The Experts below are selected from a list of 8784 Experts worldwide ranked by ideXlab platform
Mathias B Forrester - One of the best experts on this subject based on the ideXlab platform.
-
adolescent Synthetic Cannabinoid exposures reported to texas poison centers
Pediatric Emergency Care, 2012Co-Authors: Mathias B ForresterAbstract:OBJECTIVE: This study describes the pattern of adolescent Synthetic Cannabinoid exposures reported to a large statewide poison center system. METHODS: Synthetic Cannabinoid exposures among patients younger than 20 years reported to Texas poison centers during January 2010 to June 2011 were identified. The distribution of exposures by various demographic and clinical factors was determined. RESULTS: For 305 adolescent exposures, the mean age was 16.7 years (range, 12-19 y). The exposure was by inhalation in 77.4% of the cases, and 72.1% involved males. The exposure site was the patient's own residence in 70.5% of the cases, and a health care facility was the caller site in 68.9%. The patient was already at or en route to a health care facility in 80.3% of the cases, and the medical outcome was serious in 61.0%. The most frequently reported adverse clinical effects were tachycardia (41.6%), drowsiness/lethargy (24.3%), agitation/irritability (16.4%), vomiting (13.1%), hallucinations/delusions (11.5%), nausea (8.5%), confusion (8.2%), hypertension (7.5%), chest pain (6.9%), and dizziness/vertigo (5.2%). CONCLUSIONS: Adolescent Synthetic Cannabinoid exposures reported to Texas poison centers were more likely to involve inhalation. The adolescents were more likely to be male. The exposures more often occurred at the patient's own residence and managed at a health care facility with a serious outcome. This pattern of exposures was similar to that observed among adults. Language: en
-
Synthetic Cannabinoid and marijuana exposures reported to poison centers.
Human & Experimental Toxicology, 2012Co-Authors: Mathias B Forrester, Kurt C Kleinschmidt, Evan S Schwarz, Amy YoungAbstract:Synthetic Cannabinoids have recently gained popularity as a recreational drug because they are believed to result in a marijuana-like high. This investigation compared Synthetic Cannabinoids and marijuana exposures reported to a large statewide poison center system. Synthetic Cannabinoid and marijuana exposures reported to Texas poison centers during 2010 were identified. The distribution of exposures to the two agents with respect to various demographic and clinical factors were compared by calculating the rate ratio (RR) of the Synthetic Cannabinoid and marijuana percentages for each subgroup and 95% confidence interval (CI). The proportion of Synthetic Cannabinoid and marijuana exposures, respectively, were 87.3% and 46.5% via inhalation (RR 1.88, 95% CI 1.38–2.61), 74.9% and 65.7% in male (RR 1.14, 95% CI 0.87–1.51), 40.2% and 56.6% age ≤19 years (RR 0.71, 95% CI 0.52–0.98), 79.2% and 58.6% occurring at a residence (RR 1.35, 95% CI 1.02–1.82), 8.4% and 16.2% managed on-site (RR 0.52. 95% CI 0.28–1.00)...
-
Geographic distribution of Synthetic Cannabinoid exposures reported to Texas poison centers.
The American Journal of Drug and Alcohol Abuse, 2012Co-Authors: Mathias B Forrester, Tracy HaywoodAbstract:Background: Synthetic Cannabinoids have recently gained popularity as recreational drugs because they provide a marijuana-like high and cannot be detected in typical urine drug screens. However, the use of Synthetic Cannabinoids may result in a variety of adverse effects. Objectives: The intent of this investigation was to determine whether Synthetic Cannabinoid exposures in Texas demonstrated any geographic variation. Methods: A total of 1037 Synthetic Cannabinoid exposures reported to Texas poison centers during 2010–2011 were identified and the county and Texas Public Health Region (PHR) where the call originated from ascertained. The distribution of exposures by county and PHR was determined. Results: Synthetic Cannabinoid exposures were reported in 124 of the 254 Texas counties (mean exposures per county 4.1, range 0–179). The exposure rate among the 11 PHRs varied from 2.79 to 7.14 per 100,000 population. The rate was 4.02 in urban counties and 4.90 in rural counties. Conclusion: Synthetic cannabino...
-
Synthetic Cannabinoid exposures reported to texas poison centers
Journal of Addictive Diseases, 2011Co-Authors: Mathias B Forrester, Kurt C Kleinschmidt, Evan S Schwarz, Amy YoungAbstract:Synthetic Cannabinoid abuse is increasing in the United States. Synthetic Cannabinoid exposures reported to Texas poison centers in 2010 were identified, and the distribution of exposures by selected factors was determined. There were 464 total cases. The number of exposures increased each month during January-July, then remained relatively constant for the next 5 months. The patients were 73.9% male and 57.3% were 20 years or older. Moderate or major effects or potentially toxic outcome occurred in 59.9% of the exposures. The most frequently reported clinical effects were tachycardia (37.3%), agitation (18.5%), drowsiness (18.5%), vomiting (15.7%), hallucinations (10.8%), and nausea (9.9%).
Matthias E. Liechti - One of the best experts on this subject based on the ideXlab platform.
-
Symptoms, toxicities, and analytical results for a patient after smoking herbs containing the novel Synthetic Cannabinoid MAM-2201
Forensic Toxicology, 2013Co-Authors: Adrian Derungs, Andrea E. Schwaninger, Gregory Mansella, Roland Bingisser, Thomas Kraemer, Matthias E. LiechtiAbstract:We report a case of intoxication by the Synthetic Cannabinoid MAM-2201 ([1-(5-fluoropentyl)-1 H -indol-3-yl](4-methyl-1-naphthalenyl)-methanone). A 31-year-old man smoked about 300 mg of a herbal blend. He experienced an acute transient psychotic state with agitation, aggression, anxiety, and vomiting associated with a sympathomimetic syndrome. MAM-2201 was detected and quantified in a plasma sample using liquid chromatography-tandem mass spectrometry (LC–MS–MS). The level was 49 ng/ml 1 h after smoking. The use of other drugs was analytically excluded. The presence of MAM-2201 was confirmed in the herbal blend using gas chromatography–mass spectrometry (GC–MS) and LC–high resolution MS. This is the first description of an analytically confirmed intoxication and of the determination of MAM-2201 in human blood plasma.
Amy Young - One of the best experts on this subject based on the ideXlab platform.
-
Synthetic Cannabinoid and marijuana exposures reported to poison centers.
Human & Experimental Toxicology, 2012Co-Authors: Mathias B Forrester, Kurt C Kleinschmidt, Evan S Schwarz, Amy YoungAbstract:Synthetic Cannabinoids have recently gained popularity as a recreational drug because they are believed to result in a marijuana-like high. This investigation compared Synthetic Cannabinoids and marijuana exposures reported to a large statewide poison center system. Synthetic Cannabinoid and marijuana exposures reported to Texas poison centers during 2010 were identified. The distribution of exposures to the two agents with respect to various demographic and clinical factors were compared by calculating the rate ratio (RR) of the Synthetic Cannabinoid and marijuana percentages for each subgroup and 95% confidence interval (CI). The proportion of Synthetic Cannabinoid and marijuana exposures, respectively, were 87.3% and 46.5% via inhalation (RR 1.88, 95% CI 1.38–2.61), 74.9% and 65.7% in male (RR 1.14, 95% CI 0.87–1.51), 40.2% and 56.6% age ≤19 years (RR 0.71, 95% CI 0.52–0.98), 79.2% and 58.6% occurring at a residence (RR 1.35, 95% CI 1.02–1.82), 8.4% and 16.2% managed on-site (RR 0.52. 95% CI 0.28–1.00)...
-
Synthetic Cannabinoid exposures reported to texas poison centers
Journal of Addictive Diseases, 2011Co-Authors: Mathias B Forrester, Kurt C Kleinschmidt, Evan S Schwarz, Amy YoungAbstract:Synthetic Cannabinoid abuse is increasing in the United States. Synthetic Cannabinoid exposures reported to Texas poison centers in 2010 were identified, and the distribution of exposures by selected factors was determined. There were 464 total cases. The number of exposures increased each month during January-July, then remained relatively constant for the next 5 months. The patients were 73.9% male and 57.3% were 20 years or older. Moderate or major effects or potentially toxic outcome occurred in 59.9% of the exposures. The most frequently reported clinical effects were tachycardia (37.3%), agitation (18.5%), drowsiness (18.5%), vomiting (15.7%), hallucinations (10.8%), and nausea (9.9%).
Marilyn A Huestis - One of the best experts on this subject based on the ideXlab platform.
-
Urinary prevalence, metabolite detection rates, temporal patterns and evaluation of suitable LC-MS/MS targets to document Synthetic Cannabinoid intake in US military urine specimens.
Clinical Chemistry and Laboratory Medicine, 2015Co-Authors: Ariane Wohlfarth, Marisol S. Castaneto, Nathalie A. Desrosiers, Thomas M. Martin, Kevin L. Klette, Karl B. Scheidweiler, Adarsh Gandhi, Marilyn A HuestisAbstract:Identifying Synthetic Cannabinoid designer drug abuse challenges toxicologists and drug testing programs. The best analytical approach for reliably documenting intake of emerging Synthetic Cannabinoids is unknown. Primarily metabolites are found in urine, but optimal metabolite targets remain unknown, and definitive identification is complicated by converging metabolic pathways. We screened 20,017 US military urine specimens collected from service members worldwide for Synthetic Cannabinoids between July 2011 and June 2012. We confirmed 1432 presumptive positive and 1069 presumptive negative specimens by qualitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis including 29 biomarkers for JWH-018, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, RCS-4, AM2201 and MAM2201. Specimen preparation included enzyme hydrolysis and acetonitrile precipitation prior to LC-MS/MS analysis. We evaluated individual Synthetic Cannabinoid metabolite detection rates, prevalence, temporal patterns and suitable targets for analytical procedures. Prevalence was 1.4% with 290 confirmed positive specimens, 92% JWH-018, 54% AM2201 and 39% JWH-122 metabolites. JWH-073, JWH-210 and JWH-250 also were identified in 37%, 4% and 8% of specimens, respectively. The United States Army Criminal Investigation Command seizure pattern for Synthetic Cannabinoid compounds matched our urine specimen results over the time frame of the study. Apart from one exception (AM2201), no parent compounds were observed. Hydroxyalkyl metabolites accounted for most confirmed positive tests, and in many cases, two metabolites were identified, increasing confidence in the results, and improving detection rates. These data also emphasize the need for new designer drug metabolism studies to provide relevant targets for Synthetic Cannabinoid identification.
-
nontargeted swath acquisition for identifying 47 Synthetic Cannabinoid metabolites in human urine by liquid chromatography high resolution tandem mass spectrometry
Analytical and Bioanalytical Chemistry, 2015Co-Authors: Karl B. Scheidweiler, Michael Jarvis, Marilyn A HuestisAbstract:Clandestine laboratories constantly produce new Synthetic Cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463–8474, [9]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599–3609, [10]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary Synthetic Cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 Synthetic Cannabinoid metabolites from 21 Synthetic Cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). β-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-μL mobile phase consisting of 80 % A (0.1 % formic acid in water) and 20 % B (0.1 % formic acid in acetonitrile). Fifty microliters was injected, and SWATH™ MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOF® mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25–5 μg/L (N = 10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 μg/L. Extraction efficiencies and matrix effects (N = 10) were 55–104 and −65–107 %, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 Synthetic Cannabinoid metabolites in human urine.
-
Nontargeted SWATH acquisition for identifying 47 Synthetic Cannabinoid metabolites in human urine by liquid chromatography-high-resolution tandem mass spectrometry
Analytical and Bioanalytical Chemistry, 2015Co-Authors: Karl B. Scheidweiler, Michael J. Y. Jarvis, Marilyn A HuestisAbstract:Clandestine laboratories constantly produce new Synthetic Cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463–8474, [ 9 ]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599–3609, [ 10 ]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary Synthetic Cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 Synthetic Cannabinoid metabolites from 21 Synthetic Cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). β-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-μL mobile phase consisting of 80 % A (0.1 % formic acid in water) and 20 % B (0.1 % formic acid in acetonitrile). Fifty microliters was injected, and SWATH™ MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOF® mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25–5 μg/L ( N = 10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 μg/L. Extraction efficiencies and matrix effects ( N = 10) were 55–104 and −65–107 %, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 Synthetic Cannabinoid metabolites in human urine. Graphical Abstract SWATH acquisition MS experiment
Samuel D Banister - One of the best experts on this subject based on the ideXlab platform.
-
differential activation of g protein mediated signaling by Synthetic Cannabinoid receptor agonists
Pharmacology Research & Perspectives, 2020Co-Authors: Shivani Sachdev, Samuel D Banister, Marina Santiago, Chris Bladen, Michael Kassiou, Mark ConnorAbstract:Synthetic Cannabinoid receptor agonists (SCRAs) are new psychoactive substances associated with acute intoxication and even death. However, the molecular mechanisms through which SCRAs may exert their toxic effects remain unclear-including the potential differential activation of G protein subtypes by Cannabinoid receptor type 1 (CB1), a major target of SCRA. We measured CB1-mediated activation of Gαs and Gαi/o proteins by SCRAs by examining stimulation (pertussis toxin, PTX treated) as well as inhibition (non-PTX treated) of forskolin (FSK)-induced cyclic adenosine monophosphate (cAMP) accumulation in human embryonic kidney (HEK) cells stably expressing CB1. Real-time measurements of stimulation and inhibition of cAMP levels were made using a BRET biosensor. We found that the maximum concentration of SCRAs tested (10 µmol L-1 ), increased cAMP levels 12%-45% above that produced by FSK alone, while the phytoCannabinoid THC did not significantly alter cAMP levels in PTX-treated HEK-CB1 cells. All SCRAs had greater potency to inhibit FSK-induced cAMP levels than to stimulate cAMP levels. The rank order of potencies for SCRA stimulation of cAMP (Gαs ) was PB-22 > 5F-MDMB-PICA > JWH-018 ≈ AB-FUBINACA > XLR-11. By contrast, the potency of SCRAs for inhibition of cAMP (Gαi/o ) was 5F-MDMB-PICA > AB-FUBINACA > PB-22 > JWH-018 > XLR-11. The different rank order of potency and EMax of the SCRAs to stimulate Gαs -like signaling compared to Gαi/o signaling suggests differences in G protein preference between SCRAs. Understanding the apparent differences among these drugs may contribute to unravelling their complex effects in humans.
-
insights into biased signaling at Cannabinoid receptors Synthetic Cannabinoid receptor agonists
Biochemical Pharmacology, 2019Co-Authors: Elise Wouters, Samuel D Banister, Jolien Walraed, Christophe P StoveAbstract:Cannabinoid receptors type 1 (CB1) and type 2 (CB2) are promising targets for a number of diseases, including obesity, neuropathic pain, and multiple sclerosis, among others. Upon ligand-mediated activation of these receptors, multiple receptor conformations could be stabilized, resulting in a complex pattern of possible intracellular effects. Although numerous compounds have been developed and widely used to target Cannabinoid receptors, their mode of action and signaling properties are often only poorly characterized. From a drug development point of view, unraveling the underlying complex signaling mechanism could offer the possibility to generate medicines with the desired therapeutic profile. Recently, an increased interest has emerged for the development of agonists that are signaling pathway-selective and thereby do not evoke on-target adverse effects. This phenomenon, in which specific pathways are preferred upon receptor activation by certain ligands, is also known as 'biased signaling'. For a particular group of Cannabinoid receptor ligands (i.e. CB1/CB2 agonists), namely the Synthetic Cannabinoid receptor agonists (SCRAs), the research on biased signaling is still in its infancy and interesting outcomes are only recently being revealed. Therefore, this review aims at providing insights into the recent knowledge about biased agonism mediated by SCRAs so far. In addition, as these outcomes are obtained using a distinct panel of functional assays, the accompanying difficulties and challenges when comparing functional outcomes are critically discussed. Finally, some guidance on the conceptualization of ideal in vitro assays for the detection of SCRA-mediated biased agonism, which is also relevant for compounds belonging to other chemical classes, is provided.
-
the chemistry and pharmacology of Synthetic Cannabinoid sdb 006 and its regioisomeric fluorinated and methoxylated analogs
Drug Testing and Analysis, 2018Co-Authors: Samuel D Banister, Alexander Olson, Matthew Winchester, Jordyn Stuart, Amelia R Edington, Richard C Kevin, Mitchell Longworth, Marco HerreraAbstract:Synthetic Cannabinoids are the largest and most structurally diverse class of new psychoactive substances, with manufacturers often using isomerism to evade detection and circumvent legal restriction. The regioisomeric methoxy- and fluorine-substituted analogs of SDB-006 (N-benzyl-1-pentyl-1H-indole-3-carboxamide) were synthesized and could not be differentiated by gas chromatography-mass spectrometry (GC-MS), but were distinguishable by liquid chromatography-quadrupole time-of-flight-MS (LC-QTOF-MS). In a fluorescence-based plate reader membrane potential assay, SDB-006 acted as a potent agonist at human Cannabinoid receptors (CB1 EC50 = 19 nM). All methoxy- and fluorine-substituted analogs showed reduced potency compared to SDB-006, although the 2-fluorinated analog (EC50 = 166 nM) was comparable to known Synthetic Cannabinoid RCS-4 (EC50 = 146 nM). Using biotelemetry in rats, SDB-006 and RCS-4 evoked comparable reduction in body temperature (~0.7°C at a dose of 10 mg/kg), suggesting lower potency than the recent Synthetic Cannabinoid AB-CHMINACA (>2°C, 3 mg/kg).
-
the chemistry and pharmacology of Synthetic Cannabinoid receptor agonist new psychoactive substances evolution
Handbook of experimental pharmacology, 2018Co-Authors: Samuel D Banister, Mark ConnorAbstract:Synthetic Cannabinoid receptor agonists (SCRAs) are the largest and most structurally diverse class of new psychoactive substances (NPS). Although the earliest SCRA NPS were simply repurposed from historical academic manuscripts or pharmaceutical patents describing Cannabinoid ligands, recent examples bear hallmarks of rational design. SCRA NPS manufacturers have applied traditional medicinal chemistry strategies (such as molecular hybridization, bioisosteric replacement, and scaffold hopping) to existing Cannabinoid templates in order to generate new molecules that circumvent structure-based legislation. Most SCRAs potently activate Cannabinoid type 1 and type 2 receptors (CB1 and CB2, respectively), with the former contributing to the psychoactivity of these substances. SCRAs are generally more toxic than the Δ9-tetrahydrocannabinol (Δ9-THC) found in cannabis, and this may be due to ligand bias, metabolism, or off-target activity. This chapter will chart the evolution of recently identified SCRA NPS chemotypes, as well as their putative manufacturing by-products and thermolytic degradants, and describe structure-activity relationships within each class.
-
zombie outbreak caused by the Synthetic Cannabinoid amb fubinaca in new york
The New England Journal of Medicine, 2017Co-Authors: Axel Adams, Jordan Trecki, Samuel D Banister, Lisandro Irizarry, Michael W Schwartz, Roy GeronaAbstract:BackgroundNew psychoactive substances constitute a growing and dynamic class of abused drugs in the United States. On July 12, 2016, a Synthetic Cannabinoid caused mass intoxication of 33 persons in one New York City neighborhood, in an event described in the popular press as a “zombie” outbreak because of the appearance of the intoxicated persons. MethodsWe obtained and tested serum, whole blood, and urine samples from 8 patients among the 18 who were transported to local hospitals; we also tested a sample of the herbal “incense” product “AK-47 24 Karat Gold,” which was implicated in the outbreak. Samples were analyzed by means of liquid chromatography–quadrupole time-of-flight mass spectrometry. ResultsThe Synthetic Cannabinoid methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA, also known as MMB-FUBINACA or FUB-AMB) was identified in AK-47 24 Karat Gold at a mean (±SD) concentration of 16.0±3.9 mg per gram. The de-esterified acid metabolite was found in the serum or...
