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Use of synthetic cannabinoids (SCs) in the United States is increasing, as are clusters of cases of serious adverse health effects, including death. Though SC intoxication can be difficult to identify, some steps can be taken to respond more quickly to future outbreaks. Synthetic cannabinoids (SCs) were first created in the 1980s as laboratory research tools (ligands) for studying human endocannabinoid receptor systems. SC-containing products supplied by illicit manufacturers were then marketed throughout Europe as herbal incense, before arriving in the United States in November 2008. The prevalence and variety of SCs on the illicit market have steadily increased over the past 6 years, as manufacturers and distributors of SCs and dealers of SC-containing products have attempted to circumvent federal, state, and local laws. Since 2011, through actions on four separate occasions, the U.S. Drug Enforcement Administration (DEA) has placed a total of . . .

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.

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. [Display omitted]

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.

•Suicide attempt with a mix of synthetic cannabinoids and cathinones is presented.•Intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC.•GC–MS analysis of powder material, stomach content and urine was performed. 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.

•Presentation of five intoxication cases involving 5F-ADB.•Analytical confirmation of 5F-ADB and its metabolites.•Description and discussion of effects probably caused by 5F-ADB. 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.

Synthetic cannabinoid use has risen at alarming rates. This case series describes 11 patients exposed to the synthetic cannabinoid, MAB-CHMINACA who presented to an emergency department with life-threatening toxicity including obtundation, severe agitation, seizures and death. All patients required sedatives for agitation, nine required endotracheal intubation, three experienced seizures, and one developed hyperthermia. One developed anoxic brain injury, rhabdomyolysis and died. A significant number were pediatric patients. The mainstay of treatment was aggressive sedation and respiratory support. Synthetic cannabinoids pose a major public health risk. Emergency physicians must be aware of their clinical presentation, diagnosis and treatment.

Young men in Colorado presented with altered mental status and seizures after ingestion of a synthetic cannabinoid known as “black mamba.” Medical toxicologists and public health and law enforcement officials identified 263 cases of exposure to this novel substance. To the Editor: Although early reports of exposure to synthetic cannabinoids described a benign course, 1 with little need for emergency care, on August 24, 2013, patients began to present to Denver emergency departments with severe symptoms after exposure to a novel synthetic cannabinoid known locally as “black mamba.” The Colorado Department of Public Health and Environment (CDPHE) was notified on September 3. Medical toxicologists and CDPHE epidemiologists developed a case definition and began prospective monitoring with assistance from the Centers for Disease Control and Prevention. Records from poison control centers, care providers in nonhospital settings, and law enforcement were reviewed. . . .

•5F-ADB is regarded as one of the most dangerous synthetic cannabinoids.•5F-ADB is currently the most frequently consumed SC in Turkey.•Seventy 5F-ADB intoxication case reports are presented.•5F-ADB and its metabolite are detected and quantified in blood and urine.•Bucket method is used for inhalation in Turkey. 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.

Synthetic cannabinoids (SC) are chemical substances, which activate cannabinoid receptors in a similar fashion to tetrahydrocannabinol, but with increased efficacy, and are used as illicit recreational drugs. Our objective was to characterize the clinical manifestations and management of three specific, common SC exposures in a cohort of patients presenting to the emergency department of our institution. Retrospective case series of patients admitted to an urban tertiary care center between August 1, 2018 and December 31, 2021, with confirmed SC use and positive urinary immunoassay testing for AB-FUBINACA, 4F-MDMB-BUTINACA and ACHMINACA. 58 patients met inclusion criteria during the 3-year study period; median age was 35 years, 60% were male, 31% patients were exposed to >1 substance, and 31% needed hospital addition. The most common physical signs were cardiovascular (54%) and neuropsychiatric (45%). Severe outcomes included coma and seizures, necessitating intubation in 4 patients, and acute renal injury in 7 patients. SC are potentially harmful drugs of abuse which can lead to life-threatening complications. Acute care personnel should be aware of the broad range of signs and symptoms of SC use. Testing with short turn around times is available to assess SC use.