The illegal drugs market is changing—is the UK prepared?
BMJ 2023; 383 doi: https://doi.org/10.1136/bmj.p2421 (Published 19 October 2023) Cite this as: BMJ 2023;383:p2421
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Dear Editor
We very much agree with the concerns raised by Niamh Eastwood and Shayla Schlossenberg regarding the changing drug landscape within the UK. One key piece in this puzzle, correctly raised is the need for a functional surveillance system within healthcare to identify these emerging threats when they arise.
Regrettably, the availability of analytical toxicology services in the NHS is exceptionally disparate, and outside of a few very specialist laboratories, a significant amount of NHS toxicology testing is either point-of-care immunoassays which have poor sensitivity, or targeted mass spectrometric methods which only detect a limited number of drugs. These methods are unlikely to be able to detect the newer compounds and are unlikely to be responsive enough to the ever-changing nature of the emerging novel opioid picture. Isotonitazene is one such compound, but many others have now been detected in the UK posing a significant analytical challenge when targeted approaches are used.
Another concern is that many clinicians requesting toxicology analysis may have no idea what drugs are included within the scope of a screen, and so a “negative” toxicology report which has not detected a nitazene compound may be falsely reassuring, or lead to inappropriate patient management.
There is a solution – The wider use of high-resolution accurate mass techniques such as QTof or Orbitrap analysers allow both rapid changes to screening targets to be made, as well as having sufficient sensitivity for these emerging, extremely potent compounds. However, this technology is out of reach of most UK laboratories both due to capital cost as well as the extremely high skill required to interpret the analytical data. Sadly, toxicology services within NHS laboratories have largely been under invested in, and in a climate of continuing cost saving strategies are often wrongly seen as an expensive service which offers little clinical benefit. Clearly given the changing nature of the UK illicit drug supply, that may no longer be the case, and more investment in these services needs to be made.
Competing interests: No competing interests
Dear Editor
We are in complete agreement with the urgency of the concerns raised by Niamh Eastwood and Shayla Schlossenberg and would unreservedly commend their suggestions around expanding supervised consumption facilities and drug checking, both of which (as they have noted for the former), are now approved or in the final application stages for Scotland(1). Other aspects such as rapid access to treatment are already being implemented in Scotland under MAT standards(2). We would urge however, that there are other aspects of the developing drug landscape that we risk overlooking at our peril.
As the authors suggest, powerful synthetic opioids such as fentanyl (likely to fill an anticipated heroin shortage from Afghanistan), are already a real and present threat in the UK(3). Perhaps less appreciated is their rapid lethality (shortening the window of opportunity for naloxone intervention)(4) combined with recent developments in the US and Canada where a majority of fentanyl deaths arise from smoking(5). Also because fentanyl is short-acting, it is often adulterated with longer acting substances, such as the non-opioid tranquiliser Xylazine whose potent vasoconstrictive effects can also lead to tissue necrosis not confined to the injection site, leading to risks of life threatening infections(6). The first implicated UK death from Xylazine was confirmed in 2022(7).
Other non-opioid threats include benzodiazepines (implicated in over two-thirds of drug-related deaths in Scotland8) and the anti-anxiety/anti-epileptic Gabapentin (now detected in 10% of US overdose deaths)(9). Of course, in a volatile international narcotic environment, the Taliban opium ban is not the only disrupting influence that might impact UK drug supplies. In Australia for instance, a diminished heroin supply led to an epidemic of another synthetic drug, crystal meth or ‘ice’(10), which, although associated with a rise in Scotland over the pandemic(11), has not represented a significant issue to date.
Closer to home, there is another illicit substance that is long established in the UK and is associated with a steeply rising proportion of drug deaths. Whereas in 1993 there were only eleven deaths due to cocaine use in England and Wales, by 2021 the number of deaths had risen to 840(12) and cocaine is now implicated in a third of all drug deaths in Scotland (13). Cocaine’s increasing lethality may be linked to easier availability as well as substantially increased purity(14). The latter results from yet another geo-political trend: namely the increasing dominance position of Albanian drug gangs in all aspects of the cocaine production and supply chain (15): enabling them to supply Europe directly without the need to adulterate for profitability.
We are therefore in a rapidly evolving and very complex illicit drug landscape where ‘poly-drug’ use has become the norm and several parallel prominent societal and geo-political drivers seem to be converging on a new and perilous cliff-edge of substance use mortality. The co-existence of these factors in Scotland, which has always had a drug deaths picture, orders of magnitude worse than for the UK as a whole, makes the calls for vigilance, rapidly improved drug intelligence and evidence based harm reduction strategies, such as genuine moves towards decriminalisation of possession, all the more urgent.
Finally, the authors note the need for ‘safer supply’ and substitution therapies including for benzodiazepines. This requires clinician ‘buy-in’, so there needs to be investment in developing the evidence base around such suggestions. The NIHR funded ‘UK Addiction Mission’(16) has recognised that need which is very welcome although sadly, Scotland with its undisputedly greater need, lags behind in direct investment in clinical interventions. Developing clinical evidence therefore on the treatment of cocaine use disorder and poly-drug use needs to be an essential part of the strategy going forward.
1. Cook J. UK's first consumption room for illegal drugs given go-ahead. BBC News 2023, 27 September. https://www.bbc.co.uk/news/uk-scotland-66929385.
2. Scottish Government. Medication Assisted Treatment (MAT) standards: access, choice, support. 2021. https://www.gov.scot/publications/medication-assisted-treatment-mat-stan...
3. Advisory Council on the Misuse of Drugs. ACMD Report on Misuse of fentanyl and fentanyl analogues. 2020. https://www.gov.uk/government/publications/misuse-of-fentanyl-and-fentan...
4. Kings College London News Centre. First death in the UK associated with Xylazine. 2023. https://www.kcl.ac.uk/news/first-death-uk-associated-with-xylazine
5. O. Coffin P, Maya S, Kahn, JG. Modelling of overdose and naloxone distribution in the setting of fentanyl compared to heroin. Drug Alcohol Depend. 2022 Jul 1; 236: 109478. doi: 10.1016/j.drugalcdep.2022.109478
6. Lindsay B. Most toxic drug deaths are now from smoking. Advocates ask when B.C. will adjust to that reality CBC News (British Columbia) 2022, 8 October. https://www.cbc.ca/news/canada/british-columbia/toxic-drug-deaths-from-s...
7. Copeland C. Tranq: First UK death from the flesh-rotting ‘zombie drug’ Xylazine. The Conversation 2023, 25 May. https://theconversation.com/tranq-first-uk-death-from-the-flesh-rotting-...
8. Scottish Government. Benzodiazepine use - current trends: evidence review. 2022, 15 March. https://www.gov.scot/publications/evidence-review-current-trends-benzodi...
9. Bridget M. Kuehn, MSJ. Gabapentin Increasingly Implicated in Overdose Deaths. JAMA. 2022; 327(24): 2387. doi:10.1001/jama.2022.10100.
10. Scott R. Methamphetamine dependence in Australia–why is ‘ice’ (crystal meth) so addictive?, Psychiatry, Psychology and Law, 2023. DOI: 10.1080/13218719.2023.2206870
11. Horne M. ‘Breaking Bad drug’ crystal meth is on rise in Scotland amid pandemic. The Times (UK) 2021, 2 February. https://www.thetimes.co.uk/article/breaking-bad-drug-crystal-meth-is-on-...
12. Stewart C. Deaths from cocaine use in England and Wales 1993-2021. Statista (Health, Pharma & Medtech› State of Health) 2022, 24 October. https://www.statista.com/statistics/470811/drug-poisoning-deaths-cocaine...
13. Smith P. 'Everyone is taking it': Cocaine addiction spirals in Scotland. ITV News (Scotland) 2023, 17 August. https://www.itv.com/news/2023-08-17/everyone-is-taking-it-cocaine-addict...
14. Preussen W. Let it snow: Europe’s cocaine purity improves: Cops mull new narco approach as Mexican cartels gain influence in EU. Politico 2022, 23 December. https://www.politico.eu/article/europe-cocaine-purity-improves-belgium-c...
15. Franco M, Holgado YH, Poltronieri F. How the Albanian mafia conquered the cocaine market in UK. Investigative Reporting Project Italy 2022, 3 March (English Translation). https://irpimedia.irpi.eu/en-albanian-mafia-uk-cocaine-supply/
16. NIHR. Invention for Innovation (i4i) - Addiction Mission: Innovation for Treatment and Recovery Awards Call Specification. 2023, 31 May. https://www.nihr.ac.uk/documents/invention-for-innovation-i4i-addiction-...
Competing interests: No competing interests
Re: The illegal drugs market is changing—is the UK prepared?
Dear Editor,
Eastwood and Schlossenberg highlighted the need to monitor and respond to the influx of nitazene analogues and other synthetic opioids into the community. Their use has increased overdose mortality in the United States, while the United Kingdom, Europe and Australia have reported nitazene analogues in drug seizures and toxicological case reports [1–4].
Wastewater surveillance is one way that countries could detect the emergence of new nitazene analogues and other synthetic opioids. Wastewater is a valuable information source that has been used for public health purposes to monitor trends in illicit drug use for more than a decade, with programs currently funded by the European Monitoring Centre for Drugs and Drug Addiction, Australian Criminal Intelligence Commission and New Zealand Police [5–7].
Additional programs have incorporated emerging drugs to provide a snapshot of new psychoactive substance use [8]. In the case of synthetic opioids, new methods can detect trace levels down to 0.01 ng/L and around 2 ng/L without sample pre-concentration [9,10]. Despite the high potency and low doses of these new nitazene analogues, such detection limits can allow these compounds to be found in community wastewater.
Large-scale wastewater campaigns of the type carried out at the height of the COVID-19 pandemic can be leveraged for this purpose [11]. For example, wastewater surveillance programs covered 74% of the population in the United Kingdom [12], over 80% in New Zealand [13], while 1745 sampling sites (and up to 133 million people) in the United States, were monitored for SARS-CoV-2 [14]. Expanding routine monitoring to include of nitazene analogues and other synthetic opioids in the population can allow harm minimisation strategies to be employed such as warnings to drug users and drug checking and can be a cost-effective way to evaluate ongoing opioid response interventions.
1 Schumann JL, Syrjanen R, Alford K, et al. Intoxications in an Australian Emergency Department Involving ‘Nitazene’ Benzylbenzimidazole Synthetic Opioids (Etodesnitazene, Butonitazene and Protonitazene). J Anal Toxicol. 2023;47:e6–9.
2 Pergolizzi Jr J, Raffa R, LeQuang JAK, et al. Old Drugs and New Challenges: A Narrative Review of Nitazenes. Cureus. 2023;15. doi: 10.7759/cureus.40736
3 Montanari E, Madeo G, Pichini S, et al. Acute Intoxications and Fatalities Associated With Benzimidazole Opioid (Nitazene Analog) Use: A Systematic Review. Ther Drug Monit. 2022;44:494–510.
4 Lo Faro AF, Berardinelli D, Cassano T, et al. New Psychoactive Substances Intoxications and Fatalities during the COVID-19 Epidemic. Biology (Basel). 2023;12:1–37.
5 European Monitoring Centre for Drugs and Drug Addiction. Wastewater analysis and drugs: a European multi-city study. 2018;10.
6 Australian Criminal Intelligence Commission. National Wastewater Drug Monitoring Program, Report 18. 2023.
7 New Zealand Police. Wastewater Drug Testing in New Zealand : National Overview Quarter Two : April – June 2022.
8 Bade R, Rousis N, Adhikari S, et al. Three years of wastewater surveillance for new psychoactive substances from 16 countries. Water Res X. 2023;19:100179.
9 Bade R, Abdelaziz A, Nguyen L, et al. Determination of 21 synthetic cathinones, phenethylamines, amphetamines and opioids in influent wastewater using liquid chromatography coupled to tandem mass spectrometry. Talanta. 2020;208:120479.
10 Bade R, Eaglesham G, Shimko KM, et al. Quantification of new psychoactive substances in Australian wastewater utilising direct injection liquid chromatography coupled to tandem mass spectrometry. Talanta. 2023;251:123767.
11 Ahmed F, O’Brien JW, Keshaviah A, et al. Wastewater-based monitoring could help guide responses to the USA opioid epidemic. Nat Water. 2023;1:401–4.
12 UK Health Security Agency. Wastewater testing coverage data for the Environmental Monitoring for Health Protection (EMHP) programme. 2022. https://www.gov.uk/government/publications/wastewater-testing-coverage-d...
13 Institute of Environmental Science and Research. Wastewater Surveillance Report. 2023. https://www.esr.cri.nz/our-expertise/covid-19-response/covid19-insights/...
14 Centers for Disease Control and Prevention. COVID Data Tracker. 2023. https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
Competing interests: No competing interests