Dr Des Corrigan provides an update on the range of drugs that are new to the illicit drug market, including medicinal products and orphines
If you are familiar with the above drug terms, then please feel free to skip the rest of this piece. If, on the other hand, they are new to you, what follows is what you need to know about a range of drugs new to the illicit drug market. While they are newly arrived on the black market, they include not only medicinal products still used clinically or that have been discontinued, but also molecules (orphines) that can be described as failed pharmaceutical drugs that never made it into clinical use.
First up are those orphines, a group of synthetic opioids, chemically distinct from other opioid-type molecules, originally patented by Janssen in 1967. Brorphine made an appearance on the illicit market in 2019 and showed up in post-mortem toxicology samples from six countries in Europe and North America in 2020, according to a 2025 update from the United Nations Office of Drugs and Crime (UNODC).
It is a ? opioid receptor (MOR) agonist with a potency 13 times greater than morphine but comparable to or slightly less than fentanyl, according to a 2024 review in Neuropharmacology. Now, comparisons of potency are particularly problematic, firstly because they are often based on in vitro tests, but also because lurid headlines quoting stronger potencies can have the perverse effect of increasing demand for the more potent drug.
Brorphine and the related bezitramide were brought under control via Schedule 1 of the 1961 UN Convention on Narcotic Drugs in 2022 and interest in them then waned. However, in January of this year in the USA, the Centre for Forensic Research and Education (CFSRE) issued a public alert about a dramatic increase in fatal overdoses (25 within a few months) linked to another orphine called cyclorphine that is 10 times more potent than fentanyl. The CFSRE noted that in July 2025, the Chinese government had placed nitazene derivatives under control, leading to a reduction in nitazene- positive toxicology tests, but an increase in cyclorphine- positive findings.
Cyclorphine on its own was detected in 11 fatalities, while the remainder involved it in combination with a suite of other drugs, including medicinal and designer benzos, fentanils, methamphetamine, cocaine, nitazenes and yet another orphine called spirochlorphine. In mid- May this year, the UK government issued what is called a Temporary Class Drug Order based on advice from its Advisory Committee and pending permanent control of seven orphines. These drugs are sold as powders, rock or crystalline- like solids, or mixed with plant material and consumed either orally or by inhalation via vaping or smoking.
Thankfully, these molecules appear to respond to naloxone, but because of their pronounced potency, extra doses may be required to reverse any respiratory depression due to overdose.
In early June, the EU Drugs Agency (EUDA) issued Initial Reports on both cychlorphine and spirochlorphine that concluded that they pose health and social risks due to their involvement in 32 deaths, 20 cases of acute poisonings between October 2025 and Match 2026, and detection in 11 Member States. These Initial Reports are required under EU law before the Commission can request formal risk assessment that might lead to Union-wide control.
The potentially blasphemous ‘Holy Trinity’ refers to a combination of opioid, benzo and cardisoprodol to increase
the intensity of the euphoria, with the effects being likened to those of heroin, according to anecdotal reports included in a February 2026 publication by the ACMD that described a total of 42 deaths in the UK between 2020 and 2025. It also noted the detection of carisoprodol mixed with tapentadol in pill forms known as ‘Red Apples’. Cardisoprodol was licensed up to 2007 by the EMA to treat painful muscle spasm due to its relaxant properties. Its authorisation was then suspended because the increased likelihood of abuse and addiction, alongside intoxication and psychomotor impairment, meant that the risks outweighed the benefits.
Carisoprodol is used recreationally to produce relaxation, giddiness and drowsiness, with the most intense euphoria occurring when it is snorted rather than taken orally. It does so by acting on GABA-A receptors in a manner
The potentially blasphemous ‘Holy Trinity’ refers to a combination of opioid, benzo and cardisoprodol
different to barbiturates. High doses cause confusion, disorientation, partial amnesia and respiratory depression. Prolonged sedative effects are due to its main metabolite — meprobamate, which itself was used for many years to treat anxiety and painful muscle spasms under the tradename Miltown, until it lost its authorisation in 2012. Apart from the respiratory depression, death may also occur due to serotonin toxicity. The UN Commission on Narcotic Drugs included carisoprodol in Schedule IV of the UN’s 1971 Convention on Psychotropic Substances in 2025, so presumably the Dept of Health is now obliged to schedule it as a controlled drug under the Misuse of Drugs Acts.
The final drug, etomidate, is still in use as an intravenous general anaesthetic valued for its short-acting effects, especially in high risk patients. However, a UNODC alert last year drew attention to significant levels of misuse of etomidate and its analogues in e-liquids reported from China, Hong Kong, Taiwan and Oceania involving vaping of what is called ‘space oil’, or ‘k-pods’, or ‘zombie cigarettes’ due to the rapid onset/offset of desired effects. Seizures in the UK have included tablets containing mixtures of etomidate and the designer benzo bromazolam, prompting an alert by the AMCD last October. Other tablets (green in colour) contained two nitazenes, as well as etomidate and bromazolam, while other seizures in the UK have included diazepam and nitazenes. The belief is that the etomidate is illegally synthesised rather than being diverted from the pharmaceutical supply chain, although an increased awareness of the potential for misuse of a hospital-sourced product would not go amiss.
From a safety perspective, one of the major concerns about the etomidate group centres around its ability, even after a single dose, to inhibit 11?-hydroxylase, leading to reduced production of cortisol, corticosterone and aldosterone, with long- term exposure increasing morbidity and mortality due to steroid deficiency.
Hypokalaemia is another potential complication, as is the involuntary muscle movement (myoclonus) that is a recurrent side-effect of unknown aetiology involving etomidate and an analogue, according to a 2021 review in Clinical Pharmacokinetics. According to the AMCD report, animal studies show addictive liability, and acute toxicity has been reported among users from Asia. Typically, this has involved impaired cognition/confusion, fluctuating reduced consciousness, tachycardia, delirium, tremor, agitation/aggression, unsteady gait and slurred speech. Seven deaths have been reported from Asia and two from the USA, some involving polydrug misuse. In addition, there have been three analytically confirmed suicides in healthcare workers involving etomidate, highlighting the increased vulnerability of this group.
The AMCD recommended that etomidate should be controlled under their Misuse of Drugs Act and a 2025 article in the British Journal of Anaesthesia stated that it was “time to say goodbye” to etomidate. Any chance that the DoH
and the HPRA might copy?
Dr Des Corrigan, Best Contribution in Pharmacy Award (winner), GSK Medical Media Awards 2014, is an Adjunct Associate
Professor at the School of Pharmacy and Pharmaceutical Sciences at TCD where he was previously Director and won the Lifetime Achievement Award at the 2009 Pharmacist Awards. He was chair of the Government’s National Advisory Committee on Drugs from 2000 to 2011, having previously chaired the Scientific and Risk Assessment Committees at the EU’s Drugs Agency in Lisbon. He chaired the Advisory Subcommittee on Herbal Medicines and was a member of the Advisory Committee on Human Medicines at the HPRA from 2007 to 2024. He has been a National Expert on Committee 13B (Phytochemistry) at the European Pharmacopoeia in Strasbourg and served on the editorial boards of a number of scientific journals on herbal medicine.
