"Diversion of safer opioid supply drugs was examined in six qualitative studies (Giang et al., 2023; Haines & O'Byrne, 2023a; Haines et al., 2022; Kalicum, 2023;

"Overall, the currently available evidence regarding health outcomes among safer opioid supply clients is generally favorable.

"From January–June 2020 to July–December 2022, the number of overdose deaths with evidence of smoking doubled, and the percentage of deaths with evidence of smoking increased across all geographic regions. By late 2022, smoking was the predominant route of use among drug overdose deaths overall and in the Midwest and West regions. Increases were most pronounced when IMFs were detected, with or without stimulants.

"This study is the first, to our knowledge, to document the clinical sequelae and naloxone administration for patients who were in the ED following confirmed NPO drug OD. The NPO group was administered a statistically significantly higher number of in-hospital naloxone boluses compared with the fentanyl group, which corresponded to a moderately large effect size. While these findings were based on limited sample sizes, we detected a large effect size for the association between increased naloxone doses and NPO overdose.

"Novel potent opioids (NPOs) are novel nonfentanyl opioids in the illicit opioid supply. Synthetic opioids are one of the fastest growing classes of opioids being detected in patients in the emergency department (ED) with opioid overdose (OD).1

"During the 1950s, nitazenes were developed by commercial pharmaceutical companies as synthetic opioid candidates and they were described in medical and pharmaceutical literature of the era. Thus, clandestine labs needed only to turn to the historic pharmacological literature to learn about the nitazene family. The European Monitoring Center for Drugs and Drug Addiction was first notified about the presence of isotonitazene in a biological sample obtained in July 2019 [15].

"In the late 1950s, the synthesis of 2-benzylbenzimidazole opioids led to the creation of several compounds now known collectively as nitazenes - although they do not technically meet the current United States Adopted Name (USAN) definition of an “azene.” They were of particular interest because their chemical structures are distinct from the typical morphine-like phenanthrene motif and meperidine analogs like fentanyl.

"The trend towards higher potency is likely most indicative of what to expect from future illicit substance market developments. According to Canadian drug seizure statistics heroin is no longer among the top ten recovered illegal substances [32, 40].

"The current trend towards the use of high potent synthetic opioids, especially fentanyl, has caused an extreme increase in the prevalence of non-fatal and fatal overdose events [13, 14]. However, the trend towards higher opioid potency is still ongoing, with several analogues and novel opioids becoming increasingly available.

"Highly potent synthetic opioids have not played such a prominent role in rising deaths among people who use drugs in the UK. Global drug markets are, however, rapidly evolving.