Canabinoid

Translational research made with Cannabis sativa L. and its biocompounds provides data for some targeted diseases, as also symptoms associated with Autism Spectrum Disorders (ASDs). The main compounds ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are capable of modulating the endocannabinoid system since its dysregulation interferes with the pathophysiology of ASDs there are clinical evidence for its potential use in the treatment of the disease. Conventional therapy still has limitations, as it does not always treat the central symptoms, and there are many patients who do not respond to treatment, which demands more research on new therapies...

Orexin 1 receptors (Orx1R) and cannabinoid 1 receptors (CB1R) are implicated in migraine pathophysiology. This study evaluated the potential involvement of Orx1R and CB1R within the ventrolateral periaqueductal gray matter (vlPAG) in the modulation of anxiety-like behavior and social interaction of migraineurs rats. A rat model of migraine induced by recurrent administration of nitroglycerin (NTG) (5 mg/kg/i.p.). The groups of rats (n = 6) were then subjected to intra-vlPAG microinjection of orexin-A (25, 50 pM), and Orx1R antagonist SB334867 (20, 40 nM) or AM 251 (2, 4 µg) as a CB1R antagonist...

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality, and there is still no proven effective therapy. The endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the transforming growth factor beta (TGF-β) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin A. This study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1) antagonist) on NAFLD induced with a choline-deficient (CD) diet in rats, as well as to detect whether it can alter the hepatic expression of activin A and follistatin...

OBJECTIFS: L'infarctus rénal est une pathologie rare dont les manifestations cliniques peu spécifiques compliquent le diagnostic, et le retard diagnostic expose au risque d'insuffisance rénale. MéTHODES: Sur une période de 24 mois (mars 2013 - février 2015), nous avons recensé les patients présentant un infarctus rénal, hospitalisé en néphrologie, cardiologie ou médecine interne sur une base déclarative. Nous avons rapporté les facteurs de risque cardiovasculaire, la présentation clinique, biologique et scannographique...

Pharmacological blockade of N-acylethanolamine acid amidase (NAAA) activity is an available approach for inflammation and pain control through restoring the ability of endogenous PEA. But the recently reported NAAA inhibitors suffer from the chemical and biological unstable properties, which restrict functions of NAAA inhibition in vivo. It is still unrevealed whether systematic inhibition of NAAA could modulate PEA-mediated pain signalings. Here we reported an oxazolidinone imide compound 3-(6-phenylhexanoyl) oxazolidin-2-one (F96), which potently and selectively inhibited NAAA activity (IC50 = 270 nM)...

On 10th of July 2014 the European Court of Justice made in his decisions in relation to the cases D. (C-358/13) and G. (C-181/14) an interpretation, that the concept of 'medicinal product' according to the law of the European Union does not include the materials, which are - as not covering substances, such as those at issue in the main proceedings, which produce effects that merely modify physiological functions but which are not such as to have any beneficial effects, either immediately or in the long term, on human health, are consumed solely to induce a state of intoxication and are, as such, harmful to human health...

It is known from literature about antioxidant, anti-inflammatory, membrane protective and adreniregulatory properties of N-acetylethanolamines, but data concerning their participation in regulation of steroidogenesis are insufficient. In order to study the influence of a synthetic analogue of endogenous canabinoid anandamide - metanandamide - on the intensity of steroidogenesis the influence of different concentrations of the drug on the contents of 11-hydroxicorticosteroides (11-HCS) in the culture medium after incubation of adrenal tissue in rats of both sexes was investigated...

BACKGROUND: Prenatal alcohol exposure is known to result in fetal alcohol spectrum disorders, a continuum of physiological, behavioural, and cognitive phenotypes that include increased risk for anxiety and learning-associated disorders. Prenatal alcohol exposure results in life-long disorders that may manifest in part through the induction of long-term gene expression changes, potentially maintained through epigenetic mechanisms. FINDINGS: Here we report a decrease in the expression of Canabinoid receptor 1 (Cnr1) and an increase in the expression of the regulatory microRNA miR-26b in the brains of adult mice exposed to ethanol during neurodevelopment...

Fibromyalgia is a syndrome characterized by the presence of chronic widespread pain, representing sensitization of the central nervous system. The pthophysiology of fibromyalgia is a complex and remains in evolution, encompassing diverse issues such as disturbed patterns of sleep, alter processing and decreased conditioned pain modulation at the spinal level, as well as increased connectivity between various pain - processing areas of the brain. This evolution is continuously uncovering potential novel therapeutic targets...

Given that μ opioid (MOP) and canabinoid (CB1) receptors are colocalized in various regions of the central nervous system and have been reported to associate as heteromer (MOP-CB1) in cultured cells, the possibility of functional, endogenous MOP-CB1 in nociception and other pharmacologic effects has been raised. As a first step in investigating this possibility, we have synthesized a series of bivalent ligands 1-5 that contain both μ agonist and CB1 antagonist pharmacophores for use as tools to study the functional interaction between MOP and CB1 receptors in vivo...

Alzheimer's disease (AD) is one of the most well-known neurodegenerative diseases and explains 50-60% of dementia in patients. The prevalence rate of AD is positively correlated with age and AD affects ≥ 40% of those over 85 years old. The major AD therapeutics available on the market are acetylcholinesterase inhibitors, such as tacrine and donepezil. New therapeutic agents that can block the disease-inducing mechanisms are essential. Diverse efforts have been made to discover anti-AD agents from natural sources...

INTRODUCTION: Fibromyalgia is a debilitating, chronic pain disorder typically present with allodynia and hyperalgesia. Estimates from the USA suggest that fibromyalgia affects about 5% of women, and is the third most common rheumatic disorder after lower back pain and osteoarthritis. Recent research advances highlighted a role for aberrant central pain processing in fibromyalgia, and consistent with this, the first three drugs (pregabalin, duloxetine and milnacipran) approved by the FDA for fibromyalgia over the past 2 years have a predominantly central mode of action...

The endogenous canabinoid system (ECS) is involved in the regulation of an important number of central and peripheral physiological effects. Among all these functions, the control of the cellular proliferation has become a focus of major attention as opening new therapeutic possibilities for the use of cannabinoids as potential antitumor agents. The capacity of endogenous and synthetic cannabinoids to induce apoptosis of different tumoral cells in culture and in vivo, the mechanism underlying and the potential therapeutic applications are discussed in this review...

There is wide variability in the reported adverse fetal effects of cocaine and cannabinoids. The causes of this variability are largely unknown. We hypothesized that variability in placental handling of drugs affect fetal exposure. We used twin pregnancies as a paradigm to address the role of the placenta in this variability. We analyzed hair or meconium samples taken from dizygotic and monozygotic twins exposed in utero to illicit drugs. Out of 12 pairs, 5 had negative levels in both twins, and seven pairs of twins had chemical evidence of fetal exposure to cocaine (n = 5) or cannabinoids (n = 2)...

Anandamide, an endogenous canabinoid substance, is hydrolyzed by an amidohydrolase activity present in rat brain and liver. We report that the bromoenol lactone, (E)-6-(bromomethylene) tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (BTNP), is a potent inhibitor of this enzyme activity. BTNP prevented anandamide hydrolysis in rat brain microsomes with an IC50 of 0.8 +/- 0.3 microM. Kinetic and dialysis experiments indicated that this effect was non-competitive and irreversible. After chromatographic fractionation of the enzyme activity, BTNP was still effective, suggesting that it interacts directly with the enzyme...

Anandamide (arachydonylethanolamide) is a naturally-occurring ligand of the canabinoid receptor. When anandamide binds to its receptor, adenylate cyclase is inhibited. At the frog neuromuscular junction, anandamide lessened the increase in quantal size produced by pretreatment in hypertonic solution. It did not alter the increases in quantal size produced by insulin or by a permeable agonist of cAMP. It was known that hypertonic treatment increases quantal size by way of the cAMP-protein kinase A pathway. Anandamide had no effect on miniature endplate potential frequency (fmepp) in untreated preparations...

Nausea and vomiting are a serious side effect of chemotherapy, frequently leading to failure of treatment compliance. Chemotherapeutic agents act preferentially on the chemo-receptor trigger zone located at the floor of the 4th ventricle. Vomiting may develop at initiation of therapy or several days later. Phenotiazine derivatives, butyrophenones or methochlopramide are particularly useful by their anti-dopaminergic effects. Canabinoids or steroids may be also useful. Combinations of drugs are frequently required...

The present overview covers various aspects of research going on in the Cannabis field in the Department of Natural Products at the Hebrew University. In the first part we discuss, and try to explain, the reason for the absence of the term Cannabis (and possibly also opium) in the Old Testament. In the second part we bring evidence that, contrary to widely held views, stereospecificity of cannabinoid action is extremely high, and in certain cases almost absolute. Previous results seem to have been due to impurities in the samples tested...

During the last decades there has been a substantial increase in the recreational use of cocaine in young adults and parallelly there has been an increase of its use by pregnant women. We analyzed all published papers on cocaine use in pregnancy and found that for most endpoints studied (eg, prematurity, head circumference) there were many studies showing effects and many showing no effects. Upon meta-analysis, most of these effects could not be shown significant when compared to control groups. In a prospective study in Toronto, babies exposed to cocaine during the first trimester only had Bayley scores at 18-mo of life that were identical to unexposed babies or to those exposed to canabinoids...