Synthetic cathinones in drug-facilitated sexual assault: A case report involving the novel generation substituted cathinone N-ethylpentedrone and a review of the literature.

The use of 3,4-methylenedioxymethamphetamine (MDMA) in drug-facilitated sexual assault (DFSA) is not uncommon. Indeed, the effects associated with the use of this substance may lead to disinhibition. Several synthetic cathinones, such as mephedrone or methylone, also possess marked entactogenic properties. This manuscript aims to (i) report a DFSA case involving a novel cathinone derivative, namely N-ethyl-pentedrone (NEPD) and (ii) review previously reported DFSA cases involving synthetic cathinones. Using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), NEPD was detected in both plasma and urine collected from a 36-year-old male who had been victim of DFSA. Furthermore, an exhaustive, non-period-specific English-language literature search was performed using several different electronic databases to identify DFSA cases involving synthetic cathinones. Overall, five synthetic cathinones have been associated with DFSA:methylenedioxypyrovalerone, 4-methylethcathinone, α -pyrrolidinopentiophenone, mephedrone, α -pyrrolidinohexiophenone, and methylone, which appears to be the most frequently reported. Methylone is the ß-keto analog of MDMA, with which it shares substantial pharmacological similarities. Indeed, the pharmacological effects of methylone are similar to those associated with MDMA. By contrast, little is known regarding NEPD's pharmacological effects in humans. Based on subjective reports, NEPD can produce both positive and negative effects in human. Unlike what is reported in the case of methylone or mephedrone, only a small minority of NEPD users report slightly entactogenics effects. Such properties theoretically make NEPD more suitable for use in a chemsex context than in DFSA context; even though, the boundary between these two specific forms of sexualized drug use can sometimes appear tenuous.

Post mortem blood bromazolam concentrations and co-findings in 96 coronial cases within England and Wales.

Bromazolam is a newly emerging benzodiazepine drug which is not licensed for medicinal use. It may be sourced as a New Psychoactive Substance (NPS) for its desired effects or be consumed unknowingly via counterfeit Xanax® or Valium® preparations. As part of our Coronial workload, we observed an increase in the detection of bromazolam from September 2021 to November 2022. We report a series of 96 cases in which bromazolam was quantitated by high resolution accurate mass - mass spectrometry (HRAM - MS) in post-mortem blood. The mean (SD) post-mortem blood bromazolam concentration from our case series was 64.6 ( ± 79.4) µg/L (range <1-425 µg/L). Routine toxicological screening results have also been reported; the most commonly encountered drugs taken in combination with bromazolam were cocaine, gabapentinoids and diazepam. In 48% of cases at least one further designer benzodiazepine drug was also present (etizolam, flualprazolam, flubromazolam, flubromazepam). It is essential that laboratories providing toxicological investigations are aware of the limitations of their assays; and inclusion of bromazolam within targeted screening panels using LC-MS/MS is encouraged. Bromazolam has not been associated with death in isolation from resulting toxic concentrations; however, it is likely to enhance adverse clinical effects when taken in combination with stimulant and/or centrally-acting depressant drugs (poly-drug deaths). Bromazolam, similar to other benzodiazepines, may also impair cognition and decision making skills.

Designer Benzodiazepines' Activity on Opioid Receptors: A Docking Study.

BACKGROUND: Previous studies have reported that benzodiazepines (BZDs) seem to enhance euphoric and reinforcing properties of opioids in opioid users so that a direct effect on opioid receptors has been postulated, together with a possible synergistic induction of severe side effects due to co use of BDZs and opioids. This is particularly worrisome given the appearance on the market of designer benzodiazepines (DBZDs), whose activity/toxicity profiles are scarcely known. OBJECTIVES: This study aimed to evaluate, through computational studies, the binding affinity (or lack thereof) of 101 DBZDs identified online on the kappa, mu, and delta opioid receptors (K, M, DOR); and to assess whether their mechanism of action could include activation of the latter. METHODS: MOE® was used for the computational studies. Pharmacophore mapping based on strong opioids agonist binders' 3D chemical features was used to filter the DBZDs. Resultant DBZDs were docked into the crystallised 3D active conformation of KOR (PDB6B73), DOR (PDB6PT3) and MOR (PDB5C1M). Co-crystallised ligands and four strong agonists were used as reference compounds. A score (S, Kcal/mol) representative of the predicted binding affinity, and a description of ligand interactions were obtained from MOE®. RESULTS: The docking results, filtered for S < -8.0 and the interaction with the Asp residue, identified five DBZDs as putative binders of the three ORs : ciclotizolam, fluloprazolam, JQ1, Ro 48-6791, and Ro 48-8684. CONCLUSION: It may be inferred that at least some DBZDs may have the potential to activate opioid receptors. This could mediate/increase their anxiolytic, analgesic, and addiction potentials, as well as worsen the side effects associated with opioid co-use.

A retrospective analysis of the "Neverending Trip" after administration of a potent full agonist of 5-HT2A receptor - 25I-NBOMe.

BACKGROUND: 5-HT2A receptor (e.g. 25I-NBOMe) agonists not only pose risks of acute intoxication but also long-term effects and significant adverse reactions, e.g. hallucinogen persisting perception disorder (HPPD), derealization, and depersonalization. AIMS: We evaluated the risk associated with single and repeated use of 25I-NBOMe. We aimed to identify factors that may increase the risk of HPPD, increase its severity and determine the time when the first symptoms appear. Herein, we report the first extensive evaluation of 25I-NBOMe-induced HPPD. METHOD: We assessed all reports (58) collected by The Pomeranian Pharmacovigilance Centre (PPC) from 2013 to 2020. RESULTS: The study included a total of 58 reports of adverse reactions caused by 25I-NBOMe. In the case of 15 reports (in patients aged 19-26 years), symptoms persisted many months after the discontinuation of 25I-NBOMe. The most common were: pseudohallucinations, bizarre delusions, derealizations and in some cases development or worsening of depression has been diagnosed. HPPD-like symptoms were most common in patients who took the drug regularly (i.e., several times a month). The risk of HPPD-like symptoms is higher in patients who have severe visual pseudohallucinations, severe bizarre delusions, derealization and/or depersonalization onset immediately after taking the drug. Recurrence of HPPD symptoms may be provoked by many factors, however, there is some cases there is no apparent reason. HPPD after 25I-NBOMe use can last from 2 months up to 2 years. In some patients, pharmacological treatment was necessary due to 25I-NBOMe-induced HPPD and depression. CONCLUSIONS: The study showed long-lasting effects after 25I-NBOMe administration and allowed for the determination of HPPD risk factors.

New Designer Drugs.

In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic and several emerging opioids, including buprenorphine, loperamide, fentanyl, fentanyl derivatives, and others. Kratom, a plant occasionally used for opiate detoxification, along with the sedatives etizolam and phenibut, will be discussed. Lastly, this article discusses the phenethylamines and marijuana.

Reinforcing and discriminative-stimulus effects of two pyrrolidine-containing synthetic cathinone derivatives in rats.

The molecular and behavioral aspects of α-pyrrolidinopentiophenone (α-PVP) have been characterized; however, how the structural modification of α-PVP affects its abuse potential is still unknown. In this study, we investigated the abuse potential of two pyrrolidinylated second-generation cathinones:4-chloro-α-pyrrolidinopentiophenone (4cl-α-PVP) and 4-chloro-α-pyrrolidinopropiophenone (4cl-α-PPP). Male Sprague-Dawley rats were trained to self-administer methamphetamine (METH, 0.05 mg·kg-1·infusion-1), α-PVP (0.05 mg·kg-1·infusion-1), 4cl-α-PVP (0.05 mg·kg-1·infusion-1), and 4cl-α-PPP (0.5 mg·kg-1·infusion-1) under a fixed ratio (FR) 1 reinforcement schedule for 10 sessions. The discriminative-stimulus effect of METH (0.8 mg/kg) from saline was tested under an FR10 schedule of food delivery. α-PVP, 4cl-α-PVP and 4cl-α-PPP produced reinforcement behaviors and presented an inverted U-shaped dose effect. The reinforcing potency was displayed with a rank order of α-PVP (0.029 mg·kg-1·infusion-1) > METH (0.040 mg·kg-1·infusion-1) > 4cl-α-PVP (0.094 mg·kg-1·infusion-1) > 4cl-α-PPP (0.51 mg·kg-1·infusion-1). All three drugs were fully substituted for the discriminative-stimulus effects of METH in rats. The substitution potency for discriminative-stimulus effects of α-PVP (ED50 = 0.4 mg/kg) was approximately equal to that of METH (ED50 = 0.3 mg/kg), while the discriminative potency of 4cl-α-PVP (ED50 = 1.0 mg/kg) and 4cl-α-PPP (ED50 = 5 mg/kg) was approximately 3 and 16-fold less than that of METH. The rank order of potency was α-PVP ≈ METH >4cl-α-PVP > 4cl-α-PPP. The present data demonstrated that 4cl-α-PVP and 4cl-α-PPP produced reinforcing effects and fully and dose-dependently substituted for the subjective effects of METH, suggesting that both 4cl-α-PVP and 4cl-α-PPP have abuse potential that may be similar to METH.

Isquemia miocárdica por consumo de dibutilona / Myocardial ischemia from dibutylone use / Isquemia miocárdica por uso de dibutilona

Resumen: Las catinonas sintéticas son drogas estimulantes de síntesis, comercializadas en el mercado ilegal por sus propiedades estimulantes y perturbadoras del sistema nervioso central, para su uso recreativo, solas, o como adulterantes de cocaína y derivados anfetamínicos. A nivel mundial existe un número creciente de reportes de intoxicaciones agudas y complicaciones por consumo de estas sustancias. En Uruguay fueron detectadas por primera vez en el año 2015, existiendo una información epidemiológica muy limitada. Las catinonas sintéticas no se detectan por las técnicas inmunocromatográficas disponibles en los laboratorios de los servicios de urgencias de nuestro país. Se describe el primer caso de intoxicación por una catinona sintética (dibutilona) en Uruguay, en un paciente de 45 años, por consumo de un polvo vendido como "éxtasis", presentando como complicación un síndrome coronario agudo, con una buena evolución posterior. La confirmación diagnóstica se realizó mediante su detección en orina por cromatografía de gases acoplada a espectrometría de masas. La estructura química de la dibutilona y su mecanismo de acción explican las manifestaciones clínicas y la complicación isquémica por vasoespasmo coronario. En ausencia de una noción clara de exposición y ante la situación epidemiológica actual, la presencia de un cuadro clínico compatible con una droga estimulante y resultado negativo para cocaína y anfetaminas en estudios inmunocromatográficos, debe hacer plantear la sospecha de otros estimulantes de síntesis como las catinonas, tal como ocurrió en este caso.

Summary: Synthetic cathinone are stimulating synthetic drugs used for recreational purposes on their own or as adulterants in cocaine and amphetamines derivatives that are traded in illegal markets given their stimulating and disturbing properties on the central nervous system. Globally, there is a growing number of acute intoxications and complications as a consequence of consumption of these substances. In Uruguay they were first detected in 2015, there being limited epidemiological data. Synthetic cathinone are not detected by the immunochromatographic tests available at the laboratories of the emergency services in our country. The study describes the first case of intoxication by a synthetic cathinone (dibutylone) in Uruugay, in a 45 year old patient as a result of powder sold as "ecstasy". The patient presented an acute coronary syndrome, subsequent evolution being good. Diagnostic confirmation was made in urine using gas chromatography coupled with mass spectrometry. The chemical structure of dibutylone and its action mechanism explain the clinical manifestations and the coronary vasospasm causing ischemia. When there is no clear sign of a patient having been exposed to this substance and upon the current epidemiological state, the presence of clinical symptoms that are compatible with a stimulating drug and a negative result for cocaine and amphetamines in immunochromatographic tests must lead us to be suspicious about the presence of synthetic stimulating substances as cathinone, as in the case studied.

Resumo: Catinonas sintéticas são drogas estimulantes sintéticas, comercializadas no mercado ilegal por suas propriedades estimulantes e perturbadoras do sistema nervoso central, para uso recreativo isoladamente ou como adulterantes da cocaína e derivados de anfetaminas. Em todo o mundo cresce o número de relatos de intoxicações agudas e complicações decorrentes do uso dessas substâncias. No Uruguai, foram detectados pela primeira vez em 2015 com informações epidemiológicas muito limitadas. As catinonas sintéticas não são detectadas pelas técnicas imunocromatográficas disponíveis nos laboratórios de pronto-socorro de nosso país. Descreve-se o primeiro caso de intoxicação por catinona sintética (dibutilona) em nosso país, em um paciente de 45 anos, devido ao consumo de um pó vendido como "ecstasy", apresentando como complicação uma síndrome coronariana aguda, com boa evolução posterior. A confirmação diagnóstica foi feita por sua detecção na urina por cromatografia gasosa acoplada à espectrometria de massa. A estrutura química da dibutilona e seu mecanismo de ação explicam as manifestações clínicas e complicações isquêmicas devido ao vasoespasmo coronariano. Na ausência de uma noção clara de exposição e dada a situação epidemiológica atual, a presença de quadro clínico compatível com droga estimulante e resultado negativo para cocaína e anfetaminas em estudos imunocromatográficos, deve levantar a suspeita de outros estimulantes sintéticos como as catinonas, como aconteceu neste caso.

Designers Drugs-A New Challenge to Emergency Departments-An Observational Study in Poland.

Background and Objective: In the last decade, the phenomenon of using new psychoactive substances (NPS), called designer drugs, has been on rise. Though their production and marketing in Poland is prohibited, reports of the Supreme Audit Office noted that young people are increasingly reaching for new intoxication agents in the form of designer drugs. There is a significant increase in the number of patients with NPS abuse admitted to the emergency departments. As NPS cannot be detected by standard tests for the presence of psychoactive substances, it is difficult to choose the appropriate therapeutic intervention. Therefore, the aim of the present study was to evaluate the patient characteristics in the population of adults and children suspected of using NPS and formulate the protocol for diagnosis and treatment. Materials and Method: The paper is based on a retrospective analysis of medical records of hospitalized patients in the Clinical Emergency Department of The Regional Specialist Hospital in Olsztyn (SKOR WSS, emergency department (ED)) and the Pediatric Emergency Department of the Provincial Specialist Children's Hospital in Olsztyn (SORD WSSD, pediatric emergency department (PED)) between years 2013 to 2018. The patient records related to their general symptoms at admission, mental state and laboratory diagnostic tests were evaluated. Results: The majority of patients hospitalized due to the suspected use of NPS were adolescents in 2013-2016 and a reversal of this trend was observed in 2017-2018 when number of adults admitted to the emergency department (ED) due to NPS use was higher. The NPS abuse was significantly higher among male patients, alcoholics, people using other psychoactive substances, patients suffering from mental disorders and teenagers in difficult socio-economic family situations. Whereas, the most common symptoms among pediatric patients were co-ordination disorder and aggression, in adults mainly tachycardia and aggression was observed. The laboratory tests in significant number of adult patients showed leukocytosis and ketonuria. Conclusions: In the present study, no unambiguous toxidrome or biochemical pattern characteristic for using NPS was observed. However, evaluation of blood morphology, coagulation parameters, liver and kidney function can be helpful in the diagnostic and therapeutic process. Symptomatic treatment of patients, fluid therapy and sedation was sufficient in most cases to resolve the patient symptoms in 48 h.

Flualprazolam: Report of an Outbreak of a New Psychoactive Substance in Adolescents.

Flualprazolam is a nonregistered drug in the benzodiazepine family and constitutes a new psychoactive substance (NPS). Since 2014, a growing number of designer benzodiazepines have become available over the Internet and on the counterfeit drug market. In June 2019, a cluster of patients intoxicated with flualprazolam was identified by the Oregon Poison Center. As an emerging drug of abuse, the clinical characteristics of flualprazolam have been poorly characterized thus far. Over a one-week period, 6 teenagers presented to local emergency departments after ingesting illegally obtained counterfeit alprazolam, which led to sedation. Other symptoms included slurred speech, confusion, and mild respiratory depression. All 6 patients had resolution of their symptoms within 6 hours of ingestion. Blood and urine samples, as well as a tablet fragment, were obtained from 3 patients. The tablet and biological samples were analyzed by using liquid chromatography-quadrupole time-of-flight mass spectrometry and were found to contain the NPS flualprazolam without other drugs or intoxicants. With this case series, we add to the medical literature a clinical description of an emerging drug of abuse. Flualprazolam appears to share the clinical properties of other benzodiazepines. As flualprazolam and other NPSs become more common, physicians must be aware of their availability and characteristics. Sedation lasting <6 hours was observed in 6 of 6 patients exposed to flualprazolam. No effects that would be unexpected from benzodiazepine intoxication were seen among the patients. Specifically, none developed prolonged symptoms or required intubation and mechanical ventilation, ICU admission, or antidotal therapy.

Use of new psychoactive substances to mimic prescription drugs: The trend in France.

Among the expanding world of New Psychoactive Substances (NPS), Designer Medicines (DM) are designed to mimic psychoactive drugs and might lead to adverse events of various severity. The DM category includes designer benzodiazepines (DB), phenmetrazine, modafinil, methylphenidate analogs, and novel synthetic opioids (NSO). To investigate DM-related complications in France, all data on NPS collected in the French Addictovigilance network database through spontaneous reports (SRs) and the annual survey on deaths related to the abuse of licit and illicit psychoactive substances (DRAMES survey) between 2009 and 2017 were analyzed. From 2009-2017, about 800 cases of NPS-related abuse or somatic complications were reported to the French Addictovigilance Network, including 71 fatal cases (9%). DM use progressively increased over the years, particularly after 2013 (4% of all SRs on NPS in 2011 versus 14 % in 2017). Moreover, DM were implicated in 17 % of NPS-related deaths in France, just after cathinones (43 %) and dissociative drugs (22 %). NSO, DB and phenidate analogs were identified in 42 %, 25 % and 25 % of all DM-related death reports, respectively. DM seem to interest a new target group of users that includes mainly patients and healthy people rather than substance users. The availability on the Internet of compounds mimicking therapeutic drugs is a worrying phenomenon that could lead to their uncontrolled use.

Designer drugs: mechanism of action and adverse effects.

Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at µ-opioid receptors and γ-aminobutyric acid-A (GABAA) or GABAB receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.

Designer benzodiazepines' pharmacological effects and potencies: How to find the information.

BACKGROUND: Scientific data on the psychopharmacological effects of new psychoactive substances (NPSs) are scarce. Web fora contain a wealth of information posted by users as trip reports (TRs), but the reliability of the reports remains questionable because of the nature of the used molecule and the potential for dose inaccuracies. We focused on the TRs of designer benzodiazepine (DBZD) users since their psychopharmacological effects are similar to prescription benzodiazepines (BZDs). Moreover, the impact of functional groups on the BZD rings with regards to the potency has been fairly/quite studied, allowing structural analysis. METHODS: DBZDs offering more than 15 TRs with at least two accounts on experienced effects were included. Data were analyzed with the empirical phenomenological psychological method. Reported effects were analyzed and the pharmacological potencies of DBZDs were compared by calculating a 'potency score'. RESULTS: In total, 197 TRs for clonazolam, deschloroetizolam, diclazepam, etizolam, flubromazepam, flubromazolam, meclonazepam, metizolam, nifoxipam and pyrazolam were analyzed. Effects similar to prescription BZDs were reported for all the selected DBZDs. Pyrazolam was reported to be the most anxiolytic DBZD, flubromazolam the most hypnotic, etizolam the most euphoric and flubromazolam and clonazolam as the most amnesic DBZDs. Diclazepam and pyrazolam were not reported to induce euphoria. Flubromazepam, flubromazolam, clonazolam and meclonazepam were the most potent and deschloroetizolam, nifoxipam, metizolam and pyrazolam the least potent. The chemical structure of the different DBZDs and the functional groups on the BZD rings confirmed this ranking, except for nifoxipam. CONCLUSIONS: When information on NPSs obtained from Internet fora are abundant, it could be considered as an appreciable data source.

Differential effects of synthetic psychoactive cathinones and amphetamine stimulants on the gut microbiome in mice.

The list of pharmacological agents that can modify the gut microbiome or be modified by it continues to grow at a high rate. The greatest amount of attention on drug-gut microbiome interactions has been directed primarily at pharmaceuticals used to treat infection, diabetes, cardiovascular conditions and cancer. By comparison, drugs of abuse and addiction, which can powerfully and chronically worsen human health, have received relatively little attention in this regard. Therefore, the main objective of this study was to characterize how selected synthetic psychoactive cathinones (aka "Bath Salts") and amphetamine stimulants modify the gut microbiome. Mice were treated with mephedrone (40 mg/kg), methcathinone (80 mg/kg), methamphetamine (5 mg/kg) or 4-methyl-methamphetamine (40 mg/kg), following a binge regimen consisting of 4 injections at 2h intervals. These drugs were selected for study because they are structural analogs that contain a ß-keto substituent (methcathinone), a 4-methyl group (4-methyl-methamphetamine), both substituents (mephedrone) or neither (methamphetamine). Mice were sacrificed 1, 2 or 7 days after treatment and DNA from caecum contents was subjected to 16S rRNA sequencing. We found that all drugs caused significant time- and structure-dependent alterations in the diversity and taxonomic structure of the gut microbiome. The two phyla most changed by drug treatments were Firmicutes (methcathinone, 4-methyl-methamphetamine) and Bacteriodetes (methcathinone, 4-methyl-methamphetamine, methamphetamine, mephedrone). Across time, broad microbiome changes from the phylum to genus levels were characteristic of all drugs. The present results signify that these selected psychoactive drugs, which are thought to exert their primary effects within the CNS, can have profound effects on the gut microbiome. They also suggest new avenues of investigation into the possibility that gut-derived signals could modulate drug abuse and addiction via altered communication along the gut-brain axis.

New psychoactive substances: An actual problem or an overestimated phenomenon?

In last years, international and national Institutions have been completely focused on the new psychoactive substances (NPS) phenomenon. Many contrast policies have been planned in order to control their spread. Even scientific entities, such as our Forensic Toxicology Division, have spent time and resources for NPS identification in biological (from clinical and forensic caseworks) and non-biological (seized material) samples. Last reports show a low prevalence of NPS across the Europe and Italy, while the classical drugs are still the main cause of drug-related deaths. In particular, a worrisome datum is represented by the increasing number of deaths due to heroin. Seen these statistics, is the NPS phenomenon overestimated? Is the interest in classical drugs decreased? Were we diverted by NPS?

Unexpected Serotonin Syndrome, Epileptic Seizures, and Cerebral Edema Following 2,5-dimethoxy-4-bromophenethylamine Ingestion.

4-bromo-2,5-dimethoxyphenethylamine (2C-B) is a designer drug. In Europe, 2C-B is easily obtained and used for recreational purposes. It is known for its stimulating effects similar to those of 3,4-methylenedioxymethamphetamine, although in higher doses it has more hallucinogenic effects. Here, we report a case of 2C-B ingestion, confirmed by liquid chromatography-tandem mass spectrometry, in an 18-year-old man. The neurological consequences were severe, including the development of serotonin syndrome and severe brain edema. Supportive therapy resulted in a stable condition, although, after several months, the patient still suffered from severe neurological impairment due to the drug-induced toxicity. This case showed that 2C-B could not be identified with the drugs of abuse screening routinely used in Dutch hospitals. The use of 2C-B carries many risks, with potentially profound neurological damage, that both consumers and healthcare physicians are unaware of.

Death cases involving certain new psychoactive substances: A review of the literature.

In the last decades, more and more new psychoactive substances (NPS) were introduced on the drug market which were sold as "legal" alternatives for classic drugs and misused medications. Due to an increased number of available substances and a growing utilization by users of common drugs but also by inexperienced users because of the supposed "legal" status, also undesired adverse effects of these NPS, at worst leading to death, became apparent. This review summarizes fatalities previously described in scientific literature which were attributed to the use of NPS or such cases, in which intake of NPS was proven or even assumed to contribute to death. This summary includes an overview of substances involved (particularly synthetic cannabinoids ("spice"), novel opioids and synthetic cathinones ("bath salts")) as well as of postmortem concentrations determined in various biological matrices. The compiled data assist forensic toxicologists with the interpretation of death cases involving NPS.

A case of 5F-ADB / FUB-AMB abuse: Drug-induced or drug-related death?

Synthetic cannabinoids (SCs) belong to the group of new psychoactive substances (NPS) which appear sprayed on herbal mixtures on the "street" drug market and are intended for smoking like marijuana. In the present report we discuss a fatal case of 18-years-old boy, who had smoked SCs since several months and an overuse of SCs during last 48 h of his life has been apprised. The autopsy findings revealed acute respiratory distress syndrome (ARDS). Both toxicological analysis of deceased blood and urine samples and chemical analysis of the herbal mixture seized revealed presence of two SCs - 5F-ADB and FUB-AMB. The amount of 5F-ADB in blood was found to be 3.7 ng/mL by standard addition method. Severe and irreversible morphology changes in lung specimen, leading to ischemic damage of all internal organs and tissues, were observed during histological examination. The present case can be discussed as an example of both drug-induced and drug-related death resulting from acute intoxication with 5F-ADB and FUB-AMB as well as from systematic use of both synthetic cannabinoids.