Prevalence and blood concentrations of benzodiazepines and opioids in opioid-positive death investigations in Ontario, Canada, from 2017 to 2021.

The aim of this study was to investigate the incidence of benzodiazepines in opioid-positive death investigations, including trends in frequency and combination of drugs, as well as demographic data and blood concentrations, where available. Additionally, naloxone concentrations in polysubstance compared to opioid-only cases were analyzed. This was a retrospective study that consisted of all post-mortem toxicology cases in Ontario, Canada, from January 01, 2017, to December 31, 2021, with an opioid finding in any analyzed autopsy specimen. There were 11,033 death investigations identified. The overall rate of benzodiazepine co-involvement was 54.5%. Males accounted for the majority of cases (71%), and the most affected age group was 30- to 39-year-olds. The most frequently detected opioid was fentanyl and the most frequently detected benzodiazepine was etizolam, which was also the most frequently observed opioid/benzodiazepine combination. Findings related to differences in concentrations of opioids when naloxone was also present were mostly non-significant, except for methadone. The rate of benzodiazepine detection with opioids grew faster than opioid detections overall, potentially due to the increasingly toxic drug supply. Detection of novel psychoactive drugs fluctuated more unpredictably than opioids and benzodiazepines associated with clinical use. These findings can help inform policy decisions by public health agencies in exploring harm reduction efforts, for example, education and drug-checking services.

Flualprazolam and flubromazolam: Blood concentrations and prevalence of two novel psychoactive substances in forensic case work in Ontario, Canada.

Flualprazolam and flubromazolam are synthetic benzodiazepines that have not been approved for use in humans. They are categorized as novel psychoactive substances (NPS), and have been increasingly encountered in forensic case work. This report examines information from cases analyzed for flualprazolam and flubromazolam between July 1 and December 31, 2021 to identify the prevalence, trends and demographic data associated with these novel drugs in Ontario, Canada. Flualprazolam was identified in blood, serum or liver in 395 death investigations, 108 impaired driving and five sexual assault cases. Among all case types, blood concentrations were determined in 123 individuals aged 19-66 years. In impaired driving and sexual assault cases, flualprazolam blood concentrations ranged from <1.3 to 227 ng/mL (median 11.0 ng/mL), whereas a range of 3-59 ng/mL (median 6.8 ng/mL) was reported in death investigations. Flubromazolam was identified in blood, serum or liver in 137 death investigations, 55 impaired driving and one sexual assault case. Blood concentrations ranged from <1.3 to 323 ng/mL in 65 individuals, aged 14-61 years. In impaired driving and sexual assault cases, flubromazolam blood concentrations ranged from <1.3 to 323 ng/mL (median 7.7 ng/mL), which overlapped with the range of 2-220 ng/mL (median 8.0 ng/mL) reported in death investigations. Other drugs were frequently detected with flualprazolam and flubromazolam with opioids identified in more than 89% of positive flualprazolam and flubromazolam cases. These results demonstrated the prevalence of flualprazolam and flubromazolam in Ontario, Canada. Trends showed that over the 6-month period, as the number of flubromazolam cases decreased, the incidences of flualprazolam increased. An overlap in concentrations of these drugs was observed in both death investigations and cases involving living individuals. These data provide valuable information for the scientific community regarding the use of these drugs in antemortem and postmortem casework.

Opioid-related deaths in Ontario correctional facilities and penitentiaries (2009-2019).

The opioid crisis is a significant public health issue in North America that began in the 1990s with opioid-related deaths increasing each year. Although studies have been published regarding the incidence of opioid-related deaths in the general population, there is limited information regarding deaths in the prison population. To investigate the impact of the opioid epidemic in this vulnerable population, a retrospective study of all drug-related deaths that occurred in correctional facilities and penitentiaries in Ontario, Canada, between January 2009 and December 2019 was conducted. A total of 90 deaths were attributed to acute drug toxicity and the decedents ranged in age from 18 to 63 years and comprised 81 men and 9 women. The results of this study indicate the number of drug-related fatalities have increased by 375% (from 4 to 19) over the last 11 years. The detection of opioids in drug-related deaths has increased with fentanyl being the most frequently detected drug. Data also indicates the recent emergence of fentanyl-related analogues in this population. The results from this study provide valuable information about drug-related deaths in the Ontario prison system and provide insight into how the opioid crisis and the increased use of fentanyl and its analogues have affected this vulnerable population.

Strategic Decision-Making by a Forensic Toxicology Laboratory in Response to an Emerging NPS: Detection, Quantitation and Interpretation of Carfentanil in Death Investigations in Ontario, Canada, July 2017 to June 2018.

The proliferation of novel psychoactive substances (NPS) and the current opioid epidemic creates challenges for a toxicology laboratory. Methods capable of detecting and quantitating emerging compounds must be established despite limited information on toxicologically relevant concentrations. This paper will (i) describe how a publicly funded forensic laboratory reacted to the emergence of carfentanil as a public safety concern and (ii) contribute to the existing forensic literature by presenting a series of deaths involving carfentanil between July 2017 and June 2018. The Centre of Forensic Sciences is the primary provider of forensic toxicology testing in medicolegal death investigations in the province of Ontario. When carfentanil was first identified in the illicit drug supply, routine screening methods used by this laboratory were not sufficiently sensitive to detect the drug at concentrations expected in blood samples. Previously validated, multi-target liquid chromatography-tandem mass spectrometry (LC-MS-MS) quantitative methods already in use by the laboratory did show improved detectability for carfentanil. Thus, an existing LC-MS-MS method was adapted to include carfentanil, achieving improved sensitivity while also providing quantitation in suspected drug-related deaths. This approach had the added benefit that the LC-MS-MS method selected for modification was used in all death investigations requiring toxicology analysis in Ontario, thereby providing an opportunity for surveillance. Using this method, 4,953 cases were analyzed with carfentanil detected at a concentration greater than the limit of detection (0.05 ng/mL) in 160 decedents. Postmortem blood carfentanil concentrations ranged from less than 0.1 to 9.2 ng/mL. Of the 160 carfentanil-positive cases, 156 were classified as either mixed drug toxicity or carfentanil overdose. The approach described enabled this laboratory to efficiently implement a quantitative test for carfentanil in all death investigations, providing a useful template for modifying existing methods when a new psychoactive substance becomes available in the population.

Cannabis, alcohol and other drug findings in fatally injured drivers in Ontario.

OBJECTIVE: The purpose of this study was to determine the prevalence of cannabis, alcohol and other drug use in drivers of motor vehicles who died in crashes in the Canadian province of Ontario from January 2016 through December 2018 along with the characteristics of these drivers and some of the circumstances of the crash in which they were involved. METHODS: Toxicological tests were performed on blood samples obtained from 921 driver fatalities for whom postmortem blood samples were submitted to the Center of Forensic Sciences for analysis. The results were coded into a database along with basic demographic and crash characteristics and examined for prominent characteristics and patterns. RESULTS: Overall, among the 921 cases examined, 495 (53.7%) tested positive for alcohol, cannabis (tetrahydrocannabinol or THC), or another psychoactive drug. The number of cases that tested positive for THC (251) exceeded the number of cases that tested positive for alcohol (241) as well as the number that tested positive for a drug other than THC (235). In 38% of positive cases, more than one substance was detected. Alcohol and THC were most commonly detected among males; females most frequently tested positive for a drug other than THC, notably medications with depressant effects. Alcohol-involved driver fatalities were most common on weekends and most likely involved single vehicle crashes. Driver fatalities that tested positive for THC or another drug were more evenly distributed throughout the week and were more likely to have been in multi-vehicle crashes. CONCLUSIONS: The present study highlights the use of cannabis and other drugs by drivers. The patterns of crashes and the characteristics of drivers involved indicate that the characteristics of driver fatalities involving cannabis and/or other drug use differ from those of alcohol and require new, innovative approaches targeting high-risk times, groups and behaviors. Continued monitoring of the toxicological findings from blood samples obtained from drivers killed in motor vehicle crashes will be a key element in efforts to reduce the impact of drug use by drivers on road safety.

Toxicological findings in fatal motor vehicle collisions in ontario, Canada: a one-year study.

Drug-impaired driving is a complex area of forensic toxicology due in part to limited data concerning the type of drugs involved and the concentrations detected. This study analyzed toxicological findings in drivers from fatal motor vehicle collisions (FMVCs) in Ontario, Canada, over a one-year period using a standardized protocol. Of the 229 cases included in the study, 56% were positive for alcohol and/or drugs. After alcohol, cannabis was the most frequently encountered substance (27%), followed by benzodiazepines (17%) and antidepressants (17%). There were differences in drugs detected by age but no marked difference in drugs detected between single and multiple FMVC's. Not all drugs detected were considered impairing either due to drug type, concentration or case history. The findings indicate the importance of comprehensive drug testing in FMVCs and highlight the need to consider a variety of factors, in addition to drug type and concentration, when assessing the role of drugs in driving impairment.

Codeine-related deaths: The role of pharmacogenetics and drug interactions.

The objective of this study was to assess the relationship between genetic polymorphisms and drug interactions on codeine and morphine concentrations in codeine-related deaths (CRD). All CRD in Ontario, Canada between 2006 and 2008 were identified. Post-mortem blood was analyzed for 22 polymorphisms in 5 genes involved in codeine metabolism and response. Sixty-eight CRD were included in this study. The morphine-to-codeine ratio was significantly correlated with the presence of a CYP2D6 inhibitor at varying potencies (p=0.0011). The presence of other central nervous system (CNS) depressants (i.e. benzodiazepines, hypnotics, and/or alcohol) was significantly associated with lower codeine concentration as compared to CRD in which other CNS depressants were not detected (p=0.0002). Individuals who carried the ABCB1 1236T variant had significantly lower morphine concentrations (p=0.004). In this population of individuals whose cause of death was related to codeine, drug interactions and genetic polymorphisms were significantly associated with post-mortem codeine and morphine concentrations.

Oral abuse of fentanyl patches (Duragesic): seven case reports.

In order to increase the understanding regarding the oral abuse and potential toxicity of fentanyl patches seven cases were identified over a 3-year period where fentanyl, either alone or in combination with other factors, contributed to death following the oral abuse of Duragesic patches. The decedents comprised three females and four males with ages ranging from 20 to 51 years. Postmortem blood fentanyl concentrations were determined in all cases and ranged from 7 to 97 ng/mL. Two deaths were classified as a fentanyl overdose, three deaths were classified as a fentanyl and ethanol overdose, one death was considered a mixed drug intoxication and the remaining death was determined to be a combination of fentanyl and medical causes. These cases represent the largest reported series of deaths following the oral administration of transdermal fentanyl patches and provide detailed information on the potential for the abuse of transdermal Duragesic patches via this route. The postmortem blood fentanyl concentrations detected for each of the decedents demonstrate the potentially fatal blood concentrations that can arise after this relatively rare route of administration.

Fentanyl-related deaths in Ontario, Canada: toxicological findings and circumstances of death in 112 cases (2002-2004).

In order to characterize fentanyl-related deaths in the province of Ontario, Canada, a retrospective study of all cases in which fentanyl was quantitated in blood was conducted for the time period between 2002 and 2004. A total of 112 fentanyl-related deaths were identified. Decedents ranged in age from 4 to 93 years and comprised 63 men and 49 women. A variety of routes of administration of the drug were identified: transdermal application of Duragesic patches, intravenous injection of patch contents or fentanyl citrate solution, oral/transmucosal administration, and volatilization and inhalation of Duragesic systems. Blood fentanyl concentrations were determined for all modes of drug administration and are provided. There were 54 cases in which death was attributed solely to fentanyl intoxication; the mean blood concentration was 25 microg/L (range: 3.0-383 microg/L). This concentration range overlapped with blood fentanyl concentrations measured among cases where the presence of the drug was considered incidental. For example, a mean blood concentration of 12 microg/L was observed among 12 cases of natural death (range: 2.7-33 microg/L). Detailed case reports of six individuals are also included and provide additional insight into the use of this drug for both therapeutic and illicit means.