Per Trygve Normann

Prevalence of alcohol and drugs among Norwegian motor vehicle drivers: A roadside survey

The objective of the study was to determine the prevalence of alcohol, psychoactive medicinal drugs and illegal drugs among drivers in Norwegian road traffic. Drivers of motor vehicles were selected from April 2005 to April 2006 in the south-eastern part of Norway, surrounding, but not including the capital, Oslo. A stratified two-stage cluster sampling procedure was used. In the first stage, random road sites and time intervals were selected, and in the second stage, drivers were stopped by random at those sites and time intervals. Altogether about 12,000 drivers were asked to provide a sample of oral fluid (saliva) and answer a few questions. Samples of oral fluid were obtained from 88% of the drivers, of whom 30% were females and 70% males. The prevalence of each drug was estimated by a weighted average using weights adjusted for under- or over-sampling compared to traffic statistics. Alcohol or drugs were found in oral fluid samples of 4.5% of the drivers; alcohol in 0.4%, psychoactive medicinal drugs in 3.4%, and illegal drugs in 1.0%. Illegal drugs were found more frequently in samples from younger drivers, while psychoactive medicinal drugs were more frequently found in samples from older drivers. Psychoactive medicinal drugs were more prevalent among females than males, among drivers stopped on working days rather than weekends, and among those who reported annual driving distances less than 16,000 km. The drugs found most frequently were zopiclone (1.4%), benzodiazepines (1.4%), codeine (0.8%), tetrahydrocannabinol (0.6%) and amphetamines (0.3%). Two or more drugs were found in 0.6% of the samples, corresponding to 15% of the drug-positive drivers.

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.

Fatal poisoning in drug addicts in the Nordic countries in 2007

The frequency of medico-legally examined fatal poisonings in 2007 among drug addicts was investigated in five Nordic countries; Denmark, Finland, Iceland, Norway, and Sweden. The number of deaths, age, sex, place of death, main intoxicant, and other drugs present in blood samples were recorded to obtain national and comparable Nordic data, as well as data to compare with earlier studies in 2002, 1997, and 1991. Norway had the highest incidence of drug addict deaths by poisoning followed by Denmark, with 8.24 and 6.92 per 100,000 inhabitants, respectively. The death rates in Finland (4.02), Iceland (4.56), and Sweden (3.53) were about half that of Norway and Denmark. Compared with earlier studies, the death rates were unchanged in Denmark and Norway, but increased in Finland, Iceland, and Sweden. In all countries, fewer deaths (29-35%) were recorded in the capital area compared with earlier studies. Females accounted for 11-19% of the fatal poisonings. Iceland deviates with a more equal distribution between men and women (40%). Deaths from methadone overdoses increased in all Nordic countries, and methadone was the main intoxicant in Denmark in 2007, accounting for 51% of the poisonings. In Norway and Sweden, heroin/morphine was still the main intoxicant with a frequency of 68% and 48%, respectively. In Iceland, 3 deaths each were due to heroin/morphine and methadone, respectively. Finland differs from other Nordic countries in having a high number of poisonings caused by buprenorphine and very few caused by heroin/morphine. The total number of buprenorphine deaths in Finland doubled from 16 in 2002 to 32 in 2007, where it constituted 25% of deaths. The general toxicological screening program showed widespread multi-drug use in all countries. The median number of drugs per case varied from 3 to 5. The most frequently detected substances were heroin/morphine, methadone, buprenorphine, tramadol, amphetamine, cocaine, tetrahydrocannabinol, benzodiazepines and ethanol.

Alcohol, psychoactive drugs and fatal road traffic accidents in Norway: A case–control study

A case-control study was conducted on 204 drivers fatally injured in road traffic accidents in south-eastern Norway during the period 2003-2008. Cases from single vehicle accidents (N = 68) were assessed separately. As controls, 10540 drivers selected in a roadside survey in the same geographical area during 2005-2006 were used. Blood samples were collected from the cases and oral fluid (saliva) samples from the controls. Samples were analysed for alcohol, amphetamines, cannabis, cocaine, opioid analgesics, hypnotics, sedatives and a muscle relaxant; altogether 22 psychoactive substances. Equivalent cutoff concentrations for blood and oral fluid were used. The risk for fatal injury in a road traffic accident was estimated using logistic regression adjusting for gender, age, season of the year, and time of the week. The odds for involvement in fatal road traffic accidents for different substances or combination of substances were in increasing order: single drug < multiple drugs < alcohol only < alcohol+drugs. For single substance use: medicinal drug or THC < amphetamine/methamphetamine < alcohol. For most substances, higher ORs were found when studying drivers involved in single vehicle accidents than for those involved in multiple vehicle accidents, but confidence intervals were wider.

Prevalence of alcohol and other substances of abuse among injured patients in a Norwegian emergency department

BACKGROUND Studies have found a high prevalence of both alcohol and other impairing psychoactive drugs in injured patient populations. The aim of this study was to assess the prevalence of potentially impairing psychoactive substances in all patients admitted to a hospital emergency department with injuries from accidents, assault or deliberate self harm. METHODS A total of 1272 patients over 18 years of age, admitted to the hospital within 12h of injury, were included. Presence of alcohol was determined by an enzymatic method and other drugs by liquid chromatography-mass spectrometry (LC-MS) or gas chromatography-mass spectrometry (GC-MS), both highly specific analytical methods for determining recent intake. RESULTS There were 510 (40%) women in the sample. Of the patients, 38% of the women and 48% of the men had a positive blood sample for psychoactive substances on admission. The most prevalent psychoactive substance was alcohol (27%) with an average concentration of 1.5 g/kg. A further 21% of patients tested showed use of medicinal drugs, and 9% showed use of illicit substances. Cannabis was the most prevalent illicit drug (6.2%). Diazepam (7.4%) and zopiclone (5.3%) were the most prevalent medicinal drugs. In road traffic accidents, 25% of the car drivers had positive findings, about half of them for alcohol. CONCLUSION Psychoactive substances were found in nearly half the patients admitted with injuries. The most common substance was alcohol. Alcohol was particularly related to violence, whereas medicinal drugs were most prevalent in accidents at home.

Controlling for High-Density Lipoprotein Cholesterol Does Not Affect the Magnitude of the Relationship Between Alcohol and Coronary Heart Disease

Background— This study tested the hypothesis that moderate alcohol intake exerts its cardioprotective effect mainly through an increase in the serum level of high-density lipoprotein cholesterol. Methods and Results— In the Cohort of Norway (CONOR) study, 149 729 adult participants, recruited from 1994 to 2003, were followed by linkage to the Cause of Death Registry until 2006. At recruitment, questionnaire data on alcohol intake were collected, and the concentration of high-density lipoprotein cholesterol in serum was measured. Using Cox regression, we found that the adjusted hazard ratio for men for dying from coronary heart disease was 0.52 (95% confidence interval, 0.39–0.69) when consuming alcohol more than once a week compared with never or rarely. The ratio changed only slightly, to 0.55 (0.41–0.73), after the regression model included the serum level of high-density cholesterol. For women, the corresponding hazard ratios were 0.62 (0.32–1.23) and 0.68 (0.34–1.34), respectively. Conclusions— Alcohol intake is related to a reduced risk of death from coronary heart disease in the follow-up of a large, population-based Norwegian cohort study with extensive control for confounding factors. Our findings suggest that the serum level of high-density cholesterol is not an important intermediate variable in the possible causal pathway between moderate alcohol intake and coronary heart disease.

Toxicological investigations of drivers killed in road traffic accidents in Norway during 2006–2008

AIM To study the results from the toxicological investigations of drivers of cars and vans who were fatally injured in road traffic accidents in 2006-2008 and discuss the findings in relation to the proposed legal limits and impairment thresholds for drugs. METHODS Analyses for alcohol, illegal drugs and psychoactive medicinal drugs were performed by the Norwegian Institute of Public Health. Information on type of accident (single or multiple vehicles) and type of road (urban or rural) was obtained from Statistics Norway. RESULTS Toxicological analyses were requested for 59% of the fatally injured drivers. Drivers involved in single vehicle accidents were more often subject to toxicological investigations, so were also young male drivers and drivers killed on urban roads. Alcohol or drugs were found in concentrations above the current (for alcohol) or proposed (for drugs) legal limits in samples from 37.8% of the drivers; from 64.3% those killed in single-vehicle accidents and 17.9% of those killed in multiple-vehicle accidents. In total, alcohol was found in 25.0%, illicit drugs in 10.2%, and psychoactive medicinal drugs in 13.8% of the samples. Combinations of alcohol and drugs were found in 5.1% and multiple drugs without alcohol in 6.1% of the samples. The prevalence of alcohol or drugs was higher in samples from males than females, higher in samples from young drivers, and higher in samples from drivers killed during weekends. Two thirds of the drivers with alcohol or drug concentrations above the current or proposed legal limits had concentrations above the proposed high impairment threshold. About 60% of the latter ones were impaired by alcohol only, 20% by drugs in combination with alcohol, and 20% by drugs only, mainly due to multi-drug use. CONCLUSION The use of alcohol or drugs before driving was a significant contributing factor in fatal road traffic accidents, particularly in single vehicle accidents, and particularly among young male drivers. Alcohol was the most significant intoxicant, but multi-substance use was also significantly prevalent. The majority of the drivers with alcohol or drug findings were strongly impaired.

Increased Locomotor Activity Induced by Heroin in Mice: Pharmacokinetic Demonstration of Heroin Acting as a Prodrug for the Mediator 6-Monoacetylmorphine in Vivo

We investigated the relative importance of heroin and its metabolites in eliciting a behavioral response in mice by studying the relationship between concentrations of heroin, 6-monoacetylmorphine (6MAM), and morphine in brain tissue and the effects on locomotor activity. Low doses (subcutaneous) of heroin (≤5 μmol/kg) or 6MAM (≤15 μmol/kg) made the mice run significantly more than mice given equimolar doses of morphine. There were no differences in the response between heroin and 6MAM, although we observed a shift to the left of the dose-response curve for the maximal response of heroin. The behavioral responses were abolished by pretreatment with 1 mg/kg naltrexone. Heroin was detected in brain tissue after injection, but the levels were low and its presence too short-lived to be responsible for the behavioral response observed. The concentration of 6MAM in brain tissue increased shortly after administration of both heroin and 6MAM and the concentration changes during the first hour roughly reflected the changes in locomotor activity. Both the maximal and the total concentration of 6MAM were higher after administration of heroin than after administration of 6MAM itself. The morphine concentration increased slowly after injection and could not explain the immediate behavioral response. In summary, the locomotor activity response after injection of heroin was mediated by 6MAM, which increased shortly after administration. Heroin acted as an effective prodrug. The concentration of morphine was too low to stimulate the immediate response observed but might have an effect on the later part of the heroin-induced behavioral response curve.

Use of alcohol and drugs by Norwegian employees: a pilot study using questionnaires and analysis of oral fluid

BackgroundThe use of alcohol and drugs may affect workplace safety and productivity. Little is known about the magnitude of this problem in Norway.MethodsEmployee recruitment methods with or without individual follow-up were compared. The employees filled in a questionnaire and provided a sample of oral fluid. Samples were analysed for alcohol, ethyl glucuronide (EtG; a biological marker of recent large alcohol intake), psychoactive medicinal drugs and illegal drugs.ResultsParticipation rates with and without individual follow-up were 96% and 68%, respectively. Alcohol was negative (≤0.1 mg/ml) in all samples, but 21.0% reported the intake of alcohol during the last 24 h. EtG was positive (>2.2 ng/ml) in 2.1% of the samples. In-efficiency or hangover at work during the past year was reported by 24.3%, while 6.2% had been absent from work due to the use of alcohol. The combination of self-report and analytical testing indicated that medicinal or illegal drugs had been used during the last 48 h by 5.1% and 1.7% of the participants, respectively; while only 4.2% and 0.4% admitted the use in the questionnaire.ConclusionsSelf-reported data suggest that hangover after drinking alcohol appears to be the largest substance abuse problem at Norwegian workplaces, resulting in absence and inefficiency at work. Analysis of oral fluid revealed that the use of illegal drugs was more common than drinking alcohol before working or at the workplace. The analysis of oral fluid may be a valuable tool in obtaining additional information on alcohol and drug use compared to using questionnaires alone.

Morphine to codeine concentration ratio in blood and urine as a marker of illicit heroin use in forensic autopsy samples.

A morphine to codeine ratio greater than unity (M/C>1) has been suggested as an indicator of heroin use in living individuals. The aim of this study was to examine the morphine to codeine ratio in a large population (N=2438) of forensically examined autopsy cases positive for 6-monoacetylmorphine (6-MAM) and/or morphine in blood and/or urine. Blood and urine concentrations of 6-MAM, morphine and codeine were examined using GC-MS and LC-MS/MS methods. In 6-MAM positive samples, the M/C ratio was greater than unity in 98% (N=917) of the blood samples and 96% (N=665) of the urine samples. Stratification of 6-MAM negative cases by M/C above or below unity revealed similarities in morphine and codeine concentrations in cases where M/C>1 and 6-MAM positive cases. Median blood and urine morphine concentrations were 8-10 times greater than codeine for both groups. Similarly to 6-MAM positive cases, 25-44 year-old men prevailed in the M/C>1 group. In comparison to cases where M/C ≤ 1, the M/C ratio was a hundred times higher in both 6-MAM positive and M/C>1 cases. The range of morphine concentration between the lowest and the highest quintile of codeine in M/C>1 cases was similar to that in 6-MAM positive cases. This range was much higher than for M/C ≤ 1 cases. Moreover, linear regression analyses, adjusted for age and gender, revealed a strong positive association between morphine and codeine in 6-MAM positive and M/C>1 cases. The M/C ratio appeared to be a good marker of heroin use in post-mortem cases. Both blood and urine M/C>1 can be used to separate heroin users from other cases positive for morphine and codeine.