to hydromorphone.

SR-17018 is the most well-studied orphine due to its atypical effects, which should not be assumed to translate to other drugs in this class. In rodents, SR-17018 produces strong analgesia similar to morphine and fentanyl. Initial research shows mixed effects on respiratory depression, similar rewarding effects, less itch-scratching behaviours, less tolerance development and lower withdrawal effects when compared to opioids like morphine. SR-17018’s lower efficacy than classical opioids as a MOR agonist may explain its atypical effects, rather than biased agonism.

Additionally, some anecdotal evidence suggests SR-17018 does not produce euphoria typical of opioids, instead finding potential utility for supporting tapering and detoxification. However, given the unregulated nature of the online and street supplies alongside the lack of human clinical research, it is not recommended to self-medicate with SR-17018.

Interactions

Like other opioids, the combination of orphines with other depressants, such as alcohol and benzodiazepines, can increase the risk of respiratory depression and fatal overdose.

Harm Reduction

• Try not to use alone: If something goes wrong, someone is there to get help
• Be careful mixing: Mixing synthetic opioids with other depressants increases overdose risk – avoid if you can, otherwise take less of each, as they can increase the effects and risks
• Carry naloxone: Naloxone can be used in the event of a synthetic opioid overdose but you may need to give more naloxone over a longer period of time to regain consciousness.
• Test your stuff: Find out how to send a sample to WEDINOS for testing here: https://www.wedinos.wales or The Loop’s drug checking services
• If you’ve been prescribed opioids and you notice a tolerance starting to develop (you need to keep taking more to get the same effect) speak to your doctor – don’t just start increasing your dose yourself, and avoid seeking from alternative sources.
• Don’t suddenly stop taking opioids, or you may start to experience symptoms of withdrawal: these can range from a return of your original symptoms (possibly even worse than before) to totally new symptoms.
• If you have become physically dependent on a synthetic opioid, the symptoms of abruptly stopping are likely to be even worse. It’s important to get proper medical advice on how to reduce your intake slowly.
• It’s also possible to become psychologically dependent on the drug (feeling like you need it all the time). If you think this is happening, see your doctor as soon as possible, but don’t suddenly stop taking it.

History

The piperidine-benzimidazolone group of opioids (orphines) was originally developed during the 1960s through pharmaceutical research associated with Paul Janssen and Janssen Pharmaceutica. This chemistry was significant because it produced opioid activity from a scaffold distinct from those found in morphine, codeine and heroin, which contain phenanthrene frameworks; fentanyl, which belongs to the anilidopiperidine class; and nitazenes, which contain a 2-benzylbenzimidazole scaffold.

Bezitramide was the first marketed medicine based on the piperidine-benzimidazolone scaffold. It was marketed as Burgodin for pain relief in parts of Europe. Its use was later associated with serious safety concerns and fatal overdose reports, and it was ultimately withdrawn from European markets. Bezitramide was internationally controlled in 1969 and remains a Class A drug in the UK.

During the same period, Janssen was also developing fentanyl and related compounds. Fentanyl subsequently proved more commercially and clinically successful, while the orphine programme did not develop into a broad range of marketed medicines. The orphine class also presented practical challenges associated with highly potent synthetic opioids, including difficult dose control, overdose risk, limited safety data for individual analogues and the formulation difficulties involved in handling compounds with high pharmacological activity.

It was after this period that the wider benzimidazolone series became lesser known and used but remained accessible through patents, academic literature and medicinal chemistry databases.

Researchers revisited the scaffold as part of modern opioid-receptor studies in 2018 when brorphine was synthesised as part of a study investigating signalling bias and opioid pharmacology of μ-opioid receptor agonists. In March 2019, brorphine was first mentioned in a post on the forum website Reddit, before the first toxicological identification in the United States in August 2019. The first confirmed brorphine case in Europe occurred in Belgium in February 2020, where the drug was identified at high purity in a powder and in the serum of a patient seeking help for their drug use.

Following a review by the World Health Organization’s Expert Committee on Drug Dependence, the UN Commission on Narcotic Drugs voted in March 2022 to place brorphine under Schedule I of the 1961 Single Convention on Narcotic Drugs. The control subsequently entered into force through the UN notification process. Several countries also introduced national emergency or permanent controls.

As with fentanyl analogues and nitazenes, controlling a single compound did not remove the wider scaffold from circulation. Instead, from approximately 2024 onwards, several structurally related analogues began to be reported, including chlorphine, N-propionitrile chlorphine (cychlorphine), spirochlorphine and 5,6-dichloro desmethylchlorphine. In July 2026, WEDINOS found cyclorphine in a fake nutritional supplement sold as Lion's Mane.

These structural modifications include halogen substitution, cyclisation and changes to the piperidine nitrogen. Such changes can alter μ-opioid-receptor affinity and efficacy, pharmacokinetics, metabolism, duration of action and analytical detectability. However, the effects of each modification cannot be predicted reliably from structure alone, and experimental potency data should not be interpreted as direct human dose-equivalence information.

SR-17018

5,6-dichloro desmethylchlorphine (SR-17018) was developed by Laura Bohn at Scripps Research Institute in 2017, and has been the subject of several laboratory and animal studies due to its unique properties. Recent animal studies suggest SR-17018 may hold promise as a safer pain therapy, with possible utility to help reverse opioid tolerance and reduce withdrawal symptoms. Following this, some individuals including a 27 year old American woman have reported self-medicating with the drug to help come off opioids including kratom (7-OH) and nitazenes.

On 11th June 2026, the UK government enacted a Temporary Class Drug Order (TCDO) on SR-17018 alongside 6 other orphines, with the intention of placing these drugs under Class A of the Missue of Drugs Act 1971. On 1st July 2026, the US Drug Enforcement Agency (DEA) followed suit, issuing a temporary order to place SR-17018 and three other orphines, along with their derivatives, under Schedule I of the Controlled Substances Act. The temporary order quickly faced pushback from civil society: the Rights and Reason project alongside Students for Sensible Drug Policy filed an emergency petition urging the DEA not to ban SR-17018 to enable continued access by scientists studying the drug’s potential for safer pain treatment.

Law

In the UK, Orphines are subject to a developing legal framework, Brorphine and bezitramide are named Class A drugs under the Misuse of Drugs Act 1971.

7 named Orphines are currently controlled under a Temporary Class Drug Order (TDCO) pending permanent Class A control and are also treated as Schedule 1 substances.

These are;

Chlorphine.

Cychlorphine, also known as N-propionitrile chlorphine.

Spirochlorphine,

5,6-Dichloro desmethylchlorphine,

Etodezitramide.

Spirobrorphine.

5,6-Dichlorobrorphine

• Possible offences for a Class A Orphine:
• Possession
  • Maximum sentence – Up to 7 years imprisonment, an unlimited fine, or both
• Possession With Intent To Supply
  • Maximum sentence – Up to life imprisonment, an unlimited fine, or both
• Supply (including being concerned in supply, conspiracy to supply, aggravated supply and offer to supply)
  • Maximum sentence – Up to life imprisonment, an unlimited fine, or both
• Production
  • Maximum sentence – Up to life imprisonment, an unlimited fine, or both
• Possible offences under TCDO Orphine:
• Possession
  • Maximum sentence – Up to 14 years imprisonment, an unlimited fine, or both
• Possession With Intent To Supply
  • Maximum sentence – Up to 14 years imprisonment, an unlimited fine, or both
• Supply (including being concerned in supply, conspiracy to supply, aggravated supply and offer to supply)
  • Maximum sentence – Up to 14 years imprisonment, an unlimited fine, or both
• Production
  • Maximum sentence – Up to 14 years imprisonment, an unlimited fine, or both

In practice maximum sentences are rarely used, for more detailed and accurate information go to our sentencing page.