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Synthetic Cannabinoid

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https://www.readbyqxmd.com/read/29446742/development-of-an-in-vitro-drug-delivery-efficiency-test-for-a-pulmonary-toxicokinetic-pig-study
#1
Nadine Schaefer, Ann-Katrin Kroll, Matthias W Laschke, Michael D Menger, Hans H Maurer, Markus R Meyer, Peter H Schmidt
BACKGROUND: Since their appearance on the drugs of abuse market, synthetic cannabinoids (SCs) are gaining increasing toxicological relevance. They are consumed without knowledge of their toxicokinetic (TK) and toxicodynamic properties and human studies are not allowed due to ethical reasons. A controlled animal TK study following nebulization of 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1-pentyl-indole-3-yl)methanone (RCS-4) as well as Δ9-tetrahydrocannabinol (THC) to pigs should be helpful for better interpretation of analytical results in cases of misuse or poisoning...
February 14, 2018: Current Drug Delivery
https://www.readbyqxmd.com/read/29431265/blockade-of-cannabinoid-1-receptor-improves-glucose-responsiveness-in-pancreatic-beta-cells
#2
Hanho Shin, Ji Hye Han, Juhwan Yoon, Hyo Jung Sim, Tae Joo Park, Siyoung Yang, Eun Kyung Lee, Rohit N Kulkarni, Josephine M Egan, Wook Kim
Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse β-cell lines, human islets and CB1R-null (CB1R-/- ) mice, we have now investigated the role of CB1Rs in modulating β-cell function and glucose responsiveness. Synthetic CB1R agonists diminished GLP-1-mediated cAMP accumulation and insulin secretion as well as glucose-stimulated insulin secretion in mouse β-cell lines and human islets. In addition, silencing CB1R in mouse β cells resulted in an increased expression of pro-insulin, glucokinase (GCK) and glucose transporter 2 (GLUT2), but this increase was lost in β cells lacking insulin receptor...
February 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29427593/inhibition-of-aldose-reductase-activity-by-cannabis-sativa-chemotypes-extracts-with-high-content-of-cannabidiol-or-cannabigerol
#3
Antonella Smeriglio, Salvatore V Giofrè, Enza M Galati, Maria T Monforte, Nicola Cicero, Valeria D'Angelo, Gianpaolo Grassi, Clara Circosta
Aldose reductase (ALR2) is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors (ARIs) is currently very important. The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications. Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes...
February 7, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29423994/functional-effects-of-synthetic-cannabinoids-versus-%C3%AE-9-thc-in-mice-on-body-temperature-nociceptive-threshold-anxiety-cognition-locomotor-exploratory-parameters-and-depression
#4
Shaul Schreiber, Miaad Bader, Tatiana Lenchinski, Inbar Meningher, Vardit Rubovitch, Yiffat Katz, Etia Cohen, Yankel Gabet, Michal Rotenberg, Ehud Udi Wolf, Chaim G Pick
Synthetic cannabinoids are psychoactive substances designed to mimic the euphorigenic effects of the natural cannabis. Novel unregulated compounds appear once older compounds become illegal. It has been previously reported that synthetic cannabinoids are different than Δ9 -tetrahydrocannabinol (Δ9 -THC) as they have chemical structures unrelated to Δ9 -THC, different metabolism and, often, greater toxicity. This study aimed to investigate the effects of three novel synthetic cannabinoids and pure Δ9 -THC on body temperature, nociceptive threshold, anxiety, memory function, locomotor and exploratory parameters, and depression...
February 8, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29413581/analytical-studies-on-the-2-naphthoyl-substituted-1-n-pentylindoles-regioisomeric-synthetic-cannabinoids
#5
Amber Thaxton-Weissenfluh, Amsha S Alsegiani, Younis Abiedalla, Jack DeRuiter, Forrest Smith, C Randall Clark
The six 1-n-pentyl-2-, 3-, 4-, 5-, 6- and 7-(2-naphthoyl)-indoles each have the same substituents attached to the indole ring, identical elemental composition (C24H23NO) yielding identical nominal and accurate masses. The electron ionization mass spectra of the 2-naphthoyl substituted isomers share equivalent major fragment ions resulting from cleavage of the groups attached to the central indole nucleus with some differences in relative abundances. These six regioisomers were successfully resolved on an Rtx-5 and Rxi-17Sil MS stationary phases and the molecules having both substituent groups on the same side of the indole ring (1,2- and 1,7-substituents) show the least retention...
January 31, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29411732/street-drug-use-among-emergency-patients-in-a-public-hospital-in-turkey
#6
F T Caliskan, I Toker, R Toktas, Z Temizyurek, O Unek, B Zirek, O Karcioglu
BACKGROUND: Country-specific numbers of street drug (SD) users are well documented. However, little data exists regarding these patients' clinical presentations and outcomes in the emergency department (ED). Therefore, management of these patients in the emergency setting is still a subject of debate. OBJECTIVES: The aim of this study is to determine the symptoms and signs of SD users presenting to the ED, and to report the substances, treatments, and outcomes. MATERIALS AND METHODS: In this single-center study, symptoms, clinical findings, diagnoses, and outcomes of patients who reported to have used SDs or were diagnosed as SD users were investigated within a 1-year study period...
January 2018: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/29410032/the-synthetic-cannabinoid-xlr-11-induces-in-vitro-nephrotoxicity-by-impairment-of-endocannabinoid-mediated-regulation-of-mitochondrial-function-homeostasis-and-triggering-of-apoptosis
#7
João P Silva, Helena Carmo, Félix Carvalho
Synthetic cannabinoids (SCBs)-related intoxications and deaths have been increasingly reported, turning its widespread recreational use into a major public health concern. Specifically, a direct link between SCBs and acute kidney injury (AKI) has been established. XLR-11 is an SCB commonly found in the toxicological analysis of patients with SCB-associated AKI. However, the pathophysiology of AKI among SCB consumers remains unknown. This work thus represents the first in vitro assessment of SCB nephrotoxicity, as a first approach to identify its cellular targets...
February 3, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29408093/analysis-of-the-pharmacological-properties-of-jwh-122-isomers-and-thj-2201-rcs-4-and-ab-chminaca-in-hek293t-cells-and-hippocampal-neurons
#8
Willard J Costain, Ingrid Rasquinha, Tanya Comas, Melissa Hewitt, Amy Aylsworth, Yanouchka Rouleau, Vincent Marleau, Evelyn C Soo, Joseph S Tauskela
Synthetic cannabinoids are marketed as legal alternatives to Δ9-THC, and are a growing worldwide concern as these drugs are associated with severe adverse effects. Unfortunately, insufficient information regarding the physiological and pharmacological effects of emerging synthetic cannabinoids (ESCs) makes their regulation by government authorities difficult. One strategy used to evade regulation is to distribute isomers of regulated synthetic cannabinoids. This study characterized the pharmacological properties of a panel of ESCs in comparison to Δ9-THC, as well as six JWH-122 isomers relative to its parent compound (JWH-122-4)...
February 2, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29407568/evaluation-of-cognitive-functions-in-individuals-with-synthetic-cannabinoid-use-disorder-and-comparison-to-individuals-with-cannabis-use-disorder
#9
Hanife Yilmaz Cengel, Muge Bozkurt, Cuneyt Evren, Gokhan Umut, Cahit Keskinkilic, Ruken Agachanli
The use of synthetic cannabinoid has been increasing throughout the world and has become a major public health problem. The present study aims to investigate the attention, memory, visuospatial and executive functions in individuals with synthetic cannabinoid use disorder and compare the results with findings obtained from individuals with cannabis use disorder and healthy volunteers with no substance use. Fifty-two patients with synthetic cannabinoid use disorder, 45 patients with cannabis use disorder and 48 healthy control group males were included in the study...
January 31, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29404633/-bonzai-lead-and-bath-salt-poisoning-with-new-and-old-drugs-synthetic-amphetamines-cathinones-cannabinoids-and-opioids-an-overview
#10
REVIEW
J Strube, A Schaper
BACKGROUND: There has been an increase in the number of serious poisonings and deaths after the use of new psychoactive substances (NPS). These are usually bought online: sometimes legally, often illegally or "in the grey area". OBJECTIVES: Characteristics of different NPS. Legal status concerning the New Psychoactive Substances Act (NpSG). Risk assessment of several substance groups, possible complications of acute poisonings, therapeutic recommendations...
February 5, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/29403341/in-vitro-metabolite-profiling-of-adb-fubinaca-a-new-synthetic-cannabinoid
#11
Jeremy Carlier, Xingxing Diao, Ariane Wohlfarth, Karl Scheidweiler, Marilyn A Huestis
Metabolite profiling of novel psychoactive substances (NPS) is critical for documenting drug consumption. N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA) is an emerging synthetic cannabinoid whose toxicological and metabolic data are currently unavailable. We aimed to determine optimal markers for identifying ADB-FUBINACA intake. Metabolic stability was evaluated with human liver microsome incubations. Metabolites were identified after 1 and 3 h incubation with pooled human hepatocytes, liquid chromatography- high resolution mass spectrometry in positive-ion mode (5600+ TripleTOF®, Sciex) and several data mining approaches (MetabolitePilot™, Sciex)...
July 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/29399427/myocardial-ischemia-with-cannabinoid-use-in-an-adolescent
#12
Jeet J Mehta, Arjun K Mahendran, Ravi K Bajaj, Arpan R Doshi
A 16-year-old male presented to the emergency department with chest pain after smoking a synthetic cannabinoid from a vape pen. He had rising troponin I levels, and his exercise stress echocardiogram showed distal apical and septal hypokinesis that resolved at six-month follow-up. This case report raises concern about cardiac ischemia related to synthetic cannabinoid abuse in the pediatric population in the current era of cannabis legalization.
November 30, 2017: Curēus
https://www.readbyqxmd.com/read/29398403/cannabinoid-markers-in-biological-fluids-and-tissues-revealing-intake
#13
REVIEW
Marilyn A Huestis, Michael L Smith
Understanding cannabis and synthetic cannabinoid intake history is vital for treating drug dependence, investigating cannabinoid effects, and providing information to healthcare personnel, medical examiners, and public health officials; this is particularly relevant today with cannabis medicalization and legalization. Required information includes identifying exposure, time of use, frequency of use, relapse, withdrawal, and predicting cannabinoid effects. Recent controlled cannabinoid administration studies enable the development of models and markers to better identify patterns of intake and exposure...
February 2, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29388323/effects-of-repeated-long-term-psychosocial-stress-and-acute-cannabinoid-exposure-on-mouse-corticostriatal-circuitries-implications-for-neuropsychiatric-disorders
#14
Jordi Tomas-Roig, Fabiana Piscitelli, Vanesa Gil, Ester Quintana, Lluís L Ramió-Torrentà, Jose Antonio Del Río, Timothy Patrick Moore, Hope Agbemenyah, Gabriela Salinas, Claudia Pommerenke, Stephan Lorenzen, Tim Beißbarth, Sigrid Hoyer-Fender, Vincenzo Di Marzo, Ursula Havemann-Reinecke
INTRODUCTION: Vulnerability to psychiatric manifestations is achieved by the influence of genetic and environment including stress and cannabis consumption. Here, we used a psychosocial stress model based on resident-intruder confrontations to study the brain corticostriatal-function, since deregulation of corticostriatal circuitries has been reported in many psychiatric disorders. CB1 receptors are widely expressed in the central nervous system and particularly, in both cortex and striatum brain structures...
January 31, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29385930/pro-psychotic-effects-of-synthetic-cannabinoids-interactions-with-central-dopamine-serotonin-and-glutamate-systems
#15
William E Fantegrossi, Cathryn D Wilson, Michael D Berquist
An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elicited pro-psychotic effects is unknown, but given the ubiquitous neuromodulatory functions of the endocannabinoid system, it seems likely that agonist actions at cannabinoid type-1 receptors (CB1Rs) might modulate the functions of other neurotransmitter systems known to be involved in schizophrenia...
January 31, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29385414/newly-emerging-drugs-of-abuse-and-their-detection-methods-an-aclps-critical-review
#16
Li Liu, Sarah E Wheeler, Raman Venkataramanan, Jacqueline A Rymer, Anthony F Pizon, Michael J Lynch, Kenichi Tamama
Objectives: Illicit drug abuse has reached an epidemic level in the United States. Drug overdose has become the leading cause of injury-related deaths since 2008 due to the recent surge of opioid overdose by heroin, controlled prescription drugs, and nonmethadone synthetic opioids. Synthetic designer drugs such as synthetic cathinones ("bath salts") and synthetic cannabinoids ("Spice" and "K2") continue to emerge and attract recreational users. Methods: The emergence of new drugs of abuse poses a steep challenge for clinical toxicology laboratories...
January 29, 2018: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29376443/old-and-new-synthetic-cannabinoids-lessons-from-animal-models
#17
Mary Tresa Zanda, Liana Fattore
Synthetic cannabinoids have long been studied for their therapeutic potentials. However, during the last decade, new generations of synthetic cannabinoid agonists appeared on the drug market. These new psychoactive substances are currently sold as 'marijuana-like' products as they claim to mimic the effects of the psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC). Yet, their effects are more intense and potent than THC, typically last longer and are often associated to serious psychiatric consequences...
January 29, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29367864/identification-and-quantification-of-mepirapim-and-acetyl-fentanyl-in-authentic-human-whole-blood-and-urine-samples-by-gc-ms-ms-and-lc-ms-ms
#18
Akira Mochizuki, Hiroko Nakazawa, Noboru Adachi, Kenichi Takekawa, Hideki Shojo
Purpose: We encountered a curious case in which two male subjects self-administered mepirapim plus acetyl fentanyl by different routes, i.e., intravenously and by inhalation. We have thus established a detailed procedure for quantification of mepirapim and acetyl fentanyl in whole blood and urine specimens using gas chromatography (GC)-tandem mass spectrometry (MS/MS). Methods: The GC-MS/MS method was validated for linearity, extraction recovery, accuracy, and precision...
2018: Forensic Toxicology
https://www.readbyqxmd.com/read/29367862/evaluation-of-carboxamide-type-synthetic-cannabinoids-as-cb1-cb2-receptor-agonists-difference-between-the-enantiomers
#19
Takahiro Doi, Takaomi Tagami, Akihiro Takeda, Akiko Asada, Yoshiyuki Sawabe
Recently, carboxamide-type synthetic cannabinoids have been distributed globally as new psychoactive substances (NPS). Some of these compounds possess asymmetric carbon, which is derived from an amide moiety composed of amino acid derivatives (i.e., amides or esters of amino acids). In this study, we synthesized both enantiomers of synthetic cannabinoids, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(2-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA 2-fluorobenzyl isomer), N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (APP-CHMINACA), ethyl [1-(5-fluoropentyl)-1H-indazole-3-carbonyl]valinate (5F-EMB-PINACA), ethyl [1-(4-fluorobenzyl)-1H-indazole-3-carbonyl]valinate (EMB-FUBINACA), and methyl 2-[1-(4-fluorobenzyl)-1H-indole-3-carboxamido]-3,3-dimethylbutanoate (MDMB-FUBICA), which were reported as NPS found in Europe from 2014 to 2015, to evaluate their activities as CB1/CB2 receptor agonists...
2018: Forensic Toxicology
https://www.readbyqxmd.com/read/29350472/the-chemistry-and-pharmacology-of-synthetic-cannabinoid-sdb-006-and-its-regioisomeric-fluorinated-and-methoxylated-analogues
#20
Samuel D Banister, Alexander Olson, Matthew Winchester, Jordyn Stuart, Amelia R Edington, Richard C Kevin, Mitchell Longworth, Marco Herrera, Mark Connor, Iain S McGregor, Roy R Gerona, Michael Kassiou
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 analogues 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)...
January 19, 2018: Drug Testing and Analysis
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