The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.

The cardiotoxic effects of synthetic cathinones remain largely unknown. In this study, we present two cases, a case series and a scoping review, to explore synthetic cathinone associated cardiotoxicity. Case 1 involved a 28-year-old male with non-ST-elevation myocardial infarction after ingesting a substance containing 4-methylmethcathinone (4-MMC), 3-methylmethcathinon (3-MMC), and methcathinone. Case 2 involved a 49-year-old male with ventricular fibrillation after 4-methylmethcathinone ingestion, who was diagnosed with severe three-vessel disease. A retrospective analysis was performed on self-reported synthetic cathinone poisonings reported to the Dutch Poisons Information Centre from 2012 to 2022. A total of 222 mono-intoxications with cardiotoxicity were included, mostly involving 3-methylmethcathinon (63%). Often tachycardia, hypertension, palpitations, and chest pain were reported. A comprehensive literature search was performed on PubMed to identify the studies reporting cardiac arrest, myocardial infarction, cardiac inflammation, cardiomyopathy, and life-threatening arrhythmias following synthetic cathinone use. A total of 30 articles reporting 40 cases were included. The reported complications included cardiac arrest (n = 28), ventricular tachycardia (n = 4), supraventricular tachycardia (n = 1), ST-elevation myocardial infarction (n = 2), non-ST-elevation myocardial infarction (n = 2), cardiomyopathy (n = 1), and myocarditis (n = 2). A total of ten different associated synthetic cathinones were identified. Cardiac arrest, myocardial infarction, and ventricular arrhythmias have been reported following the use of synthetic cathinones, underscoring the importance of obtaining a detailed recreational drug use history from patients presenting with syncope, chest pain, or palpitations.

Synthetic cannabinoid receptor agonists (SCRAs) are one of the largest groups of new psychoactive substances (NPS). Yet, another novel analog started spreading on the NPS market around 2021. Soon after, the substance could be analytically characterized in herbal material as ADB-HEXINACA, an SCRA containing a hexyl-substituted tail on the indazole core. Here, we present suitable urinary markers to prove the consumption of this analog, a case report of acute polydrug intoxication and data on its prevalence in Germany. Anticipated phase I metabolites were detected in 12 authentic urine samples that were collected for abstinence control and analyzed by ultra-performance liquid chromatography coupled to a time-of-flight mass spectrometer (UPLC-qToF-MS). The results of in vivo samples were confirmed by analysis of in vitro incubates with pooled human liver microsomes (pHLMs). Forensic samples were used to assess the prevalence of ADB-HEXINACA. Thirty-two phase I metabolites were detected in the authentic urine samples. The main metabolites resulted from amide hydrolysis in combination with either monohydroxylation or ketone formation at the hexyl moiety (M15 and M26), the monitoring of which is recommended as a proof of consumption. ADB-HEXINACA was detected in 3.5% of SCRA positive urine samples collected for abstinence control in Freiburg up to December 2022 and in 5.5% of the SCRA positive blood/serum samples. The hexyl substituent of ADB-HEXINACA allows for the detection of specific urinary biomarkers suggested as analytical targets to confirm its prior intake. ADB-HEXINACA had a rather low prevalence in Germany, alternating months of higher prevalence with periods of total absence.

UNASSIGNED: Synthetic cathinones are a heterogenous group of new psychoactive substances (NPS) with a surging prevalence of use. They are sold under the name of \"Bath Salts,\" \"Legal Highs\" or \"Research Chemical.\" It is a heterogeneous group of substances that have a varying binding selectivity and affinity. Due to limited availability of NPS screening tests, inadequate legislation, the exponential increases in availability of new NPS and the comorbid use of other illicit substances, scientific research remains scarce. As a result, insight in their mental and psychomotor effects is limited.
UNASSIGNED: We present a case of a 21-year-old woman with daily usage of synthetic cathinones, more specifically α-Pyrrolidinopentiophenone (α-PVP-better known as \"Flakka\"), α-Pyrrolidinohexiophenone (α-PHP) and alpha-Pyrrolidinoisohexaphenone (α-PHiP). Besides a severe paranoid psychotic state of mind, characterized by persecutory and somatic delusions, there was also a very pronounced psychomotor restlessness during the whole period of hospitalization which was diagnosed as akathisia. She reported that she was unable to sit during meals, had difficulty standing still and felt a constant urge to pay attention to the restlessness. The patient did not take any antipsychotic medication at admission.
UNASSIGNED: The patient was treated in accordance with the current guidelines concerning akathisia with a combination of Quetiapine 200 mg, Propranolol 80 mg, Diazepam 10 mg, Biperiden 4 mg, and Mirtazapine 15 mg without any sufficient alleviation of complaints. Before the start of the treatment, Barnes Akathisia Rating Scale (BARS) score was 11 out of 14 which evolved toward a score of 7 over the course of the 40 day hospitalization, implying persisting severe akathisia which only improved modestly.
UNASSIGNED: The current case suggests that besides cocaine, amphetamines and methamphetamines, synthetic cathinones can also increase the risk for development of extrapyramidal symptoms such as akathisia. Especially a-PVP-analogs as used by the current patient and Pyrovalerone-analogs such as Methylenedioxypyrovalerone (MDPV) are very powerful dopamine reuptake-inhibitors which might lead to strong locomotor activation. Up to this day it remains very difficult to establish a guideline concerning the treatment of intoxication with synthetic cathinones or dependence thereof.

Synthetic cathinones comprise a large amount of substances present on the dark market, which creates an undeniably worldwide problem and still is posing a threat. A 22-year-old man was brought to the Emergency Room from a party, where he had ingested orally 20 g of mephedrone. The man exhibited a disorder of consciousness with no logical verbal contact and dilated pupils. Moreover, a metabolic acidosis was present. The patient died after an hour from an admission to the ER. Blood and vitreous humor collected during an autopsy were analyzed with the use of an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-QqQ-MS/MS) with the use of C18 column in multiple reaction monitoring (MRM) mode. Both biological specimens were prepared using liquid-liquid extraction (LLE) with the use of ethyl acetate and 0.5 M ammonium carbonate water solution (pH 9). The limit of quantification (LOQ) of the method was 0.5 ng/ml in both matrices; precision and accuracy values did not exceed ±15%. Recovery of the method was in the range of 86.1%-102.7%. Determined concentrations of 4-CMC were 8542 and 9874 ng/ml in blood and vitreous humor, respectively. Other substances present in both biological materials were: atropine, diazepam, lidocaine, and its metabolite norlidocaine, as well as methcathinone and ethyl alcohol. The concentration presented in here described case is the highest ever reported 4-CMC concentration. Important aspect is also receiving other NPS by recreational users than intended, which lead to accidental poisoning (in presented case user assumed 4-CMC was 4-MMC).

Eutylone is a synthetic cathinone that is becoming an increasingly popular drug in the US and Europe. This report describes a fatal case of eutylone intoxication. A 32-year-old man went into cardiac arrest after several minutes of abnormal behavior. Rectal temperature was 37.0 °C at 5 h after death. Autopsy revealed no remarkable injuries apart from several small abrasions and no signs of rhabdomyolysis. Toxicological examination revealed only aripiprazole in the therapeutic range and eutylone. The eutylone concentration in cardiac blood was 4290 ng/g. This case is valuable because it involved fatal intoxication from a single use of eutylone and quantitative analysis, whereas most previous reports of eutylone intoxication have involved a mixture of drugs with limited quantitative analysis.

During the last decade, only few cases of acute etizolam intoxication have been detailed. Little is known about the toxic effects of etizolam overdose. Here, the authors report the case of a 42-year-old man who was admitted to the emergency department for intense agitation following etizolam and cocaine consumption. Detection and determination of etizolam and cocaine (including metabolites) were achieved using liquid chromatography tandem mass spectrometry. Etizolam and benzoylecgonine (BZE) were detected in plasma at 64 and 10 ng/mL, respectively. The level of cocaine was below the limit of quantification (< 5 ng/mL). To the authors\' knowledge, the only report detailing an etizolam overdose was provided by O\'Connell et al. and was characterized by the presence of central nervous system (CNS) depression signs. Interestingly, here, there were no signs of CNS depression but only signs of CNS excitation. With regard to cocaine and BZE plasma concentrations, the clinical presentation cannot be only explained by the co-consumption of cocaine. It may be hypothesized that the clinical presentation was related to a paradoxical reaction to etizolam overdose. To date, no case of paradoxical excitation related to etizolam use has been reported in adults. The case presented here appears particularly interesting, given the limited data relating to high-dose etizolam toxicity.

The case report centres on analytical findings from a spice sample (mixed with tobacco (as a cigarette) for consumption), and its corresponding plasma sample, smoked by a 31-year-old man who was attended by emergency services following collapse. The man was fully conscious and cooperative during initial medical treatment. Suddenly, he suffered a complete loss of self-control, whereupon the police was notified. The man encountered the police officers when exiting the apartment, at which point he threatened them with clenched fists and reached for a plant bucket in order to strike out in the direction of the officers. At the trial, he described himself as confused and as being completely overwhelmed, having lost self-control, suffered a panic attack and \"just wanted to get out the situation\". Furthermore, he stated that he had no recollection of the incident. He feared death due to palpitations, heart pain, dizziness and repetitive anxiety states. Routine systematic as well as extended toxicological analysis of the plasma sample, taken approximately 2 h after the incident, confirmed the use of cannabis and spice. Plasma concentrations of THC, OH-THC and THC-COOH were 8.0 μg/L, 4.0 μg/L and 147 μg/L, respectively. Furthermore, analysis confirmed uptake of 5F-ADB (5F-MDMB-PINACA) via detection of both 5F-ADB and the 5F-ADB N-(5-OH-pentyl) metabolite. The spice sample additionally contained 5F-MDMB-PICA, which was not detected in the plasma sample. A differentiation between a possible co-use and a recent use of cannabis was not possible. In summary, this case once more underlines the health risks of spice use.

UNASSIGNED: The recreational use of new psychoactive substances (NPS) is increasing worldwide. Among them, the arylcyclohexylamine family including phencyclidine (PCP) and ketamine derivatives is increasing. We report a non-fatal intoxication mainly due to arylcyclohexylamine compounds illustrated by molecular networking (MN).
UNASSIGNED: A 37-year-old man with a history of drug abuse was discovered with several bags labeled as research chemicals around him and traces of powder on his nose. He was rehydrated, intubated, and admitted to the intensive care unit (ICU). Urine and drug were analyzed by liquid chromatography-mass spectrometry for NPS identification. Several NPS were quantified in urine: 3-OH-PCP at 12,085 mg/L, 3-MeO-PCP at 1100 mg/L, 2F-DCK at 147 mg/L, N-ethylhexedrone at 165 mg/L and CMC at 48 mg/L. Using a bioinformatic approach, a molecular network was built to confirm the consumption of powders contained in the bags by comparison with patient\'s urine.
UNASSIGNED: This case illustrates the interest of MN to (i) perform sample-to-sample comparison, (ii) target quantification methods, and (iii) allow proper management to confirm the relevance of the treatment.

Alpha-Pyrrolidinopentiothiophenone (α-PVT) belongs to the drug class of pyrrolidinophenones, a subgroup of synthetic cathinones, which are among the most prevalent new psychoactive substances. The study describes a series of 44 authentic forensic cases with analytical confirmed intake of α-PVT. Plasma concentrations, determined by a validated LC-MS/MS method, ranged from ca. 0.9 to 306 µg/L (median 35.6; mean 66.6 µg/L). Comprehensive toxicological analysis proved excessive co-consumption in almost all cases, including other pyrovalerones and classic stimulants as well as central depressant drugs such as opiates/opioids, benzodiazepines, pregabalin and/or ethanol. Subjects were aged between 26 and 54 years (median 35 years, mean 36 years) and appeared to be mainly experienced intravenous drug consumers. A high incidence of aberrant behavior in terms of aggressive, combative behavior and psychotic changes could be observed, as also reflected in accused offences, which frequently presented violent crimes. In consideration of several confounding factors, the study suggests a relationship between frequency of such impairment and plasma concentrations of α-PVT, but individual cases without signs of behavioral changes and high plasma concentrations also occurred, which might be explained by developed tolerance and/or individual vulnerably for the psychotic effects of pyrovalerones.