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Massimo Nabissi, Maria Beatrice Morelli, Massimo Offidani, Consuelo Amantini, Silvia Gentili, Alessandra Soriani, Claudio Cardinali, Pietro Leoni, Giorgio Santoni
Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy...
October 18, 2016: Oncotarget
Tian Hua, Kiran Vemuri, Mengchen Pu, Lu Qu, Gye Won Han, Yiran Wu, Suwen Zhao, Wenqing Shui, Shanshan Li, Anisha Korde, Robert B Laprairie, Edward L Stahl, Jo-Hao Ho, Nikolai Zvonok, Han Zhou, Irina Kufareva, Beili Wu, Qiang Zhao, Michael A Hanson, Laura M Bohn, Alexandros Makriyannis, Raymond C Stevens, Zhi-Jie Liu
Cannabinoid receptor 1 (CB1) is the principal target of Δ(9)-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study...
October 20, 2016: Cell
Dingqiang Lu, Fuping Lu, Guangchang Pang
In the current study, a novel double-layer gold nanoparticles-electrochemical immunosensor electrode immobilized with tetrahydrocannabinol (THC) antibody derived from Balb/c mice was developed. To increase the fixed quantity of antibodies and electrochemical signals, an electrochemical biosensing signal amplification system was utilized with gold nanoparticles-thionine-chitosan absorbing horseradish peroxidase (HRP). In addition, a transmission electron microscope (TEM) was used to characterize the nanogold solution...
October 17, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jenny L Wiley, Julie A Marusich, Brian F Thomas
Originally developed as research tools for use in structure-activity relationship studies, synthetic cannabinoids contributed to significant scientific advances in the cannabinoid field. Unfortunately, a subset of these compounds was diverted for recreational use beginning in the early 2000s. As these compounds were banned, they were replaced with additional synthetic cannabinoids with increasingly diverse chemical structures. This chapter focuses on integration of recent results with those covered in previous reviews...
October 18, 2016: Current Topics in Behavioral Neurosciences
Bin Lin, Heng Yu, Yuting Lin, Chao Cai, Huoquan Lu, Xinbo Zhu
The aim of the present study was to assess the neuroprotective effects of tetrahydrocurcumin (THC) in a mouse model of cerebral ischemia/reperfusion (I/R) injury, and to investigate the involvement of Golgi reassembly and stacking protein 65 (GRASP65) and the extracellular signal‑regulated kinase (ERK) signaling pathway. Cerebral I/R injury was induced using the Pulsinelli four‑vessel occlusion method. After 5 min of reperfusion, mice received THC (5, 10 or 25 mg/kg) or saline by intraperitoneal injection...
October 6, 2016: Molecular Medicine Reports
José A S Crippa, Ana C S Crippa, Jaime E C Hallak, Rocio Martín-Santos, Antonio W Zuardi
Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time...
2016: Frontiers in Pharmacology
Tingting Yue, Fahe Chai, Jingnan Hu, Ming Jia, Xiaofeng Bao, Zhenhua Li, Liqang He, Lei Zu
The natural gas vehicle market is rapidly developing throughout the world, and the majority of such vehicles operate on compressed natural gas (CNG). However, most studies on the emission characteristics of CNG vehicles rely on laboratory chassis dynamometer measurements, which do not accurately represent actual road driving conditions. To further investigate the emission characteristics of CNG vehicles, two CNG city buses and two CNG coaches were tested on public urban roads and highway sections. Our results show that when speeds of 0-10km/hr were increased to 10-20km/hr, the CO2, CO, nitrogen oxide (NOx), and total hydrocarbon (THC) emission factors decreased by (71...
October 2016: Journal of Environmental Sciences (China)
Pedram Ramin, Andreas Libonati Brock, Fabio Polesel, Ana Causanilles, Erik Emke, Pim de Voogt, Benedek Gy Plosz
Sewer pipelines, although primarily designed for sewage transport, can also be considered as bioreactors. In-sewer processes may lead to significant variations of chemical loadings from source release points to the treatment plant influent. In this study, we assessed in-sewer utilization of growth substrates (primary metabolic processes) and transformation of illicit drug biomarkers (secondary metabolic processes) by suspended biomass. Sixteen drug biomarkers were targeted, including mephedrone, methadone, cocaine, heroin, codeine and tetrahydrocannabinol (THC) and their major human metabolites...
October 14, 2016: Environmental Science & Technology
Patrick Vermersch, Maria Trojano
BACKGROUND: Tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) is an add-on therapy for moderate-to-severe multiple sclerosis (MS)-related drug-resistant spasticity (MSS). AIM: The MOVE-2 EU study collected data from everyday clinical practice concerning the effectiveness and tolerability of THC:CBD. METHODS: This was an observational, prospective, multicentre, non-interventional study. Patients with resistant MSS prescribed add-on THC:CBD oromucosal spray according to approved labelling, were followed for 3 months...
October 13, 2016: European Neurology
Folasade P May, Vineet S Rolston, Elliot B Tapper, Ashwini Lakshmanan, Sammy Saab, Vinay Sundaram
BACKGROUND: Alcoholic Hepatitis (AH) is major source of alcohol-related mortality and health care expenditures in the United States. There is insufficient information regarding the role of race and ethnicity on healthcare utilization and outcomes for patients with AH. We aimed to determine whether there are racial/ethnic differences in resource utilization and inpatient mortality in patients hospitalized with AH. METHODS: We analyzed data from the Nationwide Inpatient Sample (NIS), years 2008-2011...
October 10, 2016: BMC Gastroenterology
Lumír Ondřej Hanuš, Stefan Martin Meyer, Eduardo Muñoz, Orazio Taglialatela-Scafati, Giovanni Appendino
Covering up to January 2016Cannabis sativa L. is a prolific, but not exclusive, producer of a diverse group of isoprenylated resorcinyl polyketides collectively known as phytocannabinoids. The modular nature of the pathways that merge into the phytocannabinoid chemotype translates in differences in the nature of the resorcinyl side-chain and the degree of oligomerization of the isoprenyl residue, making the definition of phytocannabinoid elusive from a structural standpoint. A biogenetic definition is therefore proposed, splitting the phytocannabinoid chemotype into an alkyl- and a β-aralklyl version, and discussing the relationships between phytocannabinoids from different sources (higher plants, liverworts, fungi)...
October 10, 2016: Natural Product Reports
Marjan de Vries, Dagmar C M van Rijckevorsel, Kris C P Vissers, Oliver H G Wilder-Smith, Harry van Goor
BACKGROUND & AIMS: Delta-9-tetrahydrocannabinol (THC) is the most abundant cannabinoid from the plant Cannabis sativa. There is only equivocal evidence that THC has analgesic effects. We performed a phase 2 controlled trial to evaluate the analgesic efficacy, pharmacokinetics, safety, and tolerability of an oral tablet containing purified THC in patients with chronic abdominal pain. METHODS: Sixty-five patients with chronic abdominal pain for 3 months or more (numeric rating scale scores of 3 or more) after surgery or due to chronic pancreatitis were randomly assigned to groups given the THC tablet or identical matching placebos for 50-52 days...
October 5, 2016: Clinical Gastroenterology and Hepatology
Percy Bondallaz, Bernard Favrat, Haïthem Chtioui, Eleonora Fornari, Philippe Maeder, Christian Giroud
Traffic policies show growing concerns about driving under the influence of cannabis, since cannabinoids are one of the most frequently encountered psychoactive substances in the blood of drivers who are drug-impaired and/or involved in accidents, and in the context of a legalization of medical marijuana and of recreational use. The neurobiological mechanisms underlying the effects of cannabis on safe driving remain poorly understood. In order to better understand its acute and long-term effects on psychomotor functions involved in the short term ability and long-term fitness to drive, experimental research has been conducted based on laboratory, simulator or on-road studies, as well as on structural and functional brain imaging...
September 16, 2016: Forensic Science International
Courtney E Hart, Michael J Lauth, Cassidy S Hunter, Brennan R Krasny, Kristin M Hardy
The xenoestrogen 4-nonylphenol (NP) is a ubiquitous aquatic pollutant and has been shown to impair reproduction, development, growth and, more recently, immune function in marine invertebrates. We investigated the effects of short-term (7 d) exposure to low (2 μg l(-1)) and high (100 μg l(-1)) levels of NP on cellular and humoral elements of the innate immune response of Crassostrea gigas to a bacterial challenge. To this end, we measured 1) total hemocyte counts (THC), 2) relative transcript abundance of ten immune-related genes (defh1, defh2, bigdef1, bigdef2, bpi, lysozyme-1, galectin, C-type lectin 2, timp, and transglutaminase) in the hemocytes, gill and mantle, and 3) hemolymph plasma lysozyme activity, following experimental Vibrio campbellii infection...
September 28, 2016: Fish & Shellfish Immunology
Emma Gracia-Lor, Ettore Zuccato, Sara Castiglioni
The estimation of illicit drugs use through wastewater analysis has become an important issue in the last few years due to their large worldwide consumption, which results in economic, social and health costs. The amounts of urinary biomarkers of illicit drugs (selected drugs or their metabolites) measured in wastewater are used to back-calculate the consumption of a particular drug by the population and to monitor temporal and spatial trends of illicit drug use in a community. The reliability of back-calculation depends on different factors, one being the accuracy of correction factors...
September 29, 2016: Science of the Total Environment
David S Jacobs, Stephen J Kohut, Shan Jiang, Spyros P Nikas, Alexandros Makriyannis, Jack Bergman
Recent clinical and preclinical research has suggested that cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) have interactive effects on measures of cognition; however, the nature of these interactions is not yet fully characterized. To address this, we investigated the effects of Δ9-THC and CBD independently and in combination with proposed therapeutic dose ratios of 1:1 and 1:3 Δ9-THC:CBD in adult rhesus monkeys (n = 6) performing a stop signal task (SST). Additionally, the development of tolerance to the effects of Δ9-THC on SST performance was evaluated by determining the effects of acutely administered Δ9-THC (0...
October 2016: Experimental and Clinical Psychopharmacology
Ken Kulig
Workplace urine drug testing for an inactive THC metabolite is common in both federally regulated and non-regulated drug testing. A positive result does not document impairment, or even recent use, when impairment is likely the most important parameter being searched for by the drug testing procedure. Most cannabinoid testing does not detect imported synthetics. Currently, urine is the most widely tested matrix, but blood, plasma, oral fluid, and hair may also be accepted in federally regulated testing in the future...
September 29, 2016: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
Young Ah Seo, Ruvin Kumara, Herbert A Wetli, Marianne Wessling-Resnick
Divalent Metal Transporter-1 (DMT1) mediates dietary iron uptake across the intestinal mucosa and facilitates peripheral delivery of iron released by transferrin in the endosome. Here we report that classical cannabinoids (Δ(9)-THC), non-classical cannabinoids (CP55,940), aminoalkylindoles (WIN55,212-2), and endocannabinoids (anandamide) reduce (55)Fe and (54)Mn uptake by HEK293T(DMT1) cells stably expressing the transporter. siRNA knockdown of cannabinoid receptor-2 (CB2) abrogated inhibition. CB2 is G protein-coupled receptor that negatively regulates signal transduction cascades involving serine/threonine kinases...
September 28, 2016: Biochemical Journal
Camille Cohier, Bruno Mégarbane, Olivier Roussel
Driving after illicit drug use is a worldwide growing concern requiring rapid and sensitive screening at the roadside. It is noteworthy that the sampling method used to collect oral fluid (OF) may significantly influence drug concentrations in the collected sample and thus alter the accuracy of the measurement. We evaluated two OF collection devices, Quantisal(®) and Certus(®) collectors, for their suitability for collecting samples to allow laboratory confirmation of driving after illicit drug use. Four parameters were studied including (i) the collected OF volume; (ii) the recovery efficiency using OFs spiked with opiates, cannabinoids, amphetamines, cocaine and its metabolites; (iii) drug stability after storage for 1, 7 and 14 days at -20°C, +4°C and room temperature; and (iv) the impact of mouth cells present in the collected OF on drug stability...
September 27, 2016: Journal of Analytical Toxicology
R M Craft, A E Haas, J L Wiley, Z Yu, B H Clowers
The gonadal hormones testosterone (T) in adult males and estradiol (E2) in adult females have been reported to modulate behavioral effects of ∆(9)-tetrahydrocannabinol (THC). This study determined whether activational effects of T and E2 are sex-specific, and whether hormones modulate production of the active metabolite 11-hydroxy-THC (11-OH-THC) and the inactive metabolite 11-nor-9-carboxy-THC (THC-COOH). Adult male and female rats were gonadectomized (GDX) and treated with nothing (0), T (10-mm Silastic capsule/100g body weight), or E2 (1-mm Silastic capsule/rat)...
September 24, 2016: Pharmacology, Biochemistry, and Behavior
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