Near-Fatal Spice Intoxication of a Toddler.

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.

Involuntary 5F-ADB-related intoxication following e-cigarette use.

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.

Synthetic Cannabinoid Exposure in Adolescents Presenting for Emergency Care.

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.

Cannabis and synthetic cannabinoid poison control center cases among adults aged 50+, 2009-2019.

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.

Blood concentrations of synthetic cannabinoids.

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.

Brodifacoum Poisoning Linked to Synthetic Marijuana Use in Wisconsin.

INTRODUCTION: Recent outbreaks of brodifacoum-induced coagulopathy resulting from the use of synthetic cannabinoids represents a growing public health concern. Brodifacoum is a commonly used and commercially available rodenticide that has anticoagulant properties. As new, unregulated synthetic cannabinoids enter the market, the potential for further outbreaks continues to rise. CASE PRESENTATION: We report a case of severe bleeding secondary to inhalation of synthetic cannabinoids contaminated with brodifacoum. The patient had been evaluated for several months of ongoing, unexplained vaginal bleeding and developed hematemesis and rectal bleeding 2 weeks after her last reported use. DISCUSSION: There have been previous reports of hemorrhage after exposure to synthetic marijuana in rare cases, including an outbreak of severe bleeding and reported synthetic marijuana use in the Midwestern region of the United States in 2018. CONCLUSION: While hemorrhaging after exposure to synthetic cannabinoids has been reported previously, we use this case to increase awareness of the potentially deadly exposures to brodifacoum from synthetic cannabinoids use in Wisconsin. By increasing awareness, emergency department physicians and state agencies can collaborate more effectively when responding in these cases.

Cannabis and synthetic cannabinoid exposure reported to the Israel poison information center: Examining differences in exposures to medical and recreational compounds.

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.

Regional trends in suspected synthetic cannabinoid exposure from January 2016 to September 2019 in the United States.

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.

Unintentional Exposure of an Infant to Synthetic Cannabinoid (Bonzai) Related to the Parent's Use.

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.

Case Report: Synthetic Cannabinoid Deaths in State of Florida Prisoners.

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.

Cannabinoid hyperemesis syndrome.

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.

Detection and quantification of 5F-ADB and its methyl ester hydrolysis metabolite in fatal intoxication cases by liquid chromatography-high resolution mass spectrometry.

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.

Mono-/polyintoxication with 5F-ADB: A case series.

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.

Fatal intoxication of a regular drug user following N-ethyl-hexedrone and ADB-FUBINACA consumption.

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.

Bad weed: synthetic cannabinoid-associated coagulopathy.

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.

Bilateral multiple exudative retinal detachments and macular edema in a patient diagnosed with synthetic cannabinoid (Bonzai) intoxication.

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.

Cannabinoid exposure during pregnancy and its impact on immune function.

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.