Synthetic Cannabinoid Intoxication Research Articles

Synthetic cannabinoids impact on cognitive functions

BackgroundSynthetic cannabinoids SC are now becoming progressively popular among young people worldwide; little is known about their negative effects. Anger, anxiety, hallucinations, and perceptual changes were the most common psychoactive findings. Substance abuse causes cognitive impairment (CI). This study’s goal is to raise public awareness about the dangers that synthetic cannabinoid intoxication poses to public health. As well as the magnitude of CI in synthetic cannabinoids in comparison with healthy controls. The study included 30 synthetic cannabinoids SC addicts and 30 healthy people. The Wechsler memory scale (WMS), the Benton visual retention test (BVRT), and Trail Making Test (TMT) A and B were used to assess cognitive functions. Addiction Severity Index (ASI), Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I), and Structured Clinical Interview for DSM-IV Axis II Disorder (SCID II).ResultsUsing BVRT, (96.7%) of the SC use disorder cases had more impaired performance than controls (0%) (P < 0.001). Almost three quarters of the cases had impaired performance on the trail making tests A and B compared to none of the controls (P < 0.001). Similarly, there was a high statistically significant difference between SC use disorder cases and controls in all domains of the WMS. There was no statistically significant correlation between the cognitive scales (BVRT, WMS and TMT) results in relation to age of SC use patients or duration of use.ConclusionsPatients who used synthetic cannabinoids SC were more likely than controls to develop CI, which manifested as impaired visual, auditory, immediate, delayed, and working memory.

Synthetic Cannabinoids (SCs) K2 clinical manifestation-A literature review

IntroductionThere has been an increase in the use of new psychoactive substances containing synthetic cannabinoids in recent years. It is also known as K2, spice, or fake weed, and these are popular as recreational drugs [Kourouni I et al. JAMA NetW Open 2020 Jul; 1;3(7): e208516]. CB1 agonists in SCs mimic the effects of cannabis, making users feel happy and relaxed. However, recreational SCs may result in unwanted severe consequences such as acute anxiety and psychosis [Gunderson EW et al. AM J Addict 2012 Jul-Aug; 21(4): 320-6]. Relative to tetra-hydro cannabinol (THC), synthetic cannabinoids (SCs) are more potent and efficacious agonists and may exert deleterious effects on health [Gunderson EW et al. AM J Addict 2012 Jul-Aug; 21(4): 320-6].ObjectivesOur aim of this review is to focus on the typical presentation of SCs use and help clinicians to better understand and be more vigilant about K2 manifestationsMethodsIn conducting the literature review, only English language articles were selected from PubMed and PubMed Central (PMC) databases through August 14, 2022, using the search term “Synthetic cannabinoids k2 clinical manifestation”. Three reviewers conducted the initial review of the titles and abstracts of the electronic search, followed by detailed assessments of the relevant studies. Peer-reviewed Case series, case reports, and systematic review studies were included that met the inclusion criteria (articles in the English language, studies on humans, studies on synthetic cannabinoids (SC) or K2 use and its clinical manifestations.ResultsElectronic search results showed a total of 60 articles. Fifty articles were excluded based on title review (36 articles), abstract review (4 articles), and full article review (10 articles). Case series on 30 ICU patients (SC intoxication) showed agitation 33%, bizarre behavior, coma 33%, seizure 20%, Acute respiratory failure 60%, Tracheal intubation 70%, Rhabdomyolysis 26%, Invasive mechanical ventilation 40%, Acute kidney injury 26% and cardiotoxic effect [Kourouni I et al. JAMA NetW Open 2020 Jul; 1; 3(7): e208516]. Cross-sectional study on 50 male cases showed altered perception 68%, including auditory and visual hallucination, dizziness and loss of consciousness, palpitation 76%, chest pain 12%, panic attack, and convulsion [Abdelmoneim WM et al. Middle East Current Psychiatry 2022; 29 (1): 24]. Literature reviews has shown the common psychiatric presentations of SC are acute anxiety, agitation, psychosis, paranoia, disorientation, alteration of mood and perception, hallucination, and delusion [Debruyne D et al. Subst Abuse Rehabil. 2015 Oct 20; 6:113-29, Radhakrishnan R et al. Front Psychiatry 2014 May 22;5:54].ConclusionsThere are limited research related to synthetic cannabinoids in human. Based on our review, SC intoxication can be life-threatening besides psychiatric manifestation. Therefore, clinicians must understand the vast clinical manifestations of SCs.Disclosure of InterestNone Declared

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 (0.50µg/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 38h after intoxication. Neither 5F-ADB nor its metabolites could be detected in victim's hair sampled 3months 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 2days 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.

An investigation of the COMT gene Val158Met polymorphism in patients admitted to the emergency department because of synthetic cannabinoid use

Catechol-O-methyl transferase (COMT) enzyme has a role in the inactivation of catecholamine neurotransmitters. Functional polymorphism in the COMT gene has been reported to play an important role in schizophrenia, bipolar affective disorder, aggressive and antisocial behavior, suicide attempts and the pathogenesis of Parkinson’s disease. In this study, we aimed to investigate the effect of the Vall58Met polymorphism of the COMT gene on substance use, and treatment history in patients with synthetic cannabinoid (SC) intoxication. The COMT enzyme Val158Met polymorphisms from DNA of 49 patients who were evaluated in the Emergency Department after SC use and 50 healthy control groups aged 18-45 years, were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses as reported in the literature. Information regarding recurrent intake or hospitalization due to substance use was obtained from hospital records. Wild-type (WT) genotypes in 14 (28.6%) patients, heterozygous genotypes in 25 (51.0%) and homozygous genotypes in 10 (20.4%) patients were detected. Wild-type genotypes The homozygous genotype was found to be significantly higher in patients hospitalized due to drug addiction and substance use (p 0.008). The Vall58 Met polymorphism of the COMT gene was not found to be significant in the first use after substance intake, while a significant relationship was found in terms of this polymorphism in patients with substance addiction diagnosis and treatment history.

A 4-Year Retrospective Analysis of Patients Presenting at the Emergency Department With Synthetic Cannabinoid Intoxication in Turkey

The number of patients with acute synthetic cannabinoid intoxication (SCI) has increased in recent years although the prohibition of its legal sale and use in Turkey despite other countries allowing to some extent sale and use. The reported clinical findings of acute SCI are similar to the symptoms of several diseases. The first case of acute SCI seen in our hospital was in 2014. The aim of this study was to share the data of synthetic cannabinoid use in a research hospital in Turkey and to contribute the epidemiologic data globally betwen 2014 and 2017. A retrospective evaluation was made of patients who presented at emergency department (ED) because of SCI between January 2014 and December 2017. The initial diagnosis of the patients was done either via their self-report or clinician's clinical observation (family history with hallucination, lethargy, convulsions, dizziness, etc.). Totally, 352 patients were included to the study whose cannabioid use was proven with their urine drug analysis. Men were predominantly high (93.8%). Nearly all patients (93.5%) were followed up and discharged in 24 hours. Among them, 21 (5.9%) patients were admitted for hospitalization, and mortality was seen in 2 (0.6%). The mean number of previous presentations at ED with a similar diagnosis was 8.6 ± 10.31. Great care must be taken in respect of complications related to SCI, which can even result in death. Patients have a tendency to not disclose the substance they have taken because it is illegal. Patients presenting at ED with recurrent symptoms must be referred to relevant legal authorities. For patients presenting with different clinical effects, SCI must be considered.

Critical Illness Secondary to Synthetic Cannabinoid Ingestion

Synthetic cannabinoids (SCs), commonly known as K2, spice, or fake weed, are cheap, artificially manufactured recreational drugs that have emerged as a major public health threat in various regions of the US. To describe the clinical manifestations of SC intoxication. This case series assessed adults admitted to the intensive care unit from 2014 to 2016 with acute life-threatening complications of SC use. Data analysis was completed in October 2016. Use of SCs such as K2, spice, or other synthetic versions of cannabinoids. Data collected included patient demographic data, medical history, presenting symptoms, physical findings, laboratory and imaging data, and intensive care unit and hospital course. Thirty patients (mean age, 41 years [range, 21-59 years]; 24 men [80%]) with SC ingestion were admitted to the intensive care unit over a 2-year period. Thirteen patients were undomiciled. The majority had a history of polysubstance abuse, psychiatric illness, or personality disorder. The admission diagnoses were coma (10 patients [33%]), agitation (10 patients [33%]), and seizure (6 patients [20%]). Eighteen patients (60%) had acute respiratory failure, and tracheal intubation was required in 21 patients (70%) for either airway protection or acute respiratory failure. Rhabdomyolysis was noted in 8 patients (26%). A man developed transient cerebral edema with loss of gray-white differentiation but had complete recovery. A woman with history of asthma died of acute respiratory distress syndrome. All patients underwent routine toxicology testing, which was unrevealing in 16 cases and revealed coingestion in the remainder. Sixteen patients (53%) left the hospital against medical advice. Ingestion of SCs can lead to life-threatening complications, including severe toxic encephalopathy, acute respiratory failure, and death. Synthetic cannabinoids are undetectable in routine serum and urine toxicology testing but can be suspected on the basis of history and clinical presentation, which may include extreme agitation or coma. Frontline clinicians must be aware of the presentation and be vigilant in suspecting SC intoxication.

Assessment of Patients Admitted to Emergency Rooms with Synthetic Cannabinoid Intoxication: A Prospective Study

Assessment of Patients Admitted to Emergency Rooms with Synthetic Cannabinoid Intoxication: A Prospective Study

Assessing the content of a synthetic cannabinoid “research chemical” package

Introduction: Over the past several years, a new class of psychoactive substances has emerged from the drug market.[1–3] These Novel Psychoactive Substances (NPS) are defined as “a new narcotic or psychotropic drug, in pure form or in preparation, that is not controlled by the United Nations drug conventions, but which may pose a public health threat comparable to that posed by substances listed in these conventions” [1]. The largest and most popular group of NPS is Synthetic Cannabinoids (SC). SC are used as a ‘legal’ alternative to Cannabis, which means that they produce similar psychotropic effects to those of Δ9-THC. These substances are easily bought on internet shops and both blends or ‘research chemicals’ come in packets [2,3]. These packets are advertised as containing a certain SC pure. Usually, pure substances from synthesis are very expensive. On contrary, SC 1g packets are sold for 10€ or less. In the present study, a SC called THJ-018 was bought in the internet as a ‘research chemical’ and its content was assessed by GC/MS and HPLC/DAD. Materials and methods: THJ-018 was bought as a ‘research chemical’ >99% purity. A gas chromatography system coupled with a mass selective detector and an automated injector were used for the analysis of the packet content. Helium was used as the carrier gas. For purification a HPLC system coupled with a photodiode array detector (DAD) and an autosampler, operated by Clarity software, was used with a reversed-phase column. The mobile phase was a solvent gradient system consisting of (A) 5% 10mM ammonia format and (B) 95% acetonitrile, optimized to achieve the best resolution. The chromatograms were recorded at λ = 320 nm. Results: Figure 1 shows the GC/MS chromatogram of methanol extract of THJ-018. It is clear from the chromatogram the presence of two peaks: THJ-018 (33,072 min) and another compound (31,952 min). Figure 1. GC/MS analysis of THJ-018 before purification by HPLC/DAD. Discussion and conclusions: The data gathered in this study shows that THJ-018 bought as a pure “research chemical” contains a significant amount of impurities. This suggests that SC bought online might not come in their pure state. According to Couceiro et al. [3], human cell lines exposed to JWH-018 (>99% pure), do not show a significant change on cell viability, pointing that this compound is not toxic as a standard. However, various effects resulting from an acute SC intoxication have been registered, such as cognitive deficits, agitation/violent behaviors, organ related problems, nausea/vomiting, seizures, anxiety, mydriasis, among others [2]. This might be pointing that substances sold online or at the streets do not come in a pure form and impurities are also part of the problems caused by NPS.

Broad and Region-Specific Impacts of the Synthetic Cannabinoid CP 55,940 in Adolescent and Adult Female Mouse Brains.

Relative to Δ9-tetrahydrocannabinol (THC), the synthetic cannabinoid CP 55,940 (CP) is significantly more potent and efficacious at cannabinoid receptors, the primary targets for endogenous cannabinoids (eCBs). eCBs belong to a large, interconnected lipidome of bioactive signaling molecules with a myriad of effects in optimal and pathological function. Recreational use of highly potent and efficacious synthetic cannabinoids is common amongst adolescents, potentially impacting brain development. Knowledge of the molecular outcomes of synthetic cannabinoid use will be important to develop more targeted therapies for synthetic cannabinoid intoxication and to prevent long-term disruption to the CNS. Here, we test the hypothesis that CP has age and region-dependent effects on the brain lipidome. Adolescent [post-natal day (PND) 35 and PND 50] and young adult female mice were given either an acute dose of CP or vehicle and brains were collected 2 h later. Eight brain regions were dissected and levels of ∼80 lipids were screened from each region using HPLC/MS/MS. CP had widespread effects on the brain lipidome in all age groups. Interestingly, more changes were observed in the PND 35 mice and more were reductions in a lipid’s concentration, including region-dependent lowering of eCB levels. CP levels were highest in the cortex at PND 35, the hippocampus at PND 50, and in the cerebellum in the adult. These data provide novel insights into how high-potency, synthetic cannabinoids drive different, age-dependent, cellular signaling effects in the brain.

Clinical characteristics of synthetic cannabinoid-induced psychotic disorders: a single-center analysis of hospitalized patients

This study was designed to evaluate synthetic cannabinoid (SC)-induced psychotic disorders in terms of their structure and clinical characteristics among hospitalized patients in Russia. It was a longitudinal, observational cohort study which included a total of 46 male patients who underwent the inpatient treatment in the intensive care unit or emergency department due to the SC-induced psychoses. Data on sociodemographic and disease-related characteristics, psychometric assessment scales obtained in face-to-face interviews, were recorded in all patients. The duration of catamnestic follow-up period was 2 years, with the major focus on manifestation of the schizophrenic process. Mean (SD) age of the patients with psychotic disorders induced by the SC use was 23.2 (3.5) years. Among 46 patients, 29 (63%) were SC-dependent and 17 (37%) were diagnosed with SC abuse. Average age at onset was 16.4 for psychoactive substances and 19.7 years for SC use. Marijuana was the most common first used substance. Based on our observations, we identified four clinical variants of the SC-induced psychoses. Our findings revealed that psychotic disorders are typical for the SC intoxication and most commonly influence young adults. Based on our observations, we identified four clinical variants of the SC-induced psychoses and revealed the signs which may indicate them. This study emphasizes the role of appropriate psychiatric management of SC-induced psychoses, since often only catamnestic long-term follow-up enables clinicians to determine the correct diagnosis and reveal the manifestation of the schizophrenic process.

The Chameleon-Like Properties of Psychoactive Drugs: Examinations with HR LC-MS/MS Technology of Patients Presenting at the Emergency Department Following the Use of Synthetic Cannabinoids: A Case Series and Literature Review.

The chameleon can disguise itself in nature by taking on different colors and forms. As synthetic cannabinoids (SC) have clinically similar effects to those of several psychoactive agents, they are one of the most difficult intoxications to diagnose. The reasons for this are due to clinical variations throughout the world and the differences in symptoms having not been determined due to their similarity to the intoxication of several other drugs. The aim of this study was to obtain prospective data of patients presenting at the Emergency Department (ED) with suspected SC intoxication, and as a result of prospective examination of samples, to determine a new generation of SC use, SC types, clinical findings, and treatments. Method: A total of a 15 patients with suspected SC intoxication who presented at the ED of the Health Sciences University Kayseri Training and Research Hospital between January 2017 and January 2018 were examined. Samples taken prospectively from patients who were followed-up for a diagnosis of SC intoxication were examined with the HR LC-MS/MS method; SC were determined, and the test results of other psychoactive agents that were used concurrently were examined. Conclusions: Three significant findings emerged as a result of this study. Firstly, due to the different clinical forms of presentation at ED associated with SC use and the range of intoxications that cannot be diagnosed, advanced laboratory tests are required, in addition to routine tests for the determination of SC. Secondly, those diagnosed as having taken SC were also determined to have used it concurrently with substances that have a high potential for addiction, such as amphetamines and quetiapine. Thirdly, in regard to examples of cases presented in the literature, anti-psychotics, fluid hydration, and anxiolytics can be used as treatment options for those diagnosed with SC use.

Synthetic Cannabinoid Intoxication Presenting as Malignant Catatonia: a Case Report

The use of synthetic cannabinoids (SCs) has been steadily increasing in recent years and represents a new class of substances of abuse. Despite they elicit cannabimimetic effects similar to Δ9-tetrahydrocannabinol (THC), they have stronger affinities to the endocannabinoid system and cause greater psychiatric and medical effects. Case reports of catatonia following SC use have been sporadically described in the literature, but the underlying mechanisms behind these symptoms are unclear. In this article, we present a case of a patient who presented in a state of malignant catatonia following SC use, and we discuss the possible underlying mechanisms behind this association.

Retrospective Chart Review of Synthetic Cannabinoid Intoxication with Toxicologic Analysis.

IntroductionUse of synthetic cannabinoids (SC) has recently emerged as a new drug epidemic. Our emergency departments (EDs) received a surge of SC users presenting with lethargy and bradycardia, contrasting prior reports of SC-induced tachycardia and agitation. Our goal was to describe these novel presentations and characterize the compounds.MethodsWe present a case series of patients with SC intoxication who presented to our toxicology service covering two tertiary care EDs between 2/11/2015 and 6/23/2015. A retrospective chart review recorded initial vital signs, chief complaint and clinical course. Urine, blood and xenobiotic samples were analyzed using either liquid chromatography/mass spectrometry or gas chromatography/mass spectrometry. We compared resulting spectra against databases containing numerous SCs or metabolites and scored based on a reference comparison.ResultsBetween 2/11/2015 and 6/23/2015, we identified 141 visits. Males comprised 139 visits (age range 21–68 years; median 35, interquartile range 20). Sixty-eight percent presented with lethargy or loss of consciousness. Hypotension (SBP <90 mmHg) and bradycardia (HR<60 bpm) were seen in 10% and 24% of visits, respectively. While most patients were discharged after observation, three were admitted to the intensive care unit and seven to telemetry. Admissions were for vital sign instability, bradycardia requiring pacing, prolonged sedation and respiratory failure requiring mechanical ventilation.Laboratory analysis revealed SC in the XLR-11 family in 18/36 drug, 9/12 blood, and 23/31 urine samples. Carboxamide indazole derivative (CID) family compounds were detected in 13/36 drug samples, 21/31 urine samples, but no blood samples; 11/31 drug samples contained both XLR-11 and CID. Other compounds detected included PB-22 and nicotine. No JWH compounds, opiates, imidazoline receptor agonists, benzodiazepines or other sedative-hypnotics were detected.ConclusionUnlike their predecessors, novel SC may be associated with significant central nervous system depression and bradycardia. While prior reports indicated that SC mostly contained JWH compounds, none were detected in these samples. The most commonly identified compounds in this series were CID and alkyl SC derivatives, such as INACA compounds and XLR-11. These tend to be full agonists at the cannabinoid receptor and are presumably more potent. The lack of other depressants suggests that the clinical findings are due to the combination of these compounds and not coingestants or adulterants. SC intoxication should be considered for patients with undifferentiated psychomotor depression and bradycardia.

Evaluation of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in critical care patients with synthetic cannabinoid (bonzai) intoxication

ObjectiveSynthetic cannabinoid drug abuse has been dramatically increasing among young individuals in many countries. There have been reports of serious side effects with SC abuse in these patients. Previous researches have exhibited that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with mortality and morbidity in many chronic diseases. The aim of this study was to evaluate PLR and NLR in critical care patients with synthetic cannabinoid (bonzai) intoxication. Materials and methodsOne hundred and seven synthetic cannabinoid intoxication patients requiring intensive care and 40 healthy controls were included in the study. Patients characteristics and the complete blood count (CBC) variables, including white blood cell (WBC), hemoglobin (Hb), platelet count, NLR, PLR as well as AST, ALT, albumin total bilirubin, and other routine biochemical parameters were tested. Data analyses were conducted with SPSS-15 software (SPSS Inc., Chicago, Illinois, USA). Statistical significance was set at a p-value of <0.05. ResultsAll participants were male, and the mean age of the patients was 21.74 ± 1.57 and healthy controls was 22.62 ± 2.9 years (p > 0.05). All the routine laboratory tests and inflammatory markers (Erythrocyte sedimentation rate and C-reactive protein) were similar between groups. As complete blood cell count; mean WBC values were 9.43 ± 3.27 × 103/mm3 vs 7.05 ± 2.12 × 103/mm3 (p < 0.001), mean platelet counts were 237.33 ± 60 × 103/mm3 vs 263.90 ± 65.98 × 103/mm3 (p = 0.022), NLR counts were 3.17 ± 1.95 vs 2.32 ± 1.27 (p = 0.003) and PLR values were 114.43 ± 36.39 vs 133.94 ± 45.27 (p = 0.008), in patients and controls, respectively. Cardiac side effects were observed among 36 patients but nobody was died. ConclusionOur results exhibited a significant increase of NLR values and decrease of PLR counts among critical care patients with synthetic cannabinoid (bonzai) intoxication. After at least 24 h of intensive care stay without side effects, the patients might transfer out to inpatient clinic for ongoing follow up period and psychiatric consultation.

Rhabdomyolysis and Renal Insufficiency Due to Synthetic Cannabinoid Intoxication

Rhabdomyolysis and Renal Insufficiency Due to Synthetic Cannabinoid Intoxication

Rescue from Synthetic Cannabinoid Intoxication

The number of patients seeking emergency treatment for acute synthetic cannabinoid intoxication have increased over the past decade, despite laws prohibiting their legal sale and use. Reported clinical signs of acute synthetic cannabinoid intoxication include tachycardia and hypertension, lethargy, confusion, agitation, hallucinations, and seizures. Clinicians have little guidance on the best course of treatment for such patients. The current standard of care involves administering benzodiazepines to sedate agitated patients and reverse seizures, antidepressants to treat anxiety reported by patients, and antipsychotics to reverse apparent psychotomimetic effects. However, the effectiveness of these treatments remains unclear. Here, in adult male C57 mice, the ability of several clinically available medications to reverse effects including hypothermia, antinociception, and ataxia of the synthetic cannabinoid JWH‐018 are examined. Additionally, effects of JWH‐018 on blood pressure and heart rate are determined, to evaluate potential cardiac effects. JWH‐018 (0.3, 1.0, or 3.0 mg/kg) or vehicle was administered 10‐min prior to test agents which included diazepam (1 &amp; 10 mg/kg), imipramine (10 &amp; 30 mg/kg), fluvoxamine (10 &amp; 30 mg/kg), and haloperidol (0.3 &amp; 3 mg/kg). Effects of these agents are compared to those of rimonabant (1 &amp; 3 mg/kg), the CB1 antagonist. Behavioral effects were assessed immediately before, then 10, 20, 30, 40, and 50‐min after JWH‐018 administration. In other mice, cardiac effects were assessed 25–35 min after JWH‐018 administration. The potential reversal agents are administered after JWH‐018 administration because the clinical situation necessitates administration of reversal agents after cannabinoid exposure. JWH‐018 had no effect on blood pressure and only modestly decreased heart rate. As expected, JWH‐018 had dose‐dependent effects on rectal temperature, antinociception, and ataxia that persisted for at least 50‐min. Within 10–20 min of administration, rimonabant reversed hypothermic and antinociceptive effects and partially reversed ataxic effects of JWH‐018. No other agent tested affected any of the JWH‐018 effects. These results suggest that clinical reports of hypertension and tachycardia are unlikely to be due to direct effects of synthetic cannabinoids, but rather are likely due to the situation arising from intoxication requiring emergency medical care. Further, while treatment with a sedative might help calm an agitated patient, these medications are unlikely to alter the course of synthetic cannabinoid intoxication. Finally, although rimonabant was withdrawn from human use, this decision was based on adverse events during chronic rimonabant treatment for obesity. These results indicate that rimonabant or a similar drug could be useful for acute reversal of synthetic cannabinoid intoxication.Support or Funding InformationSupported by The Department of Defense (JPC‐5) project FA8650‐15‐C‐6589

Occupational transdermal poisoning with synthetic cannabinoid cumyl-PINACA

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.

Acute Poisonings from Synthetic Cannabinoids — 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010–2015

Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ(9)-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention.

Neutrophil to Lymphocyte ratio of Synthetic Cannabinoid Intoxication

Synthetic cannabinoids represent an in-creasingly popular trend, and acute intoxi-cation is widely seen in emergency rooms and intensive care units (ICU), as they are inexpensive and easily accessible. Cannab-inoids mediate their effects through bind-ing specific receptors which are members of the G protein coupled receptor super-family. Cannabinoid-2 receptors are pri-marily found in the immune system and mediate immunosuppression by inducing apoptosis, inhibition of proliferation and suppression of cytokine and chemokine production. Many studies have discussed the effects of cannabinoids on the hema-tological and immune systems but con-troversial results have been reported. The aim of this study was to identify laboratory findings of acute synthetic cannabinoid in-toxication. Forty-two patients, admitted to the ‘Anesthesia intensive care unit’ between 2014 and 2015 with synthetic cannabinoid intoxication, were studied retrospectively to assess the relationship between synthet-ic cannabinoid intoxication and complete blood count (white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils) and neutrophil to lymphocyte ratio. WBC neutrophil count decreased at ICU discharge when com-pared to ICU admission (p&lt;0.001). The ra-tio of neutrophils to lymphocytes was also lower at ICU discharge when compared to ICU admission (p&lt;0.05).

Clinical Characteristics of Patients Diagnosed with Synthetic Cannabinoid (Bonsai) Intoxication in Intensive Care Unit

Clinical Characteristics of Patients Diagnosed with Synthetic Cannabinoid (Bonsai) Intoxication in Intensive Care Unit