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Current Neuropharmacology

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ISSN (Online): 1875-6190

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Review Article

Phytocannabinoids: General Aspects and Pharmacological Potential in Neurodegenerative Diseases

Author(s): Graziella dos Reis Rosa Franco, Scott Smid and Cláudio Viegas *

Volume 19, Issue 4, 2021

Published on: 20 July, 2020

Page: [449 - 464] Pages: 16

DOI: 10.2174/1570159X18666200720172624

Price: $65

Abstract

In the last few years research into Cannabis and its constituent phytocannabinoids has burgeoned, particularly in the potential application of novel cannabis phytochemicals for the treatment of diverse illnesses related to neurodegeneration and dementia, including Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s disease (HD). To date, these neurological diseases have mostly relied on symptomatological management. However, with an aging population globally, the search for more efficient and disease-modifying treatments that could delay or mitigate disease progression is imperative. In this context, this review aims to present state of the art in the research with cannabinoids and novel cannabinoid-based drug candidates that have been emerged as novel promising alternatives for drug development and innovation in the therapeutics of a number of diseases, especially those related to CNS-disturbance and impairment.

Keywords: Phytocannabinoids, endocannabinoid system, neurodegenerative diseases, cannabis sp. cannabinoid receptors, neurological disorders.

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Graphical Abstract

[1]
Robison, R. O Grande Livro Da Cannabis, 1st ed; Vermont, USA, 1999.
[2]
Ligresti, A.; De Petrocellis, L.; Di Marzo, V. From phytocannabinoids to cannabinoid receptors and endocannabinoids: Pleiotropic physiological and pathological roles through complex pharmacology. Physiol. Rev., 2016, 96(4), 1593-1659.
[http://dx.doi.org/10.1152/physrev.00002.2016] [PMID: 27630175]
[3]
Gontijo, C.; Castro, G.L.; De Castro, A.D. Canabidiol e suas aplicações terapêuticas. Refacer., 2016, 5(1), 1-9.
[4]
Scherma, M.; Masia, P.; Deidda, M.; Fratta, W.; Tanda, G.; Fadda, P. New perspectives on the use of cannabis in the treatment of psychiatric disorders. Medicines, 2018, 5, 107.
[http://dx.doi.org/10.3390/medicines5040107]
[5]
National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research, 1st ed; The National Academies Press: Washington, DC, 2017.
[6]
Sexton, M.; Shelton, K.; Haley, P.; West, M. Evaluation of cannabinoid and terpenoid content: Cannabis flower compared to supercritical CO 2 concentrate. Planta Med., 2018, 84, 4.
[7]
Das, S.; Stark, L.; Musgrave, I.F.; Pukala, T.; Smid, S.D. Bioactive polyphenol interactions with β amyloid: a comparison of binding modelling, effects on fibril and aggregate formation and neuroprotective capacity. Food Funct., 2016, 7(2), 1138-1146.
[http://dx.doi.org/10.1039/C5FO01281C] [PMID: 26815043]
[8]
Russo, E.B. Cannabis therapeutics and the future of neurology. Front. Integr. Nuerosci., 2018, 12(October), 51.
[http://dx.doi.org/10.3389/fnint.2018.00051] [PMID: 30405366]
[9]
Pertwee, R. Pharmacological actions of cannabinoids. Eur. Neuropsychopharmacol., 2010, 20, S205.
[http://dx.doi.org/10.1016/S0924-977X(10)70232-7]
[10]
Mudge, E.M.; Murch, S.J.; Brown, P.N. Chemometric analysis of cannabinoids: chemotaxonomy and domestication syndrome. Sci. Rep., 2018, 8(1), 13090.
[http://dx.doi.org/10.1038/s41598-018-31120-2] [PMID: 30166613]
[11]
Lewis, M.M.; Yang, Y.; Wasilewski, E.; Clarke, H.A.; Kotra, L.P. Chemical profiling of medical cannabis extracts. ACS Omega, 2017, 2(9), 6091-6103.
[http://dx.doi.org/10.1021/acsomega.7b00996] [PMID: 30023762]
[12]
Hanuš, L.O.; Meyer, S.M.; Muñoz, E.; Taglialatela-Scafati, O.; Appendino, G. Phytocannabinoids: a unified critical inventory. Nat. Prod. Rep., 2016, 33(12), 1357-1392.
[http://dx.doi.org/10.1039/C6NP00074F] [PMID: 27722705]
[13]
Franco, R.R.G.; Viegas, Junior, C. The contribution of studies with canabidiol and synthetic analogues in the design of new drug candidates for neuropsychiatric disorders and neurodegenerative diseases. Rev Virtual Química., 2017, 9(4), 1773-1798.
[http://dx.doi.org/10.21577/1984-6835.20170103]
[14]
Abuhasira, R.; Schleider, L.B.L.; Mechoulam, R.; Novack, V. Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. Eur. J. Intern. Med., 2018, 49, 44-50.
[http://dx.doi.org/10.1016/j.ejim.2018.01.019] [PMID: 29398248]
[15]
Rosenberg, E.C.; Tsien, R.W.; Whalley, B.J.; Devinsky, O. Cannabinoids and epilepsy. Neurotherapeutics, 2015, 12(4), 747-768.
[http://dx.doi.org/10.1007/s13311-015-0375-5] [PMID: 26282273]
[16]
Klumpers, L.E.; Thacker, D.L. A brief background on cannabis: From plant to medical indications. J. AOAC Int., 2019, 102(2), 412-420.
[http://dx.doi.org/10.5740/jaoacint.18-0208] [PMID: 30139415]
[17]
Pisanti, S.; Malfitano, A.M.; Ciaglia, E.; Lamberti, A.; Ranieri, R.; Cuomo, G.; Abate, M.; Faggiana, G.; Proto, M.C.; Fiore, D.; Laezza, C.; Bifulco, M. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol. Ther., 2017, 175, 133-150.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.041] [PMID: 28232276]
[18]
Bonini, S.A.; Premoli, M.; Tambaro, S.; Kumar, A.; Maccarinelli, G.; Memo, M.; Mastinu, A. Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. J. Ethnopharmacol., 2018, 227, 300-315.
[http://dx.doi.org/10.1016/j.jep.2018.09.004] [PMID: 30205181]
[19]
Páez, J.A.; Campillo, N.E. Innovative therapeutic potential of cannabinoid receptors as targets in Alzheimer’s disease and less well-known diseases. Curr. Med. Chem., 2019, 26(18), 3300-3340.
[http://dx.doi.org/10.2174/0929867325666180226095132] [PMID: 29484980]
[20]
Pellati, F.; Borgonetti, V.; Brighenti, V.; Biagi, M.; Benvenuti, S.; Corsi, L. Cannabis sativa L. and nonpsychoactive cannabinoids : their chemistry and role against oxidative stress, inflammation, and cancer. BioMed Res. Int., 2018, 20181691428
[http://dx.doi.org/10.1155/2018/1691428]] [PMID: 30627539]
[21]
Maccarrone, M. Missing pieces to the endocannabinoid puzzle. Trends Mol. Med., 2019, 26(3), 263-272.
[PMID: 31822395]
[22]
Ożarowski, M.; Mikolajczak, P.Ł.; Bogacz, A.; Bartkowiak-Wieczorek, J.; Kujawski, R.; Majchrzycki, M.; Wielgus, K.; Seremak-Mrozikiewicz, A.; Czerny, B. Progress in study of Cannabis sativa leaves extracts without psychotropic cannabinoids in animal model of neuropathic pain. J Med Sci., 2016, 83, 328-335.
[23]
Zuardi, A.W. History of cannabis as a medicine: a review. Br. J. Psychiatry, 2006, 28(2), 153-157.
[http://dx.doi.org/10.1590/S1516-44462006000200015] [PMID: 16810401]
[24]
United Nations. Single Convention on Narcotic Drugs, 1961, 44
[25]
Reekie, T.A.; Scott, M.P.; Kassiou, M. The evolving science of phytocannabinoids. Nat. Rev. Chem., 2018, 2(1), 1-12.
[http://dx.doi.org/10.1038/s41570-017-0101]
[26]
Nations, U. Convention on Psychotropic Substances, 1971, 1971, 41.
[27]
Maurya, N.; Velmurugan, B.K. Therapeutic applications of cannabinoids. Chem. Biol. Interact., 2018, 293, 77-88.
[http://dx.doi.org/10.1016/j.cbi.2018.07.018] [PMID: 30040916]
[28]
Bloomfield, M.A.P.; Hindocha, C.; Green, S.F.; Wall, M.B.; Lees, R.; Petrilli, K.; Costello, H.; Ogunbiyi, M.O.; Bossong, M.G.; Freeman, T.P. The neuropsychopharmacology of cannabis: A review of human imaging studies. Pharmacol. Ther., 2019, 195, 132-161.
[http://dx.doi.org/10.1016/j.pharmthera.2018.10.006] [PMID: 30347211]
[29]
Matos, R.L.A.; Spinola, L.A.; Barboza, L.L.; Garcia, D.R.; França, T.C.C.; Affonso, R.S.O. Uso do canabidiol no tratamento da epilepsia. Rev Virtual Quim., 2017, 9(2), 786-814.
[http://dx.doi.org/10.21577/1984-6835.20170049]
[30]
Turner, S.E.; Williams, C.M.; Iversen, L.; Whalley, B.J. Phytocannabinoids. Progress in the Chemistry of Organic Natural Products; Kinghorn, A.; Falk, H.; Gibbons, S; Kobayashi, J., Ed.; Springer: Cham, 2017, Vol. 103, pp. 62-91.
[31]
Russo, E.B. Beyond cannabis: plants and the endocannabinoid system. Trends Pharmacol. Sci., 2016, 37(7), 594-605.
[http://dx.doi.org/10.1016/j.tips.2016.04.005] [PMID: 27179600]
[32]
Morales, P.; Hurst, D.P.; Reggio, P.H. Molecular targets of the phytocannabinoids: a complex picture. Prog. Chem. Org. Nat. Prod., 2017, 103, 103-131.
[http://dx.doi.org/10.1007/978-3-319-45541-9_4] [PMID: 28120232]
[33]
Russo, E.B. Cannabidiol claims and misconceptions. Trends Pharmacol. Sci., 2017, 38(3), 198-201.
[http://dx.doi.org/10.1016/j.tips.2016.12.004] [PMID: 28089139]
[34]
Pollastro, F.; Caprioglio, D.; Del Prete, D.; Rogati, F.; Minassi, A.; Taglialatela-Scafati, O.; Munoz, E.; Appendino, G. Cannabichromene. Nat. Prod. Commun., 2018, 13, 1189-1194.
[http://dx.doi.org/10.1177/1934578X1801300922]
[35]
Mechoulam, R.; Shani, A.; Edery, H.; Grunfeld, Y. Chemical basis of hashish activity. Science, 1970, 169(3945), 611-612.
[http://dx.doi.org/10.1126/science.169.3945.611] [PMID: 4987683]
[36]
Stern, E.; Lambert, D.M. Medicinal chemistry endeavors around the phytocannabinoids. Chem. Biodivers., 2007, 4(8), 1707-1728.
[http://dx.doi.org/10.1002/cbdv.200790149] [PMID: 17712816]
[37]
Di Marzo, V.; Piscitelli, F. The endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics, 2015, 12(4), 692-698.
[http://dx.doi.org/10.1007/s13311-015-0374-6] [PMID: 26271952]
[38]
Capasso, A.; Sobarzo-Sánchez, E.; Nabavi, S.F.; Rastrelli, L. Cannabinoids for the treatment of schizophrenia: an overview. Curr. Top. Med. Chem., 2016, 16(17), 1916-1923.
[http://dx.doi.org/10.2174/1568026616666160204122033] [PMID: 26845552]
[39]
Navarro, G.; Varani, K.; Reyes-Resina, I.; Sánchez de Medina, V.; Rivas-Santisteban, R.; Sánchez-Carnerero Callado, C.; Vincenzi, F.; Casano, S.; Ferreiro-Vera, C.; Canela, E.I.; Borea, P.A.; Nadal, X.; Franco, R. Cannabigerol action at cannabinoid CB 1 and CB 2 receptors and at CB1-CB2 heteroreceptor complexes. Front. Pharmacol., 2018, 9, 632.
[http://dx.doi.org/10.3389/fphar.2018.00632] [PMID: 29977202]
[40]
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]
[41]
Aguareles, J.; Paraíso-Luna, J.; Palomares, B.; Bajo-Grañeras, R.; Navarrete, C.; Ruiz-Calvo, A.; García-Rincón, D.; García-Taboada, E.; Guzmán, M.; Muñoz, E.; Galve-Roperh, I. Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration. Transl. Neurodegener., 2019, 8, 9.
[http://dx.doi.org/10.1186/s40035-019-0148-x] [PMID: 30899454]
[42]
Mammana, S.; Cavalli, E.; Gugliandolo, A.; Silvestro, S.; Pollastro, F.; Bramanti, P.; Mazzon, E. Could the combination of two non-psychotropic cannabinoids counteract neuroinflammation? Effectiveness of cannabidiol associated with cannabigerol. Medicina (Kaunas), 2019, 55(11), 1-14.
[PMID: 31752240]
[43]
Pinzi, L.; Lherbet, C.; Baltas, M.; Pellati, F.; Rastelli, G. In silico repositioning of cannabigerol as a novel inhibitor of the enoyl acyl carrier protein (ACP) reductase (INHA). Molecules, 2019, 24(14), 1-9.
[http://dx.doi.org/10.3390/molecules24142567] [PMID: 31311157]
[44]
Díaz-Alonso, J.; Paraíso-Luna, J.; Navarrete, C.; Del Río, C.; Cantarero, I.; Palomares, B.; Aguareles, J.; Fernández-Ruiz, J.; Bellido, M.L.; Pollastro, F.; Appendino, G.; Calzado, M.A.; Galve-Roperh, I.; Muñoz, E. VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease. Sci. Rep., 2016, 6, 29789.
[http://dx.doi.org/10.1038/srep29789] [PMID: 27430371]
[45]
Gugliandolo, A.; Pollastro, F.; Grassi, G.; Bramanti, P.; Mazzon, E. In vitro model of neuroinflammation: Efficacy of cannabigerol, a non-psychoactive cannabinoid. Int. J. Mol. Sci., 2018, 19(7), 1-16.
[http://dx.doi.org/10.3390/ijms19071992] [PMID: 29986533]
[46]
Mechoulam, R.; Gaoni, Y. Cannabichromene, a new active principle in hashish. Chem. Commun., 1966, 1, 20-21.
[47]
Udoh, M.; Santiago, M.; Devenish, S.; McGregor, I.S.; Connor, M. Cannabichromene is a cannabinoid CB2 receptor agonist. Br. J. Pharmacol., 2019, 176(23), 4537-4547.
[http://dx.doi.org/10.1111/bph.14815] [PMID: 31368508]
[48]
Rosenthaler, S.; Pöhn, B.; Kolmanz, C.; Huu, C.N.; Krewenka, C.; Huber, A.; Kranner, B.; Rausch, W.D.; Moldzio, R. Differences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures. Neurotoxicol. Teratol., 2014, 46, 49-56.
[http://dx.doi.org/10.1016/j.ntt.2014.09.003] [PMID: 25311884]
[49]
Hatoum, N.S.; Davis, W.M.; Elsohly, M.A.; Turner, C.E. Cannabichromene and delta 9-tetrahydrocannabinol: interactions relative to lethality, hypothermia and hexobarbital hypnosis. Gen. Pharmacol., 1981, 12(5), 357-362.
[http://dx.doi.org/10.1016/0306-3623(81)90090-2] [PMID: 6269951]
[50]
Wirth, P.W.; Watson, E.S.; ElSohly, M.A.; Seidel, R.; Murphy, J.C.; Turner, C.E. Anti-inflammatory activity of cannabichromene homologs. J. Pharm. Sci., 1980, 69(11), 1359-1360.
[http://dx.doi.org/10.1002/jps.2600691136] [PMID: 7452475]
[51]
Petrosino, S.; Verde, R.; Vaia, M.; Allarà, M.; Iuvone, T.; Di Marzo, V. Anti-inflammatory properties of cannabidiol, a nonpsychotropic cannabinoid, in experimental allergic contact dermatitis. J. Pharmacol. Exp. Ther., 2018, 365(3), 652-663.
[http://dx.doi.org/10.1124/jpet.117.244368] [PMID: 29632236]
[52]
Iuvone, T.; Di Marzo, V.; Guy, G.; Wright, S.; Stott, C. Cannabinoids for use in the treatment of neurodegenative diseases or disorders UK Patent Application GB 2492487 2012.
[53]
Schubert, D.; Kepchia, D.; Liang, Z.; Dargusch, R.; Goldberg, J.; Maher, P. Efficacy of cannabinoids in a pre-clinical drug-screening platform for Alzheimer’s disease. Mol. Neurobiol., 2019, 56(11), 7719-7730.
[http://dx.doi.org/10.1007/s12035-019-1637-8] [PMID: 31104297]
[54]
Breuer, A.; Haj, C.G.; Fogaça, M.V.; Gomes, F.V.; Silva, N.R.; Pedrazzi, J.F.; Del Bel, E.A.; Hallak, J.C.; Crippa, J.A.; Zuardi, A.W.; Mechoulam, R.; Guimarães, F.S. Fluorinated cannabidiol derivatives: Enhancement of activity in mice models predictive of anxiolytic, antidepressant and antipsychotic effects. PLoS One, 2016, 11, 1-19.
[55]
Adams, R.; Hunt, M.; Clark, J.H. Structure of cannabidiol, a product isolated from the marihuana extract of minnesota wild hemp. I. J. Am. Chem. Soc., 1939, 62, 196-200.
[http://dx.doi.org/10.1021/ja01858a058]
[56]
Mechoulam, R.; Shvo, Y.; Hashish, I. The structure of cannabidiol. Tetrahedron, 1963, 19(12), 2073-2078.
[http://dx.doi.org/10.1016/0040-4020(63)85022-X] [PMID: 5879214]
[57]
Karl, T.; Garner, B.; Cheng, D. The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease. Behav. Pharmacol, 2017, 28(2 and 3-Spec Issue), 142-160.
[http://dx.doi.org/10.1097/FBP.0000000000000247] [PMID: 27471947]
[58]
Laprairie, R.B.; Bagher, A.M.; Kelly, M.E.M.; Denovan-Wright, E.M. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br. J. Pharmacol., 2015, 172(20), 4790-4805.
[http://dx.doi.org/10.1111/bph.13250] [PMID: 26218440]
[59]
Ye, L.; Cao, Z.; Wang, W.; Zhou, N. New insights in cannabinoid receptor structure and signaling. Curr. Mol. Pharmacol., 2019, 12(3), 239-248.
[http://dx.doi.org/10.2174/1874467212666190215112036] [PMID: 30767756]
[60]
Di Marzo, V. New approaches and challenges to targeting the endocannabinoid system. Nat. Rev. Drug Discov., 2018, 17(9), 623-639.
[http://dx.doi.org/10.1038/nrd.2018.115] [PMID: 30116049]
[61]
O’Sullivan, S.E. An update on PPAR activation by cannabinoids. Br. J. Pharmacol., 2016, 173(12), 1899-1910.
[http://dx.doi.org/10.1111/bph.13497] [PMID: 27077495]
[62]
Resstel, L.B.M.; Tavares, R.F.; Lisboa, S.F.S.; Joca, S.R.L.; Corrêa, F.M.A.; Guimarães, F.S. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br. J. Pharmacol., 2009, 156(1), 181-188.
[http://dx.doi.org/10.1111/j.1476-5381.2008.00046.x] [PMID: 19133999]
[63]
Cheng, Y.; Dong, Z.; Liu, S. β-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 Mice through CB2 receptor activation and the PPARγ pathway. Pharmacology, 2014, 94(1-2), 1-12.
[http://dx.doi.org/10.1159/000362689] [PMID: 25171128]
[64]
Iuvone, T.; Esposito, G.; Esposito, R.; Santamaria, R.; Di Rosa, M.; Izzo, A.A. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on β-amyloid-induced toxicity in PC12 cells. J. Neurochem., 2004, 89(1), 134-141.
[http://dx.doi.org/10.1111/j.1471-4159.2003.02327.x] [PMID: 15030397]
[65]
Watt, G.; Karl, T. In vivo evidence for therapeutic properties of cannabidiol (CBD) for Alzheimer’s disease. Front. Pharmacol., 2017, 8, 20.
[http://dx.doi.org/10.3389/fphar.2017.00020] [PMID: 28217094]
[66]
Janefjord, E.; Mååg, J.L.V.; Harvey, B.S.; Smid, S.D. Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cell. Mol. Neurobiol., 2014, 34(1), 31-42.
[http://dx.doi.org/10.1007/s10571-013-9984-x] [PMID: 24030360]
[67]
Libro, R.; Diomede, F.; Scionti, D.; Piattelli, A.; Grassi, G.; Pollastro, F.; Bramanti, P.; Mazzon, E.; Trubiani, O. Cannabidiol modulates the expression of alzheimer’s disease-related genes in mesenchymal stem cells. Int. J. Mol. Sci., 2016, 18(1), 1-19.
[http://dx.doi.org/10.3390/ijms18010026] [PMID: 28025562]
[68]
Costiniuk, C.T.; Jenabian, M.A. Cannabinoids and inflammation: implications for people living with HIV. AIDS, 2019, 33(15), 2273-2288.
[http://dx.doi.org/10.1097/QAD.0000000000002345] [PMID: 31764093]
[69]
Scuderi, C.; Steardo, L.; Esposito, G. Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARγ involvement. Phytother. Res., 2014, 28(7), 1007-1013.
[http://dx.doi.org/10.1002/ptr.5095] [PMID: 24288245]
[70]
Esposito, G.; Scuderi, C.; Valenza, M.; Togna, G.I.; Latina, V.; de Filippis, D.; Cipriano, M.; Carratù, M.R.; Iuvone, T.; Steardo, L. Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement. PLoS One, 2011, 6, 1-8.
[http://dx.doi.org/10.1371/journal.pone.0028668]
[71]
Vallée, A.; Lecarpentier, Y.; Guillevin, R.; Vallée, J.N. Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer’s disease. Acta Biochim. Biophys. Sin. (Shanghai), 2017, 49(10), 853-866.
[http://dx.doi.org/10.1093/abbs/gmx073] [PMID: 28981597]
[72]
Martín-Moreno, A.M.; Reigada, D.; Ramírez, B.G.; Mechoulam, R.; Innamorato, N.; Cuadrado, A.; de Ceballos, M.L. Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer’s disease. Mol. Pharmacol., 2011, 79(6), 964-973.
[http://dx.doi.org/10.1124/mol.111.071290] [PMID: 21350020]
[73]
Crippa, J.A.S.; Hallak, J.E.C.; Zuardi, A.W.; Guimarães, F.S.; Tumas, V.; Dos Santos, R.G. Is cannabidiol the ideal drug to treat non-motor Parkinson’s disease symptoms? Eur. Arch. Psychiatry Clin. Neurosci., 2019, 269(1), 121-133.
[http://dx.doi.org/10.1007/s00406-019-00982-6] [PMID: 30706171]
[74]
Premoli, M.; Aria, F.; Bonini, S.A.; Maccarinelli, G.; Gianoncelli, A.; Pina, S.D.; Tambaro, S.; Memo, M.; Mastinu, A. Cannabidiol: Recent advances and new insights for neuropsychiatric disorders treatment. Life Sci., 2019, 224, 120-127.
[http://dx.doi.org/10.1016/j.lfs.2019.03.053] [PMID: 30910646]
[75]
Crivelaro do Nascimento, G.; Ferrari, D.P.; Guimaraes, F.S.; Del Bel, E.A.; Bortolanza, M.; Ferreira-Junior, N.C. Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson’s disease. Neuropharmacology, 2020, 163107808
[http://dx.doi.org/10.1016/j.neuropharm.2019.107808]] [PMID: 31706993]
[76]
Peres, F.F.; Levin, R.; Suiama, M.A.; Diana, M.C.; Gouvêa, D.A.; Almeida, V.; Santos, C.M.; Lungato, L.; Zuardi, A.W.; Hallak, J.E.C.; Crippa, J.A.; Vânia, D.; Silva, R.H.; Abílio, V.C. Cannabidiol prevents motor and cognitive impairments induced by reserpine in rats. Front. Pharmacol., 2016, 7, 343.
[http://dx.doi.org/10.3389/fphar.2016.00343] [PMID: 27733830]
[77]
Hacke, A.C.M.; Lima, D.; de Costa, F.; Deshmukh, K.; Li, N.; Chow, A.M.; Marques, J.A.; Pereira, R.P.; Kerman, K. Probing the antioxidant activity of Δ9-tetrahydrocannabinol and cannabidiol in Cannabis sativa extracts. Analyst (Lond.), 2019, 144(16), 4952-4961.
[http://dx.doi.org/10.1039/C9AN00890J] [PMID: 31318364]
[78]
Huestis, M.A.; Solimini, R.; Pichini, S.; Pacifici, R.; Carlier, J.; Busardò, F.P. Cannabidiol adverse effects and toxicity. Curr. Neuropharmacol., 2019, 17(10), 974-989.
[http://dx.doi.org/10.2174/1570159X17666190603171901] [PMID: 31161980]
[79]
Lucas, C.J.; Galettis, P.; Schneider, J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br. J. Clin. Pharmacol., 2018, 84(11), 2477-2482.
[http://dx.doi.org/10.1111/bcp.13710] [PMID: 30001569]
[80]
Izzo, L.; Castaldo, L.; Narváez, A.; Graziani, G.; Gaspari, A.; Rodríguez-Carrasco, Y.; Ritieni, A. Analysis of phenolic compounds in commercial Cannabis sativa L. Inflorescences Using UHPLC-Q-Orbitrap HRMS. Molecules, 2020, 25(3), 1-12.
[http://dx.doi.org/10.3390/molecules25030631] [PMID: 32024009]
[81]
Kinney, W.A.; McDonnell, M.E.; Zhong, H.M.; Liu, C.; Yang, L.; Ling, W.; Qian, T.; Chen, Y.; Cai, Z.; Petkanas, D.; Brenneman, D.E. Discovery of KLS-13019, a cannabidiol-derived neuroprotective agent, with improved potency, safety, and permeability. ACS Med. Chem. Lett., 2016, 7(4), 424-428.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00009] [PMID: 27096053]
[82]
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]
[83]
Wong, H.; Cairns, B.E. Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain. Arch. Oral Biol., 2019, 104, 33-39.
[http://dx.doi.org/10.1016/j.archoralbio.2019.05.028] [PMID: 31158702]
[84]
Wong, H.; Hossain, S.; Cairns, B.E. Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation. Eur. J. Pain, 2017, 21(10), 1732-1742.
[http://dx.doi.org/10.1002/ejp.1085] [PMID: 28722246]
[85]
Carroll, C.B.; Zeissler, M.L.; Hanemann, C.O.; Zajicek, J.P.Δ.Δ. 9-tetrahydrocannabinol (Δ9-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson’s disease. Neuropathol. Appl. Neurobiol., 2012, 38(6), 535-547.
[http://dx.doi.org/10.1111/j.1365-2990.2011.01248.x] [PMID: 22236282]
[86]
Nguyen, C.H.; Krewenka, C.; Radad, K.; Kranner, B.; Huber, A.; Duvigneau, J.C.; Miller, I.; Moldzio, R. THC (Δ9-Tetrahydrocannabinol) exerts neuroprotective effect in glutamate-affected murine primary mesencephalic cultures through restoring mitochondrial membrane potential and anti-apoptosis involving CB1 receptor-dependent mechanism. Phytother. Res., 2016, 30(12), 2044-2052.
[http://dx.doi.org/10.1002/ptr.5712] [PMID: 27654887]
[87]
Chen, R.; Zhang, J.; Fan, N.; Teng, Z.Q.; Wu, Y.; Yang, H.; Tang, Y.P.; Sun, H.; Song, Y.; Chen, C.Δ. 9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling. Cell, 2013, 155(5), 1154-1165.
[http://dx.doi.org/10.1016/j.cell.2013.10.042] [PMID: 24267894]
[88]
Aso, E.; Sánchez-Pla, A.; Vegas-Lozano, E.; Maldonado, R.; Ferrer, I. Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice. J. Alzheimers Dis., 2015, 43(3), 977-991.
[http://dx.doi.org/10.3233/JAD-141014] [PMID: 25125475]
[89]
Bilkei-Gorzo, A.; Albayram, O.; Draffehn, A.; Michel, K.; Piyanova, A.; Oppenheimer, H.; Dvir-Ginzberg, M.; Rácz, I.; Ulas, T.; Imbeault, S.; Bab, I.; Schultze, J.L.; Zimmer, A. A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat. Med., 2017, 23(6), 782-787.
[http://dx.doi.org/10.1038/nm.4311] [PMID: 28481360]
[90]
McPartland, J.M.; Duncan, M.; Di Marzo, V.; Pertwee, R.G. Are cannabidiol and Δ(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br. J. Pharmacol., 2015, 172(3), 737-753.
[http://dx.doi.org/10.1111/bph.12944] [PMID: 25257544]
[91]
García, C.; Palomo-Garo, C.; García-Arencibia, M.; Ramos, J.; Pertwee, R.; Fernández-Ruiz, J. Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson’s disease. Br. J. Pharmacol., 2011, 163(7), 1495-1506.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01278.x] [PMID: 21323909]
[92]
Janssens, A.; Silvestri, C.; Martella, A.; Vanoevelen, J.M.; Di Marzo, V.; Voets, T.Δ. 9-tetrahydrocannabivarin impairs epithelial calcium transport through inhibition of TRPV5 and TRPV6. Pharmacol. Res., 2018, 136, 83-89.
[http://dx.doi.org/10.1016/j.phrs.2018.08.021] [PMID: 30170189]
[93]
Deiana, S.; Watanabe, A.; Yamasaki, Y.; Amada, N.; Arthur, M.; Fleming, S.; Woodcock, H.; Dorward, P.; Pigliacampo, B.; Close, S.; Platt, B.; Riedel, G. Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ9-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour. Psychopharmacology (Berl.), 2012, 219(3), 859-873.
[http://dx.doi.org/10.1007/s00213-011-2415-0] [PMID: 21796370]
[94]
Vree, T.B.; Breimer, D.D.; van Ginneken, C.A.M.; van Rossum, J.M. Identification of cannabicyclol with a pentyl or propyl side-chain by means of combined gas chromatography-mass spectrometry. J. Chromatogr. A, 1972, 74(1), 124-127.
[http://dx.doi.org/10.1016/S0021-9673(01)94980-5] [PMID: 4635939]
[95]
Kane, V.V. Structure of cannabicyclol, a detailed NMR study of a synthetic analog. Tetrahedron Lett., 1971, 216, 4101-4104.
[http://dx.doi.org/10.1016/S0040-4039(01)97472-6]
[96]
Korte, F.; Sieper, H. Zur chemischen Klassifizierung von Pflanzen, XX Isolierung von Haschisch‐inhaltsstoffen Aus Cannabis Sativa non Indica. Justus Liebigs Ann. Chem., 1964, 13, 90-98.
[97]
Yamamoto, I.; Gohda, H.; Narimatsu, S.; Yoshimura, H. Identification of cannabielsoin, a new metabolite of cannabidiol formed by guinea-pig hepatic microsomal enzymes, and its pharmacological activity in mice. Chem. Pharm. Bull. (Tokyo), 1988, 34, 833-838.
[98]
Shani, A.; Mechoulam, R. Cannabielsoic acids. Isolation and synthesis by a novel oxidative cyclization. Tetrahedron, 1974, 30, 2437-2446.
[http://dx.doi.org/10.1016/S0040-4020(01)97114-5]
[99]
Obata, Y.; Ishikawa, Y. Studies on the constituents of hemp plant (cannabis sativa l.). Agric. Biol. Chem., 1966, 30, 619-620.
[http://dx.doi.org/10.1271/bbb1961.30.619]
[100]
Chan, W.R.; Magnus, K.E.; Watson, H.A. The strucuture of cannabitriol. Specialia., 1975, 7, 283-284.
[101]
Pacher, P.; Kogan, N.M.; Mechoulam, R. Beyond THC and endocannabinoids. Annu. Rev. Pharmacol. Toxicol., 2020, 60, 637-659.
[http://dx.doi.org/10.1146/annurev-pharmtox-010818-021441] [PMID: 31580774]
[102]
Cassano, T.; Villani, R.; Pace, L.; Carbone, A.; Bukke, V.N.; Orkisz, S.; Avolio, C.; Serviddio, G. From Cannabis sativa to Cannabidiol: Promising therapeutic candidate for the treatment of neurodegenerative diseases. Front. Pharmacol., 2020, 11, 124.
[http://dx.doi.org/10.3389/fphar.2020.00124] [PMID: 32210795]
[103]
Aso, E.; Juvés, S.; Maldonado, R.; Ferrer, I. CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 mice. J. Alzheimers Dis., 2013, 35(4), 847-858.
[http://dx.doi.org/10.3233/JAD-130137] [PMID: 23515018]
[104]
Zuardi, A.W. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Br. J. Psychiatry, 2008, 30(3), 271-280.
[http://dx.doi.org/10.1590/S1516-44462008000300015] [PMID: 18833429]
[105]
Campos, H.C.; da Rocha, M.D.; Viegas, F.P.D.; Nicastro, P.C.; Fossaluzza, P.C.; Fraga, C.A.M.; Barreiro, E.J.; Viegas, C., Jr The role of natural products in the discovery of new drug candidates for the treatment of neurodegenerative disorders I: Parkinson’s disease. CNS Neurol. Disord. Drug Targets, 2011, 10(2), 239-250.
[http://dx.doi.org/10.2174/187152711794480483] [PMID: 20874702]
[106]
Bloomfield, M.A.P.; Ashok, A.H.; Volkow, N.D.; Howes, O.D. The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature, 2016, 539(7629), 369-377.
[http://dx.doi.org/10.1038/nature20153] [PMID: 27853201]
[107]
Deiana, S. Medical use of cannabis. Cannabidiol: a new light for schizophrenia? Drug Test. Anal., 2013, 5(1), 46-51.
[http://dx.doi.org/10.1002/dta.1425] [PMID: 23109356]
[108]
Sartim, A.G.; Moreira, F.A.; Joca, S.R.L. Involvement of CB1 and TRPV1 receptors located in the ventral medial prefrontal cortex in the modulation of stress coping behavior. Neuroscience, 2017, 340, 126-134.
[http://dx.doi.org/10.1016/j.neuroscience.2016.10.031] [PMID: 27771531]
[109]
Sales, A.J.; Crestani, C.C.; Guimarães, F.S.; Joca, S.R.L. Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2018, 86, 255-261.
[http://dx.doi.org/10.1016/j.pnpbp.2018.06.002] [PMID: 29885468]
[110]
Nadal, X.; Del Río, C.; Casano, S.; Palomares, B.; Ferreiro-Vera, C.; Navarrete, C.; Sánchez-Carnerero, C.; Cantarero, I.; Bellido, M.L.; Meyer, S.; Morello, G.; Appendino, G.; Muñoz, E. Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity. Br. J. Pharmacol., 2017, 174(23), 4263-4276.
[http://dx.doi.org/10.1111/bph.14019] [PMID: 28853159]
[111]
Doty, K.R.; Guillot-Sestier, M.V.; Town, T. The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive? Brain Res., 2015, 1617, 155-173.
[http://dx.doi.org/10.1016/j.brainres.2014.09.008] [PMID: 25218556]
[112]
Aliseychik, M.P.; Andreeva, T.V.; Rogaev, E.I. Immunogenetic Factors of Neurodegenerative Diseases: The Role of HLA Class II. Biochemistry (Mosc.), 2018, 83(9), 1104-1116.
[http://dx.doi.org/10.1134/S0006297918090122] [PMID: 30472949]
[113]
Zou, S.; Kumar, U. Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. Int. J. Mol. Sci., 2018, 19(3), 1-23.
[PMID: 29533978]
[114]
Zou, M.; Li, D.; Li, L.; Wu, L.; Sun, C. Role of the endocannabinoid system in neurological disorders. Int. J. Dev. Neurosci., 2019, 76, 95-102.
[http://dx.doi.org/10.1016/j.ijdevneu.2019.03.002] [PMID: 30858029]
[115]
Bisogno, T.; Oddi, S.; Piccoli, A.; Fazio, D.; Maccarrone, M. Type-2 cannabinoid receptors in neurodegeneration. Pharmacol. Res., 2016, 111, 721-730.
[http://dx.doi.org/10.1016/j.phrs.2016.07.021] [PMID: 27450295]
[116]
Iannotti, F.A.; Di Marzo, V.; Petrosino, S. Endocannabinoids and endocannabinoid-related mediators: Targets, metabolism and role in neurological disorders. Prog. Lipid Res., 2016, 62, 107-128.
[http://dx.doi.org/10.1016/j.plipres.2016.02.002] [PMID: 26965148]
[117]
Lossignol, D. Cannabinoids: a new approach for pain control? Curr. Opin. Oncol., 2019, 31(4), 275-279.
[http://dx.doi.org/10.1097/CCO.0000000000000523] [PMID: 30789867]
[118]
Pertwee, R.G.; Howlett, A.C.; Abood, M.E.; Alexander, S.P.H.; Di Marzo, V.; Elphick, M.R.; Greasley, P.J.; Hansen, H.S.; Kunos, G. Cannabinoid receptors and their ligands : beyond cb 1 and cb 2. Pharmacol. Rev., 2010, 62, 588-631.
[http://dx.doi.org/10.1124/pr.110.003004] [PMID: 21079038]
[119]
Shao, Z.; Yin, J.; Chapman, K.; Grzemska, M.; Clark, L.; Wang, J.; Rosenbaum, D.M. High-resolution crystal structure of the human CB1 cannabinoid receptor. Nature, 2016, 540(7634), 602-606.
[http://dx.doi.org/10.1038/nature20613] [PMID: 27851727]
[120]
Hua, T.; Vemuri, K.; Pu, M.; Qu, L.; Han, G.W.; Wu, Y.; Zhao, S.; Shui, W.; Li, S.; Korde, A.; Laprairie, R.B.; Stahl, E.L.; Ho, J.H.; Zvonok, N.; Zhou, H.; Kufareva, I.; Wu, B.; Zhao, Q.; Hanson, M.A.; Bohn, L.M.; Makriyannis, A.; Stevens, R.C.; Liu, Z.J. Crystal structure of the human cannabinoid receptor CB1. Cell, 2016, 167(3), 750-762.e14.
[http://dx.doi.org/10.1016/j.cell.2016.10.004] [PMID: 27768894]
[121]
Li, X.; Hua, T.; Vemuri, K.; Ho, J.H.; Wu, Y.; Wu, L.; Popov, P.; Benchama, O.; Zvonok, N.; Locke, K.; Qu, L.; Han, G.W.; Iyer, M.R.; Cinar, R.; Coffey, N.J.; Wang, J.; Wu, M.; Katritch, V.; Zhao, S.; Kunos, G.; Bohn, L.M.; Makriyannis, A.; Stevens, R.C.; Liu, Z.J. Crystal structure of the human cannabinoid receptor cb2. Cell, 2019, 176(3), 459-467.e13.
[http://dx.doi.org/10.1016/j.cell.2018.12.011] [PMID: 30639103]
[122]
Temple, L.M. Medical marijuana and pain management. Dis. Mon., 2016, 62(9), 346-352.
[http://dx.doi.org/10.1016/j.disamonth.2016.05.014] [PMID: 27364691]
[123]
Wu, J. Cannabis, cannabinoid receptors, and endocannabinoid system: yesterday, today, and tomorrow. Acta Pharmacol. Sin., 2019, 40(3), 297-299.
[http://dx.doi.org/10.1038/s41401-019-0210-3] [PMID: 30670816]
[124]
D’Addario, C.; Di Francesco, A.; Pucci, M.; Finazzi Agrò, A.; Maccarrone, M. Epigenetic mechanisms and endocannabinoid signalling. FEBS J., 2013, 280(9), 1905-1917.
[http://dx.doi.org/10.1111/febs.12125] [PMID: 23305292]
[125]
Chanda, D.; Neumann, D.; Glatz, J.F.C. The endocannabinoid system: Overview of an emerging multi-faceted therapeutic target. Prostaglandins Leukot. Essent. Fatty Acids, 2019, 140, 51-56.
[http://dx.doi.org/10.1016/j.plefa.2018.11.016] [PMID: 30553404]
[126]
Paloczi, J.; Varga, Z.V.; Hasko, G.; Pacher, P. Neuroprotection in Oxidative stress-related neurodegenerative diseases: role of endocannabinoid system modulation. Antioxid. Redox Signal., 2018, 29(1), 75-108.
[http://dx.doi.org/10.1089/ars.2017.7144] [PMID: 28497982]
[127]
Nielsen, J.E.; Rolland, A.D.; Rajpert-De Meyts, E.; Janfelt, C.; Jørgensen, A.; Winge, S.B.; Kristensen, D.M.; Juul, A.; Chalmel, F.; Jégou, B.; Skakkebaek, N.E. Characterisation and localisation of the endocannabinoid system components in the adult human testis. Sci. Rep., 2019, 9(1), 12866.
[http://dx.doi.org/10.1038/s41598-019-49177-y] [PMID: 31537814]
[128]
Malfitano, A.M.; Basu, S.; Maresz, K.; Bifulco, M.; Dittel, B.N. What we know and do not know about the cannabinoid receptor 2 (CB2). Semin. Immunol., 2014, 26(5), 369-379.
[http://dx.doi.org/10.1016/j.smim.2014.04.002] [PMID: 24877594]
[129]
Luis, J.; Costa, G.P.; Maia, L.O.; Villares, J.C.; Fernandez, M. Neurobiology of cannabis: from the endocannabinoid system to cannabis-related disorder. J. Bras. Psiquiatr., 2011, 60, 111-122.
[http://dx.doi.org/10.1590/S0047-20852011000200006]
[130]
Battista, N.; Di Tommaso, M.; Bari, M.; Maccarrone, M. The endocannabinoid system: an overview. Front. Behav. Neurosci., 2012, 6, 9.
[http://dx.doi.org/10.3389/fnbeh.2012.00009] [PMID: 22457644]
[131]
Fezza, F.; Maccarrone, M. Endocannabinoid biochemistry: What do we know after 50 years? Cannabinoids, 1st ed; Di Marzo, V., Ed.; In: John Wiley & Sons, Ltd,; , 2014; pp. 53-94.
[132]
Han, Q-W.; Yuan, Y-H.; Chen, N-H. The therapeutic role of cannabinoid receptors and its agonists or antagonists in Parkinson’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2020, 96109745
[http://dx.doi.org/10.1016/j.pnpbp.2019.109745]] [PMID: 31442553]
[133]
Di Marzo, V. Targeting the endocannabinoid system: to enhance or reduce? Nat. Rev. Drug Discov., 2008, 7(5), 438-455.
[http://dx.doi.org/10.1038/nrd2553] [PMID: 18446159]
[134]
Fowler, C.J.; Doherty, P.; Alexander, S.P.H. endocannabinoid turnover in advances in pharmacolology. Elsevier Inc, 2017, 80, pp 31-66.
[135]
Andre, C.M.; Hausman, J.F.; Guerriero, G. Cannabis sativa: The plant of the thousand and one molecules. Front. Plant Sci., 2016, 7, 19.
[http://dx.doi.org/10.3389/fpls.2016.00019] [PMID: 26870049]
[136]
Allegrone, G.; Pollastro, F.; Magagnini, G.; Taglialatela-Scafati, O.; Seegers, J.; Koeberle, A.; Werz, O.; Appendino, G. The Bibenzyl canniprene inhibits the production of pro-inflammatory eicosanoids and selectively accumulates in some cannabis sativa strains. J. Nat. Prod., 2017, 80(3), 731-734.
[http://dx.doi.org/10.1021/acs.jnatprod.6b01126] [PMID: 28165233]
[137]
Valera, E.; Dargusch, R.; Maher, P.A.; Schubert, D. Modulation of 5-lipoxygenase in proteotoxicity and Alzheimer’s disease. J. Neurosci., 2013, 33(25), 10512-10525.
[http://dx.doi.org/10.1523/JNEUROSCI.5183-12.2013] [PMID: 23785163]
[138]
Barrett, M.L.; Gordon, D.; Evans, F.J. Isolation from Cannabis sativa L. of cannflavin--a novel inhibitor of prostaglandin production. Biochem. Pharmacol., 1985, 34(11), 2019-2024.
[http://dx.doi.org/10.1016/0006-2952(85)90325-9] [PMID: 3859295]
[139]
Werz, O.; Seegers, J.; Schaible, A.M.; Weinigel, C.; Barz, D.; Koeberle, A.; Allegrone, G.; Pollastro, F.; Zampieri, L.; Grassi, G.; Appendino, G. Cannflavins from hemp sprouts, a novel cannabinoid-free hemp food product, target microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase. PharmaNutrition, 2014, 2, 53-60.
[http://dx.doi.org/10.1016/j.phanu.2014.05.001]
[140]
Marsh, D.T.; Das, S.; Ridell, J.; Smid, S.D. Structure-activity relationships for flavone interactions with amyloid β reveal a novel anti-aggregatory and neuroprotective effect of 2′,3′,4′-trihydroxy-flavone (2-D08). Bioorg. Med. Chem., 2017, 25(14), 3827-3834.
[http://dx.doi.org/10.1016/j.bmc.2017.05.041] [PMID: 28559058]
[141]
Bieschke, J.; Russ, J.; Friedrich, R.P.; Ehrnhoefer, D.E.; Wobst, H.; Neugebauer, K.; Wanker, E.E. EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity. Proc. Natl. Acad. Sci. USA, 2010, 107(17), 7710-7715.
[http://dx.doi.org/10.1073/pnas.0910723107] [PMID: 20385841]
[142]
Eggers, C.; Fujitani, M.; Kato, R.; Smid, S. Novel cannabis flavonoid, cannflavin A displays both a hormetic and neuroprotective profile against amyloid β-mediated neurotoxicity in PC12 cells: Comparison with geranylated flavonoids, mimulone and diplacone. Biochem. Pharmacol., 2019, 169113609
[http://dx.doi.org/10.1016/j.bcp.2019.08.011]] [PMID: 31437460]
[143]
Moreau, M.; Ibeh, U.; Decosmo, K.; Bih, N.; Yasmin-Karim, S.; Toyang, N.; Lowe, H.; Ngwa, W. Flavonoid derivative of cannabis demonstrates therapeutic potential in preclinical models of metastatic pancreatic cancer. Front. Oncol., 2019, 9, 660.
[http://dx.doi.org/10.3389/fonc.2019.00660] [PMID: 31396485]
[144]
Lewis, M.A.; Russo, E.B.; Smith, K.M. Pharmacological foundations of cannabis chemovars. Planta Med., 2018, 84(4), 225-233.
[http://dx.doi.org/10.1055/s-0043-122240] [PMID: 29161743]
[145]
Russo, E.B. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br. J. Pharmacol., 2011, 163(7), 1344-1364.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01238.x] [PMID: 21749363]
[146]
Russo, E.B.; Marcu, J. Cannabis pharmacology: the usual suspects and a few promising leads. Adv. Pharmacol., 2017, 80, 67-134.
[http://dx.doi.org/10.1016/bs.apha.2017.03.004] [PMID: 28826544]
[147]
Santiago, M.; Sachdev, S.; Arnold, J.C.; McGregor, I.S.; Connor, M. Absence of entourage: terpenoids commonly found in cannabis sativa do not modulate the functional activity of Δ9-THC at Human CB1 and CB2 receptors. Cannabis Cannabinoid Res., 2019, 4(3), 165-176.
[http://dx.doi.org/10.1089/can.2019.0016] [PMID: 31559333]
[148]
Porres-Martínez, M.; González-Burgos, E.; Carretero, M.E.; Gómez-Serranillos, M.P. In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Z. Natforsch. C J. Biosci., 2016, 71(7-8), 191-199.
[http://dx.doi.org/10.1515/znc-2014-4135] [PMID: 27352445]
[149]
Shanmuganathan, B.; Suryanarayanan, V.; Sathya, S.; Narenkumar, M.; Singh, S.K.; Ruckmani, K.; Pandima Devi, K. Anti-amyloidogenic and anti-apoptotic effect of α-bisabolol against Aβ induced neurotoxicity in PC12 cells. Eur. J. Med. Chem., 2018, 143, 1196-1207.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.017] [PMID: 29150331]
[150]
Nagamatsu, R.; Mitsuhashi, S.; Shigetomi, K.; Ubukata, M. Cleavage of α-dicarbonyl compounds by terpene hydroperoxide. Biosci. Biotechnol. Biochem., 2012, 76(10), 1904-1908.
[http://dx.doi.org/10.1271/bbb.120378] [PMID: 23047102]
[151]
Santos, N.A.G.; Martins, N.M.; Sisti, F.M.; Fernandes, L.S.; Ferreira, R.S.; de Freitas, O.; Santos, A.C. The cannabinoid beta-caryophyllene (BCP) induces neuritogenesis in PC12 cells by a cannabinoid-receptor-independent mechanism. Chem. Biol. Interact., 2017, 261, 86-95.
[http://dx.doi.org/10.1016/j.cbi.2016.11.015] [PMID: 27871898]
[152]
Cheng, D.; Spiro, A.S.; Jenner, A.M.; Garner, B.; Karl, T. Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer’s disease transgenic mice. J. Alzheimers Dis., 2014, 42(4), 1383-1396.
[http://dx.doi.org/10.3233/JAD-140921] [PMID: 25024347]
[153]
Jeyakumar, M.; Sathya, S.; Gandhi, S.; Tharra, P.; Suryanarayanan, V.; Singh, S.K.; Baire, B.; Pandima Devi, K. α-bisabolol β-D-fucopyranoside as a potential modulator of β-amyloid peptide induced neurotoxicity: An in vitro &in silico study. Bioorg. Chem., 2019, 88102935
[http://dx.doi.org/10.1016/j.bioorg.2019.102935]] [PMID: 31030060]
[154]
Shin, M.; Liu, Q.F.; Choi, B.; Shin, C.; Lee, B.; Yuan, C.; Song, Y.J.; Yun, H.S.; Lee, I-S.; Koo, B-S.; Cho, K.S. Neuroprotective effects of limonene (+) against Aβ42-induced neurotoxicity in a Drosophila model of Alzheimer’s disease. Biol. Pharm. Bull., 2020, 43(3), 409-417.
[http://dx.doi.org/10.1248/bpb.b19-00495] [PMID: 31875578]
[155]
Moreno-Sanz, G. Can you pass the acid test? critical review and novel therapeutic perspectives of Δ9-Tetrahydrocannabinolic acid A. Cannabis Cannabinoid Res., 2016, 1(1), 124-130.
[http://dx.doi.org/10.1089/can.2016.0008] [PMID: 28861488]
[156]
Hillen, J.B.; Soulsby, N.; Alderman, C.; Caughey, G.E. Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia: a systematic review. Ther. Adv. Drug Saf., 2019, 102042098619846993
[http://dx.doi.org/10.1177/2042098619846993]] [PMID: 31205674]
[157]
Lim, K.; See, Y.M.; Lee, J. A systematic review of the effectiveness of medical cannabis for psychiatric, movement and neurodegenerative disorders. Clin. Psychopharmacol. Neurosci., 2017, 15(4), 301-312.
[http://dx.doi.org/10.9758/cpn.2017.15.4.301] [PMID: 29073741]
[158]
Carroll, CB; Bain, PG; Teare, L; Liu, X; Joint, C; Wroath, C; Parkin, S.G; Fox, P; Wright, D; Hobart, J Zajicek, JP Cannabis for dyskinesia in parkinson disease: a randomized double-blind crossover study neurology 2004, 63, 1245-1250.
[159]
Chagas, M.H.; Zuardi, A.W.; Tumas, V.; Pena-Pereira, M.A.; Sobreira, E.T.; Bergamaschi, M.M.; dos Santos, A.C.; Teixeira, A.L.; Hallak, J.E.; Crippa, J.A. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. J. Psychopharmacol. (Oxford), 2014, 28(11), 1088-1098.
[http://dx.doi.org/10.1177/0269881114550355] [PMID: 25237116]
[160]
Elsaid, S.; Kloiber, S.; Le Foll, B. Effects of cannabidiol (CBD) in neuropsychiatric disorders: A review of pre-clinical and clinical findings. Prog. Mol. Biol. Transl. Sci., 2019, 167, 25-75.
[http://dx.doi.org/10.1016/bs.pmbts.2019.06.005] [PMID: 31601406]
[161]
Shelef, A.; Barak, Y.; Berger, U.; Paleacu, D.; Tadger, S.; Plopsky, I.; Baruch, Y. Safety and efficacy of medical cannabis oil for behavioral and psychological symptoms of dementia: an-open label, add-on, pilot study. J. Alzheimers Dis., 2016, 51(1), 15-19.
[http://dx.doi.org/10.3233/JAD-150915] [PMID: 26757043]
[162]
López-Sendón Moreno, J.L.; García Caldentey, J.; Trigo Cubillo, P.; Ruiz Romero, C.; García Ribas, G.; Alonso Arias, 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 Ruiz, J.; Guzmán, M.; García de Yébenes Prous, 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]
[163]
Hudson, R.; Renard, J.; Norris, C.; Rushlow, W.J.; Laviolette, S.R. Cannabidiol counteracts the psychotropic side-effects of Δ9-tetrahydrocannabinol in the ventral hippocampus through bidirectional control of ERK1–2 phosphorylation. J. Neurosci., 2019, 39(44), 8762-8777.
[http://dx.doi.org/10.1523/JNEUROSCI.0708-19.2019] [PMID: 31570536]
[164]
Niesink, R.J.M.; van Laar, M.W. Does cannabidiol protect against adverse psychological effects of THC? Front. Psychiatry,, 2013, 4, 130-130.
[http://dx.doi.org/10.3389/fpsyt.2013.00130] [PMID: 24137134]
[165]
OPAS/OMS Brasil. Demência: número de pessoas afetadas triplicará nos próximos 30 anos., https://www.paho.org/bra/index.php? option=com_content&view=article&id=5560:demencia-numero-de-pessoas-afetadas-triplicara-nos-proximos-30-anos&Itemid=839

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