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Among the emerging investigative fields, forensic medicine and toxicology lead to analyzing fatalities in medico-legal expert opinion formulating. While discussing the problem, the authors have selected 96 fatal cases from their expert practice including the period from 2010 to 2023, in which deaths were connected with taking new psychoactive substances (NPS's) belonging to various chemical categories, mainly synthetic cathinones (SC), synthetic cannabinoids (SCan) and non-medical synthetic opioids (NSO). In the investigated cases, toxicological analysis revealed 37 NPS's and their 9 metabolites. The cases involved the use of SC's (64 cases - 67 %), Scan's, including their metabolites (10 cases - 10 %) and NSO's, including their metabolites (6 cases - 6 %). The remaining cases involved the simultaneous use of NSO with SC and/or SCan, including their metabolites (8 cases - 8 %), or SC with SCan (5 cases - 5 %). In three cases (3 %), compounds belonging to other groups were taken. In twenty-five cases, more than one NPS was found. Moreover, in twenty-seven cases, ethyl alcohol was also detected at the concentration range of 0.6-3.6 ‰. The concentration of xenobiotics determined in blood represented extensive ranges of concentration. The victims were at the age of 16-58 years of life. The group included eleven women (11 %). Generally, the deaths related to NPS's were predominantly of an accidental character (81 %), while the manner of death in sixteen cases (17 %) was suicide, including hanging (5 cases), jumping from a great height (3 cases), self-injury and exsanguination (1 case), as well as acute drug intoxication (6 cases) and intoxication with central nervous system hypoxia after an hanging (1 case). Among the analyzed cases there were two victims of homicide (2 %), in one of which the perpetrator being under the influence of the mixture of the synthetic opioid U-47700 and synthetic cannabinoid AB-FUBINACA. In twenty-eight cases, medications used in psychiatry were found, which suggested that the victims were struggling with mental problems before death. As it was implied by the available information, more than 36 % of the victims had mental problems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Recently, semi-synthetic cannabinoids have entered the illegal market and are produced to mimic the psychoactive effects of tetrahydrocannabinol (THC). This is a case report of a 19-year-old man, who was hospitalized due to severe sedation, hypotension and tachy- and bradycardia after ingestion of the semi-synthetic cannabinoids hexahydrocannabinol (HHC) and hexahydrocannabiphorol (HHC-P) mixed in food. HHC-P, HHC and metabolites were identified in blood samples. The amount of semi-synthetic cannabinoids in illegal products can be high, which can explain the described prolonged clinical effects., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Objectives: Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide hazard. Here, we review the spectrum of imaging findings in adulterated cannabinoid poisoning., Materials and Methods: In this retrospective study, we used the Israeli Poison Information Center database to identify patients with cannabinoid-associated coagulopathy who presented to the Rambam Health Care Campus, where most patients were treated during an outbreak in northern Israel between September 2021 and June 2022. All relevant imaging studies for these patients were reviewed. We estimated the sensitivity of findings for cannabinoid-associated coagulopathy. Associations between a continuous variable and a dichotomous outcome were assessed with the Mann-Whitney U test., Results: We identified 48 patients (mean age 40 years ± 9 [SD], 43 males) with 54 hospitalizations due to cannabinoid-associated coagulopathy. Symptomatic hemorrhage was documented in 50 (93%) cases at presentation, most of whom (78%) had hemorrhage from multiple systems. The most common bleeding site was the genitourinary collecting system, with a characteristic sign of suburothelial bleeding in 16/18 of performed abdominal CTs (sensitivity 89% [CI 65-99%] for cannabinoid-associated coagulopathy). Intramural bowel hematomas were noted in 70% (7/10) of CTs of patients with gastrointestinal bleeding. Incidental bleeding sites were identified on imaging in 24% of patients. An increased number of bleeding sites was associated with need for vasopressors (difference in bleeding sites 3.00 [95% CI 0.99-4.00], p = 0.026)., Conclusion: CT plays a key role in the diagnosis and work-up of adulterated cannabinoid-associated coagulopathy. Characteristic signs include suburothelial hemorrhage and intramural bowel hematomas., Clinical Relevance Statement: Recognition of radiological signs of adulterated synthetic cannabinoid-associated coagulopathy is critical for optimizing outbreak control on the public health level and ensuring timely treatment on the individual patient level., Key Points: • Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide threat. • Characteristic imaging signs include suburothelial bleeding, intramural bowel hematomas, and rare incidental bleeding sites. • Imaging has a pivotal role in optimizing outbreak control and ensuring timely and appropriate treatment., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Synthetic cannabinoids are a heterogenous group of novel, legally regulated psychoactive substances that can result in broad, multisystemic, dangerous effects. Despite growing literature regarding synthetic cannabinoid toxicity, little is known about the extent of these effects in young children. Caregivers of drug-endangered children may not provide an accurate history of exposure when children present with symptoms of intoxication, and lack of swift detection on routine urine drug screens may further obscure and delay the diagnosis. Clinical recognition carries forensic relevance that may support interventions to aid in protecting vulnerable children. We describe a case of near-fatal child maltreatment due to supervisory neglect resulting from ingestion of an increasingly common synthetic cannabinoid. Furthermore, we highlight clinical findings that should increase a physician's index of suspicion for synthetic cannabinoid toxicity, even in the absence of a history of exposure., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Drs Ruiz-Maldonado, Christensen, and Campbell have provided medicolegal consultation and expert testimony on cases of suspected child abuse and neglect. Dr Campbell’s institution and Dr Christensen has received compensation for providing expert testimony; and Dr Dorey has indicated she has no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

The detection of synthetic cannabinoid (SC) intoxication cases is challenging, even more when the involved SC identification is requested in a forensic context. This situation can be complicated by new modes of SC consumption, non-specific symptomatology, and analytical pitfalls. To illustrate these issues, we report the case of a 16-year-old man who presented symptoms evocating of a seizure disorder in the minutes following the use of a friend's e-cigarette. At admission in the emergency department, his electroencephalogram was interpreted as coherent with a recent seizure episode. 5F-ADB, a third generation SC, was detected in the e-liquid and in an early collected (H2 after the e-cigarette use) serum sample (0.50 µg/L), but not in urine samples (H18 and H38). One 5F-ADB metabolite, O-desmethyl-5F-ADB (M5), was detectable in urine up to at least 38 h after intoxication. Neither 5F-ADB nor its metabolites could be detected in victim's hair sampled 3 months after the intoxication. Although leading to a non-specific symptomatology, acute SC intoxication should be considered when the case history is related to e-cigarette or e-liquid use. Early biological samples are recommended, even if analytical screening can be positive for SC metabolites in urine sampled until 2 days after exposure. Accordingly, data from the literature and the present case underscore the relevance of adding both main 5F-ADB metabolites (M5 and 5-OH-pentyl-ADB) to mass spectrum databases used for toxicological screening in order to reduce the risk of false-negative results in intoxication cases involving 5F-ADB.

Objectives: Older (aged 50+) cannabis users are growing in numbers, but research on poison control center (PCC) cases has not focused on them. In this study, we examined: (1) changing trends in cannabis forms reported in PCC cases; (2) demographic and clinical factors associated with different cannabis forms; and (3) associations between cannabis forms and medical outcomes., Methods: We used the American Association of Poison Control Centers' National Poison Data System (NPDS), January 1, 2009-December 31, 2019, to examine the 5201 cases aged 50+ in which cannabis was the only or primary substance. Following descriptive analyses, multinomial logistic regression was fit to examine associations of three cannabis forms (dried/undried plant, other preparations, and synthetic cannabinoids/e-cigarettes for cannabis delivery) with cases' demographic and clinical characteristics, and binary logistic regression was fit to examine associations of medical outcomes (major/potentially major vs. nonmajor) with cannabis forms., Results: Cannabis-related cases involving older adults increased 18-fold (from 61 to 1074) between 2009 and 2019. Compared to plant forms, other preparations had 51.24 times greater odds of appearing in 2018-2019 than in 2009-2011 (95% CI = 27.74-94.67), and synthetic cannabinoids/e-cigarettes had 2.19 times greater odds of appearing in 2014-2015 (95% CI = 1.64-2.93) but lower odds of appearing in 2016-2017 (RRR = 0.67, 95% CI = 0.50-0.89). Other preparations were positively associated with older age, adverse reactions, and suicide attempts but negatively associated with medical cannabis legal states. Synthetic cannabinoids/e-cigarettes were positively associated with being male, intentional misuse/abuse, and chronic use. Compared to plant forms, major medical outcomes/death were less likely among those who used other preparations (OR = 0.75, 95% CI = 0.56-0.99) but more likely among those who used synthetic cannabinoids/e-cigarettes (OR = 2.07, 95% CI = 1.60-2.66)., Conclusions: Although PCC cannabis cases involving older adults are relatively few, cases of other cannabis preparations than plant forms increased rapidly in recent years while cases of synthetic cannabinoids decreased. The rate of major medical outcomes also appears to be high.

Introduction: Synthetic cannabinoids (SCs) are the largest and most diverse group of new psychoactive substances. Their influence on organism is unpredictable and often lead to intoxications, including fatal poisonings. The interpretation of blood concentrations of detected SC although complicated, can help to determine the effects of an administered drug. The interpretation of one's own results usually requires a comparison to previously published cases, therefore, a referenced compilation of concentration ranges would be useful., Material and Methods: The data collection was based on a search of PubMed and Google search engine. All the available data from articles and reports where SCs concentrations have been measured in whole blood, serum or plasma were included in the data analysis., Results: Presented table lists the observed concentrations in fatal and non-fatal cases involving 65 SCs. A reference list with original papers has been added for each compound, which makes it easy to find the source data., Conclusion: The observed concentrations of SCs vary widely and often have overlapping ranges for fatal and non-fatal cases. Conclusions regarding the cause of death are difficult based upon the concentrations alone and should include knowledge of the clinical situation in each case.

Objective: The objective of this study was to characterize the clinical picture and management of synthetic cannabinoid exposure in a cohort of adolescents., Methods: Using the 45 participating sites of the Toxicology Investigators Consortium Registry, a North American database, we conducted an observational study of a prospectively collected cohort. We identified all adolescent (12-19 years) cases of synthetic cannabinoid exposure who have received medical toxicology consultation between January 2012 and December 2016. Clinical and demographic data were collected including age, sex, circumstances surrounding exposure, coingestants, clinical manifestations, treatment, disposition, and outcome., Results: We identified 75 adolescents who presented to the emergency department with synthetic cannabinoid exposure. Most were male (91%) and between the ages of 16 and 19 (66%). The most common symptoms were neuropsychiatric with 50 adolescents (67%) exhibiting central nervous system (CNS) manifestations. There was no predominant toxidrome, and 9 patients (12%) were mechanically ventilated. Mainstay of treatment was supportive care. No deaths were reported., Conclusions: Synthetic cannabinoid exposure in adolescents is primarily characterized by CNS manifestations, which are varied and may be life-threatening. Frontline caregivers should maintain a high index of suspicion for synthetic cannabinoids, especially in adolescents who present with unexplained CNS manifestations, as there is no specific toxidrome or confirmatory rapid drug screen to detect them., Competing Interests: Declaration of interest: The authors report no conflicts of interest., (Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.)

The increase of available synthetic cannabinoids poses an emerging public health threat worldwide. Synthetic cannabinoid use has been mainly reported in adolescent cases in pediatric practices; there are few reported cases involving infants affected by unintentional use. In this case report, we present the youngest age of synthetic cannabinoid bonzai exposure in the literature, discussing a 3-month-old child affected by exposure to the parents' use of bonzai in the home environment. Because unintentional exposure to synthetic cannabinoids like bonzai might be encountered, pediatric emergency teams should be aware of this condition and child protection teams should be informed of suspicions of child negligence and abuse as a part of the medical approach.

Between March 2017 and November 2018, 54 prisoner fatal overdose cases submitted to the University of Florida Forensic Toxicology Laboratory involved synthetic cannabinoids including 5F-ADB, FUB-AMB, 5F-AMB, MDMB-FUBINACA and AB-CHMINACA. Analysis of blood and urine samples was performed at NMS Labs (Horsham, PA) by liquid chromatography/tandem mass spectrometry screening, confirmatory and quantitative methods validated according to Scientific Working Group for Forensic Toxicology guidelines. This work highlights the importance of effective communication between toxicologists and medical examiners/coroners, and the value of public-private partnerships to provide coverage while laboratories work to update instrumentation and validate their own new methods to keep up with the challenges of emerging substances., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Increasing use of cannabis for medical and recreational purposes has augmented concerns about associated poisoning, and specifically pediatric and adolescent poisonings. Synthetic cannabinoids, often marketed as cannabis replacement, have recently emerged and knowledge and awareness of their toxic effects is growing. The objective of this study was to characterize and compare cannabinoid poisonings (medical and recreational cannabis, and synthetic cannabinoids) in Israel during the period 2007-2018., Methods: The three types of cannabinoid exposures reported to the Israel Poison Information Center (IPIC) between 2007 and 2018 were identified. Differences in distribution of the three types of agents with respect to demographic and clinical factors were examined using univariate statistics, and time trends were plotted., Results: Out of the total 615 poison-exposure cases identified, 55% were recreational cannabis cases, 33% were synthetic cannabinoid cases and 12% were medical cannabis cases. Compared to recreational cannabis exposures, synthetic cannabinoid exposures were more likely to be male, to have both gastrointestinal and cardiovascular manifestations and less likely to be called in by the public as opposed to called in by health care professionals and less likely to be treated on-site. Medical cannabis exposures were less likely to be male, more likely to be called in by the public, less likely to present with co-use of other substances and more likely to have gastrointestinal manifestations. Throughout the study period an increase in exposure cases were observed for medical and recreational cannabis cases, whereas synthetic cannabinoid cases showed an increase until 2014 and then a steep decrease., Conclusions: Despite the low toxicity of different types of cannabinoids, training of physicians and other health care professionals related to cannabinoid poisoning is important. This is particularly important in jurisdictions where legal access to cannabis is becoming increasingly available., Competing Interests: Conflict of Interest Statement The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The unpredictable physiologic and pharmacologic effects of synthetic cannabinoids (SCs) are continuously changing as the chemical structure of SCs evolve to avoid classification as a Schedule I drug under the Controlled Substances Act in the U.S. This results in unpredictable pharmacologic effects and subsequent sequelae. Little is known about national or regional trends of SC clusters. The objective of this study is to investigate trends in SC exposure using emergency department (ED) syndromic data., Methods: We analyzed ED syndromic data to detect quarterly trends from January 2016 through September 2019 for SC-related exposures within 59 jurisdictions in 47 states by U.S. region. Pearson chi-square tests detected quarter-to-quarter changes and Joinpoint regression assessed trends over time., Results: From January 2016 to September 2019, 21,714 of 303.5 million ED visits involved suspected SC exposures. Nationally, SC-related exposures decreased by 1.9 % (p = .04) on average per quarter, yet exposures increased in the Midwest by 6.3 % (p = .002) and in the Northeast by 3.2 % (p = .03) on average per quarter, and decreased on average per quarter by 7.7% (p ≤ .001) in the Southeast and 11.4 % in the West (p ≤ .001). Known SC exposures that may align with clusters were identified in quarter-to-quarter monitoring., Conclusions: Only a small proportion of ED visits were related to suspected SC exposure. Although we did identify a small decrease in national SC exposures, there was wide variation by region. Additional efforts are needed to understand variation and to develop prevention and response strategies., (Published by Elsevier B.V.)

Cannabinoid hyperemesis syndrome (CHS) is characterized by severe cyclical nausea, vomiting, and abdominal pain relieved by compulsive hot water bathing in the setting of chronic cannabinoid use. This article reviews the characteristics, proposed pathophysiology, treatment modalities, and role of nurses caring for patients with CHS.

5F-ADB (methyl 2-{[1-(5-fluoropentyl)-1H-indazole-3-carbonyl]amino}-3,3-dimethylbutanoate) is a frequently abused new synthetic cannabinoid that has been sold since at least the end of 2014 on the drug market. It has been classified as an illicit drug in most European countries, and also in Turkey, Japan, and the United States. In this study, 5F-ADB and its methyl ester metabolite were determined in the blood and urine samples taken from fatal cases using liquid chromatography-highresolution mass spectrometry (LC-HRMS). The extraction of samples was performed using a solid-phase extraction method, followed by LC-HRMS analysis. The method was fully validated for linearities, limits of detection (LODs), limits of quantification (LOQs), recoveries, matrix effects, process efficiencies, accuracies, precisions, and stabilities and was applied to 70 blood and 36 urine samples from fatal cases where 5F-ADB was the only drug detected. The LODs were between 0.08 and 0.10ng/mL, and LOQs were between 0.10 and 0.12ng/mL for both blood and urine samples. 5F-ADB and its methyl ester hydrolysis metabolite were found at the blood concentrations ranging from 0.10 to 1.55ng/mL (mean=0.40ng/mL) and 0.15 to 23.4ng/mL (mean=2.69ng/mL), respectively. 5F-ADB was not detected in any urine samples. 5F-ADBmethyl ester hydrolysis metabolite was detected in 35 urine samples with a detection range of 0.28-72.2ng/mL and a mean of 9.02ng/mL. The synthetic cannabinoid 5F-ADB and its methyl ester metabolite were identified and quantified in authentic human blood and/or urine specimens obtained from 70 fatal cases. The method was successfully applied to postmortem blood and urine samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

5F-ADB is an indazole-based synthetic cannabinoid. In recent years, it has been detected in legal high products as well as in biological samples and is associated with serious adverse health, behavioral effects and even death. Due to the fast pace of the market of synthetic cannabinoids, data on such newly appearing substances are scarce. As pharmacological properties are often investigated in vitro or by using animal experiments, reports on synthetic cannabinoid findings in human samples along with corresponding case history descriptions are valuable for the interpretation of upcoming routine cases. Herein we report five cases with verified 5F-ADB consumption, including three fatalities, a case of driving under the influence of drugs as well as a case of grievous bodily harm. In four cases, 5F-ADB could be detected in blood or plasma. Concentrations were in the range of 0.11-0.57 μg/L. In one instance 5F-ADB consumption was verified by the detection of 5F-ADB metabolites in postmortem body fluids. The described cases illustrate various adverse effects including confusion (possibly even psychosis), collapse, loss of consciousness, unsafe driving style or changing moods that might be attributed to 5F-ADB., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In Hungary, N-ethyl-hexedrone (NEH) was the most frequently seized stimulant designer drug in 2017, while among synthetic cannabinoids ADB-FUBINACA and AB-FUBINACA were the most popular. Symptoms of intoxication by these substances are well known but less is known about the pathology of overdose-related death. NEH-induced fatal intoxication has not been described in the literature and knowledge surrounding the particular circumstances of death could be useful better public education of risk and more adequate treatment of overdose patients. In this report, we characterize the case of a 23-year-old male regular drug user who died a few hours after NEH and ADB-FUBINACA consumption. His medical history showed arrhythmia in childhood, and some seizures. Autopsy found he had a BMI of 42.9, a hypertrophic and dilated heart, severe atherosclerosis of the valves, coronaries and the arteries, and edema of the internal organs. Histology confirmed those findings. Postmortem blood levels of NEH were 285 ng/ml, along with 0.08 ng/ml ADB-FUBINACA and five ADB-FUBINACA metabolites. Based on the blood concentrations measured in suspected drug users (≤83.9 ng/ml) we hypothesize that NEH intoxication was the cause of death in this case, with heart disease being a co-factor and that the synthetic cannabinoid effect might have been accompaniment. This case also offered the opportunity to identify the metabolites of ADB-FUBINACA in the blood. We identified metabolites in the post-mortem blood by comparing them to human liver microsomal enzyme metabolites in vitro. Three major and two minor metabolites were found in the blood, of which two could only be derived from ADB-FUBINACA, as opposed to other cannabinoids. The case highlights the importance of the complex analysis of drug related deaths by medico-legal autopsy, histopathology and toxicology., (Copyright © 2019. Published by Elsevier Ltd.)

Recent multistate outbreaks of coagulopathy caused by brodifacoum-tainted synthetic cannabinoids or "fake weed" highlight the public health impact of long-acting anticoagulant rodenticides (LAARs). Patients presenting with this syndrome have had recent exposure to synthetic cannabinoids, evidence of isolated vitamin K antagonism with or without bleeding, and detectable levels of brodifacoum and other LAARs in circulation. This article will provide information on synthetic cannabinoids, LAARs, and coagulopathic manifestations arising from use of adulterated synthetic cannabinoids and their management., (© 2019 by The American Society of Hematology.)

Cannabinoids are the most commonly abused illicit drugs worldwide. While cannabis can be beneficial for certain heath conditions, abuse of potent synthetic cannabinoids has been on the rise. Exposure to cannabinoids is also prevalent in women of child-bearing age and pregnant women. These compounds can cross the placental barrier and directly affect the fetus. They mediate their effects primarily through G-protein coupled cannabinoid receptors, CB1 and CB2. In addition to significant neurological effects, cannabinoids can trigger robust immunomodulation by altering cytokine levels, causing apoptosis of lymphoid cells and inducing suppressor cells of the immune system. Profound effects of cannabinoids on the immune system as discussed in this review, suggest that maternal exposure during pregnancy could lead to dysregulation of innate and adaptive immune system of developing fetus and offspring potentially leading to weakening of immune defenses against infections and cancer later in life. Emerging evidence also indicates the underlying role of epigenetic mechanisms causing long-lasting impact following cannabinoid exposure in utero.

Purpose: To report the first case of a patient with bilateral multiple exudative retinal detachments and macular edema after smoking Bonzai., Methods: A 17-year-old girl presented with a complaint of a sudden onset of reduced vision in both eyes. She was admitted to the emergency service 3 days ago with the symptoms of hallucination and convulsion and diagnosed with synthetic cannabinoid intoxication., Results: After consultation with an internal medicine specialist, intravenous fluid treatment was initiated. Laboratory findings resolved rapidly and recovery of fundus findings was achieved at 6 months of follow-up., Conclusions: Synthetic cannabinoid abuse has been increasing in young populations in recent years and has become an important health concern. It is important for health providers to be aware of ocular signs and symptoms of intoxication.

Background: Synthetic cannabinoid intoxication has become difficult to diagnose and manage in the United States, in part due to varying clinical effects within this heterogeneous group of compounds., Case Report: A 38-year-old man was admitted with altered mental status and bradycardia. He demonstrated progressive encephalopathy, seizure activity, second-degree atrioventricular block type I, respiratory failure, hypotension, hypothermia, and hypoglycemia. A computed tomography scan of the abdomen and pelvis revealed multiple packages in the patient's stomach and rectum. Multiple attempts at gastrointestinal decontamination were unsuccessful. On hospital day 8 the patient developed hypertensive emergency and was taken to the operating room for exploratory laparotomy. Twenty-two poorly wrapped packages were removed from the bowel. Postoperatively the patient demonstrated both generalized and focal seizure activity. His mental status slowly returned to baseline over the period of about 1 week and he was ultimately discharged without neurological sequelae after 1 month. Analysis of patient serum, urine, and plant matter from the packages identified cannabis and 2.N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The case presented demonstrates the suspected toxidrome associated with severe ADB-FUBINACA intoxication, including mental status depression, bradycardia, autonomic instability, seizure, hypoglycemia, and hypothermia. Although the patient had simultaneous exposure to cannabis, his constellation of symptoms is not consistent with cannabis intoxication. A previous animal model supports the potential of this specific synthetic cannabinoid to cause the reported toxidrome., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Synthetic marijuana is a dangerous substance due to its potency, ever-changing composition, and unpredictable side effects. Recently, brodifacoum-contaminated synthetic marijuana has led to multiple deaths and morbidity throughout the USA from severe coagulopathy associated with use of this strain of the drug (brodifacoum is a rodenticide and potent Vitamin K antagonist/anticoagulant). We describe the clinical and radiologic findings in two patients who were diagnosed with, and treated for, ingestion of this new strain of synthetic marijuana. The radiologic manifestations were most notable for hemorrhagic pyelitis/ureteritis. Both patients required hospitalization with Vitamin K supplementation. The radiologic and clinical pictures in these patients are important for radiologists to recognize in order to help guide appropriate patient management.

We report a case of intoxication with a mixture of three synthetic cannabinoids and a synthetic cathinone, which have been disclosed by a highly sensitive progressing technology. A man was found dead, and his forensic autopsy was performed at our department. After further examinations of his specimens, EAM-2201 and α-PVP have been newly found in his lung. The concentrations of EAM-2201 have not been reported yet in any authentic human specimens although its existence (not quantified) in blood was reported in 2015. Therefore, a sensitive quantitation method of these compounds in blood and solid tissues has been devised using the sensitive instrument. The limits of detection of these compounds were in the range of 3-10 pg/ml with their quantification range of 10-1000 pg/ml in blood. The femoral vein blood levels of EAM-2201 and AB-PINACA were 56.6 ± 4.2 and 12.6 ± 0.1 pg/ml, respectively, and AB-FUBINACA could be detected but not quantifiable in the blood specimens; α-PVP could not be detected. The standard addition method was employed for the quantification of these compounds in the lung, liver and kidney specimens. The lung levels of EAM-2201, AB-PINACA, AB-FUBINACA and α-PVP were 348 ± 34, 355 ± 30, 124 ± 12 and 59.0 ± 7.4 pg/g, respectively. In conclusion, in this study, the concentrations of EAM-2201 in authentic human specimens including blood and solid tissues and those of AB-PINACA and AB-FUBINACA in solid tissue specimens were quantified for the first time to our knowledge., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Although the past few years have seen a significant increase in the use of synthetic cannabinoids, very few fatalities have been reported whereby synthetic cannabinoids have contributed or were solely responsible for the death of an individual. We report a rapid death of an individual following ingestion of 5 F-PB-22 and 5 F-AKB-48. Case information and autopsy findings are presented. Post-mortem blood samples were obtained and 5 F-PB-22 and 5 F-AKB-48 were detected along with 311 mg/100 ml alcohol. The cause of death was certified as the effects of a combination of alcohol and synthetic cannabinoids (5 F-PB-22 and 5 F-AKB-48)., (Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

This article describes the characteristics of individuals who used synthetic cannabinoids and the changes in the user population over time. Data sources include treatment admissions with a primary problem with synthetic cannabinoids reported to the Texas treatment dataset, synthetic cannabinoid exposures reported to the Texas Poison Center Network, and items identified in the National Forensic Laboratory Information System in 2009-2016. Statistically significant trends were identified for race/ethnicity, gender, age, education level, employment status, homelessness, criminal justice problems, use of other substances, lag time between first use and time to treatment, exposure site, chronicity, reason for exposure, and the most common types of cannabinoids. Comparisons were made between the years and the variables in the datasets. Findings suggest that the characteristics of synthetic cannabinoid users and the varieties of these drugs in Texas have changed over time. Data to link individual cases with the changing results of toxicological analysis are needed, as well as targeted prevention and treatment efforts for an aging population who may be at risk of homelessness and also have co-morbid substance use and psychiatric problems.

Tens of thousands of ED visits each year are related to synthetic psychoactive drug intoxication. Signs, symptoms, and treatment of toxicity with synthetic cathinones, synthetic cannabinoids, or dextromethorphan overlap greatly and can be challenging. This article describes signs and symptoms of psychoactive drug abuse and how to properly manage these symptoms.

Introduction: In 2014, the "European Monitoring Centre for Drugs and Drug Addiction" (EMCDDA) reported on 30 novel synthetic cannabinoids (SCs). Among these were indole- and indazole-based valine derivatives with a cyclohexylmethyl side chain (e.g., AB-CHMINACA and MDMB-CHMICA), which represent a new class of SCs., Methods: A prospective observational study of patients treated in emergency departments (EDs) after the intake of SCs was conducted. Clinical and laboratory data were combined and reported to a poison control centre. Serum and/or urine samples of ED patients were analyzed using LC-MS/MS., Results: Forty four patients (39 male, five female, 12-48 years) were included. AB-CHMINACA (MDMB-CHMICA) was identified in 20 (19) serum samples, and in 21 (25) urine samples, respectively. In 19 of the cases, more than one SC was present. Other psychoactive substances (mainly amfetamines) were identified in seven cases, but in five out of these in urine samples only. Based on the Poison Severity Score, severity of poisoning was minor (4), moderate (31) or severe (9). Most frequently reported neuropsychiatric symptoms were CNS-depression (n = 21, 61%), disorientation (n = 20, 45%), generalized seizures (n = 12, 27%), combativeness (n = 8, 18%) and extreme agitation (n = 7, 16%). Duration of symptoms lasting 24 hours or longer occurred in 15 cases (34%)., Discussion: The prevalence of certain neuropsychiatric symptoms was higher in our study than in former reports after the intake of SCs of the aminoalkylindole-type (first generation) SCs. In addition, severe poisoning and duration of symptoms were also higher., Conclusions: In this study, the valine derivative AB-CHMINACA and the tert-leucine derivative MDMB-CHMICA ("third generation of SCs") seem to be associated with more severe clinical toxicity than was previously reported in patients exposed to earlier generation SCs such as JWH-018. However, this observation needs to be confirmed with a larger cohort of patients with analytically confirmed abuse of third generation SCs. The rapid turnover of SCs on the drug market together with the occurrence of SCs such as AB-CHMINACA and MDMB-CHMICA is alarming, especially because of the unexpectedly high frequency of neuropsychiatric symptoms.

Competing Interests: No conflicts of interest were reported.

Competing Interests: No conflicts of interest were reported.

Aim: This study aims to evaluate the serum S100B levels to predict neuronal damage and poor clinical outcomes associated with the use of synthetic cannabinoids., Method: Thirty patients identified as synthetic cannabinoid users and 30 healthy controls were included in the study. S100B levels were compared between healthy controls and synthetic cannabinoid users. The following were considered to be composite outcomes: the need for endotracheal intubation, incidence of seizures, the need for intensive care unit admission, and in-hospital mortality. Clinical and laboratory findings associated with composite clinical outcomes were examined., Results: The mean S100B level was 19.3 (95% CI: 17.7 to 21.4) pg/mL in patients who use synthetic cannabinoid, and 15.9 (95% CI: 15 to 16.9) pg/mL in the controls; mean df: -3.6 (95% CI: -5.6 to -1.6). In patients with and without composite clinical outcomes, the mean S100B level measured 24.5 (95% CI: 21.2 to 27.9) pg/mL and 17.4 (95% CI: 15.8 to 18.4) pg/mL, respectively; mean df: -7.4 (95% CI: -10.2 to -4.6). With the cut-off value for S100B set at 20pg/mL based on the highest sensitivity, the sensitivity, specificity, PPV, and NPV for S100B were 89.9%, 52.0%, 44.4%, and 91.9%, respectively; odds ratio: 13.2, 95% CI (2.1 to 28.1)., Conclusion: Our data suggest that serum S100B levels are elevated in patients using synthetic cannabinoids. These results show that S100B can help clinicians stratify risk or may have a role in excluding those with neuronal damage., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Context: Despite widespread use of diverse synthetic cannabinoid (sCB) compounds, the pathophysiology associated with intoxication with many sCB compounds, including AB-CHMINACA, is poorly understood, as is their metabolism and distribution into blood and organs., Case Details: A young man died shortly after ingesting an herb product containing sCB compounds. Toxicological analyses of blood samples revealed high levels of AB-CHMINACA (7.61 ± 0.59 ng/mL) and its metabolites (M2, 56.73 ± 4.16 ng/mL; M4, 2.29 ± 0.14 ng/mL) and trace amounts of 5-fluoro-AMB, FUB-PB-22, and AB-FUBINACA. The autopsy revealed severe pulmonary edema, and histology showed air bubbles in the alveolar effusion, suggesting rapid progression of edema. Low blood levels of N-terminal pro-brain natriuretic peptide excluded cardiogenic pulmonary edema. Histological examination revealed diffuse neuronal (brain) and myocardial (sub-endocardial) hyper-eosinophilia, indicating hypoxic encephalopathy and systemic hypoxemia, respectively., Conclusions: The findings show that AB-CHMINACA induced rapid progression of pulmonary edema resulting in hypoxic encephalopathy and systemic hypoxemia, possibly through severe seizures. The high blood ratio of the M2 metabolite to the parent compound, AB-CHMINACA, demonstrates rapid metabolism. This highlights the usefulness of quantification of M2 in diagnosing AB-CHMINACA intoxication.

A 39-year-old man died of multi-organ failure complicating mixed drug toxicity that included methadone, oxazepam, oxycodone and nitrazepam. His past medical history involved alcohol and poly-substance abuse with chronic self-harm and suicidal ideation. There had been multiple hospital admissions for drug overdoses. At autopsy the most unusual finding was of two packages of 10 tablets each, wrapped in thin plastic film within the rectum. The insertion of drugs into body orifices and cavities has been termed body pushing to distinguish it from body packing where illicit drugs are wrapped and swallowed for transport and smuggling, and body stuffing where small amounts of loosely wrapped or unwrapped drugs are swallowed to conceal evidence from police. This case demonstrates that body pushing may not always involve illicit drugs or attempted concealment from police or customs officials. It appears that the drugs had been hidden to ensure an additional supply during the time of residence in hospital. The extent to which body pushing is currently being used by patients to smuggle drugs into secure medical facilities is yet to be determined.

Background: Cannabis is the most widely used illicit drug in the United States and Europe. In recent years, a range of new substances with cannabis-like effects-known as synthetic cannabinoids (SCs)-have suddenly burst on the drug scene. However, there is limited information about the clinical hazards linked to the use of these emerging substances. This review summarizes the literature to date relating the health effects of SCs., Method: A systematic literature review of original case studies was performed using PubMed and Web of Science (January 1980-July 2015). Only articles in which a drug screening was reported were included in this review., Results: Forty-six articles meeting the inclusion criteria were included in this review, reporting data on 114 patients who went to hospital emergency departments after exposure to SCs. The majority of patients were adolescent or young adult males (14-25 years; 24.5 ± 10.1 years). The most common route of administration was smoking. The SCs most involved were John William Huffman (JWH) derivatives, followed by XRL-11, ADB-PINACA, AM-2201, MAM-2201, and 5F-PB-22. This analysis showed that the use of these substances may cause minor and moderate side effects similar to those of cannabis intoxication, including tachycardia, nausea, somnolence, hallucinations, paranoia, xerostomia, and injected conjunctivae among others. However, atypical cannabis intoxication effects and worse complications (such as renal injuries, aggressiveness, cerebral ischemia, myocardial infarction, etc.) were also observed, which led to a significant morbidity were also observed. Some SCs were highlighted as being involved in 24 cases of deaths., Conclusions: In this review, the nature and frequency of the signs and symptoms of SC poisoning were estimated in order to inform health professionals about the health risks of these new and emerging substances.

Introduction: Synthetic cannabinoid (SC) abuse has resulted in numerous outbreaks of severe clinical illness across the United States over the past decade. The primary objective of this study was to determine the clinical characteristics of patients abusing SC requiring bedside consultation by medical toxicologists., Methods: This was a multicenter analysis from a prospectively collected cohort of patients presenting to medical care after synthetic cannabinoid exposure, utilizing the ToxIC Registry. Management of cases by medical toxicologists in this cohort occurred in emergency departments, inpatient medical floors, and intensive care units. Cases were identified from January 5, 2010 - July 31, 2015. We characterized the clinical presentations, treatments, outcomes, and sociologic factors associated with SC use in these patients., Results: Medical toxicologists participating in the ToxIC Registry cared for 39,925 cases between 2010 and 2015. Three hundred fifty three of these cases were determined to be SC toxicity. The median age of patients was 25 (IQR: 18, 36) and the majority were males (84%). The most common symptoms were agitation, delirium and toxic psychosis, n=146 (41%). Forty-four (12.5%) had heart rates above 140 beats per minute. Bradycardia was the second most commonly reported severe vital sign abnormality with 20 (5.7%) having heart rates of less than 50 beats per minute. Fifteen (4.2%) patients had hypotension. Fifty-nine (17%) had seizures. The most common pharmacologic treatment provided was benzodiazepines (n=131, 37%) followed by antipsychotics (n=36, 10%).Disposition was available for 276; of these 167 (61%) were managed in the emergency department, 42 (15%) were admitted to the hospital floor, and 67 (24%) were admitted to the ICU., Conclusions: Synthetic cannabinoids are associated with severe central nervous system and cardiovascular effects.

Background: The emergence of new psychoactive substances (NPS), including synthetic cannabinoid receptor agonists (SCRAs) poses novel challenges for drug regulation and public health. Misconceptions of safety and legality, coupled with the fact that NPS are undetectable on routine drugs screens contributes to their popularity. Concerns over the unpredictable toxicity and abuse potential of NPS has led to a variety of legislative responses worldwide. We wish to describe Australian trends in SCRA use, examining the effects of legislative changes on calls to Australia's largest poisons centre., Methods: A retrospective review of calls to the New South Wales Poisons Information Centre (NSWPIC). Cases occurring between 1 January 2010 and 30 June 2015 with documented use of SCRAs were included., Results: There were 146 exposures to SCRAs recorded in the NSWPIC database. Federal bans of specific SCRA compounds in 2011/2012 had little impact on call volumes. State-based legislation introduced in 2013 banning specific brand names of SCRA products was followed by a dramatic, sustained decrease in exposures. The most common symptoms reported with SCRA use were tachycardia, vomiting, drowsiness, anxiety/panic, decreased level of consciousness, chest pain, agitation, hallucinations, confusion, seizures and hypertension., Conclusion: Banning of specific brand names of SCRA (timed with raids and social media campaigns) appears effective at reducing SCRA exposures. We postulate that this raised awareness within the community of the illegality of these substances while also reducing supply through bricks-and-mortar shops. These results could help inform future legislative responses., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We report a case of mild cannabinoid poisoning in a preschool child, after 3-week ingestion of hemp seed oil prescribed by his pediatrician to strengthen his immune system. The patient presented neurological symptoms that disappeared after intravenous hydration. A possible mild withdrawal syndrome was reported after discharge. The main metabolite of Δ-tetrahydrocannabinol was detected in urine, and very low concentration of Δ-tetrahydrocannabinol was detected in the ingested product. This is, as far as we know, the first report of cannabinoid poisoning after medical prescription of hemp seed oil in a preschool child.

Context: Synthetic cannabinoids are getting more popular among young people and illicit manufacturers. We report a case series of occupational transdermal poisoning with synthetic cannabinoids., Case Details: Three customs inspectors got in contact with a sticky substance with their fingertips because they were not wearing protection gloves and the delivered package was damaged. Despite washing their hands with water, signs of synthetic cannabinoids intoxication started occurring half an hour after exposure. On arrival at the Emergency Department six hours later, they were somnolent, lethargic and confused. They showed signs of mydriasis, blurred vision, ataxia, weakness, numbness, tachycardia and one of them had orthostatic hypotension. Two days later, they were feeling much better and reported amnesia and slowed perception of time after exposure. Toxicology analysis by LC-MS/MS revealed synthetic cannabinoid cumyl-PINACA (SGT-24) in their blood samples taken on admission. cumyl-PINACA was also confirmed with NMR method in liquid samples seized at the airport. It was 98% pure substance with the purpose of being diluted and sold further in the drug market by drug dealer., Discussion: This case series highlights the possible transdermal exposure to synthetic cannabinoids oil resulting in prolonged cannabinoid syndrome.

In the early 2000s in Europe and shortly thereafter in the USA, it was reported that 'legal' forms of marijuana were being sold under the name K2 and/or Spice. Active ingredients in K2/Spice products were determined to be synthetic cannabinoids (SCBs), producing psychotropic actions via CB 1 cannabinoid receptors, similar to those of Δ 9 -tetrahydrocannabinol (Δ 9 -THC), the primary active constituent in marijuana. Often abused by adolescents and military personnel to elude detection in drug tests due to their lack of structural similarity to Δ 9 -THC, SCBs are falsely marketed as safe marijuana substitutes. Instead, SCBs are a highly structural diverse group of compounds, easily synthesized, which produce very dangerous adverse effects occurring by, as of yet, unknown mechanisms. Therefore, available evidence indicates that K2/Spice products are clearly not safe marijuana alternatives., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Sixty-one autopsy cases involving cathinones and/or cannabinoids (synthetic cathinones/cannabinoids) use have been reported. However, little is known about the demographics and autopsy findings in fatal synthetic cathinones/cannabinoids users., Objectives: To elucidate demographic and autopsy findings (i.e. major organ pathology and causes of death) in synthetic cathinones/cannabinoids cases., Methods: We reviewed forensic autopsy reports in Department of Legal Medicine of Tokyo Women's Medical University (Tokyo, Japan) between 2011 and 2015 (a total of 359). We compared demographic and autopsy findings between synthetic cathinones/cannabinoids and methamphetamine cases (as control subjects)., Results: There were 12 synthetic cathinones/cannabinoids cases and 10 methamphetamine cases. Synthetic cathinones/cannabinoids users were significantly younger than methamphetamine users (p < 0.01), and there were no cases that used both synthetic cathinones/cannabinoids and methamphetamine. Acute intoxication and cardiac ischemia were the two most prominent causes of death in both synthetic cathinones/cannabinoids users and methamphetamine users. Excited delirium syndrome and pulmonary aspiration were found only in synthetic cathinones/cannabinoids cases., Conclusions: The populations of synthetic cathinones/cannabinoids and methamphetamine users who died of an overdose are different in Japan. Acute intoxication, cardiac ischemia, excited delirium syndrome, pulmonary aspiration, and drowning are the major autopsy findings in synthetic cathinones/cannabinoids-related death. Clinicians shuld be aware of these potentially fatal complications in the medical management of synthetic cathinones/cannabinoids users.

We report on a case of intoxication with a mix of new psychoactive substances. A 38-year-old male was brought to the emergency department (ED) following the ingestion of an unknown drug in a suicide attempt. During the transport, he became progressively more somnolent and unresponsive to painful stimuli. Urine and stomach content were collected on admission to be screened for drugs of abuse and medicinal drugs. After admission, the patient's next of kin presented five small grip seal plastic bags containing different powders/crystals, and they were sent for analysis along with urine and stomach content to the toxicology laboratory. An easy and rapid sample preparation technique was applied for the extraction of urine and stomach content. Samples were extracted with liquid-liquid extraction (LLE) technique and analysed using gas chromatography-mass spectrometry (GC-MS). A small amount of powder material from the bags was diluted in methanol and injected directly into the GC-MS instrument. Obtained spectra (EI) were evaluated against SWGDRUG library. Five different designer drugs were identified in the powder material, including synthetic cannabinoids (AB-CHMINACA, AB-FUBINACA) and synthetic cathinones (alpha-PHP, alpha-PVP and 4-CMC). With the exception of 4-CMC, all of these substances were also detected in the stomach content along with the prescription drugs. This is the first time that a positive identification of these five drugs has been made by a clinical laboratory in Slovenia., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)