Detection of synthetic cannabinoid intoxication in the Emergency Department: when routine toxicological tests are not enough. / Detección de la intoxicación por cannabinoides sintéticos en Urgencias: cuando las pruebas toxicológicas rutinarias no bastan.

Letter to the editor.

Carta al Editor.

Detección de la intoxicación por cannabinoides sintéticos en Urgencias: cuando las pruebas toxicológicas rutinarias no bastan / Detection of synthetic cannabinoid intoxication in the Emergency Department: when routine toxicological tests are not enough

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Analytical confirmation of synthetic cannabinoids in a cohort of 179 presentations with acute recreational drug toxicity to an Emergency Department in London, UK in the first half of 2015.

CONTEXT: Synthetic cannabinoid receptor agonists are the largest group of new psychoactive substances reported in the last decade; in this study we investigated how commonly these drugs are found in patients presenting to the Emergency Department with acute recreational drug toxicity. METHODS: We conducted an observational cohort study enrolling consecutive adult patients presenting to an Emergency Department (ED) in London (UK) January-July 2015 (6 months) with acute recreational drug toxicity. Residual serum obtained from a serum sample taken as part of routine clinical care was analyzed using high-resolution accurate mass-spectrometry with liquid-chromatography (HRAM-LCMSMS). Minimum clinical data were obtained from ED medical records. RESULTS: 18 (10%) of the 179 patient samples were positive for synthetic cannabinoid receptor agonists. The most common was 5F AKB-48 (13 samples, concentration 50-7600 pg/ml), followed by 5F PB-22 (7, 30-400 pg/mL), MDMB-CHMICA (7, 80-8000 pg/mL), AB-CHMINACA (3, 50-1800 pg/mL), Cumyl 5F-PINACA (1, 800 pg/mL) and BB-22 (1, 60 pg/mL). Only 9/18 (50%) in whom synthetic cannabinoid receptor agonists were detected self-reported synthetic cannabinoid receptor agonist use. The most common clinical features were seizures and agitation, both recorded in four (22%) individuals. Fourteen patients (78%) were discharged from the ED, one of the four admitted to hospital was admitted to critical care. CONCLUSIONS: Synthetic cannabinoid receptor agonists were found in 10% of this cohort with acute recreational drug toxicity but self-reported in only half of these. This suggests that presentations to the ED with acute synthetic cannabinoid receptor agonist toxicity may be more common than reported.

The peripheral cannabinoid receptor 1 antagonist VD60 efficiently inhibits carbon tetrachloride-intoxicated hepatic fibrosis progression.

This study investigated a peripheral selective CB1 antagonist 3,4,22-3-demethoxycarbonyl-3-hydroxylmethyl-4-deacetyl-vindoline 3,4-thionocarbonate (VD60) that efficiently inhibited hepatic fibrosis with lower psychological side effects. A competitive radiolabeled ligand binding experiment and 3'-5'-cyclic adenosine monophosphate (cAMP) response element-driven luciferase analysis were performed to evaluate the antagonistic activity of VD60. Cell viability and collagen production were examined in the human hepatic stellate cell (HSC) line LX-2 and primary cultured rat HSCs. The antifibrotic effects of VD60 were investigated in a CCl4-induced liver fibrosis mouse model. The concentration of VD60 in the blood and the brain was determined by high-performance liquid chromatography-mass spectrum analysis. Furthermore, the potential underlying mechanisms of VD60 were investigated by Western blot. VD60 selectively competed with the radiolabeled CB1 agonist to bind to CB1. VD60 antagonized CB1 agonist-induced Akt phosphorylation and increased the accumulation of intracellular cAMP. VD60 strongly reduced the expression of α2(I) pro-collagen mRNA and exerted potent antiproliferative effects on primary HSCs and LX-2 cells. The inhibition of reactive oxygen species production and phosphorylation of Akt, extracellular-signal-regulated kinase (ERK), and Smad3 may explain the underlying mechanisms behind the antiproliferative effect of VD60. Moreover, the in vivo antifibrotic activity of VD60 was confirmed in a CCl4-induced liver fibrosis mouse model. Most importantly, the concentration of VD60 in the peripheral blood was much higher than in the brain, suggesting that VD60 could act as a novel peripheral CB1 antagonist to efficiently inhibit hepatic fibrosis and could be used as a lead compound with low brain side effects in peripheral antifibrotic agents.