CB 2 Cannabinoid Receptors as a Therapeutic Target - What does the Future Hold ? Amey Dhopeshwarkar and Ken Mackie Molecular Pharmacology, 2014, 86, 430–437 http://dx.doi.org/10.1124/mol.114.094649 ABSTRACT The past decades have seen an exponential rise in our understanding of the endocannabinoid system, comprising CB1 and CB2 cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes that synthesize and degrade endocannabinoids. The primary focus of this review is the CB2 receptor. CB2 receptors have been the subject of considerable attention, primarily due to their promising therapeutic potential for treating various pathologies while avoiding the adverse psychotropic effects that can accompany CB1 receptor–based therapies. With the appreciation that [...]
Lire la suiteBeta-caryophyllene is a dietary cannabinoid Jürg Gertsch, Marco Leonti, Stephan Raduner, Ildiko Racz, Jian-Zhong Chen, Xiang-Qun Xie, Karl-Heinz Altmann, Meliha Karsak and Andreas Zimmer PNAS (Proceedings of the National Academy of Sciences of the USA), 2008, 105, (26), 9099-9104. Doi : 10.1073/pnas.0803601105 Abstract The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB1) and CB2 receptors. Although the CB1 receptor is responsible for the psychomodulatory effects, activation of the CB2 receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis. Here, we report that the widespread plant volatile [...]
Lire la suiteCannabinoid 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 suiteA Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans Gerhard Nahler, Franjo Grotenhermen, Antonio Waldo Zuardi, and Jose´ A.S. Crippa3 Cannabis and Cannabinoid Research, 2017, 2, 1, 81-86 DOI: 10.1089/can.2017.0009 Abstract Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. Under acidic conditions, CBD can be transformed to delta9 tetrahydro-cannabinol (THC) and other cannabinoids. It has been argued that this may occur also after oral administration in humans. However, the experimental conversion of CBD to THC and delta8-THC in simulated gastric fluid (SGF) is a highly artificial approach that deviates [...]
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 suiteThe diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids : D9-tetrahydrocannabinol, cannabidiol and D9-tetrahydrocannabivarin Roger G. Pertwee British Journal of Pharmacology, 2008, 153, 199–215 doi:10.1038/sj.bjp.0707442 Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (-)-trans-D9-tetrahydrocannabinol (D9-THC), (-)- cannabidiol (CBD) and (-)-trans-D9-tetrahydrocannabivarin (D9-THCV), interact with cannabinoid CB1 and CB2 receptors. D9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by [...]
Lire la suiteMolecular Pharmacology of Phytocannabinoids Sarah E. Turner, Claire M. Williams, Leslie Iversen, and Benjamin J. Whalley © Springer International Publishing Switzerland 2017 A.D. Kinghorn, H. Falk, S. Gibbons, J. Kobayashi (eds.), Phytocannabinoids, Progress in the Chemistry of Organic Natural Products 103, 61-100. DOI 10.1007/978-3-319-45541-9_3 Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . [...]
Lire la suiteCannabinol and Neuropathic Pain P.W. Brownjohn and J.C. Ashton Neuropathic Pain, 2012, chap. 4, 79-102 1. Introduction Cannabinoids are drugs that are either derived from cannabis or that induce similar behavioural and physiological effects to cannabis. They fall into three classes: those that are produced by plants of the Cannabis genus, termed phytocannabinoids (plant cannabinoids); those that are produced within the body, termed endocannabinoids (endogenous cannabinoids); and those that are produced synthetically to mimic the pharmacology of naturally occurring cannabinoids. Cannabinoids stand in relation to cannabis as opioids such as codeine, pethidine, fentanyl, and methadone stand in relation to opium. While opium and opioids [...]
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