The upcoming synthetic ultrapotent opioid wave as a foreseeable disaster

The fentanyl-dominated recreational drug supply and the rapid rise of overdose deaths is unfortunately not the endpoint in the evolution of the North American drug market.1Krausz RM Westenberg JN Mathew N et al.Shifting North American drug markets and challenges for the system of care.Int J Ment Health Syst. 2021; 15: 86Crossref PubMed Scopus (2) Google Scholar Non-fentanyl-derived ultrapotent synthetic opioids that are several times more potent than fentanyl, such as nitazenes, are being increasingly detected in Canada and the USA.2Canadian Centre on Substance Use and AddictionNitazenes (CCENDU Drug Alert).https://www.ccsa.ca/nitazenes-ccendu-drug-alertDate: 2022Date accessed: July 5, 2022Google Scholar Despite having similar (and often more acute) physiological effects to heroin, these novel psychoactive substances are not well characterised, and there is little understanding of an effective treatment approach.3Vandeputte MM Krotulski AJ Walther D et al.Pharmacological evaluation and forensic case series of N-pyrrolidino etonitazene (etonitazepyne), a newly emerging 2-benzylbenzimidazole ‘nitazene’ synthetic opioid.Arch Toxicol. 2022; 96: 1845-1863Crossref PubMed Scopus (1) Google Scholar Moreover, these new ultrapotent synthetic substances are being rapidly produced in so-called homegrown laboratories using legal and easily available precursors. Production can be established anywhere, thereby avoiding global trafficking routes, partly as an adaptation to border closures in response to the COVID-19 pandemic.1Krausz RM Westenberg JN Mathew N et al.Shifting North American drug markets and challenges for the system of care.Int J Ment Health Syst. 2021; 15: 86Crossref PubMed Scopus (2) Google Scholar These developments will challenge nearly all existing harm-reduction and treatment options, from reversing overdoses with the appropriate naloxone response to retention in opioid agonist treatment programmes, underscoring the importance of proactively collecting evidence and adjusting our health-care systems. The inability of health-care systems to address emerging synthetic opioids exposes substantial existing inadequacies.4Humphreys K Shover CL Andrews CM et al.Responding to the opioid crisis in North America and beyond: recommendations of the Stanford–Lancet Commission.Lancet. 2022; 399: 555-604Summary Full Text Full Text PDF PubMed Scopus (14) Google Scholar There are too few well-established research centres that are able and ready to investigate pressing questions to guide evidence-based interventions; for example, how to best understand the influence of economic factors (eg, availability, price), societal factors (eg, stigma, health disparities), and individual factors (eg, trauma, mental health needs) in the ongoing developments. Expanding access to services and innovating treatment options specifically to address ultrapotent synthetic opioids could generate subtstantial cost savings in the long-term, which in turn could be re-invested into addiction research, health, and social services.4Humphreys K Shover CL Andrews CM et al.Responding to the opioid crisis in North America and beyond: recommendations of the Stanford–Lancet Commission.Lancet. 2022; 399: 555-604Summary Full Text Full Text PDF PubMed Scopus (14) Google Scholar However, beyond enhancing treatment services, could the legalisation of heroin and other substances be a successful strategy? Should there be provision of pharmaceutical grade drugs to people who are at risk of overdose, as is the case in Canada with safe supply? COVID-19 has certainly overshadowed the overdose crisis. However, given the widespread availability of fentanyl and increasing presence of ultrapotent synthetic opioids, efforts to protect people at risk of overdose must equal, if not surpass, those for COVID-19. On the current trajectory, we can expect nearly a million deaths in the USA due to overdose within the next decade.5Lim TY Stringfellow EJ Stafford CA et al.Modeling the evolution of the US opioid crisis for national policy development.Proc Natl Acad Sci USA. 2022; 119e2115714119Crossref Scopus (1) Google Scholar Without innovative and effective treatments, there will not be any noteworthy harm reduction. Similar to the COVID-19 pandemic, responsible governance means using evidence-based interventions and focusing on health outcomes, rather than watching historical records be broken. It also means mobilising all necessary resources and listening to those who are best positioned to advise and devise effective strategies (eg, specialists in addiction medicine and psychiatry). What is the role of psychiatry in this crisis? It is the part of medicine formally responsible, given that complex concurrent disorders and high-risk substance use are within the domain and require the skillset of these specialists. The prevention and treatment of substance use disorders have been kept on the sidelines of psychiatry for too long, despite the high mortality and morbidity resulting from these disorders. Reprioritising research and training in the field of mental health and high-risk substance use is a crucial part of the solution, beginning with accepting the challenge and taking action. We declare no competing interests. We would like to thank Daniel Vigo (Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada) for their feedback on the manuscript.