The 'new synthetic opioid’: Isotonitazene the secret killer?
Dear Editor
Like the US, the UK has seen an increase in drug poisoning deaths during the pandemic with approximately two-thirds of the deaths being related to drug misuse with the opioids, morphine and heroin, being the most frequently mentioned.[1] It is well established that in the US heroin and cocaine are being mixed with fentanyl and its analogues. This is very rarely observed in the UK, but another psychoactive substance is now being added to the mix: isotonitazene.
Isotonitazene is a derivative of benzimidazole and is an opioid analgesic not medically authorised. It is 500 times more potent than morphine [2] and has slightly greater potency than fentanyl.[3] Its effects are like morphine and fentanyl, causing relaxation, euphoria and respiratory depression. In 2019 the European Monitoring Centre for Drugs and Drugs Addiction (EMCDDA) became aware of isotonitazene being available on the drugs market. It is presumed that it is being used by high-risk opioid-users.[3 4] Although data is limited, deaths associated with isotonitazene have been observed in Canada, US and Europe.[5 6]
The Toxicology Unit at Imperial College London conducts toxicology analysis on behalf of coroners throughout London and the South East, handling approximately 3000 cases a year. At the end of July 2021, the Unit became aware of isotonitazene becoming a problem in the UK. Information came to light that batches of heroin were being contaminated/mixed with isotonitazene and it could potentially be contributing to death. In response to this concern, we started to screen for isotonitazene (in blood) in all post-mortem cases where the deceased’s case history or toxicological results indicated potential heroin use. Since the start of the screening programme isotonitazene has been regularly detected, primarily in combination with other drugs and often unexpectedly.
In view of our findings, isotonitazene is a risk to public health and a real danger to those who misuse drugs, especially both heroin and cocaine users. The extent of the use of isotonitazene is still emerging in the UK and its existence should be made aware to staff at emergency departments, to general practitioners and drug treatment centres so that relevant advice and potentially lifesaving treatment can be provided.
2 Vandeputte MM, Krotulski AJ, Papsun DM, Logan BK, Stove CP. The rise and fall of isotonitazene and brorphine: two recent stars in the synthetic opioid firmament. Journal of Analytical Toxicology. 2021. doi: 10.1093/jat/bkab082
3 Blanckaert P, Cannaert A, Van Uytfanghe K, Hulpia F, Deconinck E, Van Calenbergh S, Stove C. Report on a novel emerging class of highly potent benzimidazole NPS opioids: chemical and in vitro functional characterization of isotonitazene. Drug Testing and Analysis 2020; 12: 422-30.
4 European Monitoring Centre for Drugs and Drugs Addiction. Report on the risk assessment of N,N-diethyl-2-[[4-(1-methylethoxy)phenyl]methyl]-5-nitro-1H-benzimidazole-1-ethanamine (isotonitazene) in accordance with Article 5c of Regulation (EC) No 1920/2006 (as amended). 2020. https://www.emcdda.europa.eu/publications/risk-assessments/isotonitazene_en
5 Krotulski AJ, Papsun DM, Kacinko SL, Logan BK. Isotonitazene quantitation and metabolite discovery in authentic forensic casework. Journal of Analytical Toxicology 2020; 44: 521-30.
6 Mueller F, Bogdal C, Pfeiffer B, Andrello L, Ceschi A, Thomas A, Grata E. Isotonitazene: Fatal intoxication in three cases involving this unreported novel psychoactive substance in Switzerland. Forensic Sci Int. 2021; 320:110686.
Competing interests:
No competing interests
02 December 2021
Limon K Nahar
Senior Toxicologist
Dr Rebecca Andrews and Dr Sue Paterson
Toxicology Unit, Imperial College London
Toxicology Unit, Imperial College London. London W6 8RP
Rapid Response:
The 'new synthetic opioid’: Isotonitazene the secret killer?
Dear Editor
Like the US, the UK has seen an increase in drug poisoning deaths during the pandemic with approximately two-thirds of the deaths being related to drug misuse with the opioids, morphine and heroin, being the most frequently mentioned.[1] It is well established that in the US heroin and cocaine are being mixed with fentanyl and its analogues. This is very rarely observed in the UK, but another psychoactive substance is now being added to the mix: isotonitazene.
Isotonitazene is a derivative of benzimidazole and is an opioid analgesic not medically authorised. It is 500 times more potent than morphine [2] and has slightly greater potency than fentanyl.[3] Its effects are like morphine and fentanyl, causing relaxation, euphoria and respiratory depression. In 2019 the European Monitoring Centre for Drugs and Drugs Addiction (EMCDDA) became aware of isotonitazene being available on the drugs market. It is presumed that it is being used by high-risk opioid-users.[3 4] Although data is limited, deaths associated with isotonitazene have been observed in Canada, US and Europe.[5 6]
The Toxicology Unit at Imperial College London conducts toxicology analysis on behalf of coroners throughout London and the South East, handling approximately 3000 cases a year. At the end of July 2021, the Unit became aware of isotonitazene becoming a problem in the UK. Information came to light that batches of heroin were being contaminated/mixed with isotonitazene and it could potentially be contributing to death. In response to this concern, we started to screen for isotonitazene (in blood) in all post-mortem cases where the deceased’s case history or toxicological results indicated potential heroin use. Since the start of the screening programme isotonitazene has been regularly detected, primarily in combination with other drugs and often unexpectedly.
In view of our findings, isotonitazene is a risk to public health and a real danger to those who misuse drugs, especially both heroin and cocaine users. The extent of the use of isotonitazene is still emerging in the UK and its existence should be made aware to staff at emergency departments, to general practitioners and drug treatment centres so that relevant advice and potentially lifesaving treatment can be provided.
1 Office for National Statistics. Deaths related to drug poisoning in England and Wales: 2020 registration. 2021. https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarri... poisoning in England and Wales - Office for National Statistics (ons.gov.uk)
2 Vandeputte MM, Krotulski AJ, Papsun DM, Logan BK, Stove CP. The rise and fall of isotonitazene and brorphine: two recent stars in the synthetic opioid firmament. Journal of Analytical Toxicology. 2021. doi: 10.1093/jat/bkab082
3 Blanckaert P, Cannaert A, Van Uytfanghe K, Hulpia F, Deconinck E, Van Calenbergh S, Stove C. Report on a novel emerging class of highly potent benzimidazole NPS opioids: chemical and in vitro functional characterization of isotonitazene. Drug Testing and Analysis 2020; 12: 422-30.
4 European Monitoring Centre for Drugs and Drugs Addiction. Report on the risk assessment of N,N-diethyl-2-[[4-(1-methylethoxy)phenyl]methyl]-5-nitro-1H-benzimidazole-1-ethanamine (isotonitazene) in accordance with Article 5c of Regulation (EC) No 1920/2006 (as amended). 2020. https://www.emcdda.europa.eu/publications/risk-assessments/isotonitazene_en
5 Krotulski AJ, Papsun DM, Kacinko SL, Logan BK. Isotonitazene quantitation and metabolite discovery in authentic forensic casework. Journal of Analytical Toxicology 2020; 44: 521-30.
6 Mueller F, Bogdal C, Pfeiffer B, Andrello L, Ceschi A, Thomas A, Grata E. Isotonitazene: Fatal intoxication in three cases involving this unreported novel psychoactive substance in Switzerland. Forensic Sci Int. 2021; 320:110686.
Competing interests: No competing interests