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Christian Lehmann, Nicholas B Fisher, Barna Tugwell, Anna Szczesniak, Mel Kelly, Juan Zhou
BACKGROUND: Destruction of the insulin-producing beta cells in type 1 diabetes (T1D) is induced by invasion of immune cells causing pancreatic inflammation. Cannabidiol (CBD), a phytocannabinoid, derived from the plant, Cannabis sativa, was shown to lower the incidence of diabetes in non-obese diabetic (NOD) mice, an animal model of spontaneous T1D development. OBJECTIVE: The goal of this study was to investigate the impact of experimental CBD treatment on early pancreatic inflammation in T1D by intravital microscopy (IVM) in NOD mice...
October 18, 2016: Clinical Hemorheology and Microcirculation
Luara A Batista, Andrea S Haibara, Luiz C Schenberg, Fabricio A Moreira
Selective stimulation of carotid chemoreceptors by intravenous infusion of low doses of potassium cyanide (KCN) produces short-lasting escape responses that have been proposed as a model of panic attack. In turn, preclinical studies suggest that facilitation of the endocannabinoid system attenuate panic-like responses. Here, we compared the effects of cannabinoid-related compounds to those of alprazolam, a clinically effective panicolytic, on the duration of the escape reaction induced by intravenous infusion of KCN (80μg) in rats...
October 11, 2016: Behavioural Brain Research
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
Katalin Solymosi, Attila Köfalvi
Cannabis is one of the earliest cultivated plants. Cannabis of industrial utility and culinary value is generally termed as hemp. Conversely, cannabis that is bred for medical, spiritual and recreational purposes is called marijuana. The female marijuana plant produces a significant quantity of bio- and psychoactive phytocannabinoids, which regained the spotlight with the discovery of the endocannabinoid system of the animals in the early 90's. Nevertheless, marijuana is surrounded by controversies, debates and misconceptions related to its taxonomic classification, forensic identification, medical potential, legalization and its long-term health consequences...
October 4, 2016: Mini Reviews in Medicinal Chemistry
Klaudyna Fidyt, Anna Fiedorowicz, Leon Strządała, Antoni Szumny
Natural bicyclic sesquiterpenes, β-caryophyllene (BCP) and β-caryophyllene oxide (BCPO), are present in a large number of plants worldwide. Both BCP and BCPO (BCP(O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells. Nevertheless, their antineoplastic effects have hardly been investigated in vivo. In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells. The mechanisms underlying the anticancer activities of these sesquiterpenes are poorly described...
September 30, 2016: Cancer Medicine
Caroline Turcotte, Marie-Renée Blanchet, Michel Laviolette, Nicolas Flamand
Since the identification of cannabinoid receptors in the 1990s, a research field has been dedicated to exploring the role of the cannabinoid system in immunity and the inflammatory response in human tissues and animal models. Although the cannabinoid system is present and crucial in many human tissues, studying the impact of cannabinoids on the lungs is particularly relevant because of their contact with exogenous cannabinoids in the context of marijuana consumption. In the past two decades, the scientific community has gathered a large body of evidence supporting that the activation of the cannabinoid system alleviates pain and reduces inflammation...
2016: Frontiers in Pharmacology
Valerie C M Shang, David A Kendall, Richard E Roberts
Despite pharmacological treatment, bronchial hyperresponsiveness continues to deteriorate as airway remodelling persists in airway inflammation. Previous studies have demonstrated that the phytocannabinoid Δ(9)-tetrahydrocannabinol (THC) reverses bronchoconstriction with an anti-inflammatory action. The aim of this study was to investigate the effects of THC on bronchial epithelial cell permeability after exposure to the pro-inflammatory cytokine, TNFα. Calu-3 bronchial epithelial cells were cultured at air-liquid interface...
September 15, 2016: Biochemical Pharmacology
A I Fraguas-Sánchez, A Fernández-Carballido, A I Torres-Suárez
INTRODUCTION: The term "cannabinoids" designates a family of compounds with activity upon cannabinoid receptors. Cannabinoids are classified in three groups: phytocannabinoids, endocannabinoids, and the synthetic analogues of both groups. They have become a promising tool in the treatment of cancer disease, not only as palliative agents, but also as antitumor drugs, due to their ability to inhibit the proliferation, adhesion, migration, invasion, and angiogenesis of tumour cells. Two of the cancers where they have shown high anticancer activity are breast and prostate tumours...
September 16, 2016: Expert Opinion on Investigational Drugs
Alessia Ligresti, Luciano De Petrocellis, Vincenzo Di Marzo
Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one Δ(9)-tetrahydrocannabinol, and 2) the adaptive pro-homeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs...
October 2016: Physiological Reviews
Pellegrino Lippiello, Simona Balestrini, Antonio Leo, Antonietta Coppola, Rita Citraro, Maurizio Elia, Emilio Russo, Giovambattista De Sarro
BACKGROUND: Several antiepileptic drugs (AEDs), about 25, are currently clinically available for the treatment of patients with epilepsy. Despite this armamentarium and the many recently introduced AEDs, no major advances have been achieved considering the number of drug resistant patients, while many benefits have been indeed obtained for other clinical outcomes (e.g. better tolerability, less interactions). Cannabinoids have long been studied for their potential therapeutical use and more recently phytocannabinoids have been considered a valuable tool for the treatment of several neurological disorders including epilepsy...
August 31, 2016: Current Pharmaceutical Design
Khalid A Jadoon, Stuart H Ratcliffe, David A Barrett, E Louise Thomas, Colin Stott, Jimmy D Bell, Saoirse E O'Sullivan, Garry D Tan
OBJECTIVE: Cannabidiol (CBD) and Δ(9)-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks...
October 2016: Diabetes Care
Mason M Silveira, Wendy K Adams, Maria Morena, Matthew N Hill, Catharine A Winstanley
BACKGROUND: Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ9-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana...
August 23, 2016: Journal of Psychiatry & Neuroscience: JPN
Huan Huang, Avery L McIntosh, Gregory G Martin, Danilo Landrock, Sarah Chung, Kerstin K Landrock, Lawrence J Dangott, Shengrong Li, Ann B Kier, Friedhelm Schroeder
Endocannabinoids (ECs) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecules to intracellular targets. While three different fatty acid binding proteins (FABP3, -5, and -7) serve this function in brain, relatively little is known about how such hydrophobic ECs and cannabinoids are transported within the liver. The most prominent hepatic FABP, liver fatty acid binding protein (FABP1 or L-FABP), has high affinity for arachidonic acid (ARA) and ARA-CoA, suggesting that FABP1 may also bind ARA-derived ECs (AEA and 2-AG)...
September 20, 2016: Biochemistry
Travis W Grim, Anthony J Morales, Maciej M Gonek, Jenny L Wiley, Brian F Thomas, Gregory W Endres, Laura J Sim-Selley, Dana E Selley, Sidney S Negus, Aron H Lichtman
Synthetic cannabinoids (SCs) represent an emerging new class of abused drugs that widely differ from each other and from the phytocannabinoid Δ9-tetrahydrocannabinol (THC) in cannabinoid-1 receptor (CB1R) selectivity, potency, and efficacy. As these pharmacological parameters offer critical information to understand drug action, the present study investigated in vivo CB1R efficacy and selectivity of THC, two well-characterized SCs (WIN55,212-2 and CP55,940), and three abused SCs possessing largely unknown pharmacology (JWH-073, CP47,497, and A-834,735-D) in CB1 (+/+), (+/-), and (-/-) mice...
August 17, 2016: Journal of Pharmacology and Experimental Therapeutics
Xiaoru Dong, Liliang Li, Yonghong Ye, Lixing Zheng, Yan Jiang
Simultaneous determination of major phytocannabinoids (THC, CBD, CBN), their main metabolites (11-OH-THC, THC-COOH, THC-COOH-glucuronide) and common synthetic cannabinoids (HU-210, JWH-018, JWH-073, JWH-250) remains an issue in forensic toxicology. The present study has developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to simultaneously detect the above 10 analytes in human urine samples. The chromatographic separation was performed on an ACQUITY UPLC(®)BEH Phenyl 1.7μm (2.1×100mm) column, using a mobile phase consisting of 0...
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Daniel I Brierley, James Samuels, Marnie Duncan, Benjamin J Whalley, Claire M Williams
RATIONALE: The appetite-stimulating properties of cannabis are well documented and have been predominantly attributed to the hyperphagic activity of the psychoactive phytocannabinoid, ∆(9)-tetrahydrocannabinol (∆(9)-THC). However, we have previously shown that a cannabis extract devoid of ∆(9)-THC still stimulates appetite, indicating that other phytocannabinoids also elicit hyperphagia. One possible candidate is the non-psychoactive phytocannabinoid cannabigerol (CBG), which has affinity for several molecular targets with known involvement in the regulation of feeding behaviour...
October 2016: Psychopharmacology
David J Marcus, Michael L Zee, Brian J Davis, Chris P Haskins, Mary-Jeanette Andrews, Randa Amin, Angela N Henderson-Redmond, Ken Mackie, Traci A Czyzyk, Daniel J Morgan
Multiple lines of evidence implicate the endocannabinoid signaling system in the modulation of metabolic disease. Genetic or pharmacological inactivation of CB1 in rodents leads to reduced body weight, resistance to diet-induced obesity, decreased intake of highly palatable food, and increased energy expenditure. Cannabinoid agonists stimulate feeding in rodents and increased levels of endocannabinoids can disrupt lipid metabolism. Therefore, the hypothesis that sustained endocannabinoid signaling can lead to obesity and diabetes was examined in this study using S426A/S430A mutant mice expressing a desensitization-resistant CB1 receptor...
2016: PloS One
Barbara Romano, Ester Pagano, Pierangelo Orlando, Raffaele Capasso, Maria Grazia Cascio, Roger Pertwee, Vincenzo Di Marzo, Angelo A Izzo, Francesca Borrelli
Historical and scientific evidence suggests that Cannabis use has immunomodulatory and anti-inflammatory effects. We have here investigated the effect of the non-psychotropic phytocannabinoid Δ(9)-tetrahydrocannabivarin (THCV) and of a Cannabis sativa extract with high (64.8%) content in THCV (THCV-BDS) on nitric oxide (NO) production, and on cannabinoid and transient receptor potential (TRP) channel expression in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. THCV-BDS and THCV exhibited similar affinity in radioligand binding assays for CB1 and CB2 receptors, and inhibited, via CB2 but not CB1 cannabinoid receptors, nitrite production evoked by LPS in peritoneal macrophages...
August 3, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Tim Karl, Brett Garner, David Cheng
Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by progressive loss of cognition. Over 35 million individuals currently have AD worldwide. Unfortunately, current therapies are limited to very modest symptomatic relief. The brains of AD patients are characterized by the deposition of amyloid-β and hyperphosphorylated forms of tau protein. AD brains also show neurodegeneration and high levels of oxidative stress and inflammation. The phytocannabinoid cannabidiol (CBD) possesses neuroprotective, antioxidant and anti-inflammatory properties and reduces amyloid-β production and tau hyperphosphorylation in vitro...
July 28, 2016: Behavioural Pharmacology
Robert B Zurier, Sumner H Burstein
Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs). As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis. A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ(9)-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented...
July 19, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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