Las nuevas drogas psicoactivas: populares y peligrosas / New psychoactive substances: Popular and dangerous

La popularidad de las nuevas sustancias psicoactivas (NPS) se ha incrementado a pesar del posible riesgo asociado a su uso. Ante un perfil sin precedentes, la puesta en común de datos toxicológicos es vital para entender los daños asociados al consumo, y disponer de revisiones bibliográficas constituye una importante herramienta para mantener un conocimiento actualizado. Esta revisión se ha enfocado hacia los efectos tóxicos y el riesgo para la salud, así como a proporcionar datos toxicológicos forenses sobre casos en que alguna NPS haya sido identificada y relacionada con la muerte

New psychoactive substances (NPS) have become increasingly popular, despite the potential harm associated with their use. Due to its unknown profile, it is of vital importance that any toxicological data collected is shared, in order to understand the effects associated with the use of these substances, and this data are shared with the scientific community in order to update the knowledge available. This report deals has two objectives. The first one is to focus on the toxicological effects and health risks linked to the use of NPS. The second one is to provide information for forensic toxicologists in cases where an NPS has been identified and may have been involved in the cause of death

Critical analysis of forensic cut-offs and legal thresholds: A coherent approach to inference and decision.

In this paper we critically discuss the definition and use of cut-off values by forensic scientists, for example in forensic toxicology, and point out when and why such values - and ensuing categorical conclusions - are inappropriate concepts for helping recipients of expert information with their questions of interest. Broadly speaking, a cut-off is a particular value of results of analyses of a target substance (e.g., a toxic substance or one of its metabolites in biological sample from a person of interest), defined in a way such as to enable scientists to suggest conclusions regarding the condition of the person of interest. The extent to which cut-offs can be reliably defined and used is not unanimously agreed within the forensic science community, though many practitioners - especially in operational laboratories - rely on cut-offs for reasons such as ease of use and simplicity. In our analysis, we challenge this practice by arguing that choices made for convenience should not be to the detriment of balance and coherence. To illustrate our discussion, we will choose the example of alcohol markers in hair, used widely by forensic toxicologists to reach conclusions regarding the drinking behaviour of individuals. Using real data from one of the co-authors' own work and recommendations of cut-offs published by relevant professional organisations, we will point out in what sense cut-offs are incompatible with current evaluative guidelines (e.g., [31]) and show how to proceed logically without cut-offs by using a standard measure for evidential value. Our conclusions run counter to much current practice, but are inevitable given the inherent definitional and conceptual shortcomings of scientific cut-offs. We will also point out the difference between scientific cut-offs and legal thresholds and argue that the latter - but not the former - are justifiable and can be dealt with in logical evaluative procedures.

Stability of Synthetic Piperazines in Human Whole Blood.

While circumventing legislative controls, synthetic piperazines are encountered as "legal" alternatives to ecstasy. Unforeseeable challenges may delay quantitative analysis of these compounds in biological fluids. Enzymatic reactions, matrix interferences and limited knowledge of analyte stability further complicate interpretation of calculated concentrations. The objective of this study was to investigate the stability of synthetic piperazines in human blood under various storage conditions over time. All samples were prepared by spiking certified reference standards (Cayman Chemical, MI, U.S.A.) of eight synthetic piperazine into certified drug-free human whole blood (UTAK Laboratories, Inc., CA, U.S.A.) independently at 1000 ng/mL as well as mixtures containing all tested piperazines in this study. Samples were stored at room temperature (~20°C), 4°C and -20°C for 1, 3, 6, 9 and 12 months in dark sealed containers. Solid phase extraction (SPE) was performed using mixed-mode copolymeric cartridges (Clean Screen®, UCT Inc., PA, U.S.A.). Analytes were assessed on their degrees of degradation using a Shimadzu Ultra-Fast Liquid Chromatograph with SCIEX 4000 Q-Trap Electrospray Ionization Tandem Mass Spectrometer (UFLC-ESI-MS/MS) in positive ionization mode. Of the two categories, benzyl piperazines were more stable than phenyl piperazines under all storage conditions, in which 1-(4-methylbenzyl)-piperazine (MBZP) had more than 70% (769-1,047 ng/mL) remaining after 12 months. 1-(4-methoxyphenyl)-piperazine (MeOPP) was not detected under room and refrigerated temperatures after 6 months and was the least stable. Matrix interferences and drug-drug interaction were observed. Storing samples at room temperature should be avoided due to detrimental impacts on stability of piperazine compounds. For backlog situations, case samples suspected to contain synthetic piperazines should be kept frozen or refrigerated even for time periods as short as 30 days for optimal result. Phenyl piperazines stored for more than 6 months showed analyte degradation and loss of parent compounds after extended storage regardless of storage conditions.

Dificultades forenses y procesales de la sumisión química / Forensic and judicial issues regarding drug-facilitated sexual assault

El uso de sustancias químicas para manipular la voluntad en los delitos sexuales ha venido cobrando protagonismo los últimos años. El presente artículo se desarrolla a propósito de un caso médico-forense en el que una paciente acudió a urgencias y relató haberse despertado en una vivienda junto a un desconocido que intentó mantener una relación sexual con ella agrediéndola ante su oposición. Refiriendo, además, una laguna amnésica en las 3 horas previas. La principal sospecha diagnóstica fue que se tratara de una agresión sexual por sumisión química premeditada. En el trabajo se describen los datos obtenidos tras la exploración de la víctima, las muestras tomadas por el forense y los resultados del Instituto Nacional de Toxicología. Finalmente se plantean las dificultades asociadas a la detección de las sustancias químicas que anulan la voluntad de la persona, así como el enfoque judicial del caso (AU)

The public's awareness of drug-facilitated sexual assault has increased in recent years. This article concerns a forensic case-study regarding a female patient who visited the emergency room to report that she had woken up in a strange house next to an unknown person, who then tried to have sexual relations with her, and who subsequently assaulted her when she offered resistance. Moreover, she has no memory of what happened in the 3hours prior to the incident. he main diagnostic suspicion was that it was a premeditated drug-facilitated sexual assault case. This article describes the data obtained after the physical examination of the victim, the samples taken for forensic analysis and the laboratory results provided by the National Institute of Toxicology. Finally, the difficulties associated with the detection of knock-out drugs, as well as the judicial treatment of the case are presented (AU)

[Uniform analyzes of drugs in urine needed for rule of law]. / Enhetliga analyser av narkotika i urin krävs för rättssäkerheten.

Drugs of abuse testing is used in various areas of society for detection and follow-up of drug use. In routine laboratory drug testing, immunoassays are employed for initial screening of specimens to indicate the presence of drugs. To confirm a positive screening test, a secondary analysis by mass spectrometry is performed. The "cut-off" is the pre-defined concentration threshold of a drug or drug metabolite above which the sample is considered positive. A reading below this level implies a negative test result. Swedish drug testing laboratories currently employ varying cut-offs to distinguish between a positive and a negative test result. Because a positive drug test may have serious legal consequences to the individual, it is of importance that testing is performed and judged equally, regardless of where it is performed. A national harmonization of cut-offs is therefore warranted. Based on data from four major Swedish drug testing laboratories, and considering the recommendations in international guidelines, a proposal for national harmonization of urine cut-offs for the most common set of drugs of abuse is presented.

Forensic pharmacovigilance: Newer dimension of pharmacovigilance.

Drug safety for the patients is of paramount importance for a medical professional. Pharmacovigilance attempts to ensure the safety of patients by keeping a close vigil on the pattern of adverse events secondary to drug use. Number of medicolegal cases is at rise since last few years. Forensic sciences and pharmacovigilance need to work hand in hand to unlock the mystery of many criminal and civil proceedings. Pharmacovigilance offers its wide scope in forensic sciences by putting forward its expertise on adverse profile of drugs which may be instrumental in solving the cases and bringing the justice forth. It may range from as simple affairs as defining the adverse drug reaction on one hand to putting expert advice in critical criminal cases on the other one. Pharmacovigilance experts have to abide by the ethics of the practice while executing their duties as expert else it may tarnish the justice and loosen its dependability. As a budding discipline of science, it is confronted with several hurdles and challenges which include reluctance of medical professionals for being involved in court proceedings, extrapolations of facts and data and variations in law across the globe etc. These challenges and hurdles call the medical fraternity come forward to work towards the momentous application of pharmacovigilance in the forensic sciences. Evidence based practice e.g. testing the biological samples for the presence of drugs may prove to be pivotal in the success of this collaboration of sciences.

Newspaper reports from the Coroners Court in Ireland are used to reveal the potential complexity and need for reform in forensic toxicology and medicine services.

Newspapers devote regular space to inquests in the public interest. Accuracy in determining the causes of death is important for public health. Expert opinion features prominently in press reports and is an important channel of public education. How expert are the experts and how complex are apparently simple cases? Toxicology cases involving cannabis and stroke, 'junk food' diet, unexplained sudden death, potential drug interactions, allergy during caesarean section, and ecstacy-type drugs are used to illustrate the complexities. A template for reform is suggested to reform the Coroners Laws in Ireland to recognise the complexity of forensic toxicology and medicine.

Interpretación de resultados toxicológicos post-mórtem: criterios de garantía de calidad / Postmortem toxicological results interpretation: quality assurance criteria

La correcta interpretación de los resultados toxicológicos post mórtem debe ser capaz de ofrecer una explicación sobre el significado y la trascendencia de los resultados analíticos obtenidos en el caso forense estudiado. El ajuste de la interpretación de resultados a la realidad de los hechos acontecidos será función de la calidad de la muestra analizada y de los resultados analíticos y del conocimiento de la existencia diversos fenómenos post mórtem y de las circunstancias en la que ocurrió la muerte. Todo el proceso está dificultado por la inexistencia de recomendaciones o protocolos que guíen al toxicólogo en el proceso de la interpretación. Constituye, por tanto, la etapa más compleja de la investigación toxicológica. Con el objetivo de ayudar al toxicólogo forense en esta tarea, se presenta esta revisión bibliográfica sobre los conocimientos existentes (AU)

The correct interpretation of postmortem toxicology results offers an explanation on the meaning and significance of the obtained analytical results. Interpretation agreement to reality will depend on the quality of the sample and analytical results. It will also depends on the knowledge of the existence of different postmortem phenomena and the circumstances in which the death occurred. The whole process is hampered by the lack of recommendations or protocols to guide the toxicologist in the process of interpretation. Therefore, it is the more complex stage of toxicological research. In order to assist the forensic toxicologist in this task, this review of the existing knowledge on this matter is presented (AU)

[Toxicological evaluation in the childhood]. / Evaluación toxicológica del menor.

Intoxications in infancy require urgent medical treatment within national health systems. In our country they represent 0.3% of paediatric urgencies. Most of them are accidental intoxications but is not infrequent to find some related to child abuse or to suicidal intentions, especially in adolescence. The objectives of the study are to evaluate both clinical health care and medical legal aspects in intoxications in infancy. Medical assistance is described and it includes clinical diagnosis, typology of the more common toxics, percentages and referral to social work and emergency care equipment units of the Ministry of Social Welfare and the Department of Health or, where appropriate, directly to prosecutors and courts for their intervention. In cases of detection of alcohol, drugs or medication in infants, the importance of the correct interpretation of the results of toxicological findings is discussed. Several studies for the interpretation of results concerning the detection of these toxics are reported. Both legal aspects and the forensic medical opinion are assessed. The findings will be analysed by the judicial authority in order to circumscribe responsibilities or to take appropriate decisions concerning the protection of infants' interests. In conclusion intoxication in infancy can lead to legal proceedings requiring specific actions for their protection. Both physicians and hospitals must comply with the legal requirement of the submission to the court of judicial parties. On the other hand, this information is an interesting step toward reinforcing public health surveillance.

Autopsias judiciales en personas mayores de 65 años / Forensic autopsies of elderly patients

Introducción. Las personas mayores de 65 años son pacientes con pluripatología, siendo la causa de muerte la confluencia de múltiples factores. El objetivo del presente estudio es conocer el perfil y las causas de muerte en una serie de autopsias judiciales de personas de la tercera edad en Barcelona. Material y métodos. Estudio descriptivo y retrospectivo de las autopsias judiciales en mayores de 65 años realizadas en el Servicio de Patología Forense de Barcelona del Instituto de Medicina Legal de Cataluña entre octubre de 2010 y septiembre de 2011. Resultados. Se practicaron 1.494 autopsias, de las cuales 641 (42,9%) correspondieron a fallecidos de una edad de 65 o más años (63,8% varones y 36,2% mujeres). De estas 179 (28%) fueron muertes violentas (57% accidentales, 31,3% suicidas, 8,4% indeterminadas y 3,4% homicidios). Se solicitó análisis toxicológico en 277 casos y las sustancias más frecuentemente halladas fueron etanol en 34 casos (12,8%) y antidepresivos en 30 (11,3%). Conclusiones. La información procedente de las autopsias judiciales en personas mayores de 65 años aporta más información clínica que judicial (AU)

Introduction. Comorbidity is common in people over 65 years, where the confluence of multiple factors can be the cause of death. The aim of this study is to know the profile and the causes of death in a series of judicial autopsies of elderly persons in Barcelona. Material and methods. Descriptive and retrospective study of the judicial autopsies of persons aged 65 years or more that were performed at the Forensic Pathology Service of Barcelona of the Institute of Legal Medicine of Catalonia between October 2010 and September 2011. Results. Among 1494 autopsies performed, 641 (42.9%) were from people aged 65 years or more (63.8% men and 36.2% women). Among them, 179 (28%) were violent deaths (57% accidents, 31.3% suicides, 8.4% undetermined and 3.4% homicides). A toxicological analysis was performed in 277 cases and the substances more commonly found were ethanol in 34 cases (12.8%) and antidepressants in 30 (11.3%). Conclusions. The information provided by the forensic autopsies of persons aged 65 years or more is more clinical than judicial (AU)

Consideraciones toxicológicas sobre supuestos casos de sumisión química en delitos de índole sexual en el sur de España entre los años 2010-2012 / Toxicological considerations on alleged cases of drug facilitated sexual assault in southern Spain between 2010-2012

Introducción. La sumisión química consiste en la incapacitación de la víctima de delitos como violación o robo mediante la administración de sustancias químicas. La obtención de evidencias forenses en este tipo de delitos supone un importante reto para el toxicológo forense. Aunque en los últimos años se han publicado diversos protocolos de actuación con el objetivo de armonizar los procedimientos a seguir frente a estos delitos, se carece en general de datos que reflejen la situación real en los distintos países. Material y métodos. Este trabajo presenta los resultados obtenidos en un estudio retrospectivo realizado en los casos de agresión sexual recibidos en el Departamento de Sevilla del Instituto Nacional de Toxicología y Ciencias Forenses entre los años 2010 y 2012 en los que se sospechaba una posible sumisión química. Se realizó una investigación toxicológica encaminada a poner de manifiesto la presencia de alcohol etílico u otras sustancias psicoactivas. Se determinó también la presencia de semen. Resultados. Más de la mitad de los 73 casos estudiados presentaron resultados negativos, pudiendo considerar, a partir de la información sobre la víctima y los hechos y los resultados obtenidos, únicamente 3 como sumisión química. Conclusiones. Los resultados obtenidos están en consonancia con lo previamente publicado, si bien la evaluación de la situación de los casos de sumisión química en delitos de índole sexual depende del desarrollo y cumplimiento de protocolos de actuación adecuados (AU)

Introduction. Drug facilitated crime consists in incapacitating victims of rape or robbery by administering different chemical substances. Forensic evidence of this type of crime implies an important challenge for the forensic toxicologist. Although different guidelines with the objective of harmonizing existing procedures have been published, there is a general lack of data that could reflect the actual situation in different countries. Material and methods We present here the results obtained in cases of alleged sexual assault received at the Department of Seville of the National Institute of Toxicology and Forensic Sciences between 2010 and 2012, in which a possible drug facilitated sexual assault was suspected. A toxicological investigation designed to determine blood alcohol concentration and to establish the presence of psychoactive substances and drugs of abuse was performed. Semen presence was also determined. Results More than half of the 73 studied cases yielded negative results. From the received information and obtained results we could only classify 3 of the cases as a drug facilitated sexual assault. Conclusions. Obtained results are similar to those previously published, although the assessment of the current status of alleged cases of drug facilitated sexual assault depends on the development and implementation of appropriate protocols (AU)

Sumisión química en casos de presuntos delitos contra la libertad sexual analizados en el Instituto Nacional de Toxicología y Ciencias Forenses (Departamento de Madrid) durante los años 2010, 2011 y 2012 / Alleged drug-facilitated sexual assault cases analyzed at the National Institute of Toxicology and Forensic Science (Madrid Department) during the years 2010, 2011 and 2012

Introducción. La sumisión química en relación con los delitos contra la libertad sexual se puede aplicar tanto a los casos de administración subrepticia de determinadas sustancias, como a los casos oportunistas por una mayor vulnerabilidad de la víctima debido al consumo voluntario de las mismas. Material y métodos. Se ha realizado un estudio descriptivo retrospectivo de los casos de agresiones sexuales relacionados con el consumo de sustancias químicas, remitidos durante los años 2010, 2011 y 2012 al Departamento de Madrid del Instituto Nacional de Toxicología y Ciencias Forenses. Se ha recogido información en relación con el perfil de la víctima, el tipo de muestras biológicas remitidas y los resultados toxicológicos. Resultados. De los 306 casos de agresión o abuso sexual remitidos, 107 han cumplido los criterios de inclusión. El perfil de la víctima es el de una mujer española o latinoamericana joven (edad media: 25,9 años), que admite consumo de alcohol previo al episodio, y que sufre de amnesia total o parcial de los hechos. Las muestras remitidas han sido sangre (27,1%), orina (14%) o ambas (57%). El análisis toxicológico ha sido positivo en el 87,9% de los casos, y las sustancias identificadas han sido etanol (61,7%), fármacos (40,2%, fundamentalmente benzodiacepinas) y drogas ilícitas (27,1%, fundamentalmente cocaína), solas o en combinación. Conclusiones. El estudio refleja la necesidad de trabajar en prevención e información de potenciales víctimas y personal sanitario, que una temprana y adecuada toma de muestras son factores claves a la hora de confirmar el diagnóstico, y que las sustancias detectadas, lícitas e ilícitas, pertenecen a un patrón de consumo frecuente en nuestra sociedad (AU)

Introduction. Drug-facilitated sexual assault crimes can be applied in cases of covert administration of certain substances, as well as cases in which the victim voluntarily consumes these same substances. Materials and methods. This study describes retrospectively cases of sexual assault related to the consumption of chemical substances. They were reported to the Madrid Department of the National Institute of Toxicology and Forensic Sciences during 2010, 2011 and 2012. We collected information related to the victim's profile, the type of biological samples given and the results of the toxicological analysis. Results. Out of 306 cases of sexual assault or abuse referred, 107 have met the inclusion criteria. The victim's profile is of a young Spanish or Latin-American woman (mean age: 25.9 years) who admits to consuming alcohol prior to the episode and suffering from total or partial amnesia with regard to the facts. The given samples were blood (27.1%), urine (14%) or both (57%). Toxicological analysis was positive in 87.9% of cases and the substances identified were ethanol (61.7%), pharmaceuticals (40.2%, mainly benzodiazepines), and illicit drugs (27.1%, primarily cocaine) either alone or in combination. Conclusions. This study reflects the requirement to work in prevention and training of potential victims and healthcare personnel, proves that an early and adequate collection of samples are key factors to confirm the diagnosis and identifies that detected licit or illicit substances belong to a frequent consumption pattern (AU)

Evaluación toxicológica del menor / Toxicological evaluation in the childhood

Las intoxicaciones en la infancia requieren la atención médica urgente dentro del sistema sanitario. En nuestro país supone el 0,3% de las urgencias pediátricas. La mayoría son intoxicaciones accidentales, pero no son infrecuentes las relacionadas con el maltrato infantil o las intencionales con finalidad autolítica, especialmente en la adolescencia. Los objetivos del estudio son valorar la intoxicación en el menor en los aspectos clínicos asistenciales y medicolegales. Se valora la asistencia médica que comprende el diagnóstico clínico, el tipo de tóxicos más comunes, su frecuencia y la derivación a las unidades de trabajo social y equipos de asistencia urgente, dependientes de la Consejería de Bienestar Social y Consejería de Salud o, en su caso, la intervención directa de fiscalías y juzgados. Se discute la importancia de la correcta interpretación de los resultados toxicológicos en los casos de la detección en los menores de alcohol, drogas o medicamentos y se describen varios estudios de interpretación de resultados relativos a la detección de estos tóxicos Se valoran los aspectos legales y el dictamen médico forense. Las conclusiones se analizarán por la autoridad judicial a fin de delimitar responsabilidades o tomar decisiones que protejan los intereses del menor. En conclusión, la intoxicación de los menores puede derivar en procedimientos legales que requieran actuaciones concretas para su protección. El envío al juzgado de los partes judiciales es un requisito legal que deben cumplir los facultativos y centros sanitarios. Al mismo tiempo, esta información supone una vía de vigilancia epidemiológica de interés en salud pública (AU)

Intoxications in infancy require urgent medical treatment within national health systems. In our country they represent 0.3% of paediatric urgencies. Most of them are accidental intoxications but is not infrequent to find some related to child abuse or to suicidal intentions, especially in adolescence. The objectives of the study are to evaluate both clinical health care and medical legal aspects in intoxications in infancy. Medical assistance is described and it includes clinical diagnosis, typology of the more common toxics, percentages and referral to social work and emergency care equipment units of the Ministry of Social Welfare and the Department of Health or, where appropriate, directly to prosecutors and courts for their intervention. In cases of detection of alcohol, drugs or medication in infants, the importance of the correct interpretation of the results of toxicological findings is discussed. Several studies for the interpretation of results concerning the detection of these toxics are reported. Both legal aspects and the forensic medical opinion are assessed. The findings will be analysed by the judicial authority in order to circumscribe responsibilities or to take appropriate decisions concerning the protection of infants’ interests. In conclusion intoxication in infancy can lead to legal proceedings requiring specific actions for their protection. Both physicians and hospitals must comply with the legal requirement of the submission to the court of judicial parties. On the other hand, this information is an interesting step toward reinforcing public health surveillance (AU)

The measurand problem in breath alcohol testing.

Proper interpretation of forensic measurements can be critical to the administration of justice. Breath alcohol testing is commonly relied upon to measure the concentration of alcohol in breath or, indirectly, in blood. The concentration sought constitutes the "quantity intended to be measured," referred to as the measurand. Although breath tests always probe the same physical quantity, their measurand is dictated by statute and varies between jurisdictions. Thus, identical numerical values obtained from tests in disparate jurisdictions may refer to different quantities and may not indicate the relevant statutory measurand. This can lead to misinterpretation of results, referred to as the "measurand problem." We first illustrate the concept of the measurand. Thereafter, the measurand problem is illustrated through application of Hlastala's breath test paradigm and Gullberg's work on breath test uncertainty. It is shown that where the measurand is not properly accounted for, conclusions based upon breath test evidence are undermined.

Managing uncertainty in the academy and the courtroom: normal arsenic and nineteenth-century toxicology.

This essay explores how the enhanced sensitivity of chemical tests sometimes produced unforeseen and puzzling problems in nineteenth-century toxicology. It focuses on the earliest uses of the Marsh test for arsenic and the controversy surrounding "normal arsenic"--that is, the existence of traces of arsenic in healthy human bodies. The essay follows the circulation of the Marsh test in French toxicology and its appearance in the academy, the laboratory, and the courtroom. The new chemical tests could detect very small quantities of poison, but their high sensitivity also offered new opportunities for imaginative defense attorneys to undermine the credibility of expert witnesses. In this context, toxicologists had to dispel the uncertainty associated with the new method and come up with arguments to refute the many possible criticisms of their findings, among them the appeal to normal arsenic. Meanwhile, new descriptions of animal experiments, autopsies, and cases of poisoning produced a steady flow of empirical data, sometimes supporting but in many cases questioning previous conclusions about the reliability of the chemical tests. This challenging scenario provides many clues about the complex interaction between science and the law in the nineteenth century, particularly how expert authority, credibility, and trustworthiness were constructed, and frequently challenged, in the courtroom.

A cluster of deaths involving 5-(2-aminopropyl)indole (5-IT).

During 2012, the designer drug 5-(2-aminopropyl)indole emerged in Sweden, and became available at different web sites under the name 5-IT or 5-API. This compound is an indole derivative and a positional isomer of alpha-methyltryptamine. In this paper, we report the pathology and toxicology from 15 deaths involving 5-IT. Routine postmortem toxicology was performed in femoral blood, using a targeted screening for pharmaceuticals and drugs of abuse with liquid chromatography time-of-flight technology, and positive results were quantified using chromatographic techniques. For 5-IT, a new method was developed using ultra-high-performance liquid chromatography and tandem mass spectrometry. In 11 cases, intoxication was the cause of death. Two cases were signed out as causa ignota, and they were considered to be natural deaths. All determinations of 5-IT were performed in femoral blood and the concentrations ranged from 0.7 to 18.6 µg/g. Two cases had 5-IT as the only drug identified, while the others presented with other psychotropic drugs or medications in the blood as well. Shortly after this series of deaths, 5-IT was scheduled as a hazardous substance according to the regulation Certain Goods Dangerous to Health on 18 September 2012 prohibiting the handling and selling of the drug. Since then, no positive cases have been found.

[Clozapine intoxication: theoretical aspects and forensic-medical examination ].

This literature review is focused on diagnostics of acute clozapine intoxication with the fatal outcome. According to the Russian authors, clozapine intoxication ranks first in the structure of criminal poisoning and accounted for 99.7% of all the cases that occurred in Moscow during the period from 2003 to 2006. Toximetric investigations of clinical manifestations of clozapine intoxication revealed that the threshold clozapine concentration in blood is 0.12 ± 0.06 mg/I, the critical and lethal concentrations are 1.01 ± 0.2 mg/I and 3.5 ± 1.5 mg/I respectively. Autopsy on corpses of the victims of clozapine intoxication showed that most clozapine-induced pathological changes have a non-specific character (including largely circulatory disorders and dystrophic changes in parenchymatous organs). Clozapine poisoning is associated with the lengthening of QT-interval on ECG; at the values in excess of 500 ms, the risk of severe arrhythmia and sudden death significantly increases. Clozapine intake may lead to the development of potentially fatal myocarditis (the so-called clozapine-associated eosinophilic myocardium) in somatically healthy subjects. Foreign researchers report the possibility of a post-mortem increase of blood clozapine content compared with its antemortem level. They also showed that simultaneous use of substances stimulating activity of cytochrome P-450 enzymes (ethyl alcohol, finlepsin, fenitrin, nicotine) and clozapine accelerates metabolism and thereby reduces clozapine concentration in blood. It is concluded that comprehensive investigations of clozapine intoxication are needed taking into consideration pathomorphological changes induced by this agent, its potential interaction with other factors influencing human body, and the results of forensic chemical expertise of the fatal cases.