A new synthetic opioid, cychlorphine, is spreading through illicit drug markets in Europe and North America.
Reportedly more potent than fentanyl, the drug has been linked to a string of overdose deaths.
AP spoke with Professor Suzanne Nielsen MPS, Deputy Director of the Monash Addiction Research Centre, about the local risks and what pharmacists need to know.
What is cychlorphine and where did it come from?
Cychlorphine belongs to the ‘orphine’ class of opioids and is structurally related to brorphine and bezitramide – both of which are internationally controlled drugs.
‘Similar to nitazenes, it was explored by pharmaceutical companies back in the 60s as a different kind of opioid,’ Prof Nielsen said. ‘But these drugs didn’t progress to therapeutic use, largely because they are quite potent, and as we know with nitazenes, the side effect profile wasn’t favourable.’
Cychlorphine has no approved medical use, with its emergence linked to China’s move to generically schedule nitazenes in July 2025.
‘There is an illicit market for substances that aren’t yet under international control. It’s a bit of a loophole, where they can be imported and sold without penalties,’ Prof Nielsen said.
‘Once international restrictions came in around the fentanyls, we started to see the nitazenes emerge. Now more nitazenes are more controlled internationally, we’re starting to see orphines emerge, which aren’t covered by international restrictions.’
How potent is it?
Laboratory studies suggest cychlorphine is approximately ten times more potent than fentanyl.
The World Health Organization’s (WHO) Expert Committee on Drug Dependence Critical Review Report cited that cychlorphine has a higher binding affinity to μ-opioid receptors than both morphine and fentanyl.
But Prof Nielsen said the evidence base is still thin. ‘We have studies that give us an estimate of how potent it is, but these are not human studies – they are animal or in vitro studies,’ she said. ‘We don’t have a really good direct comparison with nitazenes, and we don’t have very good data in human studies.’
While Prof Nielsen said that it’s hard to directly extrapolate the potency of cychlorphine from these studies, ‘it’s definitely at least as potent as, if not more, than fentanyl’.
‘Fentanyl is an incredibly potent opioid, so anything similar or potentially greater, is going to have a very serious effect on respiration.’
Where has it been detected?
Cychlorphine was first detected in Florida in mid-2024, with the first confirmed European detection identified in Sweden that August. Since then, the WHO’s critical review has recorded it in seizures across 15 or more countries, with 228 seizures logged across eight EU member states and Norway by March 2026.
One Latvian study found cychlorphine residue in 56% of 200 syringes tested.
‘These drugs are commonly missold as other drugs, as we’ve seen with nitazenes and fentanyl. Concerningly, we’ve seen them popping up in all kinds of different drugs – in stimulants, falsified oxycodone tablets and counterfeit benzodiazepines,’ Prof Nielsen said.
At this stage, confirmed harm remains concentrated in the northern hemisphere.
‘There’s been over 70 deaths through some of the bigger data systems captured internationally, and those numbers keep going up,’ she said.
By March 2026, cychlorphine-linked overdoses or deaths had been reported in at least 24 US states, including a cluster of 19 confirmed deaths in East Tennessee.
Last month, it was reported that a 16-year-old boy’s overdose death in San Francisco in April was linked to cychlorphine.
Could cychlorphine harm be more widespread than we know?
Standard hospital toxicology relies on immunoassays to recognise the chemical structures of established opioids such as morphine, codeine and oxycodone – with separate assays required to reliably detect fentanyl, hydrocodone and certain opioid pharmacotherapies including methadone and buprenorphine.
With cychlorphine belonging to the orphine class, it’s structural difference means these antibodies don’t reliably detect it – so a patient can test negative on a routine opioid screen even when cychlorphine is responsible for an overdose.
At-home test strips that detect nitazenes and fentanyl also don’t cross-react with orphine analogs.
In one 2026 case, a woman presenting with respiratory depression responded to naloxone despite an initial hospital screen being negative for fentanyl and other opioids. Comprehensive toxicological analysis later identified cychlorphine as the sole opioid present, with clinicians believing it was contained in a counterfeit alprazolam tablet.
Prof Nielsen said that as many clinical services won’t be able to test for cychlorphine, the true extent of related harm is underestimated.
‘Quite often the first signals we’re getting are from coroners, or from forensic labs overseas identifying these drugs in samples.’
Has it reached Australia?
Not as far as the evidence shows. At this stage, Australia’s opioid harm is still dominated by heroin and prescription opioids, Prof Nielsen said.
‘We haven’t really seen fentanyl arrive in any kind of meaningful way – but that could change, and we need to be ready for that to change.’
In fact, United Nations Office on Drugs and Crime monitoring flagged cychlorphine’s presence on international cryptomarkets accessible to Australian buyers.
But Prof Nielsen emphasised that emerging drugs shouldn’t distract from existing opioid-related harm that continues to occur.
‘Heroin-related harms in Australia are almost as high as they’ve ever been in some states,’ she said. ‘Opioid-related deaths overtook Australia’s road toll decades ago.’
Will naloxone still work?
Yes, but we don’t have good data on dose requirements. We have seen for other potent opioids that usual therapeutic doses are often effective, which is reassuring.
‘We’ve had some cases where naloxone reversed the effects of cychlorphine, which is positive,’ Prof Nielsen said.
In a non-fatal cychlorphine overdose, a 37-year-old man who ‘snorted a substance he believed to be alprazolam’ received 4 mg of intranasal naloxone (a standard dose product in the United States) – but had only a partial response, which can occur with multiple-drug toxicity. Emergency medical services administered a further 1 mg.
‘If someone has taken a massive dose of these potent opioids, you might not be able to get enough naloxone on board fast enough,’ Prof Nielsen said. ‘But as a general rule, naloxone does tend to work for these overdoses, and it’s still our best defense.’
Her advice for safeguarding against more potent opioids is to have more naloxone on hand.
The administration instructions remain the same: administer one dose, wait 2–3 minutes, and provide another if there’s no response.
‘It doesn’t matter what the opioid is, the approach is the same with respect to dosing. And if it happens to not be an opioid, you’re unlikely to do any harm by re-administering naloxone – particularly if you’ve already got an ambulance on the way,’ she said.
Given that overdoses have been documented in products not marketed as opioids, the pool of patients who could benefit from take-home naloxone (THN) is wider than opioid users alone.
‘This information could be relevant to anyone accessing a needle and syringe program, anyone purchasing illicit drugs, or people who’ve run out of prescribed pain medication and are sourcing it online instead,’ she said.
Prof Nielsen encouraged a non-judgemental approach: offering naloxone to anyone who might be at risk of illicit drug contamination, and explaining what unexpected symptoms can indicate.
‘For example, we wouldn’t expect someone to get sedated from a stimulant, so that’s a good indicator that the substance could be contaminated.’
With almost three-quarters of Australian pharmacies now offering THN, Prof Nielsen said pharmacy should be a place people know they can turn to – ‘even if you don’t know very much about opioids, but you think you might witness an overdose or know someone who might be using illicit drugs.’
