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•DUID cases related to drugs abuse have been reported in Asia, USA, and Europe.•Amphetamine, cocaine, cannabis, BZDs, and opiates were frequently reported in DUID.•Regular testing of drivers was needed to collect data for DUID in traffic accident. Driving Under the Influence of Drugs (DUID) is considered a serious issue related to the abuse of illegal drugs. DUID cases, including deaths, are being continuously reported in Asia, USA, and Europe. This literature review focuses on illegal drug abuse in recent DUID cases reported in Asia, USA, and Europe. To determine illegal drug abuse in DUID suspects, previous studies collected and analyzed biological samples, such as blood, urine, oral fluids, and hair. In addition, there were forensic autopsies and surveys for investigation of illegal drugs in DUID cases and drivers. In previous studies, ketamine, morphine, methamphetamine (MA), and khat were mainly reported in Asia, whereas amphetamine, benzodiazepines (BZDs), and cannabinoids were mainly reported in USA, and synthetic cannabinoids (SCs), opiates, and cocaine were mainly reported in Europe. Since DUID suspects related to illegal drugs have been frequently reported in Asia, USA, and Europe, there is a need to plan for national monitoring for drivers or motor vehicles to regulate and prevent drug abuse and relevant DUID cases.

Recreational use of synthetic cannabinoid receptor agonists—so-called “Spice” products—became very popular during the last few years. Several reports on clinical symptoms and poisonings were published. Unfortunately, most of these reports do not contain any analytical data on synthetic cannabinoids in body fluids, and no or only a limited number of cases were reported concerning driving under the influence (DUI) of this kind of drugs. In this article, several cases of DUI of synthetic cannabinoids (AM-2201, JWH-018, JWH-019, JWH-122, JWH-210, JWH-307, MAM-2201 (JWH-122 5-fluoropentyl derivative), and UR-144) are presented, focusing on analytical results and signs of impairment documented by the police or the physicians who had taken the blood sample from the suspects. Consumption of synthetic cannabinoids can lead to impairment similar to typical performance deficits caused by cannabis use which are not compatible with safe driving. These deficits include centrally sedating effects and impairment of fine motor skills necessary for keeping the vehicle on track. Police as well as forensic toxicologists and other groups should become familiar with the effects of synthetic cannabinoid use, and be aware of the fact that drug users may shift to these “legal” alternatives due to their nondetectability by commonly used drug screening tests based on antibodies. Sophisticated screening procedures covering the complete range of available compounds or their metabolites have to be developed for both blood/serum and urine testing.

Driving under the influence of alcohol and drugs (DUID) is a major field of study to improve road safety. In Switzerland, during controls whether or not they follow an accident, the police can request toxicological analysis targeted either on alcohol only (ALC cases), or on drugs and alcohol (DUID cases). To evaluate both the drugs consumption on the road and whether or not these requests are well correlated with toxicological results, we built a database recording 4003 offenders (3443 males, 550 females) over a two-year period (2018–2019) in Western Switzerland. ALC case samples were then analyzed to target other substances than ethanol. We found one or more psychoactive drugs in 89% of DUID cases and alcohol alone was found in 56% of ALC cases. In ALC cases, alcohol alone was found in 72% of non-accident cases and in 52% of accident cases. This highlights an influence of accident context, inducing a too high suspicion of alcohol after accidents, and therefore an underestimation of the prevalence of other drugs. The most frequently detected drugs in DUID cases were cannabinoids (58%), ethanol (30%), cocaine (21%), benzodiazepines (11%), amphetamines (7%), opiates (6%), and antidepressants (5%). For the ALC cases, the drugs found were ethanol (84%), cannabinoids (13%), benzodiazepines (9%), antidepressants (6%), opiates (5%), cocaine (4%), methadone (3%), and amphetamines (1%). Prescription drugs, such as benzodiazepines, were common in accidents (22%) but rare in non-accidents DUID cases (5%). Thus, these drugs highly impact driving skills while being hard to suspect. This is of first concern as prescription drugs are largely found in poly-drug consumption, especially in combination with alcohol in accident cases. This emphasizes the emerging issue of prescription drugs and should motivate a strategy of prevention focused on the noxious effect of combining alcohol and prescription drugs on driving skills. •After an accident, alcohol is more suspected than other psychoactive drugs.•In ALC cases, 13% involved cannabis use, 9% BZD use, and 6% antidepressants use.•Supratherapeutic concentrations of BZD should motivate introduction of legal limits.•Implication of bicycles in accident is increasing while they are rarely controlled.

Blood concentrations of new designer benzodiazepines. [Display omitted] •Blood detections of designer benzodiazepines in criminal offenders increase.•Flubromazolam and flubromazepam are the most frequent drugs.•Designer benzodiazepines are often seen together with THC and amphetamine. A number of new designer benzodiazepines have reached the illegal drug market over the past years. Toxicological interpretation of concentrations of these drugs in blood is quite challenging as very limited human data have previously been published. The aim of this study was to report blood concentrations of new designer benzodiazepines in a population of drugged drivers as well as some other criminal offenders, and to relate this to clinical impairment. The present material represents cases involving new designer benzodiazepines (clonazolam, diclazepam, flubromazepam, flubromazolam and pyrazolam) and etizolam, submitted for analyses during the period July 1, 2013–May 31, 2016. Analyses were performed using an ultra-performance liquid chromatography–tandem mass spectrometry method. Blood concentrations and results from the clinical test of impairment are reported. New designer benzodiazepines were detected in 77 cases during the study period. The median (range) concentrations were 0.012mg/L (0.00048–0.10) for flubromazolam (n=25), 0.055mg/L (0.0047–1.2) for flubromazepam (n=24), 0.013mg/L (0.0021–0.057) for diclazepam (n=15), 0.050mg/L (0.019–0.17) for etizolam (n=14), 0.0053mg/L (0.0019–0.011) for clonazolam (n=7) and 0.074mg/L for pyrazolam (n=1). In six cases, designer benzodiazepines were the only drugs detected in blood, and in two of those cases, the physician had given the conclusion of “considerably impaired” upon performing the clinical test for impairment. Given the lack of previously published data on human concentrations, results presented in this study could be helpful in interpretation of blood concentrations of new designer benzodiazepines. This is crucial for the assessment of the importance of toxicological results in suspected drugged drivers, rape victims, etc.

Background According to the World Health Organization, road traffic injuries lead to 1.3 million deaths each year and represent the leading cause of death for young adults under 30 years old. The use of psychoactive substances, including alcohol, drugs and pharmaceuticals, is a well-known risk factor for road traffic injuries. Our study aims to assess the prevalence of substances consumed by drivers in western Switzerland. Such studies are pivotal to improving prevention and developing public awareness campaigns. Methods To assess the prevalence of psychoactive substances among drivers, roadside controls were performed in collaboration with local police, using their classical sampling procedures to detect drivers under the influence of drugs or alcohol over two time periods (P1: 2006-2008, P2: 2017-2020). When impaired driving was not suspected by the police, minimally invasive sampling strategies (i.e., oral fluids during P1 and dried blood spots during P2) were performed on volunteer drivers after a road safety survey. A posteriori analyses and statistical interpretation were then performed . Results Among the 1605 drivers included in the study, 1048 volunteers provided an oral fluid sample, while 299 provided a dried blood spot sample. The percentage of drivers testing positive for at least one substance that can impact driving abilities was stable over time, with a rate of 10.5% positivity measured over both periods. Considering the different categories of substances, a slight variation was observed between both periods, with 7.6 and 6.3% of pharmaceuticals and 3.6 and 4.9% of illicit drugs for P1 and P2, respectively. Regarding the consumption of illicit drugs, the highest percentage of positivity was measured in biological fluids of drivers under the age of 35, during nights and week-ends, periods which are considered particularly prone to fatal accidents for this age group. Disturbingly, the road safety survey highlighted that drivers’ perception of the risk of getting positively controlled while driving after drug consumption is low (3.3 on a 1-to-10 scale, N  = 299). Conclusion The number of positive cases measured in voluntary drivers who passed the preliminary police check demonstrates the importance of systematic biofluid sampling strategies regarding driving under the influence of psychoactive substances. Although the number of fatal road accidents globally has decreased over time, the results of this study reveal the need for both better prevention and deterrent processes that could potentially reduce the risk of fatal road accidents associated with drug consumption.

New psychoactive drugs, so-called legal highs, have gained more and more popularity during the last years. One of the most important groups of these legal high substances are the synthetic phenethylamines that share a common phenethylamine moiety. Based on certain structural characteristics, these synthetic phenethylamines can be divided into further subclasses, among which the synthetic cathinones (‘bath salts’) are particularly noteworthy. Synthetic cathinones are characterized by an additional carbonyl group attached at the beta position on the amino alkyl chain. Consumption of synthetic phenethylamines can lead to impairments similar to those observed after the use of, for instance, amphetamine or 3,4-methylenedioxy- N -methylamphetamine (MDMA, ‘ecstasy’). These impairments include diverse neurological and psychological symptoms which can affect a safe driving behaviour. Although several reports on clinical symptoms and poisonings due to these substances have been published, most of these publications do not contain any analytical data. Additionally, there is still a lack of information concerning pharmacological and toxicological effects of these rather new psychoactive substances. In particular, the knowledge of the impact on the ability to drive following consumption of synthetic phenethylamines is relevant for the police as well as for forensic toxicologists. In this publication, several cases of individuals driving under the influence (DUI) of synthetic phenethylamines (4-fluoroamphetamine, mephedrone (4-methylmethcathinone, 4-MMC), 2-DPMP (desoxypipradol), methylenedioxypyrovalerone (MDPV), benzedrone, N -ethylamphetamine (etilamfetamine), 3-methylmethcathinone (3-MMC)) are presented, focusing on analytical results and signs of impairment.

GHB is an endogenous short-chain organic acid presumably also widely applied as a rape and knock out drug in cases of drug-facilitated crimes or sexual assaults (DFSA). Due to the endogenous nature of GHB and its fast metabolism in vivo , the detection window of exogenous GHB is however narrow, making it challenging to prove use of GHB in DFSA cases. Alternative markers of GHB intake have recently appeared though none has hitherto been validated for forensic use. UHPLC-HRMS based screening of blood samples for drugs of abuse is routinely performed in several forensic laboratories which leaves an enormous amount of unexploited data. Recently we devised a novel metabolomics approach to use archived data from such routine screenings for elucidating both direct metabolites from exogenous compounds, but potentially also regulation of endogenous metabolism and metabolites. In this paper we used UHPLC-HRMS data acquired over a 6-year period from whole blood analysis of 51 drivers driving under the influence of GHB as well as a matched control group. The data were analyzed using a metabolomics approach applying a range of advanced analytical methods such as OPLS-DA, LASSO, random forest, and Pearson correlation to examine the data in depth and demonstrate the feasibility and potential power of the approach. This was done by initially detecting a range of potential biomarkers of GHB consumption, some that previously have been found in controlled GHB studies, as well as several new potential markers not hitherto known. Furthermore, we investigate the impact of GHB intake on human metabolism. In aggregate, we demonstrate the feasibility to extract meaningful information from archived data here exemplified using GHB cases. Hereby we hope to pave the way for more general use of the principle to elucidate human metabolites of e.g. new legal or illegal drugs as well as for applications in more global and large scale metabolomics studies in the future.

Background/Objectives: Due to its potent local anesthetic and vasoconstrictive properties, cocaine is sometimes used in otolaryngologic surgical interventions. However, cocaine topical administration is not always adequately documented by practitioners, which can lead to serious legal consequences, particularly in the context of drug-impaired driving (DUID) investigations. This study retrospectively analyzes five road accident cases where cocaine was detected in biological samples after medical interventions. Case descriptions: Following pedestrian–car, or car–car accidents, five distinct patients aged between 30 and 84 years underwent maxillofacial surgery due to significant injuries. Given the severity of the accident and the circumstances, the police requested blood toxicological analysis to determine whether the patients were under the influence of psychoactive substances at the moment of the accidents. Results: The five cases described in this manuscript had blood cocaine concentrations exceeding the Swiss legal limit for drivers (15 µg/L). Since no information was initially provided about the medical use of cocaine after the crash, recreational use of cocaine was suspected. However, subsequent investigations confirmed that the cases involved medical administration. Conclusions: After sinonasal procedures involving the topical application of cocaine, patients may yield positive results on urine and blood drug tests, potentially resulting in serious legal repercussions, including the withdrawal of their driving license. Therefore, practitioners should thoroughly document the medical use of topical cocaine, particularly in DUID cases. These results also raise questions about the benefit–risk ratio of such use, considering that alternatives exist.

In Switzerland, a two-tier system based on impairment by any psychoactive substances which affect the capacity to drive safely and zero tolerance for certain illicit drugs came into force on 1 January 2005. According to the new legislation, the offender is sanctioned if Δ 9-tetrahydrocannabinol THC is ≥1.5 ng/ml or amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), cocaine, free morphine are ≥15 ng/ml in whole blood (confidence interval ± 30%). For all other psychoactive substances, impairment must be proven in applying the so-called “three pillars expertise”. At the same time the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.80 to 0.50 g/kg. The purpose of this study was to analyze the prevalence of drugs in the first year after the introduction of the revision of the Swiss Traffic Law in the population of drivers suspected of driving under the influence of drugs (DUID). A database was developed to collect the data from all DUID cases submitted by the police or the Justice to the eight Swiss authorized laboratories between January and December 2005. Data collected were anonymous and included the age, gender, date and time of the event, the type of vehicle, the circumstances, the sampling time and the results of all the performed toxicological analyses. The focus was explicitly on DUID; cases of drivers who were suspected to be under the influence of ethanol only were not considered. The final study population included 4794 DUID offenders (4243 males, 543 females). The mean age of all drivers was 31 ± 12 years (range 14–92 years). One or more psychoactive drugs were detected in 89% of all analyzed blood samples. In 11% ( N = 530) of the samples, neither alcohol nor drugs were present. The most frequently encountered drugs in whole blood were cannabinoids (48% of total number of cases), ethanol (35%), cocaine (25%), opiates (10%), amphetamines (7%), benzodiazepines (6%) and methadone (5%). Other medicinal drugs such as antidepressants and benzodiazepine-like were detected less frequently. Poly-drug use was prevalent but it may be underestimated because the laboratories do not always analyze all drugs in a blood sample. This first Swiss study points out that DUID is a serious problem on the roads in Switzerland. Further investigations will show if this situation has changed in the following years.

In forensic toxicology, amphetamine intoxications represent one of the most common case groups and present difficult questions for toxicologists. Estimating the time of consumption and the current influence of the stimulant is particularly difficult when only total amphetamine concentrations are considered. Stereoselective analysis and the consideration of metabolites can provide valuable information to facilitate interpretation. An enantioselective liquid chromatography−tandem mass spectrometry (LC-MS/MS) method for detection of amphetamine, norephedrine and 4-hydroxyamphetamine was developed. Validation showed satisfactory selectivity, sensitivity, linearity (0.5–250 ng/mL), precision and accuracy for all enantiomers. The method was applied to a collective of 425 forensic serum samples and 30 serum samples from psychiatric inpatients stating their last time of amphetamine consumption. Norephedrine and 4-hydroxyamphetamine were detected more frequently at higher amphetamine concentrations and at lower amphetamine (R)/(S) concentration ratios, possibly indicating recent consumption. Mean (R)/(S) ratio of amphetamine was 1.14, whereas higher ratios (mean 1.36) were found for amphetamine concentrations below 100 ng/mL. The (R)/(S) ratios of psychiatric inpatients significantly correlated with the reported time intervals to last consumption. The use of amphetamine (R)/(S) ratios and the simultaneous detection of metabolites are promising factors that can facilitate estimation of consumption time and current impairment.