Cannabinoid CB1 and CB2 Receptor Signaling and Bias Mikkel Soes Ibsen, Mark Connor, Michelle Glass Cannabis and Cannabinoid Research, 2017, Volume 2.1, 48-60 https://doi.org/10.1089/can.2016.0037 Abstract An agonist that acts through a single receptor can activate numerous signaling pathways. Recent studies have suggested that different ligands can differentially activate these pathways by stabilizing a limited range of receptor conformations, which in turn preferentially drive different downstream signaling cascades. This concept, termed “biased signaling” represents an exciting therapeutic opportunity to target specific pathways that elicit only desired effects, while avoiding undesired effects mediated by different signaling cascades. The cannabinoid receptors CB1 and CB2 each activate multiple pathways, [...]
Lire la suiteAn Update on Non-CB1, Non-CB2 Cannabinoid Related G-Protein-Coupled Receptors Paula Morales and Patricia H. Reggio Cannabis and Cannabinoid Research, 2017, Volume 2.1, 265-273 DOI: 10.1089/can.2017.0036 Abstract The endocannabinoid system (ECS) has been shown to be of great importance in the regulation of numerous physiological and pathological processes. To date, two Class A G-protein-coupled receptors (GPCRs) have been discovered and validated as the main therapeutic targets of this system: the cannabinoid receptor type 1 (CB1), which is the most abundant neuromodulatory receptor in the brain, and the cannabinoid receptor type 2 (CB2), predominantly found in the immune system among other organs and tissues. Endogenous cannabinoid receptor [...]
Lire la suiteEndocannabinoid Signaling and Synaptic Function Pablo E. Castillo, Thomas J. Younts, Andres E. Chavez, and Yuki Hashimotodani Neuron, Cell Press, 2012. http://dx.doi.org/10.1016/j.neuron.2012.09.020 Endocannabinoids are key modulators of synaptic function. By activating cannabinoid receptors expressed in the central nervous system, these lipid messengers can regulate several neural functions and behaviors. As experimental tools advance, the repertoire of known endocannabinoid-mediated effects at the synapse, and their underlying mechanism, continues to expand. Retrograde signaling is the principal mode by which endocannabinoids mediate short- and long-term forms of plasticity at both excitatory and inhibitory synapses. However, growing evidence suggests that endocannabinoids can also signal in a nonretrograde manner. [...]
Lire la suiteN-Arachidonoyl Dopamine : A Novel Endocannabinoid and Endovanilloid with Widespread Physiological and Pharmacological Activities Urszula Grabiec and Faramarz Dehghani Cannabis and Cannabinoid Research, 2017, 2, (1), 183-196 DOI: 10.1089/can.2017.0015 Abstract N-arachidonoyl dopamine (NADA) is a member of the family of endocannabinoids to which several other N-acyldopamines belong as well. Their activity is mediated through various targets that include cannabinoid receptors or transient receptor potential vanilloid (TRPV)1. Synthesis and degradation of NADA are not yet fully understood. Nonetheless, there is evidence that NADA plays an important role in nociception and inflammation in the central and peripheral nervous system. The TRPV1 receptor, for which NADA is a [...]
Lire la suiteThe Clinical Significance of Endocannabinoids in Endometriosis Pain Management Jerome Bouaziz, Alexandra Bar On, Daniel S. Seidman, and David Soriano Cannabis and Cannabinoid Research, 2017, 2, 1, 72-80 DOI : 10.1089/can.2016.0035 Abstract Introduction : Patients with endometriosis often suffer from diffuse and poorly localized severe pain. The current pain management strategies include medical and hormonal therapy, as well as surgery. Medical management of pain is often insufficient and is associated with high rate of recurrence. Better pain management is therefore of urgent need. Methods : Among the various candidates, the endocannabinoid system (ECS) has recently emerged as a relevant pharmacological target for themanagement of endometriosis-related pain. [...]
Lire la suiteTherapeutic Potential of Cannabinoids in Psychosis. Leweke F.M., Mueller J.K., Lange B., Rohleder C. Biological Psychiatry, 2016, 79, (7) 604-612. doi: 10.1016/j.biopsych.2015.11.018. Abstract Over recent years, the interest in the endocannabinoid system (ECS) as a new target for the treatment of schizophrenia has evolved. The ECS represents one of the most relevant neurotransmitter systems in the brain and mainly fulfills a homeostatic role in terms of neurotransmission but also with respect to inflammatory processes. Two main approaches to the modulation of endocannabinoid functioning have been chosen so far. First, the selective blockade or inverse agonism of the type 1 cannabinoid receptor has been tested for [...]
Lire la suiteFamilial abnormalities of endocannabinoid signaling in schizophrenia Dagmar Koethe, Franziska Pahlisch, Martin Hellmich , Cathrin Rohleder , Juliane K. Mueller, Andreas Meyer-Lindenberg , E. Fuller Torrey, Daniele Piomelli and F. Markus Leweke, THE WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, 2018 https://doi.org/10.1080/15622975.2018.1449966 ABSTRACT Objectives : Epidemiological and experimental evidence suggests that the endocannabinoid system plays a pathophysiological role in schizophrenia. This is reflected by elevated cerebrospinal levels of the endocannabinoid anandamide in schizophrenia and its initial prodromal states. Methods : We analyzed plasma concentrations of anandamide, 2-arachidonoyl-sn-glycerol, palmitoylethanolamide and oleoylethanolamide from 25 twin pairs discordant for schizophrenia, six discordant for bipolar disorder and eight healthy twin pairs to [...]
Lire la suiteMarijuana and the Cannabinoids Edited by Mahmoud A. ElSohly, PhD, Humana Press, Totowa, New Jersey, USA, 2007 www.humanapress.com 1. Cannabinoids. I. ElSohly, Mahmoud A. II. Series. [DNLM: 1. Cannabinoids. 2. Cannabis. QV 77.7 M33515 2006] QP801.C27M355 2006 615'.7827--dc22 333 pages, Preface Although primarily used today as one of the most prevalent illicit leisure drugs, the use of Cannabis sativa L., commonly referred to as marijuana, for medicinal purposes has been reported for more than 5000 years. Marijuana use has been shown to create numerous health problems, and, consequently, the expanding use beyond medical purposes into recreational use (abuse) resulted in control of the drug through international treaties. Much research has been [...]
Lire la suiteThe Endocannabinoid System and its Modulation by Phytocannabinoids Vincenzo Di Marzo & Fabiana Piscitelli Neurotherapeutics, 2015, 12, 692–698 DOI 10.1007/s13311-015-0374-6 Abstract : The endocannabinoid system is currently defined as the ensemble of the two 7-transmembrane-domain and G protein-coupled receptors for Δ9-tetrahydrocannabinol (but not for most other plant cannabinoids or phytocannabinoids)—cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R); their two most studied endogenous ligands, the “endocannabinoids” N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG); and the enzymes responsible for endocannabinoid metabolism. However, anandamide and 2-AG, and also the phytocannabinoids, have more molecular targets than just CB1R and CB2R. Furthermore, the endocannabinoids, like most other lipid mediators, have more [...]
Lire la suiteThe Use of Cannabis for Headache Disorders Bryson C. Lochte, Alexandre Beletsky, Nebiyou K. Samuel, Igor Grant Cannabis and Cannabinoid Research, 2017, Vol. 2, No 1., 61-71 https://doi.org/10.1089/can.2016.0033 Abstract Headache disorders are common, debilitating, and, in many cases, inadequately managed by existing treatments. Although clinical trials of cannabis for neuropathic pain have shown promising results, there has been limited research on its use, specifically for headache disorders. This review considers historical prescription practices, summarizes the existing reports on the use of cannabis for headache, and examines the preclinical literature exploring the role of exogenous and endogenous cannabinoids to alter headache pathophysiology. Currently, there is not [...]
Lire la suite