Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® - A Cannabis-derived Spray

Author(s): Sina Motamedy, Bahareh Soltani, Halimeh Kameshki, Asmae Alipour Kermani, Reza Saboori Amleshi, Masoud Nazeri and Mohammad Shabani*

Volume 24, Issue 15, 2024

Published on: 02 February, 2024

Page: [1427 - 1448] Pages: 22

DOI: 10.2174/0113895575285934240123110158

Price: $65

conference banner
Abstract

Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.

Keywords: Sativex, multiple sclerosis, neuroprotective, amyotrophic lateral sclerosis, antitumoral, huntington's disease.

Graphical Abstract
[1]
Russo, E.B. History of cannabis and its preparations in saga, science, and sobriquet. Chem. Biodivers., 2007, 4(8), 1614-1648.
[http://dx.doi.org/10.1002/cbdv.200790144] [PMID: 17712811]
[2]
Russo, E.B. Synthetic and natural cannabinoids: The cardiovascular risk. Br. J. Cardiol., 2015, 22, 7-9.
[3]
Pertwee, R.G. Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br. J. Pharmacol., 2009, 156(3), 397-411.
[http://dx.doi.org/10.1111/j.1476-5381.2008.00048.x] [PMID: 19226257]
[4]
Russo, E.; Guy, G.W. A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med. Hypotheses, 2006, 66(2), 234-246.
[http://dx.doi.org/10.1016/j.mehy.2005.08.026] [PMID: 16209908]
[5]
Hernández-Tiedra, S.; Fabriàs, G.; Dávila, D.; Salanueva, Í.J.; Casas, J.; Montes, L.R.; Antón, Z.; García-Taboada, E.; Salazar-Roa, M.; Lorente, M.; Nylandsted, J.; Armstrong, J.; López-Valero, I.; McKee, C.S.; Serrano-Puebla, A.; García-López, R.; González- Martínez, J.; Abad, J.L.; Hanada, K.; Boya, P.; Goñi, F.; Guzmán, M.; Lovat, P.; Jäättelä, M.; Alonso, A.; Velasco, G. Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization. Autophagy, 2016, 12(11), 2213-2229.
[http://dx.doi.org/10.1080/15548627.2016.1213927] [PMID: 27635674]
[6]
Spray, S.O. Summary of product characteristics; GW Pharma Ltd., 2020.
[7]
D’hooghe, M.; Willekens, B.; Delvaux, V.; D’haeseleer, M.; Guillaume, D.; Laureys, G.; Nagels, G.; Vanderdonckt, P.; Van Pesch, V.; Popescu, V. Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: The Belgian experience. BMC Neurol., 2021, 21(1), 227.
[http://dx.doi.org/10.1186/s12883-021-02246-0] [PMID: 34157999]
[8]
Messina, S.; Solaro, C.; Righini, I.; Bergamaschi, R.; Bonavita, S.; Bossio, R.B.; Brescia Morra, V.; Costantino, G.; Cavalla, P.; Centonze, D.; Comi, G.; Cottone, S.; Danni, M.C.; Francia, A.; Gajofatto, A.; Gasperini, C.; Zaffaroni, M.; Petrucci, L.; Signoriello, E.; Maniscalco, G.T.; Spinicci, G.; Matta, M.; Mirabella, M.; Pedà, G.; Castelli, L.; Rovaris, M.; Sessa, E.; Spitaleri, D.; Paolicelli, D.; Granata, A.; Zappia, M.; Patti, F. Sativex in resistant multiple sclerosis spasticity: Discontinuation study in a large population of Italian patients (SA.FE. study). PLoS One, 2017, 12(8), e0180651.
[http://dx.doi.org/10.1371/journal.pone.0180651] [PMID: 28763462]
[9]
Console-Bram, L.; Marcu, J.; Abood, M.E. Cannabinoid receptors: nomenclature and pharmacological principles. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2012, 38(1), 4-15.
[http://dx.doi.org/10.1016/j.pnpbp.2012.02.009] [PMID: 22421596]
[10]
Cabral, G.A.; Raborn, E.S.; Griffin, L.; Dennis, J.; Marciano-Cabral, F. CB 2 receptors in the brain: Role in central immune function. Br. J. Pharmacol., 2008, 153(2), 240-251.
[http://dx.doi.org/10.1038/sj.bjp.0707584] [PMID: 18037916]
[11]
Fernández-Ruiz, J.; Hernández, M.; Ramos, J.A. Cannabinoid-dopamine interaction in the pathophysiology and treatment of CNS disorders. CNS Neurosci. Ther., 2010, 16(3), e72-e91.
[http://dx.doi.org/10.1111/j.1755-5949.2010.00144.x] [PMID: 20406253]
[12]
Boczek, T.; Zylinska, L. Receptor-dependent and independent regulation of voltage-gated Ca2+ channels and Ca2+-permeable channels by endocannabinoids in the brain. Int. J. Mol. Sci., 2021, 22(15), 8168.
[http://dx.doi.org/10.3390/ijms22158168] [PMID: 34360934]
[13]
Lin, Y.F. Potassium channels as molecular targets of endocannabinoids. Channels, 2021, 15(1), 408-423.
[http://dx.doi.org/10.1080/19336950.2021.1910461] [PMID: 34282702]
[14]
Haghani, M.; Shabani, M.; Javan, M.; Motamedi, F.; Janahmadi, M. CB1 cannabinoid receptor activation rescues amyloid β-induced alterations in behaviour and intrinsic electrophysiological properties of rat hippocampal CA1 pyramidal neurones. Cell. Physiol. Biochem., 2012, 29(3-4), 391-406.
[http://dx.doi.org/10.1159/000338494] [PMID: 22508047]
[15]
Sancho, M.; Fletcher, J.; Welsh, D.G. Inward rectifier potassium channels: Membrane lipid-dependent mechanosensitive gates in brain vascular cells. Front. Cardiovasc. Med., 2022, 9, 869481.
[http://dx.doi.org/10.3389/fcvm.2022.869481] [PMID: 35419431]
[16]
Li, Y.; Aziz, Q.; Tinker, A. The pharmacology of ATP-sensitive K+ channels (KATP). Handb. Exp. Pharmacol., 2021, 267, 357-378.
[17]
Hager, N.A.; McAtee, C.K.; Lesko, M.A.; O’Donnell, A.F. Inwardly rectifying potassium channel kir2.1 and its “kir-ious” regulation by protein trafficking and roles in development and disease. Front. Cell Dev. Biol., 2022, 9, 796136.
[http://dx.doi.org/10.3389/fcell.2021.796136] [PMID: 35223865]
[18]
De Petrocellis, L.; Vellani, V.; Schiano-Moriello, A.; Marini, P.; Magherini, P.C.; Orlando, P.; Di Marzo, V. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J. Pharmacol. Exp. Ther., 2008, 325(3), 1007-1015.
[http://dx.doi.org/10.1124/jpet.107.134809] [PMID: 18354058]
[19]
Petrosino, S.; Di Marzo, V. FAAH and MAGL inhibitors: Therapeutic opportunities from regulating endocannabinoid levels. Curr. Opin. Investig. Drugs, 2010, 11(1), 51-62.
[PMID: 20047159]
[20]
Blankman, J.L.; Gabriel, M.S.; Benjamin, F.S. A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem. Biol., 2007, 14(12), 1347-1356.
[21]
Basu, S.; Dittel, B.N. Unraveling the complexities of cannabinoid receptor 2 (CB2) immune regulation in health and disease. Immunol. Res., 2011, 51(1), 26-38.
[http://dx.doi.org/10.1007/s12026-011-8210-5] [PMID: 21626285]
[22]
Rieder, S.A.; Chauhan, A.; Singh, U.; Nagarkatti, M.; Nagarkatti, P. Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression. Immunobiology, 2010, 215(8), 598-605.
[http://dx.doi.org/10.1016/j.imbio.2009.04.001] [PMID: 19457575]
[23]
Karschner, E.L.; Darwin, W.D.; McMahon, R.P.; Liu, F.; Wright, S.; Goodwin, R.S.; Huestis, M.A. Subjective and physiological effects after controlled Sativex and oral THC administration. Clin. Pharmacol. Ther., 2011, 89(3), 400-407.
[http://dx.doi.org/10.1038/clpt.2010.318] [PMID: 21289620]
[24]
Molnar, A.; Fu, S. Techniques and technologies for the bioanalysis of Sativex ®, metabolites and related compounds. Bioanalysis, 2016, 8(8), 829-845.
[http://dx.doi.org/10.4155/bio-2015-0021] [PMID: 27005853]
[25]
Novotna, A.; Mares, J.; Ratcliffe, S.; Novakova, I.; Vachova, M.; Zapletalova, O.; Gasperini, C.; Pozzilli, C.; Cefaro, L.; Comi, G.; Rossi, P.; Ambler, Z.; Stelmasiak, Z.; Erdmann, A.; Montalban, X.; Klimek, A.; Davies, P. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex ®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur. J. Neurol., 2011, 18(9), 1122-1131.
[http://dx.doi.org/10.1111/j.1468-1331.2010.03328.x] [PMID: 21362108]
[26]
Karst, M.; Wippermann, S.; Ahrens, J. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs, 2010, 70(18), 2409-2438.
[http://dx.doi.org/10.2165/11585260-000000000-00000] [PMID: 21142261]
[27]
Rahn, E.J.; Hohmann, A.G. Cannabinoids as pharmacotherapies for neuropathic pain: From the bench to the bedside. Neurotherapeutics, 2009, 6(4), 713-737.
[http://dx.doi.org/10.1016/j.nurt.2009.08.002] [PMID: 19789075]
[28]
Treede, R.D.; Jensen, T.S.; Campbell, J.N.; Cruccu, G.; Dostrovsky, J.O.; Griffin, J.W.; Hansson, P.; Hughes, R.; Nurmikko, T.; Serra, J. Neuropathic pain. Neurology, 2008, 70(18), 1630-1635.
[http://dx.doi.org/10.1212/01.wnl.0000282763.29778.59] [PMID: 18003941]
[29]
Jensen, T.S.; Baron, R. Haanpää, M.; Kalso, E.; Loeser, J.D.; Rice, A.S.C.; Treede, R.D. A new definition of neuropathic pain. Pain, 2011, 152(10), 2204-2205.
[http://dx.doi.org/10.1016/j.pain.2011.06.017] [PMID: 21764514]
[30]
Vadivelu, N.; Kai, A.M.; Kodumudi, V.; Sramcik, J.; Kaye, A.D. The opioid crisis: A comprehensive overview. Curr. Pain Headache Rep., 2018, 22(3), 16.
[http://dx.doi.org/10.1007/s11916-018-0670-z] [PMID: 29476358]
[31]
Yang, J.; Bauer, B.A.; Wahner-Roedler, D.L.; Chon, T.Y.; Xiao, L. The modified WHO analgesic ladder: Is it appropriate for chronic non-cancer pain? J. Pain Res., 2020, 13, 411-417.
[http://dx.doi.org/10.2147/JPR.S244173] [PMID: 32110089]
[32]
Johnson, J.R.; Burnell-Nugent, M.; Lossignol, D.; Ganae-Motan, E.D.; Potts, R.; Fallon, M.T. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J. Pain Symptom Manage., 2010, 39(2), 167-179.
[http://dx.doi.org/10.1016/j.jpainsymman.2009.06.008] [PMID: 19896326]
[33]
Aviram, J.; Samuelly-Leichtag, G. Efficacy of cannabis-based medicines for pain management: A systematic review and metaanalysis of randomized controlled trials. Pain Physician, 2017, 6(20;6), E755-E796.
[http://dx.doi.org/10.36076/ppj.20.5.E755] [PMID: 28934780]
[34]
Mücke, M.; Phillips, T.; Radbruch, L.; Petzke, F. Häuser, W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst. Rev., 2018, 3(3), CD012182.
[PMID: 29513392]
[35]
van de Donk, T.; Niesters, M.; Kowal, M.A.; Olofsen, E.; Dahan, A.; van Velzen, M. An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain, 2019, 160(4), 860-869.
[http://dx.doi.org/10.1097/j.pain.0000000000001464] [PMID: 30585986]
[36]
VanDolah, H.J.; Bauer, B.A.; Mauck, K.F. Clinicians’ Guide to cannabidiol and hemp oils. Mayo Clin. Proc., 2019, 94(9), 1840-1851.
[http://dx.doi.org/10.1016/j.mayocp.2019.01.003] [PMID: 31447137]
[37]
Capano, A.; Weaver, R.; Burkman, E. Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: A prospective cohort study. Postgrad. Med., 2020, 132(1), 56-61.
[http://dx.doi.org/10.1080/00325481.2019.1685298] [PMID: 31711352]
[38]
Medicines, C-B.J.D.R.D. Cannabis-based medicines--GW pharmaceuticals: High CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD. Drugs R D., 2003, 4(5), 306-309.
[PMID: 12952500]
[39]
Häuser, W.; Finn, D.P.; Kalso, E.; Krcevski-Skvarc, N.; Kress, H.G.; Morlion, B.; Perrot, S.; Schäfer, M.; Wells, C.; Brill, S. European pain federation (EFIC) position paper on appropriate use of cannabis-based medicines and medical cannabis for chronic pain management. Eur. J. Pain, 2018, 22(9), 1547-1564.
[http://dx.doi.org/10.1002/ejp.1297] [PMID: 30074291]
[40]
Prieto González, J.M.; Vila Silván, C. Safety and tolerability of nabiximols oromucosal spray: A review of more than 15 years” accumulated evidence from clinical trials. Expert Rev. Neurother., 2021, 21(7), 755-778.
[http://dx.doi.org/10.1080/14737175.2021.1935879] [PMID: 34092180]
[41]
Barnes, M.P. Sativex ®: Clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert Opin. Pharmacother., 2006, 7(5), 607-615.
[http://dx.doi.org/10.1517/14656566.7.5.607] [PMID: 16553576]
[42]
Turner, M.R.; Cagnin, A.; Turkheimer, F.E.; Miller, C.C.J.; Shaw, C.E.; Brooks, D.J.; Leigh, P.N.; Banati, R.B. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol. Dis., 2004, 15(3), 601-609.
[http://dx.doi.org/10.1016/j.nbd.2003.12.012] [PMID: 15056468]
[43]
Berman, J.S.; Symonds, C.; Birch, R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: Results of a randomised controlled trial. Pain, 2004, 112(3), 299-306.
[http://dx.doi.org/10.1016/j.pain.2004.09.013] [PMID: 15561385]
[44]
Turri, M.; Teatini, F.; Donato, F.; Zanette, G.; Tugnoli, V.; Deotto, L.; Bonetti, B.; Squintani, G. Pain modulation after oromucosal cannabinoid spray (SATIVEX®) in patients with multiple sclerosis: A study with quantitative sensory testing and laser-evoked potentials. Medicines, 2018, 5(3), 59.
[http://dx.doi.org/10.3390/medicines5030059] [PMID: 29933552]
[45]
Langford, R.M.; Mares, J.; Novotna, A.; Vachova, M.; Novakova, I.; Notcutt, W.; Ratcliffe, S. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J. Neurol., 2013, 260(4), 984-997.
[http://dx.doi.org/10.1007/s00415-012-6739-4] [PMID: 23180178]
[46]
Watkins, A.R. Cannabinoid interactions with ion channels and receptors. Channels, 2019, 13(1), 162-167.
[http://dx.doi.org/10.1080/19336950.2019.1615824] [PMID: 31088312]
[47]
Ghovanloo, M.R.; Shuart, N.G.; Mezeyova, J.; Dean, R.A.; Ruben, P.C.; Goodchild, S.J. Inhibitory effects of cannabidiol on voltage-dependent sodium currents. J. Biol. Chem., 2018, 293(43), 16546-16558.
[http://dx.doi.org/10.1074/jbc.RA118.004929] [PMID: 30219789]
[48]
Bisogno, T. Hanuš, L.; De Petrocellis, L.; Tchilibon, S.; Ponde, D.E.; Brandi, I.; Moriello, A.S.; Davis, J.B.; Mechoulam, R.; Di Marzo, V. Molecular targets for cannabidiol and its synthetic analogues: Effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol., 2001, 134(4), 845-852.
[http://dx.doi.org/10.1038/sj.bjp.0704327] [PMID: 11606325]
[49]
Gülck, T. Møller, B.L. Phytocannabinoids: Origins and biosynthesis. Trends Plant Sci., 2020, 25(10), 985-1004.
[http://dx.doi.org/10.1016/j.tplants.2020.05.005] [PMID: 32646718]
[50]
Yang, Y.; Vyawahare, R.; Lewis-Bakker, M.; Clarke, H.A.; Wong, A.H.C.; Kotra, L.P. Bioactive chemical composition of cannabis extracts and cannabinoid receptors. Molecules, 2020, 25(15), 3466.
[http://dx.doi.org/10.3390/molecules25153466] [PMID: 32751516]
[51]
Millar, S.A.; Stone, N.L.; Yates, A.S.; O’Sullivan, S.E. A systematic review on the pharmacokinetics of cannabidiol in humans. Front. Pharmacol., 2018, 9, 1365.
[http://dx.doi.org/10.3389/fphar.2018.01365] [PMID: 30534073]
[52]
Gruber, S.A.; Sagar, K.A. Marijuana on the mind? The impact of marijuana on cognition, brain structure, and brain function, and related public policy implications. Policy Insights Behav. Brain Sci., 2017, 4(1), 104-111.
[http://dx.doi.org/10.1177/2372732216684851]
[53]
Becker, B.; Wagner, D.; Gouzoulis-Mayfrank, E.; Spuentrup, E.; Daumann, J. The impact of early-onset cannabis use on functional brain correlates of working memory. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2010, 34(6), 837-845.
[http://dx.doi.org/10.1016/j.pnpbp.2010.03.032] [PMID: 20363277]
[54]
Theiler, M. Spontaneous encephalomyelitis of mice, a new virus disease. J. Exp. Med., 1937, 65(5), 705-719.
[http://dx.doi.org/10.1084/jem.65.5.705] [PMID: 19870629]
[55]
Denic, A.; Johnson, A.J.; Bieber, A.J.; Warrington, A.E.; Rodriguez, M.; Pirko, I. The relevance of animal models in multiple sclerosis research. Pathophysiology, 2011, 18(1), 21-29.
[http://dx.doi.org/10.1016/j.pathophys.2010.04.004] [PMID: 20537877]
[56]
Pirko, I.; Gamez, J.; Johnson, A.J.; Macura, S.I.; Rodriguez, M. Dynamics of MRI lesion development in an animal model of viral-induced acute progressive CNS demyelination. Neuroimage, 2004, 21(2), 576-582.
[http://dx.doi.org/10.1016/j.neuroimage.2003.09.037] [PMID: 14980559]
[57]
Pirko, I.; Suidan, G.L.; Rodriguez, M.; Johnson, A.J. Acute hemorrhagic demyelination in a murine model of multiple sclerosis. J. Neuroinflam., 2008, 5(1), 31.
[http://dx.doi.org/10.1186/1742-2094-5-31] [PMID: 18606015]
[58]
Kipp, M.; Clarner, T.; Dang, J.; Copray, S.; Beyer, C. The cuprizone animal model: New insights into an old story. Acta Neuropathol., 2009, 118(6), 723-736.
[http://dx.doi.org/10.1007/s00401-009-0591-3] [PMID: 19763593]
[59]
Zhan, J.; Mann, T.; Joost, S.; Behrangi, N.; Frank, M.; Kipp, M. The cuprizone model: Dos and do nots. Cells, 2020, 9(4), 843.
[http://dx.doi.org/10.3390/cells9040843] [PMID: 32244377]
[60]
Rivers, T.M.; Sprunt, D.H.; Berry, G.P. Observations on attempts to produce acute disseminated encephalomyelitis in monkeyS. J. Exp. Med., 1933, 58(1), 39-53.
[http://dx.doi.org/10.1084/jem.58.1.39] [PMID: 19870180]
[61]
Gerhauser, I.; Hansmann, F.; Ciurkiewicz, M. Löscher, W.; Beineke, A. Facets of theiler’s murine encephalomyelitis virus-induced diseases: An update. Int. J. Mol. Sci., 2019, 20(2), 448.
[http://dx.doi.org/10.3390/ijms20020448] [PMID: 30669615]
[62]
Wolf, A.; Kabat, E.A.; Bezer, A. The pathology of acute disseminated encephalomyelitis produced experimentally in the rhesus monkey and its resemblance to human demyelinating disease. J. Neuropathol. Exp. Neurol., 1947, 6(4), 333-357.
[http://dx.doi.org/10.1097/00005072-194710000-00003] [PMID: 20267714]
[63]
Bruni, N.; Della Pepa, C.; Oliaro-Bosso, S.; Pessione, E.; Gastaldi, D.; Dosio, F. Cannabinoid delivery systems for pain and inflammation treatment. Molecules, 2018, 23(10), 2478.
[http://dx.doi.org/10.3390/molecules23102478] [PMID: 30262735]
[64]
Vlachou, S.; Nomikos, G.G.; Stephens, D.N.; Panagis, G. Lack of evidence for appetitive effects of Δ9-tetrahydrocannabinol in the intracranial self-stimulation and conditioned place preference procedures in rodents. Behav. Pharmacol., 2007, 18(4), 311-319.
[http://dx.doi.org/10.1097/FBP.0b013e3282186cf2] [PMID: 17551324]
[65]
Losseff, N.A.; Webb, S.L.; O’Riordan, J.I.; Page, R.; Wang, L.; Barker, G.J.; Tofts, P.S.; McDonald, W.I.; Miller, D.H.; Thompson, A.J. Spinal cord atrophy and disability in multiple sclerosis. Brain, 1996, 119(3), 701-708.
[http://dx.doi.org/10.1093/brain/119.3.701] [PMID: 8673483]
[66]
Lassmann, H. Neuropathology in multiple sclerosis: New concepts. Mult. Scler., 1998, 4(3), 93-98.
[http://dx.doi.org/10.1177/135245859800400301] [PMID: 9762654]
[67]
Rudick, R.A. Disease-modifying drugs for relapsing-remitting multiple sclerosis and future directions for multiple sclerosis therapeutics. Arch. Neurol., 1999, 56(9), 1079-1084.
[http://dx.doi.org/10.1001/archneur.56.9.1079] [PMID: 10488808]
[68]
Milo, R.; Miller, A. Revised diagnostic criteria of multiple sclerosis. Autoimmun. Rev., 2014, 13(4-5), 518-524.
[http://dx.doi.org/10.1016/j.autrev.2014.01.012] [PMID: 24424194]
[69]
Eisenreich, W.; Schwarz, M.; Cartayrade, A.; Arigoni, D.; Zenk, M.H.; Bacher, A. The deoxyxylulose phosphate pathway of terpenoid biosynthesis in plants and microorganisms. Chem. Biol., 1998, 5(9), R221-R233.
[http://dx.doi.org/10.1016/S1074-5521(98)90002-3] [PMID: 9751645]
[70]
Appendino, G.; Chianese, G.; Taglialatela-Scafati, O. Cannabinoids: Occurrence and medicinal chemistry. Curr. Med. Chem., 2011, 18(7), 1085-1099.
[http://dx.doi.org/10.2174/092986711794940888] [PMID: 21254969]
[71]
Jones, É.; Vlachou, S. A critical review of the role of the cannabinoid compounds δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) and their combination in multiple sclerosis treatment. Molecules, 2020, 25(21), 4930.
[http://dx.doi.org/10.3390/molecules25214930] [PMID: 33113776]
[72]
Hilliard, A.; Stott, C.; Wright, S.; Guy, G.; Pryce, G.; Al-Izki, S.; Bolton, C.; Giovannoni, G. Evaluation of the effects of sativex (THC BDS: CBD BDS) on inhibition of spasticity in a chronic relapsing experimental allergic autoimmune encephalomyelitis: A model of multiple sclerosis. ISRN Neurol., 2012, 2012, 1-7.
[http://dx.doi.org/10.5402/2012/802649] [PMID: 22928118]
[73]
Dybowski, M.P.; Dawidowicz, A.L.; Typek, R.; Rombel, M. Conversion of cannabidiol (CBD) to Δ9-tetrahydrocannabinol (Δ9-THC) during protein precipitations prior to plasma samples analysis by chromatography – Troubles with reliable CBD quantitation when acidic precipitation agents are applied. Talanta, 2020, 220, 121390.
[http://dx.doi.org/10.1016/j.talanta.2020.121390] [PMID: 32928411]
[74]
Banister, S.D.; Arnold, J.C.; Connor, M.; Glass, M.; McGregor, I.S. Dark classics in chemical neuroscience: Δ9 -Tetrahydrocannabinol. ACS Chem. Neurosci., 2019, 10(5), 2160-2175.
[http://dx.doi.org/10.1021/acschemneuro.8b00651] [PMID: 30689342]
[75]
Moreno-Martet, M. Feliú, A.; Espejo-Porras, F.; Mecha, M.; Carrillo-Salinas, F.J.; Fernández-Ruiz, J.; Guaza, C.; de Lago, E. The disease-modifying effects of a Sativex-like combination of phytocannabinoids in mice with experimental autoimmune encephalomyelitis are preferentially due to Δ-tetrahydrocannabinol acting through CB1 receptors. Mult. Scler. Relat. Disord., 2015, 4(6), 505-511.
[http://dx.doi.org/10.1016/j.msard.2015.08.001] [PMID: 26590655]
[76]
Al-Ghezi, Z.Z.; Busbee, P.B.; Alghetaa, H.; Nagarkatti, P.S.; Nagarkatti, M. Combination of cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigates experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome. Brain Behav. Immun., 2019, 82, 25-35.
[http://dx.doi.org/10.1016/j.bbi.2019.07.028] [PMID: 31356922]
[77]
Sriram, S.; Steiner, I. Experimental allergic encephalomyelitis: A misleading model of multiple sclerosis. Ann. Neurol., 2005, 58(6), 939-945.
[http://dx.doi.org/10.1002/ana.20743] [PMID: 16315280]
[78]
Rog, D.J.; Nurmikko, T.J.; Friede, T.; Young, C.A. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology, 2005, 65(6), 812-819.
[http://dx.doi.org/10.1212/01.wnl.0000176753.45410.8b] [PMID: 16186518]
[79]
Schimrigk, S.; Marziniak, M.; Neubauer, C.; Kugler, E.M.; Werner, G.; Abramov-Sommariva, D. Dronabinol is a safe long-term treatment option for neuropathic pain patients. Eur. Neurol., 2017, 78(5-6), 320-329.
[http://dx.doi.org/10.1159/000481089] [PMID: 29073592]
[80]
Goncharov, N. Nutraceuticals: Efficacy, Safety and Toxicity; Gupta, R.C., Ed.; Academic Press, 2016, p. 177.
[http://dx.doi.org/10.1016/B978-0-12-802147-7.00014-0]
[81]
Elliott, D.M.; Singh, N.; Nagarkatti, M.; Nagarkatti, P.S. Cannabidiol attenuates experimental autoimmune encephalomyelitis model of multiple sclerosis through induction of myeloid-derived suppressor cells. Front. Immunol., 2018, 9, 1782.
[http://dx.doi.org/10.3389/fimmu.2018.01782] [PMID: 30123217]
[82]
González-García, C.; Irene, M.T.; García-Hernández, R. Mechanisms of action of cannabidiol in adoptively transferred experimental autoimmune encephalomyelitis. Exp Neurol, 2017, 298(Pt A), 57-67.
[http://dx.doi.org/10.1016/j.expneurol.2017.08.017]
[83]
Al-Ghezi, Z.Z.; Miranda, K.; Nagarkatti, M.; Nagarkatti, P.S. Combination of cannabinoids, δ9- tetrahydrocannabinol and cannabidiol, ameliorates experimental multiple sclerosis by suppressing neuroinflammation through regulation of miRNA-mediated signaling pathways. Front. Immunol., 2019, 10, 1921.
[http://dx.doi.org/10.3389/fimmu.2019.01921] [PMID: 31497013]
[84]
Ujváry, I.; Hanuš, L. Human metabolites of cannabidiol: A review on their formation, biological activity, and relevance in therapy. Cannabis Cannabinoid Res., 2016, 1(1), 90-101.
[http://dx.doi.org/10.1089/can.2015.0012] [PMID: 28861484]
[85]
Marková, J. Newest evidence for tetrahydrocannabinol: Cannabidiol oromucosal spray from randomized clinical trials. Neurodegener. Dis. Manag., 2019, 9(2s), 9-13.
[http://dx.doi.org/10.2217/nmt-2018-0050] [PMID: 30657024]
[86]
Markovà, J.; Essner, U.; Akmaz, B.; Marinelli, M.; Trompke, C.; Lentschat, A.; Vila, C. Sativex ® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: A double-blind, placebo-controlled randomised clinical trial. Int. J. Neurosci., 2019, 129(2), 119-128.
[http://dx.doi.org/10.1080/00207454.2018.1481066] [PMID: 29792372]
[87]
Marinelli, L.; Mori, L.; Canneva, S.; Colombano, F.; Currà, A.; Fattapposta, F.; Bandini, F.; Capello, E.; Abbruzzese, G.; Trompetto, C. The effect of cannabinoids on the stretch reflex in multiple sclerosis spasticity. Int. Clin. Psychopharmacol., 2016, 31(4), 232-239.
[http://dx.doi.org/10.1097/YIC.0000000000000126] [PMID: 27003093]
[88]
Ferrè, L.; Nuara, A.; Pavan, G.; Radaelli, M.; Moiola, L.; Rodegher, M.; Colombo, B.; Keller Sarmiento, I.J.; Martinelli, V.; Leocani, L.; Martinelli, B.F.; Comi, G.; Esposito, F. Efficacy and safety of nabiximols (Sativex®) on multiple sclerosis spasticity in a real-life Italian monocentric study. Neurol. Sci., 2016, 37(2), 235-242.
[http://dx.doi.org/10.1007/s10072-015-2392-x] [PMID: 26474875]
[89]
Leocani, L.; Nuara, A.; Houdayer, E.; Schiavetti, I.; Del Carro, U.; Amadio, S.; Straffi, L.; Rossi, P.; Martinelli, V.; Vila, C.; Sormani, M.P.; Comi, G. Sativex® and clinical–neurophysiological measures of spasticity in progressive multiple sclerosis. J. Neurol., 2015, 262(11), 2520-2527.
[http://dx.doi.org/10.1007/s00415-015-7878-1] [PMID: 26289497]
[90]
Savinainen, J.R.; Saario, S.M.; Niemi, R. Järvinen, T.; Laitinen, J.T. An optimized approach to study endocannabinoid signaling: evidence against constitutive activity of rat brain adenosine A 1 and cannabinoid CB 1 receptors. Br. J. Pharmacol., 2003, 140(8), 1451-1459.
[http://dx.doi.org/10.1038/sj.bjp.0705577] [PMID: 14623770]
[91]
Russo, M.; Naro, A.; Leo, A.; Sessa, E.; D’Aleo, G.; Bramanti, P. Calabrò, R.S. Evaluating sativex ® in neuropathic pain management: A clinical and neurophysiological assessment in multiple sclerosis. Pain Med., 2016, 17(6), pnv080.
[http://dx.doi.org/10.1093/pm/pnv080] [PMID: 26764336]
[92]
Schneider, L.S.; Clark, C.M.; Doody, R.; Ferris, S.H.; Morris, J.C.; Raman, R.; Reisberg, B.; Schmitt, F.A. ADCS prevention instrument project: Adcs-clinicians’ global impression of change scales (ADCS-CGIC), self-rated and study partner-rated versions. Alzheimer Dis. Assoc. Disord., 2006, 20(4), S124-S138.
[http://dx.doi.org/10.1097/01.wad.0000213878.47924.44] [PMID: 17135806]
[93]
Im, D.D.; Jambaulikar, G.D.; Kikut, A.; Gale, J.; Weiner, S.G. Brief pain inventory–short form: A new method for assessing pain in the emergency department. Pain Med., 2020, 21(12), 3263-3269.
[http://dx.doi.org/10.1093/pm/pnaa269] [PMID: 32918473]
[94]
Caprariello, A.V.; Rogers, J.A.; Morgan, M.L.; Hoghooghi, V.; Plemel, J.R.; Koebel, A.; Tsutsui, S.; Dunn, J.F.; Kotra, L.P.; Ousman, S.S.; Wee Yong, V.; Stys, P.K. Biochemically altered myelin triggers autoimmune demyelination. Proc. Natl. Acad. Sci., 2018, 115(21), 5528-5533.
[http://dx.doi.org/10.1073/pnas.1721115115] [PMID: 29728463]
[95]
Manterola, A.; Bernal-Chico, A.; Cipriani, R.; Canedo-Antelo, M. Moreno-García, Á.; Martín-Fontecha, M.; Pérez-Cerdá, F.; Sánchez-Gómez, M.V.; Ortega-Gutiérrez, S.; Brown, J.M.; Hsu, K.L.; Cravatt, B.; Matute, C.; Mato, S. Deregulation of the endocannabinoid system and therapeutic potential of ABHD6 blockade in the cuprizone model of demyelination. Biochem. Pharmacol., 2018, 157, 189-201.
[http://dx.doi.org/10.1016/j.bcp.2018.07.042] [PMID: 30075103]
[96]
Allsop, D.J.; Copeland, J.; Lintzeris, N.; Dunlop, A.J.; Montebello, M.; Sadler, C.; Rivas, G.R.; Holland, R.M.; Muhleisen, P.; Norberg, M.M.; Booth, J.; McGregor, I.S. Nabiximols as an agonist replacement therapy during cannabis withdrawal: A randomized clinical trial. JAMA Psychiatry, 2014, 71(3), 281-291.
[http://dx.doi.org/10.1001/jamapsychiatry.2013.3947] [PMID: 24430917]
[97]
Nicholson, A.N.; Turner, C.; Stone, B.M.; Robson, P.J. Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. J. Clin. Psychopharmacol., 2004, 24(3), 305-313.
[http://dx.doi.org/10.1097/01.jcp.0000125688.05091.8f] [PMID: 15118485]
[98]
Hardiman, O.; van den Berg, L.H.; Kiernan, M.C. Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat. Rev. Neurol., 2011, 7(11), 639-649.
[http://dx.doi.org/10.1038/nrneurol.2011.153] [PMID: 21989247]
[99]
Renton, A.E. Chiò, A.; Traynor, B.J. State of play in amyotrophic lateral sclerosis genetics. Nat. Neurosci., 2014, 17(1), 17-23.
[http://dx.doi.org/10.1038/nn.3584] [PMID: 24369373]
[100]
Ferraiuolo, L.; Kirby, J.; Grierson, A.J.; Sendtner, M.; Shaw, P.J. Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nat. Rev. Neurol., 2011, 7(11), 616-630.
[http://dx.doi.org/10.1038/nrneurol.2011.152] [PMID: 22051914]
[101]
Foran, E.; Trotti, D. Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis. Antioxid. Redox Signal., 2009, 11(7), 1587-1602.
[http://dx.doi.org/10.1089/ars.2009.2444] [PMID: 19413484]
[102]
Habib, A.A.; Mitsumoto, H. Emerging drugs for amyotrophic lateral sclerosis. Expert Opin. Emerg. Drugs, 2011, 16(3), 537-558.
[http://dx.doi.org/10.1517/14728214.2011.604312] [PMID: 21806316]
[103]
Bilsland, L.; Greensmith, L. The endocannabinoid system in amyotrophic lateral sclerosis. Curr. Pharm. Des., 2008, 14(23), 2306-2316.
[http://dx.doi.org/10.2174/138161208785740081] [PMID: 18781981]
[104]
Raman, C.; McAllister, S.D.; Rizvi, G.; Patel, S.G.; Moore, D.H.; Abood, M.E. Amyotrophic lateral sclerosis: Delayed disease progression in mice by treatment with a cannabinoid. Amyotroph. Lateral Scler. Other Motor Neuron Disord., 2004, 5(1), 33-39.
[http://dx.doi.org/10.1080/14660820310016813] [PMID: 15204022]
[105]
Weydt, P.; Hong, S.; Witting, A. Möller, T.; Stella, N.; Kliot, M. Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival. Amyotroph. Lateral Scler., 2005, 6(3), 182-184.
[http://dx.doi.org/10.1080/14660820510030149] [PMID: 16183560]
[106]
Bilsland, L.G.; Dick, J.R.T.; Pryce, G.; Petrosino, S.; Di Marzo, V.; Baker, D.; Greensmith, L.; Bilsland, L.G.; Dick, J.R.T.; Pryce, G.; Petrosino, S.; Di Marzo, V.; Baker, D.; Greensmith, L. Increasing cannabinoid levels by pharmacological and genetic manipulation delays disease progression in SOD1 mice. FASEB J., 2006, 20(7), 1003-1005.
[http://dx.doi.org/10.1096/fj.05-4743fje] [PMID: 16571781]
[107]
Kim, K.; Moore, D.H.; Makriyannis, A.; Abood, M.E. AM1241, a cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis. Eur. J. Pharmacol., 2006, 542(1-3), 100-105.
[http://dx.doi.org/10.1016/j.ejphar.2006.05.025] [PMID: 16781706]
[108]
Shoemaker, J.L.; Seely, K.A.; Reed, R.L.; Crow, J.P.; Prather, P.L. The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. J. Neurochem., 2007, 101(1), 87-98.
[http://dx.doi.org/10.1111/j.1471-4159.2006.04346.x] [PMID: 17241118]
[109]
Yiangou, Y.; Facer, P.; Durrenberger, P.; Chessell, I.P.; Naylor, A.; Bountra, C.; Banati, R.R.; Anand, P. COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol., 2006, 6(1), 12.
[http://dx.doi.org/10.1186/1471-2377-6-12] [PMID: 16512913]
[110]
Fernández-Ruiz, J.; Romero, J.; Velasco, G.; Tolón, R.M.; Ramos, J.A.; Guzmán, M. Cannabinoid CB2 receptor: A new target for controlling neural cell survival? Trends Pharmacol. Sci., 2007, 28(1), 39-45.
[http://dx.doi.org/10.1016/j.tips.2006.11.001] [PMID: 17141334]
[111]
Ashton, J.; Glass, M. The cannabinoid CB2 receptor as a target for inflammation-dependent neurodegeneration. Curr. Neuropharmacol., 2007, 5(2), 73-80.
[http://dx.doi.org/10.2174/157015907780866884] [PMID: 18615177]
[112]
Witting, A.; Weydt, P.; Hong, S.; Kliot, M. Mőller, T.; Stella, N. Endocannabinoids accumulate in spinal cord of SOD1 G93A transgenic mice. J. Neurochem., 2004, 89(6), 1555-1557.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02544.x] [PMID: 15189359]
[113]
Moreno-Martet, M.; Espejo-Porras, F. Fernández-Ruiz, J.; de Lago, E. Changes in endocannabinoid receptors and enzymes in the spinal cord of SOD1(G93A) transgenic mice and evaluation of a Sativex(®) -like combination of phytocannabinoids: interest for future therapies in amyotrophic lateral sclerosis. CNS Neurosci. Ther., 2014, 20(9), 809-815.
[http://dx.doi.org/10.1111/cns.12262] [PMID: 24703394]
[114]
Sastre-Garriga, J.; Vila, C.; Clissold, S.; Montalban, X. THC and CBD oromucosal spray (Sativex ®) in the management of spasticity associated with multiple sclerosis. Expert Rev. Neurother., 2011, 11(5), 627-637.
[http://dx.doi.org/10.1586/ern.11.47] [PMID: 21456949]
[115]
Pertwee, R.G. Targeting the endocannabinoid system with cannabinoid receptor agonists: Pharmacological strategies and therapeutic possibilities. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2012, 367(1607), 3353-3363.
[http://dx.doi.org/10.1098/rstb.2011.0381] [PMID: 23108552]
[116]
Roze, E.; Bonnet, C.; Betuing, S. Caboche, J. Huntington’s Disease. Adv. Exp. Med. Biol., 2010, 685, 45-63.
[http://dx.doi.org/10.1007/978-1-4419-6448-9_5] [PMID: 20687494]
[117]
Zuccato, C.; Valenza, M.; Cattaneo, E. Molecular mechanisms and potential therapeutical targets in Huntington’s disease. Physiol. Rev., 2010, 90(3), 905-981.
[http://dx.doi.org/10.1152/physrev.00041.2009] [PMID: 20664076]
[118]
Johnson, C.D.; Davidson, B.L. Huntington’s disease: Progress toward effective disease-modifying treatments and a cure. Hum. Mol. Genet., 2010, 19(R1), R98-R102.
[http://dx.doi.org/10.1093/hmg/ddq148] [PMID: 20421366]
[119]
Curtis, A.; Mitchell, I.; Patel, S.; Ives, N.; Rickards, H. A pilot study using nabilone for symptomatic treatment in Huntington’s disease. Mov. Disord., 2009, 24(15), 2254-2259.
[http://dx.doi.org/10.1002/mds.22809] [PMID: 19845035]
[120]
Curtis, A.; Rickards, H. Nabilone could treat chorea and irritability in Huntington’s disease. J. Neuropsychiatry Clin. Neurosci., 2006, 18(4), 553-554.
[http://dx.doi.org/10.1176/jnp.2006.18.4.553] [PMID: 17135385]
[121]
Müller-Vahl, K.R.; Schneider, U.; Emrich, H.M. Nabilone increases choreatic movements in Huntington’s disease. Mov. Disord., 1999, 14(6), 1038-1040.
[http://dx.doi.org/10.1002/1531-8257(199911)14:6<1038:AID-MDS1024>3.0.CO;2-7] [PMID: 10584686]
[122]
Consroe, P.; Laguna, J.; Allender, J.; Snider, S.; Stern, L.; Sandyk, R.; Kennedy, K.; Schram, K. Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol. Biochem. Behav., 1991, 40(3), 701-708.
[http://dx.doi.org/10.1016/0091-3057(91)90386-G] [PMID: 1839644]
[123]
Sagredo, O.; Ramos, J.A.; Decio, A.; Mechoulam, R. Fernández-Ruiz, J. Cannabidiol reduced the striatal atrophy caused 3-nitropropionic acid in vivo by mechanisms independent of the activation of cannabinoid, vanilloid TRPV 1 and adenosine A 2A receptors. Eur. J. Neurosci., 2007, 26(4), 843-851.
[http://dx.doi.org/10.1111/j.1460-9568.2007.05717.x] [PMID: 17672854]
[124]
Valdeolivas, S.; Navarrete, C.; Cantarero, I.; Bellido, M.L. Muñoz, E.; Sagredo, O. Neuroprotective properties of cannabigerol in Huntington’s disease: Studies in R6/2 mice and 3-nitropropionate-lesioned mice. Neurotherapeutics, 2015, 12(1), 185-199.
[http://dx.doi.org/10.1007/s13311-014-0304-z] [PMID: 25252936]
[125]
Blázquez, C.; Chiarlone, A.; Sagredo, O.; Aguado, T.; Pazos, M.R.; Resel, E.; Palazuelos, J.; Julien, B.; Salazar, M.; Börner, C.; Benito, C.; Carrasco, C.; Diez-Zaera, M.; Paoletti, P.; Díaz-Hernández, M.; Ruiz, C.; Sendtner, M.; Lucas, J.J.; de Yébenes, J.G.; Marsicano, G.; Monory, K.; Lutz, B.; Romero, J.; Alberch, J.; Ginés, S.; Kraus, J.; Fernández-Ruiz, J.; Galve-Roperh, I.; Guzmán, M. Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington’s disease. Brain, 2011, 134(1), 119-136.
[http://dx.doi.org/10.1093/brain/awq278] [PMID: 20929960]
[126]
Palazuelos, J.; Aguado, T.; Pazos, M.R.; Julien, B.; Carrasco, C.; Resel, E.; Sagredo, O.; Benito, C.; Romero, J.; Azcoitia, I. Fernández-Ruiz, J.; Guzmán, M.; Galve-Roperh, I. Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain, 2009, 132(11), 3152-3164.
[http://dx.doi.org/10.1093/brain/awp239] [PMID: 19805493]
[127]
Sagredo, O. González, S.; Aroyo, I.; Pazos, M.R.; Benito, C.; Lastres-Becker, I.; Romero, J.P.; Tolón, R.M.; Mechoulam, R.; Brouillet, E.; Romero, J.; Fernández-Ruiz, J. Cannabinoid CB 2 receptor agonists protect the striatum against malonate toxicity: Relevance for Huntington’s disease. Glia, 2009, 57(11), 1154-1167.
[http://dx.doi.org/10.1002/glia.20838] [PMID: 19115380]
[128]
Pintor, A.; Tebano, M.T.; Martire, A.; Grieco, R.; Galluzzo, M.; Scattoni, M.L.; Pèzzola, A.; Coccurello, R.; Felici, F.; Cuomo, V.; Piomelli, D.; Calamandrei, G.; Popoli, P. The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum. Neuropharmacology, 2006, 51(5), 1004-1012.
[http://dx.doi.org/10.1016/j.neuropharm.2006.06.013] [PMID: 16895732]
[129]
Lastres-Becker, I.; Bizat, N.; Boyer, F.; Hantraye, P. Fernández-Ruiz, J.; Brouillet, E. Potential involvement of cannabinoid receptors in 3-nitropropionic acid toxicity in vivo. Neuroreport, 2004, 15(15), 2375-2379.
[http://dx.doi.org/10.1097/00001756-200410250-00015] [PMID: 15640759]
[130]
Lastres-Becker, I.; Bizat, N.; Boyer, F.; Hantraye, P.; Brouillet, E. Fernández-Ruiz, J. Effects of cannabinoids in the rat model of Huntington’s disease generated by an intrastriatal injection of malonate. Neuroreport, 2003, 14(6), 813-816.
[http://dx.doi.org/10.1097/00001756-200305060-00007] [PMID: 12858038]
[131]
Sagredo, O.; Pazos, M.R.; Satta, V.; Ramos, J.A.; Pertwee, R.G. Fernández-Ruiz, J. Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington’s disease. J. Neurosci. Res., 2011, 89(9), 1509-1518.
[http://dx.doi.org/10.1002/jnr.22682] [PMID: 21674569]
[132]
Valdeolivas, S.; Satta, V.; Pertwee, R.G. Fernández-Ruiz, J.; Sagredo, O. Sativex-like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington’s disease: Role of CB1 and CB2 receptors. ACS Chem. Neurosci., 2012, 3(5), 400-406.
[http://dx.doi.org/10.1021/cn200114w] [PMID: 22860209]
[133]
Valdeolivas, S.; Sagredo, O.; Delgado, M.; Pozo, M. Fernández-Ruiz, J. Effects of a sativex-like combination of phytocannabinoids on disease progression in R6/2 mice, an experimental model of huntington’s disease. Int. J. Mol. Sci., 2017, 18(4), 684.
[http://dx.doi.org/10.3390/ijms18040684] [PMID: 28333097]
[134]
Dowie, M.J.; Howard, M.L.; Nicholson, L.F.B.; Faull, R.L.M.; Hannan, A.J.; Glass, M. Behavioural and molecular consequences of chronic cannabinoid treatment in Huntington’s disease transgenic mice. Neuroscience, 2010, 170(1), 324-336.
[http://dx.doi.org/10.1016/j.neuroscience.2010.06.056] [PMID: 20600638]
[135]
Wade, D. Evaluation of the safety and tolerability profile of Sativex ®: is it reassuring enough? Expert Rev. Neurother., 2012, 12(S4), 9-14.
[http://dx.doi.org/10.1586/ern.12.12] [PMID: 22509986]
[136]
López-Sendón, M.J.L.; García, C.J.; Trigo, C.P.; Ruiz, R.C.; García, R.G.; Alonso, A.M.A.A.; García de Yébenes, M.J.; Tolón, R.M.; Galve-Roperh, I.; Sagredo, O.; Valdeolivas, S.; Resel, E.; Ortega-Gutierrez, S.; García-Bermejo, M.L.; Fernández, R.J.; Guzmán, M.; García de, Y.P.J. A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease. J. Neurol., 2016, 263(7), 1390-1400.
[http://dx.doi.org/10.1007/s00415-016-8145-9] [PMID: 27159993]
[137]
Ferrante, R.J.; Andreassen, O.A.; Jenkins, B.G.; Dedeoglu, A.; Kuemmerle, S.; Kubilus, J.K.; Kaddurah-Daouk, R.; Hersch, S.M.; Beal, M.F. Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. J. Neurosci., 2000, 20(12), 4389-4397.
[http://dx.doi.org/10.1523/JNEUROSCI.20-12-04389.2000] [PMID: 10844007]
[138]
Andreassen, O.A.; Dedeoglu, A.; Ferrante, R.J.; Jenkins, B.G.; Ferrante, K.L.; Thomas, M.; Friedlich, A.; Browne, S.E.; Schilling, G.; Borchelt, D.R.; Hersch, S.M.; Ross, C.A.; Beal, M.F. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington’s disease. Neurobiol. Dis., 2001, 8(3), 479-491.
[http://dx.doi.org/10.1006/nbdi.2001.0406] [PMID: 11447996]
[139]
Tabrizi, S.J.; Blamire, A.M.; Manners, D.N.; Rajagopalan, B.; Styles, P.; Schapira, A.H.V.; Warner, T.T. Creatine therapy for Huntington’s disease: Clinical and MRS findings in a 1-year pilot study. Neurology, 2003, 61(1), 141-142.
[http://dx.doi.org/10.1212/01.WNL.0000070186.97463.A7] [PMID: 12847181]
[140]
Louis, D.N.; Perry, A.; Reifenberger, G.; von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K.; Ohgaki, H.; Wiestler, O.D.; Kleihues, P.; Ellison, D.W. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol., 2016, 131(6), 803-820.
[http://dx.doi.org/10.1007/s00401-016-1545-1] [PMID: 27157931]
[141]
Nieder, C.; Adam, M.; Molls, M.; Grosu, A.L. Therapeutic options for recurrent high-grade glioma in adult patients: Recent advances. Crit. Rev. Oncol. Hematol., 2006, 60(3), 181-193.
[http://dx.doi.org/10.1016/j.critrevonc.2006.06.007] [PMID: 16875833]
[142]
Wong, M.L.H.; Kaye, A.H.; Hovens, C.M. Targeting malignant glioma survival signalling to improve clinical outcomes. J. Clin. Neurosci., 2007, 14(4), 301-308.
[http://dx.doi.org/10.1016/j.jocn.2006.11.005] [PMID: 17276069]
[143]
Ostrom, Q.T.; Bauchet, L.; Davis, F.G.; Deltour, I.; Fisher, J.L.; Langer, C.E.; Pekmezci, M.; Schwartzbaum, J.A.; Turner, M.C.; Walsh, K.M.; Wrensch, M.R.; Barnholtz-Sloan, J.S. The epidemiology of glioma in adults: A “state of the science” review. Neuro-oncol., 2014, 16(7), 896-913.
[http://dx.doi.org/10.1093/neuonc/nou087] [PMID: 24842956]
[144]
Reni, M.; Mazza, E.; Zanon, S.; Gatta, G.; Vecht, C.J. Central nervous system gliomas. Crit. Rev. Oncol. Hematol., 2017, 113, 213-234.
[http://dx.doi.org/10.1016/j.critrevonc.2017.03.021] [PMID: 28427510]
[145]
Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.; Burger, P.C.; Jouvet, A.; Scheithauer, B.W.; Kleihues, P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol., 2007, 114(2), 97-109.
[http://dx.doi.org/10.1007/s00401-007-0243-4] [PMID: 17618441]
[146]
Yang, L.J.; Zhou, C.F.U.; Lin, Z.X. Temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme: A systematic review. Cancer Invest., 2014, 32(2), 31-36.
[http://dx.doi.org/10.3109/07357907.2013.861474] [PMID: 24328555]
[147]
Brandes, A.A.; Bartolotti, M.; Tosoni, A.; Franceschi, E. Nitrosoureas in the management of malignant gliomas. Curr. Neurol. Neurosci. Rep., 2016, 16(2), 13.
[http://dx.doi.org/10.1007/s11910-015-0611-8] [PMID: 26750128]
[148]
Brennan, C.W.; Verhaak, R.G.W.; McKenna, A.; Campos, B.; Noushmehr, H.; Salama, S.R.; Zheng, S.; Chakravarty, D.; Sanborn, J.Z.; Berman, S.H.; Beroukhim, R.; Bernard, B.; Wu, C.J.; Genovese, G.; Shmulevich, I.; Barnholtz-Sloan, J.; Zou, L.; Vegesna, R.; Shukla, S.A.; Ciriello, G.; Yung, W.K.; Zhang, W.; Sougnez, C.; Mikkelsen, T.; Aldape, K.; Bigner, D.D.; Van Meir, E.G.; Prados, M.; Sloan, A.; Black, K.L.; Eschbacher, J.; Finocchiaro, G.; Friedman, W.; Andrews, D.W.; Guha, A.; Iacocca, M.; O’Neill, B.P.; Foltz, G.; Myers, J.; Weisenberger, D.J.; Penny, R.; Kucherlapati, R.; Perou, C.M.; Hayes, D.N.; Gibbs, R.; Marra, M.; Mills, G.B.; Lander, E.; Spellman, P.; Wilson, R.; Sander, C.; Weinstein, J.; Meyerson, M.; Gabriel, S.; Laird, P.W.; Haussler, D.; Getz, G.; Chin, L.; Benz, C.; Barnholtz-Sloan, J.; Barrett, W.; Ostrom, Q.; Wolinsky, Y.; Black, K.L.; Bose, B.; Boulos, P.T.; Boulos, M.; Brown, J.; Czerinski, C.; Eppley, M.; Iacocca, M.; Kempista, T.; Kitko, T.; Koyfman, Y.; Rabeno, B.; Rastogi, P.; Sugarman, M.; Swanson, P.; Yalamanchii, K.; Otey, I.P.; Liu, Y.S.; Xiao, Y.; Auman, J.T.; Chen, P-C.; Hadjipanayis, A.; Lee, E.; Lee, S.; Park, P.J.; Seidman, J.; Yang, L.; Kucherlapati, R.; Kalkanis, S.; Mikkelsen, T.; Poisson, L.M.; Raghunathan, A.; Scarpace, L.; Bernard, B.; Bressler, R.; Eakin, A.; Iype, L.; Kreisberg, R.B.; Leinonen, K.; Reynolds, S.; Rovira, H.; Thorsson, V.; Shmulevich, I.; Annala, M.J.; Penny, R.; Paulauskis, J.; Curley, E.; Hatfield, M.; Mallery, D.; Morris, S.; Shelton, T.; Shelton, C.; Sherman, M.; Yena, P.; Cuppini, L.; DiMeco, F.; Eoli, M.; Finocchiaro, G.; Maderna, E.; Pollo, B.; Saini, M.; Balu, S.; Hoadley, K.A.; Li, L.; Miller, C.R.; Shi, Y.; Topal, M.D.; Wu, J.; Dunn, G.; Giannini, C.; O’Neill, B.P.; Aksoy, B.A.; Antipin, Y.; Borsu, L.; Berman, S.H.; Brennan, C.W.; Cerami, E.; Chakravarty, D.; Ciriello, G.; Gao, J.; Gross, B.; Jacobsen, A.; Ladanyi, M.; Lash, A.; Liang, Y.; Reva, B.; Sander, C.; Schultz, N.; Shen, R.; Socci, N.D.; Viale, A.; Ferguson, M.L.; Chen, Q-R.; Demchok, J.A.; Dillon, L.A.L.; Shaw, K.R.M.; Sheth, M.; Tarnuzzer, R.; Wang, Z.; Yang, L.; Davidsen, T.; Guyer, M.S.; Ozenberger, B.A.; Sofia, H.J.; Bergsten, J.; Eckman, J.; Harr, J.; Myers, J.; Smith, C.; Tucker, K.; Winemiller, C.; Zach, L.A.; Ljubimova, J.Y.; Eley, G.; Ayala, B.; Jensen, M.A.; Kahn, A.; Pihl, T.D.; Pot, D.A.; Wan, Y.; Eschbacher, J.; Foltz, G.; Hansen, N.; Hothi, P.; Lin, B.; Shah, N.; Yoon, J.; Lau, C.; Berens, M.; Ardlie, K.; Beroukhim, R.; Carter, S.L.; Cherniack, A.D.; Noble, M.; Cho, J.; Cibulskis, K.; DiCara, D.; Frazer, S.; Gabriel, S.B.; Gehlenborg, N.; Gentry, J.; Heiman, D.; Kim, J.; Jing, R.; Lander, E.S.; Lawrence, M.; Lin, P.; Mallard, W.; Meyerson, M.; Onofrio, R.C.; Saksena, G.; Schumacher, S.; Sougnez, C.; Stojanov, P.; Tabak, B.; Voet, D.; Zhang, H.; Zou, L.; Getz, G.; Dees, N.N.; Ding, L.; Fulton, L.L.; Fulton, R.S.; Kanchi, K-L.; Mardis, E.R.; Wilson, R.K.; Baylin, S.B.; Andrews, D.W.; Harshyne, L.; Cohen, M.L.; Devine, K.; Sloan, A.E.; VandenBerg, S.R.; Berger, M.S.; Prados, M.; Carlin, D.; Craft, B.; Ellrott, K.; Goldman, M.; Goldstein, T.; Grifford, M.; Haussler, D.; Ma, S.; Ng, S.; Salama, S.R.; Sanborn, J.Z.; Stuart, J.; Swatloski, T.; Waltman, P.; Zhu, J.; Foss, R.; Frentzen, B.; Friedman, W.; McTiernan, R.; Yachnis, A.; Hayes, D.N.; Perou, C.M.; Zheng, S.; Vegesna, R.; Mao, Y.; Akbani, R.; Aldape, K.; Bogler, O.; Fuller, G.N.; Liu, W.; Liu, Y.; Lu, Y.; Mills, G.; Protopopov, A.; Ren, X.; Sun, Y.; Wu, C-J.; Yung, W.K.A.; Zhang, W.; Zhang, J.; Chen, K.; Weinstein, J.N.; Chin, L.; Verhaak, R.G.W.; Noushmehr, H.; Weisenberger, D.J.; Bootwalla, M.S.; Lai, P.H.; Triche, T.J., Jr; Van Den Berg, D.J.; Laird, P.W.; Gutmann, D.H.; Lehman, N.L.; VanMeir, E.G.; Brat, D.; Olson, J.J.; Mastrogianakis, G.M.; Devi, N.S.; Zhang, Z.; Bigner, D.; Lipp, E.; McLendon, R. The somatic genomic landscape of glioblastoma. Cell, 2013, 155(2), 462-477.
[http://dx.doi.org/10.1016/j.cell.2013.09.034] [PMID: 24120142]
[149]
Verhaak, R.G.W.; Hoadley, K.A.; Purdom, E.; Wang, V.; Qi, Y.; Wilkerson, M.D.; Miller, C.R.; Ding, L.; Golub, T.; Mesirov, J.P.; Alexe, G.; Lawrence, M.; O’Kelly, M.; Tamayo, P.; Weir, B.A.; Gabriel, S.; Winckler, W.; Gupta, S.; Jakkula, L.; Feiler, H.S.; Hodgson, J.G.; James, C.D.; Sarkaria, J.N.; Brennan, C.; Kahn, A.; Spellman, P.T.; Wilson, R.K.; Speed, T.P.; Gray, J.W.; Meyerson, M.; Getz, G.; Perou, C.M.; Hayes, D.N. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell, 2010, 17(1), 98-110.
[http://dx.doi.org/10.1016/j.ccr.2009.12.020] [PMID: 20129251]
[150]
Anjum, K.; Shagufta, B.I.; Abbas, S.Q.; Patel, S.; Khan, I.; Shah, S.A.A.; Akhter, N.; Hassan, S.S. Current status and future therapeutic perspectives of glioblastoma multiforme (GBM) therapy: A review. Biomed. Pharmacother., 2017, 92, 681-689.
[http://dx.doi.org/10.1016/j.biopha.2017.05.125] [PMID: 28582760]
[151]
Szopa, W.; Burley, T.A.; Kramer-Marek, G.; Kaspera, W. Diagnostic and therapeutic biomarkers in glioblastoma: Current status and future perspectives. BioMed Res. Int., 2017, 2017, 1-13.
[http://dx.doi.org/10.1155/2017/8013575] [PMID: 28316990]
[152]
Velasco, G. Hernández-Tiedra, S.; Dávila, D.; Lorente, M. The use of cannabinoids as anticancer agents. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2016, 64, 259-266.
[http://dx.doi.org/10.1016/j.pnpbp.2015.05.010] [PMID: 26071989]
[153]
Velasco, G. Sánchez, C.; Guzmán, M. Towards the use of cannabinoids as antitumour agents. Nat. Rev. Cancer, 2012, 12(6), 436-444.
[http://dx.doi.org/10.1038/nrc3247] [PMID: 22555283]
[154]
Carracedo, A.; Lorente, M.; Egia, A. Blázquez, C.; García, S.; Giroux, V.; Malicet, C.; Villuendas, R.; Gironella, M.; González-Feria, L.; Piris, M.Á; Iovanna, J.L.; Guzmán, M.; Velasco, G. The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell, 2006, 9(4), 301-312.
[http://dx.doi.org/10.1016/j.ccr.2006.03.005] [PMID: 16616335]
[155]
Salazar, M.; Carracedo, A. Salanueva, Í.J.; Hernández-Tiedra, S.; Lorente, M.; Egia, A.; Vázquez, P.; Blázquez, C.; Torres, S.; García, S.; Nowak, J.; Fimia, G.M.; Piacentini, M.; Cecconi, F.; Pandolfi, P.P.; González-Feria, L.; Iovanna, J.L.; Guzmán, M.; Boya, P.; Velasco, G. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J. Clin. Invest., 2009, 119(5), 1359-1372.
[http://dx.doi.org/10.1172/JCI37948] [PMID: 19425170]
[156]
Guzmán M.; Duarte, M.J.; Blázquez, C.; Ravina, J.; Rosa, M.C.; Galve-Roperh, I.; Sánchez, C.; Velasco, G.; González-Feria, L. A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br. J. Cancer, 2006, 95(2), 197-203.
[http://dx.doi.org/10.1038/sj.bjc.6603236] [PMID: 16804518]
[157]
Izzo, A.A.; Borrelli, F.; Capasso, R.; Di Marzo, V.; Mechoulam, R. Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herb. Trends Pharmacol. Sci., 2009, 30(10), 515-527.
[http://dx.doi.org/10.1016/j.tips.2009.07.006] [PMID: 19729208]
[158]
Massi, P.; Vaccani, A.; Bianchessi, S.; Costa, B.; Macchi, P.; Parolaro, D. The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells. Cell. Mol. Life Sci., 2006, 63(17), 2057-2066.
[http://dx.doi.org/10.1007/s00018-006-6156-x] [PMID: 16909207]
[159]
Massi, P.; Vaccani, A.; Ceruti, S.; Colombo, A.; Abbracchio, M.P.; Parolaro, D. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. J. Pharmacol. Exp. Ther., 2004, 308(3), 838-845.
[http://dx.doi.org/10.1124/jpet.103.061002] [PMID: 14617682]
[160]
Massi, P.; Valenti, M.; Vaccani, A.; Gasperi, V.; Perletti, G.; Marras, E.; Fezza, F.; Maccarrone, M.; Parolaro, D. 5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. J. Neurochem., 2008, 104(4), 1091-1100.
[http://dx.doi.org/10.1111/j.1471-4159.2007.05073.x] [PMID: 18028339]
[161]
McAllister, S.D.; Christian, R.T.; Horowitz, M.P.; Garcia, A.; Desprez, P.Y. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Mol. Cancer Ther., 2007, 6(11), 2921-2927.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-0371] [PMID: 18025276]
[162]
Ligresti, A.; Moriello, A.S.; Starowicz, K.; Matias, I.; Pisanti, S.; De Petrocellis, L.; Laezza, C.; Portella, G.; Bifulco, M.; Di Marzo, V. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J. Pharmacol. Exp. Ther., 2006, 318(3), 1375-1387.
[http://dx.doi.org/10.1124/jpet.106.105247] [PMID: 16728591]
[163]
Marcu, J.P.; Christian, R.T.; Lau, D.; Zielinski, A.J.; Horowitz, M.P.; Lee, J.; Pakdel, A.; Allison, J.; Limbad, C.; Moore, D.H.; Yount, G.L.; Desprez, P.Y.; McAllister, S.D. Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol. Cancer Ther., 2010, 9(1), 180-189.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0407] [PMID: 20053780]
[164]
Scott, K.A.; Dalgleish, A.G.; Liu, W.M. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol. Cancer Ther., 2014, 13(12), 2955-2967.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0402] [PMID: 25398831]
[165]
Torres, S.; Lorente, M. Rodríguez-Fornés, F.; Hernández-Tiedra, S.; Salazar, M.; García-Taboada, E.; Barcia, J.; Guzmán, M.; Velasco, G. A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol. Cancer Ther., 2011, 10(1), 90-103.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0688] [PMID: 21220494]
[166]
López-Valero, I.; Torres, S.; Salazar-Roa, M.; García-Taboada, E.; Hernández-Tiedra, S.; Guzmán, M.; Sepúlveda, J.M.; Velasco, G.; Lorente, M. Optimization of a preclinical therapy of cannabinoids in combination with temozolomide against glioma. Biochem. Pharmacol., 2018, 157, 275-284.
[http://dx.doi.org/10.1016/j.bcp.2018.08.023] [PMID: 30125556]
[167]
López-Valero, I.; Saiz-Ladera, C.; Torres, S.; Hernández-Tiedra, S.; García-Taboada, E.; Rodríguez-Fornés, F.; Barba, M.; Dávila, D.; Salvador-Tormo, N.; Guzmán, M.; Sepúlveda, J.M.; Sánchez-Gómez, P.; Lorente, M.; Velasco, G. Targeting glioma initiating cells with a combined therapy of cannabinoids and temozolomide. Biochem. Pharmacol., 2018, 157, 266-274.
[http://dx.doi.org/10.1016/j.bcp.2018.09.007] [PMID: 30195736]
[168]
Nair, A.; Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm., 2016, 7(2), 27-31.
[http://dx.doi.org/10.4103/0976-0105.177703] [PMID: 27057123]
[169]
Deng, L.; Ng, L.; Ozawa, T.; Stella, N. Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture. J. Pharmacol. Exp. Ther., 2017, 360(1), 215-224.
[http://dx.doi.org/10.1124/jpet.116.236968] [PMID: 27821713]
[170]
Würstle, S.; Schneider, F.; Ringel, F.; Gempt, J. Lämmer, F.; Delbridge, C.; Wu, W.; Schlegel, J. Temozolomide induces autophagy in primary and established glioblastoma cells in an EGFR independent manner. Oncol. Lett., 2017, 14(1), 322-328.
[http://dx.doi.org/10.3892/ol.2017.6107] [PMID: 28693171]
[171]
Patti, F. Cognitive impairment in multiple sclerosis. Mult. Scler., 2009, 15(1), 2-8.
[http://dx.doi.org/10.1177/1352458508096684] [PMID: 18805842]
[172]
Lynch, S.G.; Parmenter, B.A.; Denney, D.R. The association between cognitive impairment and physical disability in multiple sclerosis. Mult. Scler., 2005, 11(4), 469-476.
[http://dx.doi.org/10.1191/1352458505ms1182oa] [PMID: 16042232]
[173]
Rogers, J.M.; Panegyres, P.K. Cognitive impairment in multiple sclerosis: Evidence-based analysis and recommendations. J. Clin. Neurosci., 2007, 14(10), 919-927.
[http://dx.doi.org/10.1016/j.jocn.2007.02.006] [PMID: 17659875]
[174]
McDonald, J.; Schleifer, L.; Richards, J.B.; de Wit, H. Effects of THC on behavioral measures of impulsivity in humans. Neuropsychopharmacology, 2003, 28(7), 1356-1365.
[http://dx.doi.org/10.1038/sj.npp.1300176] [PMID: 12784123]
[175]
D’Souza, D.C.; Abi-Saab, W.M.; Madonick, S.; Forselius-Bielen, K.; Doersch, A.; Braley, G.; Gueorguieva, R.; Cooper, T.B.; Krystal, J.H. Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction. Biol. Psychiatry, 2005, 57(6), 594-608.
[http://dx.doi.org/10.1016/j.biopsych.2004.12.006] [PMID: 15780846]
[176]
Moore, C.; Rana, S.; Coulter, C.; Day, D.; Vincent, M.; Soares, J. Detection of conjugated 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in oral fluid. J. Anal. Toxicol., 2007, 31(4), 187-194.
[http://dx.doi.org/10.1093/jat/31.4.187] [PMID: 17555641]
[177]
Russo, M.; De Luca, R.; Torrisi, M.; Rifici, C.; Sessa, E.; Bramanti, P.; Naro, A. Calabrò, R.S. Should we care about sativex-induced neurobehavioral effects? A 6-month follow-up study. Eur. Rev. Med. Pharmacol. Sci., 2016, 20(14), 3127-3133.
[PMID: 27460745]
[178]
Rekand, T. THC:CBD spray and MS spasticity symptoms: Data from latest studies. Eur. Neurol., 2014, 71(Suppl. 1), 4-9.
[http://dx.doi.org/10.1159/000357742] [PMID: 24457846]
[179]
Aragona, M.; Onesti, E.; Tomassini, V.; Conte, A.; Gupta, S.; Gilio, F.; Pantano, P.; Pozzilli, C.; Inghilleri, M. Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: A double-blind, placebo controlled, crossover study. Clin. Neuropharmacol., 2009, 32(1), 41-47.
[http://dx.doi.org/10.1097/WNF.0b013e3181633497] [PMID: 18978501]
[180]
Russo, M.; Rifici, C.; Sessa, E.; D’Aleo, G.; Bramanti, P. Calabrò, R.S. Sativex-induced neurobehavioral effects: Causal or concausal? A practical advice! Daru, 2015, 23(1), 25.
[http://dx.doi.org/10.1186/s40199-015-0109-6] [PMID: 25881038]
[181]
Fava, M.; Kendler, K.S. Major depressive disorder. Neuron, 2000, 28(2), 335-341.
[http://dx.doi.org/10.1016/S0896-6273(00)00112-4] [PMID: 11144343]
[182]
Mechoulam, R.; Parker, L.A.; Gallily, R. Cannabidiol: An overview of some pharmacological aspects. J. Clin. Pharmacol., 2002, 42(S1), 11S-19S.
[http://dx.doi.org/10.1002/j.1552-4604.2002.tb05998.x] [PMID: 12412831]
[183]
Ilan, A.B.; Gevins, A.; Coleman, M.; ElSohly, M.A.; de Wit, H. Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids. Behav. Pharmacol., 2005, 16(5-6), 487-496.
[http://dx.doi.org/10.1097/00008877-200509000-00023] [PMID: 16148455]
[184]
Fadda, P.; Robinson, L.; Fratta, W.; Pertwee, R.G.; Riedel, G. Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats. Neuropharmacology, 2004, 47(8), 1170-1179.
[http://dx.doi.org/10.1016/j.neuropharm.2004.08.009] [PMID: 15567426]
[185]
Hall, W.; Degenhardt, L. Adverse health effects of non-medical cannabis use. Lancet, 2009, 374(9698), 1383-1391.
[http://dx.doi.org/10.1016/S0140-6736(09)61037-0] [PMID: 19837255]
[186]
Organization, W.H. Health and Social Effects of Nonmedical Cannabis Use (The); World Health Organization, 2016.
[187]
Marlatt, G.A. Cannabis dependence: its nature, consequences and treatment; Cambridge university press, 2006.
[188]
Gates, P.J.; Sabioni, P.; Copeland, J.; Le Foll, B.; Gowing, L. Psychosocial interventions for cannabis use disorder. Cochrane Database Syst. Rev., 2016, 2016(5), CD005336.
[PMID: 27149547]
[189]
Johnston, J. A double blind, randomised, placebo controlled trial of lithium carbonate for the management of cannabis withdrawal: Paper 220. Drug Alcohol Rev., 2013, 32.
[190]
Danovitch, I.; Gorelick, D.A. State of the art treatments for cannabis dependence. Psychiatr. Clin. North Am., 2012, 35(2), 309-326.
[http://dx.doi.org/10.1016/j.psc.2012.03.003] [PMID: 22640758]
[191]
Vandrey, R.; Haney, M. Pharmacotherapy for cannabis dependence: how close are we? CNS Drugs, 2009, 23(7), 543-553.
[http://dx.doi.org/10.2165/00023210-200923070-00001] [PMID: 19552483]
[192]
Copeland, J.; Clement, N.; Swift, W. Cannabis use, harms and the management of cannabis use disorder. Neuropsychiatry, 2014, 4(1), 55-63.
[http://dx.doi.org/10.2217/npy.13.90]
[193]
Carpenter, K.M.; McDowell, D.; Brooks, D.J.; Cheng, W.Y.; Levin, F.R. A preliminary trial: Double-blind comparison of nefazodone, bupropion-SR, and placebo in the treatment of cannabis dependence. Am. J. Addict., 2009, 18(1), 53-64.
[http://dx.doi.org/10.1080/10550490802408936] [PMID: 19219666]
[194]
Haney, M.; Hart, C.L.; Vosburg, S.K.; Nasser, J.; Bennett, A.; Zubaran, C.; Foltin, R.W. Marijuana withdrawal in humans: Effects of oral THC or divalproex. Neuropsychopharmacology, 2004, 29(1), 158-170.
[http://dx.doi.org/10.1038/sj.npp.1300310] [PMID: 14560320]
[195]
Haney, M.; Hart, C.L.; Vosburg, S.K.; Comer, S.D.; Reed, S.C.; Foltin, R.W. Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology, 2008, 197(1), 157-168.
[http://dx.doi.org/10.1007/s00213-007-1020-8] [PMID: 18161012]
[196]
Gray, K.M.; Carpenter, M.J.; Baker, N.L.; DeSantis, S.M.; Kryway, E.; Hartwell, K.J.; McRae-Clark, A.L.; Brady, K.T. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am. J. Psychiatry, 2012, 169(8), 805-812.
[http://dx.doi.org/10.1176/appi.ajp.2012.12010055] [PMID: 22706327]
[197]
Darke, S.; Farrell, M. Would legalizing illicit opioids reduce overdose fatalities? Implications from a natural experiment. Addiction, 2014, 109(8), 1237-1242.
[http://dx.doi.org/10.1111/add.12456] [PMID: 24456133]
[198]
Budney, A.J.; Radonovich, K.J.; Higgins, S.T.; Wong, C.J. Adults seeking treatment for marijuana dependence: A comparison with cocaine-dependent treatment seekers. Exp. Clin. Psychopharmacol., 1998, 6(4), 419-426.
[http://dx.doi.org/10.1037/1064-1297.6.4.419] [PMID: 9861556]
[199]
Bhardwaj, A.K.; Allsop, D.J.; Copeland, J.; McGregor, I.S.; Dunlop, A.; Shanahan, M.; Bruno, R.; Phung, N.; Montebello, M.; Sadler, C.; Gugusheff, J.; Jackson, M.; Luksza, J.; Lintzeris, N. Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: A study protocol. BMC Psychiatry, 2018, 18(1), 140.
[http://dx.doi.org/10.1186/s12888-018-1682-2] [PMID: 29776349]
[200]
Karschner, E.L.; Darwin, W.D.; Goodwin, R.S.; Wright, S.; Huestis, M.A. Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin. Chem., 2011, 57(1), 66-75.
[http://dx.doi.org/10.1373/clinchem.2010.152439] [PMID: 21078841]
[201]
Trigo, J.M.; Soliman, A.; Staios, G.; Quilty, L.; Fischer, B.; George, T.P.; Rehm, J.; Selby, P.; Barnes, A.J.; Huestis, M.A.; Le Foll, B. Sativex associated with behavioral-relapse prevention strategy as treatment for cannabis dependence. J. Addict. Med., 2016, 10(4), 274-279.
[http://dx.doi.org/10.1097/ADM.0000000000000229] [PMID: 27261670]
[202]
Trigo, J.M.; Lagzdins, D.; Rehm, J.; Selby, P.; Gamaleddin, I.; Fischer, B.; Barnes, A.J.; Huestis, M.A.; Le Foll, B. Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings. Drug Alcohol Depend., 2016, 161, 298-306.
[http://dx.doi.org/10.1016/j.drugalcdep.2016.02.020] [PMID: 26925704]
[203]
Mantovani, L.G.; Cozzolino, P.; Cortesi, P.A.; Patti, F. Cost-effectiveness analysis of cannabinoid oromucosal spray use for the management of spasticity in subjects with multiple sclerosis. Clin. Drug Investig., 2020, 40(4), 319-326.
[http://dx.doi.org/10.1007/s40261-020-00895-6] [PMID: 32130684]
[204]
Freidel, M.; Tiel-Wilck, K.; Schreiber, H.; Prechtl, A.; Essner, U.; Lang, M. Drug-resistant MS spasticity treatment with Sativex ® add-on and driving ability. Acta Neurol. Scand., 2015, 131(1), 9-16.
[http://dx.doi.org/10.1111/ane.12287] [PMID: 25208898]
[205]
Grao-Castellote, C.; Torralba-Collados, F.; Gonzalez, L.M.; Giner-Pascual, M. [Delta-9-tetrahydrocannabinol-cannabidiol in the treatment of spasticity in chronic spinal cord injury: A clinical experience]. Rev. Neurol., 2017, 65(7), 295-302.
[PMID: 28929471]
[206]
Vermersch, P.; Trojano, M. Tetrahydrocannabinol: Cannabidiol oromucosal spray for multiple sclerosis-related resistant spasticity in daily practice. Eur. Neurol., 2016, 76(5-6), 216-226.
[http://dx.doi.org/10.1159/000449413] [PMID: 27732980]
[207]
Serpell, M.G.; Notcutt, W.; Collin, C. Sativex long-term use: An open-label trial in patients with spasticity due to multiple sclerosis. J. Neurol., 2013, 260(1), 285-295.
[http://dx.doi.org/10.1007/s00415-012-6634-z] [PMID: 22878432]
[208]
Maniscalco, G.T.; Aponte, R.; Bruzzese, D.; Guarcello, G.; Manzo, V.; Napolitano, M.; Moreggia, O.; Chiariello, F.; Florio, C. THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: A pilot prospective study. Neurol. Sci., 2018, 39(1), 97-102.
[http://dx.doi.org/10.1007/s10072-017-3148-6] [PMID: 29052091]
[209]
Patti, F.; Chisari, C.G.; Solaro, C.; Benedetti, M.D.; Berra, E.; Bianco, A.; Bruno Bossio, R.; Buttari, F.; Castelli, L.; Cavalla, P.; Cerqua, R.; Costantino, G.; Gasperini, C.; Guareschi, A.; Ippolito, D.; Lanzillo, R.; Maniscalco, G.T.; Matta, M.; Paolicelli, D.; Petrucci, L.; Pontecorvo, S.; Righini, I.; Russo, M.; Saccà, F.; Salamone, G.; Signoriello, E.; Spinicci, G.; Spitaleri, D.; Tavazzi, E.; Trotta, M.; Zaffaroni, M.; Zappia, M. Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: Results from a retrospective multicenter study. Neurol. Sci., 2020, 41(10), 2905-2913.
[http://dx.doi.org/10.1007/s10072-020-04413-6] [PMID: 32335779]
[210]
Meuth, S.G.; Henze, T.; Essner, U.; Trompke, C. Vila Silván, C. Tetrahydrocannabinol and cannabidiol oromucosal spray in resistant multiple sclerosis spasticity: consistency of response across subgroups from the SAVANT randomized clinical trial. Int. J. Neurosci., 2020, 130(12), 1199-1205.
[http://dx.doi.org/10.1080/00207454.2020.1730832] [PMID: 32065006]
[211]
Coghe, G.; Pau, M.; Corona, F.; Frau, J.; Lorefice, L.; Fenu, G.; Spinicci, G.; Mamusa, E.; Musu, L.; Massole, S.; Massa, R.; Marrosu, M.G.; Cocco, E. Walking improvements with nabiximols in patients with multiple sclerosis. J. Neurol., 2015, 262(11), 2472-2477.
[http://dx.doi.org/10.1007/s00415-015-7866-5] [PMID: 26239223]
[212]
Patti, F.; Messina, S.; Solaro, C.; Amato, M.P.; Bergamaschi, R.; Bonavita, S.; Bruno Bossio, R.; Brescia Morra, V.; Costantino, G.F.; Cavalla, P.; Centonze, D.; Comi, G.; Cottone, S.; Danni, M.; Francia, A.; Gajofatto, A.; Gasperini, C.; Ghezzi, A.; Iudice, A.; Lus, G.; Maniscalco, G.T.; Marrosu, M.G.; Matta, M.; Mirabella, M.; Montanari, E.; Pozzilli, C.; Rovaris, M.; Sessa, E.; Spitaleri, D.; Trojano, M.; Valentino, P.; Zappia, M. Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity. J. Neurol. Neurosurg. Psychiatry, 2016, 87(9), 944-951.
[http://dx.doi.org/10.1136/jnnp-2015-312591] [PMID: 27160523]
[213]
Russo, M. Calabrò, R.S.; Naro, A.; Sessa, E.; Rifici, C.; D’Aleo, G.; Leo, A.; De Luca, R.; Quartarone, A.; Bramanti, P. Sativex in the management of multiple sclerosis-related spasticity: role of the corticospinal modulation. Neural Plast., 2015, 2015, 1-6.
[http://dx.doi.org/10.1155/2015/656582] [PMID: 25699191]
[214]
Cooper, R.E.; Williams, E.; Seegobin, S.; Tye, C.; Kuntsi, J.; Asherson, P. Cannabinoids in attention-deficit/hyperactivity disorder: A randomised-controlled trial. Eur. Neuropsychopharmacol., 2017, 27(8), 795-808.
[http://dx.doi.org/10.1016/j.euroneuro.2017.05.005] [PMID: 28576350]
[215]
Wade, D.T.; Makela, P.; Robson, P.; House, H.; Bateman, C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult. Scler., 2004, 10(4), 434-441.
[http://dx.doi.org/10.1191/1352458504ms1082oa] [PMID: 15327042]
[216]
Rog, D.; Nurmikko, T.; Young, C. Oromucosal Δ9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: An uncontrolled, open-label, 2-year extension trial. Clin. Ther., 2007, 29(9), 2068-2079.
[http://dx.doi.org/10.1016/j.clinthera.2007.09.013] [PMID: 18035205]
[217]
Trojano, M.; Vila, C. Effectiveness and tolerability of THC/CBD oromucosal spray for multiple sclerosis spasticity in Italy: First data from a large observational study. Eur. Neurol., 2015, 74(3-4), 178-185.
[http://dx.doi.org/10.1159/000441619] [PMID: 26571097]
[218]
Wade, D.T.; Makela, P.M.; House, H.; Bateman, C.; Robson, P. Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult. Scler., 2006, 12(5), 639-645.
[http://dx.doi.org/10.1177/1352458505070618] [PMID: 17086911]
[219]
Collin, C.; Davies, P.; Mutiboko, I.K.; Ratcliffe, S. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur. J. Neurol., 2007, 14(3), 290-296.
[http://dx.doi.org/10.1111/j.1468-1331.2006.01639.x] [PMID: 17355549]
[220]
Haupts, M.; Vila, C.; Jonas, A.; Witte, K. Álvarez-Ossorio, L. Influence of previous failed antispasticity therapy on the efficacy and tolerability of THC:CBD oromucosal spray for multiple sclerosis spasticity. Eur. Neurol., 2016, 75(5-6), 236-243.
[http://dx.doi.org/10.1159/000445943] [PMID: 27160412]
[221]
Collin, C.; Ehler, E.; Waberzinek, G.; Alsindi, Z.; Davies, P.; Powell, K.; Notcutt, W.; O’Leary, C.; Ratcliffe, S. Nováková, I.; Zapletalova, O.; Piková, J.; Ambler, Z. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol. Res., 2010, 32(5), 451-459.
[http://dx.doi.org/10.1179/016164109X12590518685660] [PMID: 20307378]
[222]
Kavia, R.B.C.; De Ridder, D.; Constantinescu, C.S.; Stott, C.G.; Fowler, C.J. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult. Scler., 2010, 16(11), 1349-1359.
[http://dx.doi.org/10.1177/1352458510378020] [PMID: 20829244]
[223]
Notcutt, W.; Langford, R.; Davies, P.; Ratcliffe, S.; Potts, R. A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols). Mult. Scler., 2012, 18(2), 219-228.
[http://dx.doi.org/10.1177/1352458511419700] [PMID: 21878454]
[224]
Alessandria, G.; Meli, R.; Infante, M.T.; Vestito, L.; Capello, E.; Bandini, F. Long-term assessment of the cognitive effects of nabiximols in patients with multiple sclerosis: A pilot study. Clin. Neurol. Neurosurg., 2020, 196, 105990.
[http://dx.doi.org/10.1016/j.clineuro.2020.105990] [PMID: 32526487]
[225]
Squintani, G.; Donato, F.; Turri, M.; Deotto, L.; Teatini, F.; Moretto, G.; Erro, R. Cortical and spinal excitability in patients with multiple sclerosis and spasticity after oromucosal cannabinoid spray. J. Neurol. Sci., 2016, 370, 263-268.
[http://dx.doi.org/10.1016/j.jns.2016.09.054] [PMID: 27772772]
[226]
Nurmikko, T.J.; Serpell, M.G.; Hoggart, B.; Toomey, P.J.; Morlion, B.J.; Haines, D. Sativex successfully treats neuropathic pain characterised by allodynia: A randomised, double-blind, placebo-controlled clinical trial. Pain, 2007, 133(1), 210-220.
[http://dx.doi.org/10.1016/j.pain.2007.08.028] [PMID: 17997224]
[227]
Feliú, A.; Moreno-Martet, M.; Mecha, M.; Carrillo-Salinas, F.J.; de Lago, E.; Fernández-Ruiz, J.; Guaza, C. A S ativex ® -like combination of phytocannabinoids as a disease-modifying therapy in a viral model of multiple sclerosis. Br. J. Pharmacol., 2015, 172(14), 3579-3595.
[http://dx.doi.org/10.1111/bph.13159] [PMID: 25857324]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy