Pirkko Kriikku

New designer drug of abuse: 3,4-Methylenedioxypyrovalerone (MDPV). Findings from apprehended drivers in Finland.

Starting in 2008 a new designer drug, 3,4-methylenedioxypyrovalerone (MDPV) appeared among users of illegal drugs in Finland. Since then there have been several seizures of MDPV by police and customs and it has been connected to many crimes of different types. In this study the incidence and impact of the use of MDPV in drivers suspected of being under the influence of drugs (DUID) in Finland was assessed. Since autumn 2009, blood samples from drivers suspected of DUID in Finland have been analysed for the presence of MDPV. A new LC-MS/MS method for the determination of MDPV in serum was established. In order to assess the impact of MDPV on driving performance, drug and alcohol findings of positive MDPV cases were compared with data from the clinical examination carried out while the suspect was under arrest. In a period of one year there were 259 positive MDPV cases from apprehended drivers (5.7% of all confirmed DUID cases). In 80% of the cases in which MDPV was found, amphetamine was also present. Benzodiazepines were also frequently found together with MDPV, which was to be expected since in Finland, in our experience, stimulants are very often used together with benzodiazepines. In most cases it remained unclear whether the observed psycho-physical achievement deficiency was induced by MDPV because the concentrations of other drugs, especially other stimulants, were often high. However, in some subjects, MDPV, or MDPV in combination with other substances was the most probable cause of the impairment. The concentrations of MDPV varied from 0.016mg/L to over 8.000mg/L. Little is known about the pharmacology of MDPV. However, based on our findings it is clear that MDPV has a serious impact on traffic safety in Finland.

Phenazepam abuse in Finland: Findings from apprehended drivers, post-mortem cases and police confiscations

Phenazepam is a long-acting benzodiazepine that, unlike other benzodiazepines, is currently not scheduled as a narcotic in Finland, most other European countries or the USA. It is used as an anxiolytic, sedative-hypnotic and anti-epileptic, mainly in Russia. In Finland, as well as in some other countries, an increase in the unauthorized use of phenazepam has been observed in recent years. In the one year period between July 1, 2010 and June 30, 2011 the prevalence of phenazepam in Finland was assessed among drivers apprehended for driving under the influence of drugs (DUID), in medico-legal autopsy cases and in police confiscations of illicit drugs. In DUID cases an LC-MS/MS method preceded by solid phase extraction was used for the determination of phenazepam. In the post-mortem investigations the sample preparation consisted of liquid-liquid extraction followed by derivatization and the determination was carried out by GC-MS. The police confiscations were analysed by GC-MS. There were 141 positive phenazepam cases among apprehended drivers, representing approximately 3.5% of all confirmed drug cases (n=4007) in this time period. The median (range) phenazepam blood concentration in DUID cases was 0.061 mg/L (0.004-3.600 mg/L). The median phenazepam concentration in cases with no concomitant stimulant use was significantly higher than the overall median concentration. Phenazepam was found in 17 medico-legal autopsy cases and the median (range) blood concentration was 0.048 mg/L (0.007-1.600 mg/L). Phenazepam was not considered by the medico-legal team to be the sole cause of death in any of the cases, the majority of them being accidental opiod overdoses. There were 26 seizures of phenazepam by the Police in the time period studied, some of the batches consisted of a mixture of phenazepam and stimulant designer drugs. The data show that phenazepam abuse is a widespread phenomenon in Finland. A typical user was a male multi-drug user in his 30s. The concentration range of phenazepam among apprehended drivers and medico-legal autopsy cases was wide and the drug was usually found along with other psychoactive drugs. Therefore, although it seems likely that phenazepam contributed to impairment of driving in some DUID cases, the extent of its effect remains unclear and further studies are needed to define the concentrations causing impairment and toxicity.

Pregabalin serum levels in apprehended drivers

Pregabalin is a medicinal drug used mainly for the treatment of epilepsy and neuropathic pain. It has been shown to possess an abuse potential and in recent years some reports of illegal use have been published. In order to further evaluate the extent and nature of pregabalin abuse, serum pregabalin levels of drivers apprehended for driving under the influence of drugs (DUID) in Finland in 2012 were assessed. The samples were analysed by an LC-MS/MS system and the results were evaluated in relation to the typical therapeutic range of pregabalin as well as the age and gender of the driver. Pregabalin was detected in 206 samples in the study period. The median (range) serum concentration was 6.2 (0.68-111.6)mg/L. In nearly 50% of the cases the serum concentration was above the typical therapeutic range. In most of the cases the driver had also taken other drugs besides pregabalin, the mean number of concomitantly taken drugs being four. Our data indicate that pregabalin is being used at high doses, probably for recreational purposes. The vast majority of the drivers positive for pregabalin in our study material had used pregabalin as a part of a spectrum of psycho-active drugs and thus qualified as probable drug abusers. In these cases pregabalin probably contributed to their driving impairment but to what extent remained unclear in this study.

The effect of banning MDPV on the incidence of MDPV-positive findings among users of illegal drugs and on court decisions in traffic cases in Finland

In this study, we sought to determine what impact the banning of 3, 4- methylenedioxypyrovalerone (MDPV) had on the incidence of MDPV-positive findings and on user profiles in driving under the influence of drugs (DUID) and postmortem (PM) investigations in Finland. All MDPV-positive cases and a selection of corresponding court cases between 2009 and 2012 were examined. The median serum concentration of MDPV in DUID cases was 0.030 mg/L and in PM blood 0.12 mg/L. The number of MDPV-positive cases decreased both in DUID and PM investigations after the drug was banned. The decrease in the mean monthly numbers of MDPV-positive DUID cases was 51.1%. In court cases, MDPV was rarely mentioned until banned and frequently mentioned thereafter. Of the convicted, 37% were without a fixed abode, 98% had other charges besides that of DUID, and 13% appeared in the study material more than once. In MDPV-positive PM cases, the proportion of suicides was very high (24%). Research on new psychoactive substances is required not only to support banning decisions but more importantly to be able to provide a scientific assessment of the risks of these new substances to the public and potential users.

Comparison of breath-alcohol screening test results with venous blood alcohol concentration in suspected drunken drivers

Hand-held electronic breath-alcohol analyzers are widely used by police authorities in their efforts to detect drunken drivers and to improve road-traffic safety. Over a three month period, the results of roadside breath-alcohol tests of drivers apprehended in Finland were compared with venous blood alcohol concentration (BAC). The mean (median) time between sampling blood and breath was 0.71h (0.58h) with a range from 0 to 6h. Some hand-held instruments gave results as the concentration of alcohol in breath and were converted into BAC assuming a blood-breath alcohol ratio (BBR) of 2260. The mean venous BAC (1.82g/kg) in traffic offenders was higher than the result predicted by the hand-held breath analyzers (1.72g/kg). In 1875 roadside tests, the relationship between venous BAC (x) and BrAC (y) was defined by the regression equation y=0.18+0.85x. The coefficients show both a constant bias (y-intercept 0.18g/kg) and a proportional bias (slope=0.85). The residual standard deviation (SD), an indicator of random variation, was ±0.40g/kg. After BAC results were corrected for the time elapsed between sampling blood and breath, the y-intercept decreased to 0.10g/kg and 0.004g/kg, respectively, when low (0.1g/kg/h) and high (0.25g/kg/h) rates of alcohol elimination were used. The proportional bias of 0.85 shows that the breath-alcohol test result reads lower than the actual BAC by 15% on average. This suggests that the BBR of 2260 used for calibration should be increased by about 15% to give closer agreement between BAC and BrAC. Because of the large random variation (SD±0.40g/kg), there is considerable uncertainty if and when results from the roadside screening test are used to estimate venous BAC. The roadside breath-alcohol screening instruments worked well for the purpose of selecting drivers above the statutory limit of 0.50g/kg.

Sedative-hypnotics are widely abused by drivers apprehended for driving under the influence of drugs.

Background: Sedative-hypnotics are commonly encountered in drivers apprehended for driving under the influence of drugs (DUID). Previous research has mainly concentrated on the residual effects of the drugs. Methods: In this study, the extent of sleep medication use and abuse among drivers apprehended on suspicion of DUID was assessed. Additionally, the prevalence and concentrations of the drugs, concomitant use of other drugs of abuse, and the age and sex of the drivers positive for the most commonly prescribed sedative-hypnotics (temazepam, midazolam, nitrazepam, zopiclone, and zolpidem) in DUID cases in Finland in 2009 to 2011 were examined. Results: Sedative-hypnotics were found in 3155 samples of the 13,248 that were analyzed. Temazepam was present in over half of the cases (57.9%), along with other benzodiazepines such as midazolam (13.1%) and nitrazepam (7.0%) and the non-benzodiazepine hypnotics zopiclone (12.2%) and zolpidem (9.8%). The mean age of the drivers using the studied sedative-hypnotics was 33.5 years. Many of the drivers were polydrug users; concomitant stimulant use was found in nearly half of the cases. Cannabis and alcohol were also very common co-findings. In nearly 20% of the cases, the driver had taken more than 1 of the studied sedative-hypnotics; only 2.5% had no findings other than a single sedative-hypnotic in their blood. The drug use pattern of those positive for zopiclone and zolpidem was somewhat different from that of users of benzodiazepine sedative-hypnotics; their age was higher and the concomitant use of illegal stimulants was markedly less prevalent than among the users of temazepam, midazolam, and nitrazepam. Conclusions: There were very few cases in our study population where the positive sedative-hypnotic finding could have been due to appropriate medical use. The extremely prevalent concomitant use of other psychoactive drugs and the high median serum concentrations of the studied sedative-hypnotics suggest their widespread abuse among apprehended drivers.

Prevalence and blood concentrations of desoxypipradrol (2-DPMP) in drivers suspected of driving under the influence of drugs and in post-mortem cases.

The aim of this study was to assess the incidence of the use of desoxypipradrol (2-DPMP) among drivers apprehended on suspicion of driving under the influence of drugs (DUID) and the prevalence of the drug in post-mortem cases in Finland. Serum samples from drivers apprehended on suspicion of DUID and blood samples from post-mortem cases in Finland between October 2010 and May 2012 were analysed for the presence of desoxypipradrol. All samples were analysed for desoxypipradrol by mass spectrometric methods following comprehensive drug screening. Psychomotor performance of subjects was assessed by a clinician. There were 106 positive desoxypipradrol samples from apprehended drivers (1.7% of all confirmed DUID cases) in the study period. In most cases amphetamine and/or benzodiazepines were also present. The median (range) desoxypipradrol concentration was 0.073 mg/L (0.006-0.890 mg/L). The presence of other psychoactive drugs confounded assessment of the effect of desoxypipradrol on psychomotor performance except for one case in which it was the only drug present at pharmacologically active levels. Desoxypipradrol was found in 5 autopsy cases (0.05% of the investigated cases) and thought to contribute to death in two of these. Even though there are few data available on the pharmacology of desoxypipradrol, based on our findings, and the growing number of users, it is reasonable to assume that desoxypipradrol - a long-acting psychostimulant with dangerous side effects has an increasing detrimental impact on traffic safety in Finland. However, it was only rarely found to be the cause of death in post-mortem cases.

The relationship between bupropion and suicide in post-mortem investigations

We reviewed the 33727 postmortem toxicology investigations performed in Finland over a period of 5years (2009-2013) and identified those in which the antidepressant bupropion was detected. Cases positive for other antidepressant drugs were reviewed for comparison. The postmortem toxicological examination included, in all cases, the routine screening and quantification of hundreds of drugs and poisons using quality-controlled methods. Bupropion was detected in 65 cases. A large proportion of the bupropion-positive deaths resulted from suicide (55%). In fatal poisoning cases found positive for bupropion, the proportion of suicide was even higher (77%). The measured median bupropion postmortem blood concentration (0.69mg/L) was markedly higher than the normal therapeutic range in plasma in the treatment of depression (up to 0.1mg/L) and even higher in fatal bupropion poisonings (13mg/L). Only 14% of the deceased positive for bupropion were estimated to be drug abusers. However, nearly all of the drug abuse cases were from the last year of the study (2013), indicating a recent increase of the use of bupropion among drug abusers and possibly even abuse of bupropion itself. Suicide victims positive for bupropion were younger than those who died with other antidepressant drugs in their blood. In addition, the percentage of fatal poisonings among bupropion-positive postmortem cases was higher than among the users of other antidepressant drugs. Suicide was significantly more common among the deceased positive for bupropion than among users of other antidepressant drugs. An unknown degree of bupropion degradation before the assay and post-mortem redistribution of bupropion may have impacted the measured levels. Nonetheless, all post-mortem concentrations of bupropion were elevated and especially high concentrations were detected in suicides.

High buprenorphine-related mortality is persistent in Finland

Sublingual buprenorphine is used in opioid maintenance treatment but buprenorphine is also widely abused and causes fatal poisonings. The aim of this study was to investigate buprenorphine-positive fatalities in order to gain novel information on the magnitude and nature of buprenorphine abuse. All post-mortem toxicology cases positive for urinary buprenorphine, including fatal poisonings caused by buprenorphine and fatalities in which the cause of death was unrelated to buprenorphine, in the five year period of 2010-2014 in Finland were characterized according to urine buprenorphine and naloxone concentrations (n=775). Urine concentrations were used to assess which buprenorphine preparation had been used; mono-buprenorphine or a buprenorphine-naloxone combination, and whether they had been administered parenterally. In at least 28.8% of the buprenorphine-positive cases the drug had been administered parenterally. The majority of the parenteral users (68.6%) had taken mono-buprenorphine. Fatal poisoning was significantly more common among the identified parenteral users (65.5%) than among other users of buprenorphine products (45.3%). The proportion of buprenorphine-related poisoning was similar in identified parenteral users of mono-buprenorphine (68.6%) and buprenorphine-naloxone (64.1%). In nearly all of the fatal poisoningss the deceased had used other drugs and/or alcohol along with buprenorphine (98.7%). The median age of the deceased increased significantly over the study period, from 32 to 38 years. Our results show that there is ongoing parenteral abuse of both mono-buprenorphine and buprenorphine-naloxone combination. Parenteral users of buprenorphine put themselves into a great risk of fatal poisoning or other accidental injury death which is further exacerbated by the frequent poly-drug use.

373 Manner of death in fatal prescription drug poisonings

Background In Finland, post-mortem toxicology is performed in 13% of all deceased as part of medico-legal cause-of-death investigation. Of all toxicology cases, approximately every 6th case is determined by a forensic pathologist to be a fatal poisoning. Medicinal and illegal drugs form the biggest group of intoxicants causing fatal poisonings. Methods All fatal drug poisoning cases in 2013 were examined in terms of toxicological findings, background information and the manner of death. In these cases, comprehensive post-mortem toxicology had been performed by using chromatographic and mass spectrometric techniques in an accredited central laboratory serving the whole country. Results There were 476 fatal poisonings by medicinal and illegal drugs in 2013. Buprenorphine, tramadol, pregabalin, codeine, oxycodone, amitriptyline, quetiapine, paracetamol, venlafaxine and insulin were the ten most prevalent major factors in the cause of death. The most common manner of death in all drug poisonings was suicide (41%, median age 49), followed by unintentional poisoning (40%, median age 37), and unknown manner of death (18%, median age 51). Unintentional poisoning was the most common manner of death in opioid poisonings, especially with the strong opioids possessing high abuse potential. In cases involving antipsychotics and antidepressants, such as quetiapine, amitriptyline and venlafaxine, as well as with insulin, the percentage of suicide was higher than that of unintentional poisoning. Conclusions Information on fatal poisonings reveals trends in drug use, which can help monitor adverse effects of medicines as well as the emergence of new abused substances. The extensive post-mortem toxicology data collected in the cause-of-death investigations in Finland enable reliable statistical analysis and research on a population-based level.