Uudet huumeet liikenteessä ja kuolemantapauksissa

Driving under the influence of drugs (DUID) can adversely affect driving skills in numerous ways and put lives at risk. Legal approaches to DUID vary considerably from country to country, even within Europe, and, in the last decades the emergence of new psychoactive substances (NPS) has further complicated the scene. DUID is an unlawful act if the substance taken is banned or impairs driving. The latter is hard to define and prove, putting pressure on governments to ban NPS as quickly as possible in order to protect the public by facilitating enforcement of DUID laws. However, banning requires knowledge on several aspects of NPS such as prevalence, pharmacology, abuse potential and toxicity. Up-to-date, evidence-based information on NPS is needed by legislators, toxicologists, clinicians, and other health care professionals. Such information would enable potential drug users and the public to be more aware of the risks associated with illicit use of NPS. This study aimed to add to the knowledge of the NPS most relevant in Finland. In this thesis, the prevalence, blood concentrations in drivers and in post-mortem cases, and demographic details of 3,4-methylenedioxypyrovalerone (MDPV) and desoxypipradrol (2-DPMP), were investigated. Changes in prevalence and other characteristics of MDPV were monitored over a time span covering a period before its banning as well as a few years after banning. Phenazepam, a Russian therapeutic benzodiazepine now illegal in Finland, was studied by examining both DUID and post-mortem cases. The use by apprehended drivers of pregabalin, a prescription anticonvulsant with therapeutic indications for neuropathic pain, partial seizures and generalised anxiety disorder, was also studied. The results of this study showed that DUID cases provide a valuable source of information on NPS prevalence and user profiles. However, little specific information could be gained about the impact on driving performance and health risks of NPS mainly due to the fact that NPS were usually used together with a spectrum of other psychoactive substances. It could, however, be concluded that all of the studied NPS were frequently detected in the samples collected from apprehended drivers and, in the case of MDPV, the prevalence changed with time. The number of MDPV-positive cases among apprehended drivers decreased by 51.1% after the drug was banned. The concentrations of NPS found in DUID cases were within the range anticipated to produce significant adverse effects on driving performance, or, in some cases, in the range found in post-mortem cases where the drug may have contributed to the fatality. The presence of the medicinal drug, pregabalin, was found to be connected to abuse rather than appropriate medical use since it was in most cases found in concentrations higher than those recommended for therapeutic use and together with illegal drugs such as amphetamine or cannabis. In post-mortem cases positive for MDPV, the prevalence of suicide was much greater than in fatalities related to other drugs. Three independent registries, namely the DUID toxicology data, the post-mortem toxicology database, and court documents, were examined to gain novel information on the characteristics of NPS use and those abusing them. The large number of cases studied produced information on concentration ranges associated with abuse of the studied substances.Viime vuosina Suomenkin huumemarkkinoille on ilmaantunut lukuisia uusia päihdekäyttöön soveltuvia aineita. Tämän väitöstutkimuksen tarkoituksena oli selvittää aineiden merkitystä ja yleisyyttä liikennejuopumustapauksissa ja kuolemissa Suomessa. Väitöstutkimuksessa keskityttiin pääasiassa neljään aineeseen: kahteen amfetamiinin kaltaisesti vaikuttavaan huumausaineeseen (MDPV ja 2-DPMP), Venäjällä lääkekäytössä olevaan pitkävaikutteiseen rauhoittavaan lääkeaineeseen (fenatsepaami) sekä Suomessa epilepsian ja hermoperäisen kivun hoidossa käytettävään lääkeaineeseen (pregabaliini). Tutkimuksessa tarkasteltiin uusien huumeiden käyttöä ja käyttäjiä oikeuskemiallisten analyysitulosten ja taustatietojen valossa sekä kartoitettiin mahdollisia eroja näiden uusien aineiden väärinkäyttäjien ja perinteisempien huumeiden käyttäjien välillä. Kaikkia tutkimuksen kohteeksi valittuja aineita havaittiin säännöllisesti liikennejuopumustapauksissa, yleensä yhdessä muiden huumaavien aineiden kanssa. Löydösten lukumäärä oli huomattavasti pienempi oikeuslääketieteellisissä kuolemansyynselvityksissä. Liikenteessä todetut pitoisuudet olivat usein hyvin korkeita, joten niiden voidaan arvioida heikentäneen kuljettajien ajokykyä merkittävästi. Usein kuljettajista todetut pitoisuudet olivat samansuuruisia tai jopa suurempia kuin kuolemantapauksissa. Vainajatapauksissa MDPV liittyi poikkeuksellisen usein itsemurhiin. MDPV-tapausten määrä väheni alle puoleen sen jälkeen, kun aine oli luokiteltu huumeeksi Suomessa. Tämä viittaa siihen, että lainsäädännöllä voidaan vaikuttaa huumekäytössä olevien aineiden suosioon. Fenatsepaamin käyttäjät voitiin jakaa kahteen ryhmään: osa oli käyttänyt fenatsepaamia suurina annoksina ilmeisesti aineen oman päihdyttävän vaikutuksen vuoksi, osalle se taas vaikutti olevan lääke stimulanttien vieroitusoireisiin. Stimulantti 2-DPMP:n ( Daisy ) suosio jäi Suomessa hyvin lyhyeksi, vaikka sitä löydettiinkin vuoden 2011 loppuun mennessä kaikkiaan lähes sadassa liikennejuopumustapauksessa. Pregabaliinilöydökset liikennejuopumustapauksissa eivät juuri milloinkaan liittyneet asianmukaiseen lääkinnälliseen käyttöön. Tässä väitöstutkimuksessa tarkasteltiin laajoja aineistoja käyttäen useita eri viranomaisrekistereitä. Tutkimuksen tulosten avulla voidaan edesauttaa uusien huumaavien aineiden merkityksen arviointia myrkytys- ja kuolemantapauksissa, liikennejuopumuksissa, lainsäädäntötyössä ja huumeriippuvaisten hoitotyössä

Fatal toxicity index of medicinal drugs based on a comprehensive toxicology database

The fatal toxicity index (FTI) is the absolute number of fatal poisonings caused by a particular drug divided by its consumption figure. Consequently, it is a useful measure in evaluating toxicity of the drug and its relevance in fatal poisonings. In this study, we assessed the FTI of medicinal drugs in 3 years (2005, 2009, and 2013) in Finland. As the measure of drug consumption, we used the number of defined daily doses (DDD) per population in each year. There were 70 medicinal drugs in Finland for which the mean FTI expressed as the number of deaths per million DDD over the three study years was higher or equal to 0.1. The Anatomical Therapeutic Chemical (ATC) classification system was used for the classification of the active ingredients of medicinal drugs according to the organ or system which they act on. Of these 70 drugs, 55 drugs (78.6 %) acted on the nervous system (denoted by ATC code N), 11 (15.7 %) on the cardiovascular system (C), three (4.3 %) on the alimentary tract and metabolism (A), and one (1.4 %) on the musculoskeletal system (M). The nervous system drugs consisted of 20 psycholeptics, (ATC code N05), 20 psychoanaleptics (N06), eight analgesics (N02), six antiepileptics (N03), and one other nervous system drug (N07). The highest individual FTIs were associated with the opioids methadone, dextropropoxyphene, oxycodone, tramadol, and morphine; the antipsychotics levomepromazine and chlorprothixene; and the antidepressants doxepin, amitriptyline, trimipramine, and bupropion. Buprenorphine was not included in the study, because most of the fatal buprenorphine poisonings were due to smuggled tablets. A clearly increasing trend in FTI was observed with pregabalin and possibly with bupropion, both drugs emerging as abused substances.Peer reviewe

Concomitant drugs with buprenorphine user deaths

Background: Buprenorphine is abused in several countries notwithstanding its benefits as an analgesic and as an opioid agonist treatment medication. Benzodiazepines and alcohol have previously been associated with buprenorphine toxicity. This study elucidates the role of emerging concomitant drugs in different groups of buprenorphine user deaths. Methods: All cases in the Finnish national post-mortem toxicology database from 2016-2019 in which buprenorphine or norbuprenorphine was a laboratory finding in any post-mortem specimen and age at death of 15-64 years were investigated for cause and manner of death, concurrent drug and alcohol findings, age, and gender. Results: There were 792 deaths with a buprenorphine finding, of which buprenorphine was implicated in poisoning without other opioids in 271 cases (34 %). In this group of buprenorphine poisoning deaths, concomitant benzodiazepines were found in 94 % (clonazepam 53 %), illicit drugs in 63 %, gabapentinoids in 50 % (pregabalin 41 %), alcohol in 41 %, antidepressants in 32 %, and antipsychotics in 28 % of cases; only three deaths showed no benzodiazepines, alcohol, or gabapentinoids. Polydrug use was common regardless of the cause of death. In the age group 15 to 24 years, concomitant use of benzodiazepines and illicit drugs, and buprenorphine poisoning were more prevalent than in the age group 25-64 years. Conclusions: The unprecedentedly high concomitant use of benzodiazepines in buprenorphine user deaths obscures other possible pharmacological risk factors for buprenorphine poisoning that could be relevant for prevention. Higher mortality in the younger age group suggests particularly unsafe drug use patterns that should be addressed.Peer reviewe

Investigation of buprenorphine-related deaths using urinary metabolite concentrations

Quantitative analysis of postmortem urine, instead of blood, for buprenorphine and metabolites may provide additional evidence for the diagnosis of fatal buprenorphine poisoning. In this study, 247 autopsy urine samples, previously testing positive for buprenorphine or norbuprenorphine, were quantitatively reanalysed with a recently developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for unconjugated buprenorphine (BUP), norbuprenorphine (NBUP), naloxone (NAL), and their respective conjugated metabolites, buprenorphine glucuronide (BUPG), norbuprenorphine glucuronide (NBUPG), and naloxone glucuronide (NALG). The cases were divided, according to medical examiners' decision, to buprenorphine poisonings and other causes of death. The groups were compared for urinary concentrations and metabolite concentration ratios of the six analytes. All median concentrations were higher in the buprenorphine poisoning group. The median concentration of BUPG was significantly higher and the median metabolite ratios NBUP/BUP, NBUPG/BUPG, and NBUPtotal/BUPtotal were significantly lower in poisonings than in other causes of death. Naloxone-related concentrations and ratios were not significantly different between the groups.Peer reviewe

Buprenorphine, Polydrug Use and Deaths

Peer reviewe

Increase in drugs-of-abuse findings in post-mortem toxicology due to COVID-19 restrictions-First observations in Finland

A lot has been published on the anticipated effects of the current COVID-19 pandemic on users of illegal drugs. In this study, we present evidence-based data on such effects, namely, the increased number of drug findings in post-mortem investigations. All post-mortem toxicology cases positive for at least one of the following: buprenorphine, amphetamine or cannabis, were investigated in the first 8 months of the year 2020, and the monthly numbers were compared to those in the previous 5 years from 2015 to 2019. These substances served as indicator analytes that could reveal changes in the drug using population. Right after the government restrictions came into force in March 2020, the numbers of buprenorphine, amphetamine and cannabis findings increased. The increase was most noticeable for amphetamine and was evident in all age groups. Our findings indicate that the assumptions on the increased risk of drug-related harm (including death) have become reality. Reduced access to harm-reduction services seems to have increased the mortality among individuals that use buprenorphine, amphetamine or cannabis. Significant and prompt actions need to be taken in order to find new ways in helping this vulnerable group of people.Non peer reviewe

Post-mortem oxycodone blood concentrations of hospitalized cancer and surgery patients compared with fatal poisonings

Oxycodone is a strong opioid drug commonly used to treat acute, cancer, and chronic non-malignant pain. In this study, all oxycodone-related medico-legal cases where death had occurred in a hospital or nursing home in Finland were investigated to determine the range of post-mortem (PM) oxycodone blood concentrations in a therapeutic setting. All toxicology cases in which oxycodone was detected in PM femoral blood during the 4-year period of 2016-2019 in Finland were retrieved from the national PM toxicology database. In this material, the 365 deceased hospital patient cases that met the study inclusion criteria were divided into four groups according to the cause and manner of death. The reference group of 121 fatal oxycodone poisoning cases comprised two groups: those with verified associated drug abuse and those without drug abuse. The median oxycodone concentration in PM blood was significantly higher in cancer patients (0.10 mg/L) than in patients with recent surgery (0.07 mg/L) or other disease (0.06 mg/L) (p < 0.05). In addition, the median oxycodone concentration was significantly lower in all hospital patient groups than in the poisoning groups, the latter displaying 0.38 mg/L (abuse) and 0.64 mg/L (no abuse) (p < 0.001). This study shows that half of the subjects in the cancer patient group had PM blood oxycodone concentrations above the typical clinical therapeutic plasma concentration range (0.005-0.10 mg/L). Appropriate medication of hospitalized surgery and cancer patients can result in concentrations of up to 0.2 and 0.6 mg/L, respectively, while higher concentrations are exceptional.Peer reviewe

Alkoholimyrkytyskuolemat ovat vähentyneet, huumekuolemat eivät

VertaisarvioituLÄHTÖKOHDAT Suomessa tehdään paljon oikeuslääketieteellisiä ruumiinavauksia ja niihin liittyviä oikeuskemiallisia tutkimuksia. Tämä mahdollistaa alkoholin, lääkkeiden, huumeiden ja palokaasujen aiheuttamien myrkytyskuolemien luotettavan seurannan. MENETELMÄT Tulokset koottiin kuolemansyyn selvittämiseen liittyvästä laboratorioaineistosta ja asiakirjoista keskittyen vuosiin 2014–2017. TULOKSET Alkoholimyrkytyskuolemat vähentyivät ajanjaksolla 279:stä 229:ään (18 %). Lääke- ja huumemyrkytykset vähenivät vuosina 2014–2016, mutta lisääntyivät jälleen vuonna 2017. Opioidimyrkytysten osuus lääke- ja huumemyrkytyksistä pienentyi tasaisesti 38 %:sta 31 %:iin. Buprenorfiinikuolemat olivat edelleen yleisiä. PÄÄTELMÄT Myrkytyskuolemien kokonaismäärä on vähentynyt tasaisesti vuoden 2006 jälkeen. Alkoholimyrkytyskuolemien määrän myönteinen kehitys heijastaa alkoholin kulutuksen vähenemistä. Suomessa opioidit eivät tällä hetkellä aiheuta vastaavaa uhkaa kuin monissa muissa maissa.Peer reviewe

Toxic lifespan of the synthetic opioid U-47,700 in Finland verified by re-analysis of UPLC-TOF-MS data

U-47,700 is a synthetic opioid that emerged on the novel psychoactive substance market a few years ago. After incorporating the substance into the urine UPLC-TOF-MS screening used in post-mortem toxicology, the drug was detected in 10 autopsy cases within routine case work. In all cases, the cause of death was accidental poisoning by U-47,700 alone or in combination with other psychoactive substances. The concentration of U-47,700 in the blood samples ranged between 0.15-2.0 mg/L with a median of 0.30 mg/L. In one of the cases with a U-47,700 concentration of 0.27 mg/L, no other psychoactive substances were detected. The stored TOF-MS analytical data from the year preceding the incorporation of U-47,700 into the screening was reprocessed in order to search for more positive cases. The data-independent acquisition of the original screening allowed for retrospective re-analysis of the full-scan data without additional experiments on the actual sample. The retrospective data-analysis revealed two additional cases positive for U-47,700. The first mention of U-47,700 on a Finnish internet discussion forum was in March 2015. After having been detected in several death cases, the drug was put under national control in November 2016 and the last fatality occurred in 2017. The toxic lifespan of U-47,700 thus lasted for approximately 2 years in Finland. Forensic and clinical laboratories need to rapidly adjust their screening procedures in order to adapt to the continuously expanding field of novel psychoactive substances. Retrospective data-analysis is a practical tool for monitoring the emergence of new substances onto the market. (C) 2019 Elsevier B.V. All rights reserved.Peer reviewe