Semiquantitative activity-based detection of JWH-018, a synthetic cannabinoid receptor agonist, in oral fluid after vaping

The rapid proliferation of new synthetic cannabinoid receptor agonists (SCRAs) has initiated considerable interest in the development of so-called “untargeted” screening strategies. One of these new screening technologies involves the activity-based detection of SCRAs. In this study, we evaluated whether (synthetic) cannabinoid activity can be detected in oral fluid (OF) and, if so, whether it correlates with SCRA concentrations. OF was collected at several time points in a placebo-controlled JWH-018 administration study. The outcome of the cell-based cannabinoid reporter system, which monitored the cannabinoid receptor activation, was compared to the quantitative data for JWH-018, obtained via a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. A total of 175 OF samples were collected and analyzed via both methods. The cannabinoid reporter assay correctly classified the vast majority of the samples as either negative (<0.25 ng/mL; 74/75 = 99%) or having low (0.25−1.5 ng/mL; 16/16 = 100% and 1.5−10 ng/mL; 37/41 = 90%), mid (10−100 ng/mL; 23/25 = 92%) or high (>100 ng/mL; 16/18 = 89%) JWH-018 concentrations. Passing−Bablok regression analysis yielded a good linear correlation, with no proportional difference between both methods (slope 0.97; 95% confidence interval 0.86−1.14) and only a small systematic difference. This is the first study to demonstrate the applicability of an untargeted, activity-based approach for SCRA detection in OF. Additionally, the outcome of the cannabinoid reporter assay was compared to the gold standard (LC-MS/MS), showing a good correlation between both methods, indicating that the cannabinoid reporter assay can be used for an estimation of drug concentrations

Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies

Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation

Бухгалтерский учет основных средств

Inflammatory pseudotumors (IPs), mostly benign lesions characterized by fibrotic ground tissue and polyclonal mononuclear infiltrate, may affect all organ systems. IPs originating in the central nervous system (IP-CNS) are very rare, and their distinct histopathologic features are poorly characterized. Three otherwise healthy patients (age 8, 15, and 17 years) presented with focal neurologic symptoms (seizures, n = 2; headaches, n = 1), corresponding to a left temporal, left occipital, and left frontal IP, respectively, extending from meningeal structures into brain tissue. After resection, no recurrence was observed in patient 1 during 5 years of follow-up, whereas patient 2 developed a rapidly progressive local recurrence and a second intracerebral lesion despite antiviral, immunosuppressive, antibiotic, and radiation therapy. In patient 3, who also showed local recurrences, sequential histopathologic investigations revealed transformation to a semimalignant fibrohistiocytic tumor. In this patient, anaplastic lymphoma kinase (ALK) expression was also positive, whereas it was negative in patient 1. A detailed literature analysis confirmed that most IP-CNS arise from dural/meningeal structures (n = 34). Intraparenchymatous (n = 7), mixed intraparenchymatous/meningeal (n = 4), and intraventricular lesions (n = 7) or IP extending per continuitatem from intracerebral to extracerebral sites (n = 5) were rare. The recurrence rate was 40% within 2 years in general. It was increased after incomplete resection and in female patients (multivariate Cox regression model, P < 0.02). Although rare, IP-CNS are important differential diagnoses among tumor-like intracranial lesions. Their potential risk of malignant transformation and high risk of recurrence necessitate close follow-up, especially when resection is incomplete. Prospective multicenter trials are needed to optimize classification and treatment of this rare inflammatory lesion. Copyright 2003, Elsevier Inc. All rights reserved

Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype

INTRODUCTION: Esmirtazapine is evaluated as a novel drug for treatment of insomnia. PURPOSE: The present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control. METHODS: Treatments were administered in the evening. Driving performance was assessed in the morning, 11 h after drug intake, in a standardized on-the-road highway driving test. The primary study parameter was standard deviation of lateral position (SDLP), a measure of "weaving". All subjects were subjected to CYP2D6 phenotyping in order to distinguish poor metabolizers from extensive metabolizers of esmirtazapine. RESULTS: Overall, esmirtazapine 1.5 mg did not produce any clinically relevant change in SDLP after single and repeated dosing. Driving impairment, i.e., a rise in SDLP, did occur after a single-dose administration of esmirtazapine 4.5 mg but was resolved after repeated doses. Acute driving impairment was more pronounced after both doses of esmirtazapine in a select group of poor metabolizers (N = 7). A single-dose zopiclone 7.5 mg also increased SDLP as expected. CONCLUSION: It is concluded that single and repeated doses of 1.5 mg esmirtazapine are generally not associated with residual impairment. Single-dose administration of 4.5 mg esmirtazapine was associated with residual impairment that generally resolved after repeated administration. Exploratory analysis in a small group of poor CYP 2D6 metabolizers suggested that these subjects are more sensitive to the impairing effects of esmirtazapine on car driving