Extended Detection of Amphetamine and Methamphetamine in Oral Fluid.

BACKGROUND: Amphetamine and methamphetamine are popular drugs of abuse worldwide and are important components of drug monitoring programs. Windows of detection for amphetamine and methamphetamine in oral fluid after high doses have not been investigated. Repeated high-dose ingestions are likely to cause positive samples for extended periods. Common routes of administration of amphetamine/methamphetamine in Norway are oral intake or injection. The aim of this study was to investigate windows of detection for amphetamine and methamphetamine in oral fluid from drug addicts under sustained abstinence during detoxification. METHODS: Twenty-five patients admitted to a closed detoxification unit were included in this study. Oral fluid samples were collected daily in the morning and evening, and urine every morning for 10 days. A blood sample was drawn during the first 5 days after admission if the patient consented. Oral fluid results were compared with urine results to determine whether a new ingestion occurred. Oral fluid was collected with the Intercept oral fluid collection device. In-house cutoff concentrations for amphetamine and methamphetamine were 6.8 and 7.5 mcg/L, respectively, in oral fluid, and 135 and 149 mcg/L, respectively, in urine. RESULTS: Amphetamines were detected in 11 oral fluid, 5 urine, and 2 blood specimens from 25 patients. Patients self-reported amphetamines intake of up to 0.5-2 g daily. Windows of detection for amphetamine and methamphetamine in oral fluid were up to 8 days, longer than in urine at the applied cutoff values. CONCLUSIONS: These data confirm that oral fluid is a viable alternative to urine for monitoring amphetamine abuse, and that these substances might be detected in oral fluid for at least 1 week after ingestion of high doses. Such long detection times were, as far as we are aware, never reported previously for oral fluid amphetamines.

Detection Times of Diazepam, Clonazepam, and Alprazolam in Oral Fluid Collected From Patients Admitted to Detoxification, After High and Repeated Drug Intake.

BACKGROUND: Clonazepam, diazepam, and alprazolam are benzodiazepines with sedative, anticonvulsant, and anxiolytic effects, but their prevalence in drug abuse and drug overdoses has long been recognized. When detection times for psychoactive drugs in oral fluid are reported, they are most often based on therapeutic doses administered in clinical studies. Repeated ingestions of high doses, as seen after drug abuse, are however likely to cause positive samples for extended time periods. Findings of drugs of abuse in oral fluid collected from imprisoned persons might lead to negative sanctions, and the knowledge of detection times of these drugs is thus important to ensure correct interpretation. The aim of this study was to investigate the time window of detection for diazepam, clonazepam, and alprazolam in oral fluid from drug addicts admitted to detoxification. METHODS: Twenty-five patients with a history of heavy drug abuse admitted to a detoxification ward were included. Oral fluid was collected daily in the morning and the evening and urine samples every morning for 10 days, using the Intercept device. Whole blood samples were collected if the patient accepted. The cutoff levels in oral fluid were 1.3 ng/mL for diazepam, N-desmethyldiazepam, and 7-aminoclonazepam and 1 ng/mL for clonazepam and alprazolam. In urine, the cutoff levels for quantifications were 30 ng/mL for alprazolam, alpha-OH-alprazolam, and 7-aminoclonazepam, 135 ng/mL for N-desmethyldizepam, and 150 ng/mL for 3-OH-diazepam and for all the compounds, the cutoff for the screening analyses were 200 ng/mL. RESULTS: The maximum detection times for diazepam and N-desmethyldiazepam in oral fluid were 7 and 9 days, respectively. For clonazepam and 7-aminoclonazepam, the maximum detection times in oral fluid were 5 and 6 days, respectively. The maximum detection time for alprazolam in oral fluid was 2.5 days. New ingestions were not suspected in any of the cases, because the corresponding concentrations in urine were decreasing. Results from blood samples revealed that high doses of benzodiazepines had been ingested before admission, and explains the longer detection times in oral fluids than reported previously after intake of therapeutic doses of these drugs. CONCLUSIONS: This study has shown that oral fluid might be a viable alternative medium to urine when the abuse of benzodiazepines is suspected.

Detection time for THC in oral fluid after frequent cannabis smoking.

BACKGROUND: The use of oral fluid for detecting drugs of abuse has become increasingly more frequent. Few studies have, however, investigated the detection times for drugs of abuse in oral fluid, compared with that of in urine or in blood. Cannabis is the world's most widely used drug of abuse, and the detection times for cannabis, in different types of matrixes, are therefore important information to the laboratories or institutions performing and evaluating drugs of abuse analyses. It is well known that frequent use of high dosages of cannabis, for longer periods of time, might lead to prolonged detection times for THC-COOH in urine. Cannabis intake is detected in oral fluid as THC, and a positive finding is considered to be a result of recent smoking, although some studies have already reported longer detection times. The aim of this study was to investigate the detection time for THC in oral fluid, collected from drug addicts admitted for detoxification. Findings in oral fluid were compared with findings in urine, among 26 patients admitted to a closed detoxification unit. METHODS: The study, being the first in doing so, describes the concentration-time profiles for THC in oral fluid among chronic cannabis users, during monitored abstinence, using the Intercept collection kit. The study also includes the concentration-time profiles for creatinine-corrected THC-COOH ratios in urine samples, included to monitor for the possibility of new intakes. RESULTS: THC was detected in oral fluid collected from 11 of the 26 patients in the study. The elimination curves for THC in oral fluid revealed that negative samples could be interspersed among positive samples several days after cessation, whereas the THC-COOH concentrations in urine were decreasing. THC was, in this study, detected in oral fluid for up to 8 days after admission. CONCLUSIONS: The study shows that frequent use of high dosages of cannabis may lead to prolonged detection times, and that positive samples can be interspersed among negative samples. These results are of great importance when THC results from oral fluid analyses are to be interpreted.

[Effect and occurrence of synthetic cannabinoids]. / Syntetiske cannabinoider--effekt og forekomst.

BACKGROUND: ''Spice'' is the term used for various products that contain synthetic cannabinoids. In recent years a growing number of products have been reported on the illegal market, also in Norway. The substances are sold over the internet as 'legal' cannabis. A number of the substances have gradually been classified as narcotics, also in Norway, but new variants continue to be developed. An overview is provided here of current knowledge of the efficacy and occurrence of synthetic cannabinoids. METHOD: The article is based on a discretionary selection of relevant articles found by means of a literature search in PubMed and on reports from Norwegian and European authorities and research institutions. RESULTS: Synthetic cannabinoids are a large group of drugs of abuse that have an effect similar to cannabis, but may be considerably more potent. The contents of the various Spice products vary with respect to potency, purity and the number and types of additives, and this implies a risk of unintentional overdose. There are reports from abroad of cardiac infarction in teenagers, severe psychoses, anxiety, unconsciousness and deaths following use. INTERPRETATION: Synthetic cannabinoids are marketed over the internet as legal and harmless cannabis, but can cause severe intoxication and death. There is a considerable need for more knowledge about the action and harmful effects of these substances.

Geographical mapping of road traffic injuries in Lilongwe, Malawi.

BACKGROUND: Road traffic injuries are a leading cause of death and disability, especially in low- and middle-income countries. Identifying injury hotspots are valuable for introducing preventive measures. This is usually accomplished by using police data, but these are often unreliable in low-income countries. This study aimed to identify hotspots for injuries by collecting geographical data in the emergency room. METHODS: This was a cross-sectional study of adult road traffic injury patients presenting to the Casualty Department in the central hospital in Lilongwe, the capital of Malawi. An electronic tablet with downloaded maps and satellite photos was used to establish the exact location of the injuries. The geographical data were analyzed with geographic information software. RESULTS: We included 1244 road traffic injured patients, of which 23.9% were car passengers or drivers, 18.6% were motorcyclists, 17.8% were pedestrians and 18.0% were cyclists or bicycle passengers. Heatmaps of the injuries identified 5 locations where the incidence of injuries was especially high, and 148 patients were injured in these hotspots during the 90 days of inclusion. Four of these hotspots were along the main road through the capital. Age over 55, rural setting, alcohol use before the injury, high speed limit at the site of injury and being a pedestrian or motorcyclist were significantly associated with a higher degree of injury severity. Around half of the patients that were injured in a four-wheeled vehicle did not use a seat belt, and these patients had a much higher risk of getting a more severe injury. CONCLUSION: We have identified specific locations with a high incidence of road traffic injuries in Lilongwe, Malawi, with a simple methodology and within a short time frame. The study demonstrates the feasibility of collecting geographical data at admission to hospital.

The implementation of per-se limits for driving under the influence of benzodiazepines and related drugs: No increased risk for arrest during therapeutic use in Norway.

Objective: To investigate whether the use of recommended therapeutic doses of medicinal drugs has led to suspicion of driving under the influence of drugs (DUID) after implementation of legislative limits for illicit and medicinal drugs in 2012.Methods: Data from suspected drug-impaired drivers apprehended by the police from 2013 to 2015 were selected from the Norwegian Forensic Toxicology Database. The blood samples had been analyzed for benzodiazepines (BZDs), z-hypnotics, opioids, stimulants, certain hallucinogens, and alcohol. Drivers who tested positive for one BZD or a z-hypnotic only, were included in the study. Drug concentrations measured in their blood samples were compared to the maximal obtainable steady state concentrations if the drug had been used in accordance with the recommendations set by the Norwegian Directorate of Health.Results: BZDs or z-hypnotics were found in 10 248 samples, representing 59.6% of the total number of drivers arrested for suspected DUID (n = 17 201). Only one BZD or z-hypnotic with a blood drug concentration above the legislative limit was detected in 390 (2.3%) of the total number of samples. Clonazepam was the most frequently detected BZD (n = 4656), while as a single drug above the legislative limit, it was detected in only 3.6% (n = 168) of the clonazepam-positive blood samples. For drivers testing positive for only one z-hypnotic, drug concentrations above the legislative limit were found in 27% (n = 55) of the blood samples that tested positive for zolpidem and 12.4% (n = 53) of the samples that tested positive for zopiclone. In total, 155 subjects out of 10 248 testing positive for BZDs or z-hypnotics displayed concentrations above the legislative limit but within the concentration ranges that are expected when taking recommended therapeutic drug doses, and 77 below the legislativel limit.Conclusions: The results show that the implementation of legislative limits for BZDs and z-hypnotics may have contributed to DUID suspicion for a small group of patients using therapeutic drug doses; only 1.3% of the suspected DUID offenders had concentrations of only one of those drugs in-line with recommended therapeutic dosing.

Adult pedestrian and cyclist injuries in Lilongwe, Malawi: a cross-sectional study.

Background: Pedestrian and cyclist injuries are a major concern globally, but especially in low-income countries. Locally conducted research is needed to measure the size of the problem and advise policy on road safety interventions. We wanted to investigate the precise circumstances of these injuries in Lilongwe, Malawi and to identify risk factors for severe injuries. Methods: Cross-sectional study of all adult pedestrian and cyclist injuries presenting to a large central hospital. This was a sub-study of a larger study with all types of road users included. All patients provided detailed information about the incidents leading to injury and were tested for alcohol. Results: There were 222 pedestrians, 183 bicycle riders and 42 bicycle passengers among the 1259 adult road traffic injury victims that were treated at Kamuzu Central Hospital during a 90-day period in 2019. Of these injuries, 60.2% occurred while the victim was walking/cycling along the road and 22.3% when the victim was trying to cross the road. The majority of the victims were men (89.1%). Helmet use for bicyclists was almost non-existent. Only 1 patient had used reflective devices when injured in the dark, despite 44.7% of these injuries occurring in reduced light conditions. There was an increased risk for serious and fatal injuries for pedestrians compared with bicyclists, and also compared with all types of road users. Patients injured in rural areas and those hit by lorries were more severely injured. Consuming alcohol before being injured was associated with more severe injuries in bicyclists. Being injured while crossing the road at painted zebra crossings was associated with an increased risk of serious and potentially fatal injuries. Conclusion: This study identified important risk factors for severe injuries in pedestrians and cyclists. Implications for preventive measures are presented in a Haddon Matrix.

Prevalence of alcohol use among road traffic crash victims presenting to a Malawian Central Hospital: A cross-sectional study.

BACKGROUND: Alcohol consumption is a well-known risk factor for sustaining road traffic injuries worldwide. Malawi is a low-income country with a large and increasing burden of road traffic injuries. It has generally been viewed as a country with relatively little alcohol consumption. This study investigates the role of alcohol in road traffic injuries in and around the capital Lilongwe. METHODS: All patients presenting to the emergency department of Kamuzu Central Hospital after being injured in road traffic crashes were asked to participate in the study. Alcohol testing was done with a breathalyzer or a saliva test. Participants were asked about alcohol use before the injury as well as hazardous drinking using the AUDIT-C questionnaire. RESULTS: Of 1347 patients age 18 years or older who were asked to participate, 1259 gave informed consent, and data on alcohol use (alcohol test results and/or self-reported intake) were available for 1251 participants. Of those, 251 (20.1%) tested positive for alcohol, whereas 221 (17.7%) reported alcohol use before the crash; in total 311 (24.9%, 95% CI 22.5-27.3) either tested positive, reported use, or both. Females had a low prevalence of alcohol use (2.5%), while 30.6% of males had consumed alcohol before the injuries. Pedestrians had the highest prevalence at 41.8% (95% CI 35.5-48.4), while car drivers had 23.8% (95% CI 18.2-30.5). Among male pedestrians, 49.5% had used alcohol before the injury. Alcohol-associated injuries had a peak in the evening and at night, especially in the weekends. Of the patients, 63.1% reported that they had not consumed alcohol during the last year, while 21.4% had an AUDIT-C score suggesting hazardous drinking, and 66.2% of those had used alcohol before the injury. CONCLUSIONS: A large percentage of road traffic injured patients had been drinking alcohol before their injury, especially male pedestrians. A large proportion of the patients were abstaining from alcohol, but those not abstaining had a high prevalence both of alcohol use when injured and hazardous drinking identified by AUDIT-C. This has important implications for prevention.

Relationship between oral fluid and blood concentrations of drugs of abuse in drivers suspected of driving under the influence of drugs.

In recent years, the interest in the use of oral fluid as a biological matrix has increased significantly, particularly for detecting driving under the influence of drugs (DUID). In this study, the relationship between the oral fluid and the blood concentrations of drugs of abuse in drivers suspected of DUID is discussed. Blood and oral fluid samples were collected from drivers suspected of DUID or stopped during random controls by the police in Belgium, Germany, Finland, and Norway for the ROSITA-2 project. The blood samples were analyzed by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS), sometimes preceded by immunoassay screening of blood or urine samples. The oral fluid samples were analyzed by GC-MS or LC-MS(/MS). Scatter plots and trend lines of the blood and oral fluid concentrations and the median, mean, range, and SD of the oral fluid to blood (OF:B) ratios were calculated for amphetamines, benzodiazepines, cocaine, opiates, and Delta(9)-2 tetrahydrocannabinol. The ratios found in this study were comparable with those that were published previously, but the range was wider. The OF:B ratios of basic drugs such as amphetamines, cocaine, and opiates were >1 [amphetamine: median (range) 13 (0.5-182), methylenedioxyamphetamine: 4 (1-15), methylenedioxymethamphetamine: 6 (0.9-88), methamphetamine: 5 (2-23), cocaine: 22 (4-119), benzoylecgonine: 1 (0.2-11), morphine: 2 (0.8-6), and codeine: 10 (0.8-39)]. The ratios for benzodiazepines were very low, as could be expected as they are highly protein bound and weakly acidic, leading to low oral fluid concentrations [diazepam: 0.02 (0.01-0.15), nordiazepam: 0.04 (0.01-0.23), oxazepam: 0.05 (0.03-0.14), and temazepam: 0.1 (0.06-0.54)]. For tetrahydrocannabinol, an OF:B ratio of 15 was found (range 0.01-569). In this study, the time of last administration, the dose, and the route of administration were unknown. Nevertheless, the data reflect the variability of the OF:B ratios in drivers thought to be under the influence of drugs. The wide range of the ratios, however, does not allow reliable calculation of the blood concentrations from oral fluid concentrations.

Determination of opiates and cocaine in urine by high pH mobile phase reversed phase UPLC-MS/MS.

A fast and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of opiates (morphine, codeine, 6-monoacetylmorphine (6-MAM), pholcodine, oxycodone, ethylmorphine), cocaine and benzoylecgonine in urine has been developed and validated. Sample preparation was performed by solid phase extraction (SPE) on a mixed mode cation exchange (MCX) cartridge. For optimized chromatographic performance with repeatable retention times, narrow and symmetrical peaks, and focusing of all analytes at the column inlet at gradient start, a basic mobile phase consisting of 5mM ammonium bicarbonate, pH 10.2, and methanol (MeOH) was chosen. Positive electrospray ionization (ESI(+)) MS/MS detection was performed with a minimum of two multiple reaction monitoring (MRM) transitions for each analyte. Deuterium labelled-internal standards were used for six of the analytes. Between-assay retention time repeatabilities (n=10 series, 225 injections in total) had relative standard deviation (RSD) values within 0.1-0.6%. Limit of detection (LOD) and limit of quantification (LOQ) values were in the range 0.003-0.05 microM (0.001-0.02 microg/mL) and 0.01-0.16 microM (0.003-0.06 microg/mL), respectively. The RSD values of the between-assay repeatabilities of concentrations were

Determination of heroin and its main metabolites in small sample volumes of whole blood and brain tissue by reversed-phase liquid chromatography-tandem mass spectrometry.

A high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been developed for the quantitative analysis of heroin and its major metabolites 6-acetylmorphine, morphine, morphine-3-glucuronide and morphine-6-glucuronide in blood and brain tissue, using 0.1-mL samples. We evaluated this method for analysis of heroin and its metabolites in samples from heroin treated mice. Ice-cold acidic buffer containing sodium fluoride was immediately added to blood and brain homogenate samples. Sample preparation was achieved by protein precipitation on ice-bath, using a mixture of ice-cold acetonitrile and methanol. The supernatant was evaporated to dryness, reconstituted with mobile phase, and injected into the chromatographic system. Separation was performed on a Xterra C18 column with gradient elution. The MS analysis was performed in positive ion mode, and multiple reaction monitoring (MRM) was used for drug quantification. The limits of quantification for the different opiates varied from 0.0007 to 0.02 mg/L in blood and from 0.002 to 0.06 microg/g in brain tissue. Day-to-day relative standard deviation ranged from 3.1 to 14.5%, and within-day variation ranged from 2.1 to 11.4%. The recoveries were between 80 and 111%. The stability of heroin was tested, and the study showed that heroin is more stable in brain tissue than in blood.

Lethal poisoning with ethiofencarb and ethanol.

Ethiofencarb is one of the carbamate compounds, which are, in general, less toxic than organophosphorus insecticides. This is due to their reversible acetylcholinesterase inhibition and relative inability to cross the blood-brain barrier. Generally, ethiofencarb is regarded to be of low toxicity (LD(50) > 200 mg/kg); however, severe poisoning and death are not uncommon. To our knowledge, no measurements of ethiofencarb and its metabolites in human postmortem whole blood have been published. We present here a case report of fatal ethiofencarb intoxication with quantitative analysis of ethiofencarb and its metabolites in ante- and postmortem blood. In addition, postmortem urine was collected and analyzed. A 56-year-old man, who worked as a gardener, was found in poor condition, sitting in his car seat. He had been vomiting. The man was admitted to the local hospital about 1 h later. At admission, he was conscious, but unable to speak clearly. His condition deteriorated, and he developed severe pulmonary edema. Resuscitation with atropine and adrenaline were attempted, but he died approximately 3 h after admission. The analysis of postmortem peripheral blood revealed 0.12 g/100 mL ethanol, 26.4 mg/L ethiofencarb, 37.9 mg/L ethiofencarbsulfoxide, and 0.9 mg/L ethiofencarbsulfone. Ethanol (0.26 g/100 mL), ethiofencarb, ethiofencarbsulfoxide, and ethiofencarbsulfone were also detected in urine.

Serum/whole blood concentration ratio for ethylglucuronide and ethyl sulfate.

Serum/blood (S/B) concentration ratios for ethyl glucuronide (EtG) and ethyl sulfate (EtS) are missing from the literature, and the aim of this study was to determine these ratios in samples from patients at admission to an alcohol rehabilitation clinic. Two blood samples were collected simultaneously, and EtG and EtS were analyzed in whole blood and serum, respectively, using a liquid chromatography-mass spectrometry method. Separate calibration standards were prepared in both whole blood and serum for the calculation of whole blood and serum concentrations, respectively. Thirteen pairs of serum and whole blood were analyzed. The median S/B value for EtG was 1.69, and the range was 1.33-1.90. For EtS, the median S/B ratio was 1.30, and the range was 1.08-1.47. The S/B ratio was significantly lower for EtS than for EtG (p < 0.001). The higher concentrations of EtG and EtS in serum than in whole blood have to be considered when whole blood results obtained from forensic toxicology are compared to serum or plasma results from clinical laboratories.

Comparison between the urinary alcohol markers EtG, EtS, and GTOL/5-HIAA in a controlled drinking experiment.

AIM: Urinary ethyl glucuronide (EtG), ethyl sulfate (EtS), and the ratio between 5-hydroxytryptophol-glucuronide and 5-hydroxyindole-3-acetic acid (GTOL/5-HIAA) are all suggested as biomarkers for recent alcohol ingestion with longer detection times than measurement of ethanol itself. The aim of this controlled study was to compare the sensitivities and detection times of EtG, EtS, and GTOL/5-HIAA, after a single ingestion of ethanol. METHODS: 0.5 g ethanol/kg body weight was ingested by 10 healthy male volunteers in a fasted state. Ethanol, EtG, EtS, and GTOL/HIAA levels were measured in urine samples collected during a 45-50 h period. The total amount of ethanol excreted as EtG and EtS was also determined. RESULTS: Urinary EtG, EtS, and GTOL/5-HIAA showed 100% sensitivity as biomarkers for recent drinking. Compared to ethanol testing in urine, the detection times for GTOL/5-HIAA were approximately 5 h longer and for EtG and EtS approximately 25 h longer. The maximum EtG concentrations were higher than for EtS in all subjects, and a higher fraction of the ethanol dose was excreted as EtG (median 0.019%) compared with EtS (median 0.011%). CONCLUSIONS: This study is the first controlled experiment comparing the time-courses for ethanol, EtG, EtS, and GTOL/5-HIAA in urine. In cases where surveillance of alcohol relapse is needed, measurements of urinary EtG and EtS are sensitive and specific alternatives to ethanol testing. The GTOL/5-HIAA ratio is equally sensitive but with a much shorter window of detection.

[Determination of buprenorphine in urine]. / Bestemmelse av buprenorfinkonsentrasjon i urin.

Buprenorphine is one of the drugs used for treatment of opioid-dependent patients enrolled in rehabilitation programs in Norway. Buprenorphine is metabolized in the liver by cytochrome P450 to the active metabolite norbuprenorphine, and further to buprenorphine-glucuronide and norbuprenorphine-glucuronide. The Division of Forensic Toxicology and Drug Abuse at the Norwegian Institute of Public Health has during the past 5 years received an increasing number of urine samples for buprenorphine analysis. All urine samples with question of buprenorphine have since August 2005 been analysed with a new method, which analyses the glucuronides of buprenorphine and norbuprenorphine in urine. This method is fast and simple and saves time and resources in our routine laboratory.

A study of ethyl glucuronide in post-mortem blood as a marker of ante-mortem ingestion of alcohol.

The possibility of post-mortem production of ethanol makes correct interpretation of ethanol detection in forensic autopsy samples difficult. Even though the levels of ethanol formed post-mortem are generally low, this may be highly relevant in cases where intake of alcohol was forbidden, for instance for pilots, professional drivers and countries with low legal alcohol limits for driving. Different criteria are used to determine whether a finding of ethanol is of exogenous origin, but there is no marker for alcohol ingestion that has been studied in detail. In this study, we wanted to evaluate the sensitivity and specificity of ethyl glucuronide (EtG), a direct minor metabolite of ethanol, measured in blood, as a marker of ante-mortem alcohol ingestion. Forensic autopsy cases were divided into groups with and without ante-mortem alcohol ingestion, according to strict inclusion criteria. In 93 cases with information on ante-mortem alcohol ingestion, EtG was detected in blood in all cases, even when levels of ethanol were low. In another 53 cases where there were no indications of ante-mortem alcohol intake, EtG could not be detected in blood in a single case, also in 11 cases in which ethanol was detected and considered to be most probably formed post-mortem. In conclusion, blood EtG determination seems to be a reliable marker of ante-mortem ingestion of alcohol, and it could be considered in forensic autopsy cases when post-mortem formation of ethanol is questioned.

[Cannabis affects driving skills]. / Cannabisbruk påvirker kjøreferdighetene.

Delta (9)-tetrahydrocannabinol (THC), the most important psychoactive substance in cannabis, is frequently detected in blood from apprehended drivers suspected for drugged driving. Both experimental and epidemiological studies have demonstrated the negative effects of THC upon cognitive functions and psychomotor skills. These effects could last longer than a measurable concentration of THC in blood. Culpability studies have recently demonstrated an increased risk of becoming responsible in fatal or injurious traffic accidents, even with low blood concentrations of THC. It has also been demonstrated that there is a correlation between the degree of impairment, the drug dose and the THC blood concentration. It is very important to focus on the negative effect of cannabis on fitness to drive in order to prevent injuries and loss of human life and to avoid large economic consequences to the society.

[Routines upon suspicion of driving under influence]. / Rutiner ved mistanke om kjøring i påvirket tilstand.

Norway was the first country in the world to introduce an act, in 1936, that prohibits driving with a blood alcohol concentration (BAC) above 0.5 g/kg. This Norwegian Road Traffic Act was expanded in 1959 to include illegal drugs and other medicinal psychoactive drugs. Upon suspicion of drugged driving, a clinical test for impairment (CTI) is performed and blood samples are taken. The Norwegian police have been allowed to request blood analysis for illegal and prescribed drugs affecting driving performance, even by force if drug influence is suspected. There is currently no legal limit for drugs other than alcohol. The Division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Health analyse blood samples from all drivers suspected of drugged driving in Norway. Based on results of the blood sample analysis and the CTI, the DFTDA makes a preliminary conclusion of the probability of impairment comparable to BAC above 0.5 g/kg. Then the prosecuting authority decides whether to charge the suspected driver. The impairment has to be proven to the court in each individual case. The court decision is based on the outcome of the CTI, the blood sample analyses, other information that may be given and in most cases an expert witness statement. The sentences can be conditional or unconditional imprisonment, depending on the BAC or the degree of drug impairment and withdrawal of the driving licence for a period of at least 2 years..

Mortality among subjects previously apprehended for driving under the influence of traffic-hazardous medicinal drugs.

BACKGROUND: Most studies in the field of impaired driving have focused on the hazards represented by impaired drivers to the rest of society; there has been little follow-up of the drivers themselves. The aim of this study was to establish mortality rates among subjects previously apprehended for driving under the influence of traffic-hazardous medicinal drugs, alone or in combination with alcohol. METHODS: A prospective cohort study of all drivers aged 20-49 years, apprehended in Norway in 1992-1996 and testing positive for traffic-hazardous medicinal drugs in blood, outcome variable: death. STUDY POPULATION: 805 drivers (598 males, 207 females). Mean follow-up period: 6.8 years. Information on deaths was collected from Statistics Norway. RESULTS: During the follow-up period, 139 of the previously apprehended drivers died (110 males, 29 females). The calculated standardised mortality ratio (SMR) was 15.8 (95% CI: 13.0-19.0) for male and 20.0 (95% CI: 13.4-28.7) for female drivers. CONCLUSIONS: Apprehension on suspicion of driving under the influence of drugs, combined with detection of traffic-hazardous medicinal drugs in the blood, seems to indicate an elevated risk of premature death in the age group 20-49 years. Secondary prevention of continued drug use could save lives in this drug user group.

The concentrations, appearance and taste of nine sedating drugs dissolved in four different beverages.

Sedating drugs are reported to be used in cases where people have been drugged unwittingly. In the present experiments we studied whether nine sedating medicinal drugs would dissolve in four different beverages to reach concentrations which could possibly cause impairment and whether the drugs altered the appearance and taste of the beverages. Nine sedating medicinal drugs were added separately to water, beer, Coca-Cola and ethanol. Drug concentrations were measured 5, 10, 20 and 40 min after spiking. The amount of drug in one swallow (50 mL) was calculated. Appearance and taste were recorded after 10 min. Flunipam, Sobril, Valium and Xanor dissolved faster than Rohypnol, Imovane, Somadril, Rivotril and Dolcontin. Ten minutes after adding Flunipam, Sobril, Imovane (in beer and Coca-Cola), Valium and Xanor, the concentrations had reached more than 50% of maximum theoretical concentration. Most of the drugs caused sediment, pieces and/or turbidity in one or more of the beverages. Some of the solutions were dyed from added Rohypnol (turquoise or green), Dolcontin (red) and Valium (yellow). Flunipam and Valium caused extensive frothing in beer. The tastes of Imovane and Somadril were distinct in all the beverages, while the taste of other drug solutions was less distinct. The ingestion of all solutions could probably have caused impairment. All the nine drugs were, however, apparent to the consumer from the altered appearance and/or taste of the beverages.