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Finally, oftheendocannabinoidergic pharmacological be new will the i.e. of the involvement to pathologies system, metabolic endocannabinoidergic pharmacological An overview and the the neuroinflammatory Furthermore, beoutlined. of in described. will protagonists be the will of cannabinoids receptors, and main effects cannabinoids and of enzymes degradation history response. and re- brief inflammatory synthesis mesolimbic reduce a and to review able limbic are this the agonists cannabinoid modulates In Moreover, craving. system food cannabinoidergic to leads the phenom- which pathophysiological of sponse many inthe activation regulates central inhibition, system particular, or the cannabinoidergic stimulation, In of its ena. districts, peripheral diffusion the widespread of in the and to preparations brain thanks synthetic Indeed, diseases. and/or many natural for strategies different of use The Mastinu Andrea Article Review GRUYTER DE 21 atrd rye mH Berlin/Boston. GmbH, Gruyter de Walter ©2018 Mastinu Andrea Maccarinelli Giuseppina 4 3 2 1 neuroinflammation and syndrome metabolic in potential pharmacological disease: and health in Cannabinoids Abstract: eateto oeua n rnltoa eiie eto fPamclg,Uiest fBeca rsi,Iay E-mail: Italy, Brescia, Brescia, of University Pharmacology, of Section Medicine, Translational and Molecular of Department siuoCiioCtàd rsi,Beca Italy Brescia, Brescia, di Città Clinico Istituto eateto oeua n rnltoa eiie eto fPamclg,Uiest fBeca rsi,Italy Brescia, Brescia, of University Pharmacology, of Section Medicine, Translational and Molecular of Department eateto erbooy aeSine n oit,Cne o lhie eerh iiino ergrarc,Karolin- Neurogeriatrics, of Division Research, Alzheimer for Center Society, and Sciences Care Neurobiology, of Department k ntttt udne Sweden Huddinge, Institutet, ska https://orcid.org/0000-0002-8862-2896. [email protected]. 10.1515/hmbci-2018-0013 eray2 2018; 2, February anbssativa Cannabis stecrepnigauthor. corresponding the is 1 aiaPremoli Marika / noanbnis eaoi ydoe neuroinflammation syndrome, metabolic endocannabinoids, , 2 Accepted: arzoMemo Maurizio / anbssativa Cannabis ac ,2018 2, March 2 ilaFerrari-Toninelli Giulia / 2 aaAn Bonini Anna Sara / h aua oreo anbnis a enue o many for used been has cannabinoids, of source natural the , omn oeua ilg n lnclIvsiain 08 20180013 2018; Investigation. 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Evaluation Lazzari A, Mastinu Res. MA, Immunol Casu disease. S, Tambaro and [31] health in regulation immune (CB2) 2 receptor cannabinoid of complexities the Unraveling Sin. BN. Pharmacol Dittel Acta S, modulation. Basu and [30] function expression, 2: receptor cannabinoid Brain J. Wu QX, Su FF, Gao M, Gao 2017;363:11 DJ, Neuroscience. Chen hippocampus. [29] mouse the in receptors cannabinoid CB2 microglial and neuronal of roles 2010;58:1017 Distinct Glia. J. astrocytomas. Kim Y, and Li astrocytes, [28] microglia, in receptors cannabinoid-like J and Br Cannabinoid pain. N. neuropathic Stella and [27] inflammatory of treatment the for 2008;153:299 target Pharmacol. therapeutic J a Br way. receptors: either CB2 go Cannabinoid can AG. Hohmann it J, cells: Guindon immune [26] of migration receptor-mediated CB2 N. Stella stimulates AM, receptors Miller CB1 [25] hepatic at activation Endocannabinoid al. et S, Bátkai S, Radaeva J, P, Liu Pacher M, DePetrillo Chem. D, Osei-Hyiaman Med Curr [24] unknown. remains what and known is what receptors: cannabinoid the to binding Endocannabinoid PH. Reggio [23] channels potassium rectifying inwardly G-protein-coupled and channels calcium N-type modulate Endocannabinoids subcu- SR. and Ikeda visceral J, on Guo effects [22] molecular specific exerts Antagonism P. CB1 Degrace B, Vergès J, Gresti L, Demizieux L, Djaouti T, Jourdan [21] nociceptive trigeminovascular dural modulate brainstem the in Endocannabinoids PJ. 2008;20:10 MP, Goadsby Neuroendocrinol. Lasalandra J PR, do. Holland they S, what Akerman and [20] are they where receptors: Cannabinoid K. Mackie possible [19] their and 2-arachidonoylglycerol and anandamide of degradation and Biosynthesis K. Waku S, Oka Y, Kobayashi T, Sugiura N-acylphosphatidylethanolamine- [18] human of Structure al. et D, Piomelli R, Marotta Sci. 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J migraine. in implications receptors: ’ elA ac A olnS ta.S ersini nifamtr ies,btweede h inflam- the does where but disease, inflammatory an is depression So al. et S, Moylan JA, Pasco A, Neil ’ ies sa nlmaoydsae imlCnet.2017;8:37 Concepts. Biomol disease. inflammatory an as disease s anbssativa Cannabis h ln ftetosn n n oeue.FotPatSi 2016;7:19. Sci. Plant Front molecules. one and thousand the of plant the : ’ ies.AvPoenCe tutBo.2012;88:69 Biol. Struct Chem Protein Adv disease. s – 74. – 92. – 7. – – 305. 9. – – 34. 77. – 25. – 223. – – 4. 2. – 43. – – 74. – 37. 15. – atn tal. et Mastinu – 30. 66. – 604. – 132. – 308. – – 11 Automatically generated rough PDF by ProofCheck from River Valley Technologies Ltd 6]WseB.Teifamtr ydoe h oeo dps isectknsi eaoi iodr ikdt bst.JA o Nephrol. 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X). 2014;55:791 Epilepsia. disorders. neuropsychiatric other and epilepsy 2011;25:121 Psychopharmacol. J report. preliminary a disorder: anxiety social generalized in (CBD) 2009;66:95 Psychiatry. Gen Arch processing. emotional during activation neural on cannabidiol and 2009;24:515 Psychopharmacol. Hum dence. 2015;313:2456 Assoc. Med Am J Meta-analysis. 2017;15:301 Neurosci. Psychopharmacol Clin disorders. 2003;61:1196 rology. 2014;39:2041 chopharmacology. 1999;283:1908 Science. study. vivo in lescents: 2012;135:2245 Brain. 2008;65:694 Psychiatry. Gen Arch use. cannabis 2012;53:1738 Res. Lipid J diseases. cardiometabolic of treatment the for targets lipoprotein and lipid new series: 2009;17:1830 Obesity. upregulation. receptor CB1 and PPARgamma causes and 2010;17:1430 Chem. Med Curr drugs. therapeutic endocannabinoid-based new develop osadcrimtblcrs atr nsvrl bs dls admzdtil mMdAsc 2010;304:1795 Assoc. 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Automatically generated rough PDF by ProofCheck from River Valley Technologies Ltd 12 ora ,DmzexL rsiJ jot ,Gb ,Vrè ,e l naoimo eihrlhptccnaiodrcpo- improves receptor-1 cannabinoid hepatic peripheral of Antagonism al. et B, Vergès L, Gaba L, Djaouti J, Gresti L, car- Demizieux improves T, blockade Jourdan receptor [102] cannabinoid CB1 Peripheral al. et G, Godlewski B, Mukhopadhyay S, Bátkai J, provides Liu antagonism VK, Vemuri CB1 J, central, Tam not [101] but Peripheral, al. et C, Caldwell J, Tschöp M, Klein PM, re- Suchanek by C, obesity Veyrat-Durebex reduces R, agonism Nogueiras inverse [100] receptor cannabinoid-1 Peripheral al. et T, Jourdan D, Wesley G, Godlewski J, Liu R, Cinar cardio- J, Tam and [99] metabolism, balance, energy regulate that mechanisms peripheral and central for evidence emerging receptors: CB1 D. Springer; Cota Cham: [98] studies. case and topics current pharmacology: Clinical editor. 2008;9:1116 M, Drugs. Müller Investig In: Opin Safety. Curr Drug agonist. Pharmaceutical inverse M. receptor Brunner 1 [97] type cannabinoid novel a , ST. Boyd other for BA, Fremming potential [96] trials: controlled randomized in rimonabant of effects metabolic the of overview An DN. Kiortsis FD, Christopoulou [95] car- multiple of improvement for rimonabant of safety and Efficacy A. Scheen 2008;29:1709 C, J. JP, McCarthy Heart Després Eur STRADIVARIUS. X, Pi-Sunyer and RIO-Europe L, of Gaal years Van 2 [94] after rimonabant: drug cardiometabolic The U. Curr Kintscher diseases. [93] associated and obesity in potential therapeutic its and system ex- endocannabinoid leptin the altered Re-visiting O. an Woolcott with JM, associated Richey is [92] rimonabant by induced loss Weight L. Pani I, Manca S, Cabasino A, Mastinu A, the P, Sanna and Lazzari overactivity [91] endocannabinoid peripheral of inhibitors other and blockers receptor CB1 generation 2005;76:1307 Second V. Sci. Marzo Life Di receptors. 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