Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Critical Review on the Chemical Aspects of Cannabidiol (CBD) and Harmonization of Computational Bioactivity Data

Author(s): Andrea Mastinu*, Giovanni Ribaudo, Alberto Ongaro, Sara Anna Bonini, Maurizio Memo and Alessandra Gianoncelli

Volume 28, Issue 2, 2021

Published on: 10 February, 2020

Page: [213 - 237] Pages: 25

DOI: 10.2174/0929867327666200210144847

Price: $65

Abstract

Cannabidiol (CBD) is a non-psychotropic phytocannabinoid which represents one of the constituents of the “phytocomplex” of Cannabis sativa. This natural compound is attracting growing interest since when CBD-based remedies and commercial products were marketed. This review aims to exhaustively address the extractive and analytical approaches that have been developed for the isolation and quantification of CBD. Recent updates on cutting-edge technologies were critically examined in terms of yield, sensitivity, flexibility and performances in general, and are reviewed alongside original representative results. As an add-on to currently available contributions in the literature, the evolution of the novel, efficient synthetic approaches for the preparation of CBD, a procedure which is appealing for the pharmaceutical industry, is also discussed. Moreover, with the increasing interest on the therapeutic potential of CBD and the limited understanding of the undergoing biochemical pathways, the reader will be updated about recent in silico studies on the molecular interactions of CBD towards several different targets attempting to fill this gap. Computational data retrieved from the literature have been integrated with novel in silico experiments, critically discussed to provide a comprehensive and updated overview on the undebatable potential of CBD and its therapeutic profile.

Keywords: Cannabis sativa, cannabidiol, extractive methods, chromatography, synthesis of CBD, in silico studies.

[1]
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]
[2]
Kumar, A.; Premoli, M.; Aria, F.; Bonini, S.A.; Maccarinelli, G.; Gianoncelli, A.; Memo, M.; Mastinu, A. Cannabimimetic plants: are they new cannabinoidergic modulators? Planta, 2019, 249(6), 1681-1694.
[http://dx.doi.org/10.1007/s00425-019-03138-x] [PMID: 30877436]
[3]
Mastinu, A.; Premoli, M.; Ferrari-Toninelli, G.; Tambaro, S.; Maccarinelli, G.; Memo, M.; Bonini, S.A. Cannabinoids in health and disease: pharmacological potential in metabolic syndrome and neuroinflammation. Horm. Mol. Biol. Clin. Investig., 2018, 36(2)
[http://dx.doi.org/10.1515/hmbci-2018-0013] [PMID: 29601300]
[4]
Lazzari, P.; Pau, A.; Tambaro, S.; Asproni, B.; Ruiu, S.; Pinna, G.; Mastinu, A.; Curzu, M.M.; Reali, R.; Bottazzi, M.E.; Pinna, G.A.; Murineddu, G. Synthesis and pharmacological evaluation of novel 4-alkyl-5-thien-2′-yl pyrazole carboxamides. Cent. Nerv. Syst. Agents Med. Chem., 2012, 12(4), 254-276.
[http://dx.doi.org/10.2174/187152412803760636] [PMID: 22931442]
[5]
Lazzari, P.; Sanna, A.; Mastinu, A.; Cabasino, S.; Manca, I.; Pani, L. Weight loss induced by rimonabant is associated with an altered leptin expression and hypothalamic leptin signaling in diet-induced obese mice. Behav. Brain Res., 2011, 217(2), 432-438.
[http://dx.doi.org/10.1016/j.bbr.2010.11.022] [PMID: 21074566]
[6]
Lazzari, P.; Serra, V.; Marcello, S.; Pira, M.; Mastinu, A. Metabolic side effects induced by olanzapine treatment are neutralized by CB1 receptor antagonist compounds co-administration in female rats. Eur. Neuropsychopharmacol., 2017, 27(7), 667-678.
[http://dx.doi.org/10.1016/j.euroneuro.2017.03.010] [PMID: 28377074]
[7]
Manca, I.; Mastinu, A.; Olimpieri, F.; Falzoi, M.; Sani, M.; Ruiu, S.; Loriga, G.; Volonterio, A.; Tambaro, S.; Bottazzi, M.E.; Zanda, M.; Pinna, G.A.; Lazzari, P. Novel pyrazole derivatives as neutral CB1 antagonists with significant activity towards food intake. Eur. J. Med. Chem., 2013, 62, 256-269.
[http://dx.doi.org/10.1016/j.ejmech.2012.12.056] [PMID: 23357307]
[8]
Mastinu, A.; Pira, M.; Pani, L.; Pinna, G.A.; Lazzari, P. NESS038C6, a novel selective CB1 antagonist agent with anti-obesity activity and improved molecular profile. Behav. Brain Res., 2012, 234(2), 192-204.
[http://dx.doi.org/10.1016/j.bbr.2012.06.033] [PMID: 22771813]
[9]
Mastinu, A.; Pira, M.; Pinna, G.A.; Pisu, C.; Casu, M.A.; Reali, R.; Marcello, S.; Murineddu, G.; Lazzari, P. NESS06SM reduces body weight with an improved profile relative to SR141716A. Pharmacol. Res., 2013, 74, 94-108.
[http://dx.doi.org/10.1016/j.phrs.2013.06.001] [PMID: 23756200]
[10]
Tambaro, S.; Casu, M.A.; Mastinu, A.; Lazzari, P. Evaluation of selective cannabinoid CB(1) and CB(2) receptor agonists in a mouse model of lipopolysaccharide-induced interstitial cystitis. Eur. J. Pharmacol., 2014, 729, 67-74.
[http://dx.doi.org/10.1016/j.ejphar.2014.02.013] [PMID: 24561047]
[11]
Klieger, S.B.; Gutman, A.; Allen, L.; Pacula, R.L.; Ibrahim, J.K.; Burris, S. Mapping medical marijuana: state laws regulating patients, product safety, supply chains and dispensaries, 2017. Addiction, 2017, 112(12), 2206-2216.
[http://dx.doi.org/10.1111/add.13910] [PMID: 28696583]
[12]
Pollastro, F.; De Petrocellis, L.; Schiano-Moriello, A.; Chianese, G.; Heyman, H.; Appendino, G.; Taglialatela-Scafati, O. Amorfrutin-type phytocannabinoids from Helichrysum umbraculigerum. Fitoterapia, 2017, 123, 13-17.
[http://dx.doi.org/10.1016/j.fitote.2017.09.010] [PMID: 28941742]
[13]
Starks, C.M.; Williams, R.B.; Norman, V.L.; Rice, S.M.; O’Neil-Johnson, M.; Lawrence, J.A.; Eldridge, G.R. Antibacterial chromene and chromane stilbenoids from Hymenocardia acida. Phytochemistry, 2014, 98, 216-222.
[http://dx.doi.org/10.1016/j.phytochem.2013.11.012] [PMID: 24361290]
[14]
Quaghebeur, K.; Coosemans, J.; Toppet, S.; Compernolle, F. Cannabiorci- and 8-chlorocannabiorcichromenic acid as fungal antagonists from Cylindrocarpon olidum. Phytochemistry, 1994, 37(1), 159-161.
[http://dx.doi.org/10.1016/0031-9422(94)85016-X] [PMID: 7765609]
[15]
Weidner, C.; de Groot, J.C.; Prasad, A.; Freiwald, A.; Quedenau, C.; Kliem, M.; Witzke, A.; Kodelja, V.; Han, C.T.; Giegold, S.; Baumann, M.; Klebl, B.; Siems, K.; Müller-Kuhrt, L.; Schürmann, A.; Schüler, R.; Pfeiffer, A.F.; Schroeder, F.C.; Büssow, K.; Sauer, S. Amorfrutins are potent antidiabetic dietary natural products. Proc. Natl. Acad. Sci. USA, 2012, 109(19), 7257-7262.
[http://dx.doi.org/10.1073/pnas.1116971109] [PMID: 22509006]
[16]
Lourens, A.C.; Viljoen, A.M.; van Heerden, F.R. South African Helichrysum species: a review of the traditional uses, biological activity and phytochemistry. J. Ethnopharmacol., 2008, 119(3), 630-652.
[http://dx.doi.org/10.1016/j.jep.2008.06.011] [PMID: 18606217]
[17]
Iijima, M.; Munakata, R.; Takahashi, H.; Kenmoku, H.; Nakagawa, R.; Kodama, T.; Asakawa, Y.; Abe, I.; Yazaki, K.; Kurosaki, F.; Taura, F. Identification and characterization of daurichromenic acid synthase active in anti-HIV biosynthesis. Plant Physiol., 2017, 174(4), 2213-2230.
[http://dx.doi.org/10.1104/pp.17.00586] [PMID: 28679557]
[18]
Morales, P.; Reggio, P.H.; Jagerovic, N. An overview on medicinal chemistry of Synthetic and natural derivatives of cannabidiol. Front. Pharmacol., 2017, 8, 422.
[http://dx.doi.org/10.3389/fphar.2017.00422] [PMID: 28701957]
[19]
Pacifici, R.; Pichini, S.; Pellegrini, M.; Tittarelli, R.; Pantano, F.; Mannocchi, G.; Rotolo, M.C.; Busardò, F.P. Determination of cannabinoids in oral fluid and urine of “light cannabis” consumers: a pilot study. Clin. Chem. Lab. Med., 2018, 57(2), 238-243.
[http://dx.doi.org/10.1515/cclm-2018-0566] [PMID: 30332386]
[20]
Jikomes, N.; Zoorob, M. The cannabinoid content of legal cannabis in Washington State varies systematically across testing facilities and popular consumer products. Sci. Rep., 2018, 8(1), 4519.
[http://dx.doi.org/10.1038/s41598-018-22755-2] [PMID: 29540728]
[21]
Fasinu, P.S.; Phillips, S.; ElSohly, M.A.; Walker, L.A. Current status and prospects for cannabidiol preparations as new therapeutic agents. Pharmacotherapy, 2016, 36(7), 781-796.
[http://dx.doi.org/10.1002/phar.1780] [PMID: 27285147]
[22]
Pickrell, W.O.; Robertson, N.P. Cannabidiol as a treatment for epilepsy. J. Neurol., 2017, 264(12), 2506-2508.
[http://dx.doi.org/10.1007/s00415-017-8663-0] [PMID: 29124331]
[23]
Ridler, C. Epilepsy: Cannabidiol reduces seizure frequency in Dravet syndrome. Nat. Rev. Neurol., 2017, 13(7), 383.
[http://dx.doi.org/10.1038/nrneurol.2017.86] [PMID: 28621765]
[24]
Citti, C.; Linciano, P.; Russo, F.; Luongo, L.; Iannotta, M.; Maione, S.; Laganà, A.; Capriotti, A.L.; Forni, F.; Vandelli, M.A.; Gigli, G.; Cannazza, G. A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ9-tetrahydrocannabinol: Δ9-tetrahydrocannabiphorol. Sci. Rep., 2019, 9(1), 20335.
[http://dx.doi.org/10.1038/s41598-019-56785-1] [PMID: 31889124]
[25]
Tham, M.; Yilmaz, O.; Alaverdashvili, M.; Kelly, M.E.M.; Denovan-Wright, E.M.; Laprairie, R.B. Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol-dimethylheptyl at the type 1 and type 2 cannabinoid receptors. Br. J. Pharmacol., 2018.
[http://dx.doi.org/10.1016/j.phytochem.2013.11.012] [PMID: 29981240]
[26]
Leweke, F.M.; Piomelli, D.; Pahlisch, F.; Muhl, D.; Gerth, C.W.; Hoyer, C.; Klosterkötter, J.; Hellmich, M.; Koethe, D. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl. Psychiatry, 2012, 2(3)e94
[http://dx.doi.org/10.1038/tp.2012.15] [PMID: 22832859]
[27]
Bakas, T.; van Nieuwenhuijzen, P.S.; Devenish, S.O.; McGregor, I.S.; Arnold, J.C.; Chebib, M. The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABAA receptors. Pharmacol. Res., 2017, 119, 358-370.
[http://dx.doi.org/10.1016/j.phrs.2017.02.022] [PMID: 28249817]
[28]
Gonca, E.; Darıcı, F. The effect of cannabidiol on ischemia/reperfusion-induced ventricular arrhythmias: the role of adenosine A1 receptors. J. Cardiovasc. Pharmacol. Ther., 2015, 20(1), 76-83.
[http://dx.doi.org/10.1177/1074248414532013] [PMID: 24853683]
[29]
Mahgoub, M.; Keun-Hang, S.Y.; Sydorenko, V.; Ashoor, A.; Kabbani, N.; Al Kury, L.; Sadek, B.; Howarth, C.F.; Isaev, D.; Galadari, S.; Oz, M. Effects of cannabidiol on the function of α7-nicotinic acetylcholine receptors. Eur. J. Pharmacol., 2013, 720(1-3), 310-319.
[http://dx.doi.org/10.1016/j.ejphar.2013.10.011] [PMID: 24140434]
[30]
Sartim, A.G.; Guimarães, F.S.; Joca, S.R. Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex-Possible involvement of 5-HT1A and CB1 receptors. Behav. Brain Res., 2016, 303, 218-227.
[http://dx.doi.org/10.1016/j.bbr.2016.01.033] [PMID: 26801828]
[31]
Seeman, P. Cannabidiol is a partial agonist at dopamine D2 High receptors, predicting its antipsychotic clinical dose. Transl. Psychiatry, 2016, 6(10)e920
[http://dx.doi.org/10.1038/tp.2016.195] [PMID: 27754480]
[32]
Watkins, A.R. Cannabinoid interactions with ion channels and receptors. Channels (Austin), 2019, 13(1), 162-167.
[http://dx.doi.org/10.1080/19336950.2019.1615824] [PMID: 31088312]
[33]
Bondarenko, A.I.; Panasiuk, O.; Drachuk, K.; Montecucco, F.; Brandt, K.J.; Mach, F. The quest for endothelial atypical cannabinoid receptor: BKCa channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells. Vascul. Pharmacol., 2018, 102, 44-55.
[http://dx.doi.org/10.1016/j.vph.2018.01.004] [PMID: 29355732]
[34]
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]
[35]
Citti, C.; Pacchetti, B.; Vandelli, M.A.; Forni, F.; Cannazza, G. Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA). J. Pharm. Biomed. Anal., 2018, 149, 532-540.
[http://dx.doi.org/10.1016/j.jpba.2017.11.044] [PMID: 29182999]
[36]
Jenkins, R.W.; Patterson, D.A. The relationship between chemical composition and geographical origin of cannabis. Forensic Sci., 1973, 2(1), 59-66.
[http://dx.doi.org/10.1016/0300-9432(73)90014-9] [PMID: 4266193]
[37]
Vollner, L.; Bieniek, D.; Korte, F. Review of analytical methods for identification and quantification of cannabis products. Regul. Toxicol. Pharmacol., 1986, 6(4), 348-358.
[http://dx.doi.org/10.1016/0273-2300(86)90003-6] [PMID: 3027768]
[38]
Raharjo, T.J.; Verpoorte, R. Methods for the analysis of cannabinoids in biological materials: a review. Phytochem. Anal., 2004, 15(2), 79-94.
[http://dx.doi.org/10.1002/pca.753] [PMID: 15116938]
[39]
Aizpurua-Olaizola, O.; Omar, J.; Navarro, P.; Olivares, M.; Etxebarria, N.; Usobiaga, A. Identification and quantification of cannabinoids in Cannabis sativa L. plants by high performance liquid chromatography-mass spectrometry. Anal. Bioanal. Chem., 2014, 406(29), 7549-7560.
[http://dx.doi.org/10.1007/s00216-014-8177-x] [PMID: 25338935]
[40]
Giese, M.W.; Lewis, M.A.; Giese, L.; Smith, K.M. Development and validation of a reliable and robust method for the analysis of cannabinoids and terpenes in Cannabis. J. AOAC Int., 2015, 98(6), 1503-1522.
[http://dx.doi.org/10.5740/jaoacint.15-116] [PMID: 26651562]
[41]
Villamor, J.L.; Bermejo, A.M.; Tabernero, M.J.; Fernández, P. Determination of cannabinoids in human hair by GC/MS. Anal. Lett., 2007, 37(3), 517-528.
[http://dx.doi.org/10.1081/AL-120028624]
[42]
Lehmann, T.; Brenneisen, R. A new chromatographic method for the isolation of (−)-Δ9-(trans)-tetrahydro-cannabinolic acid A. Phytochem. Anal., 1992, 3(2), 88-90.
[http://dx.doi.org/10.1002/pca.2800030210]
[43]
Alemany, G.; Gamundí, A.; Nicolau, M.C.; Saro, D. A simple method for plasma cannabinoid separation and quantification. Biomed. Chromatogr., 1993, 7(5), 273-274.
[http://dx.doi.org/10.1002/bmc.1130070507] [PMID: 8305858]
[44]
Joern, W.A. Marijuana testing in urine: use of a hexadeuterated internal standard for extended linearity, and ion trap vs. mass selective detector gas chromatograph/mass spectrometer systems. Clin. Chem., 1992, 38(5), 717-719.
[http://dx.doi.org/10.1093/clinchem/38.5.717] [PMID: 1316244]
[45]
Heo, S.; Yoo, G.J.; Choi, J.Y.; Park, H.J.; Do, J.A.; Cho, S.; Baek, S.Y.; Park, S.K. Simultaneous analysis of cannabinoid and synthetic cannabinoids in dietary supplements using UPLC with UV and UPLC-MS-MS. J. Anal. Toxicol., 2016, 40(5), 350-359.
[http://dx.doi.org/10.1093/jat/bkw027] [PMID: 27185817]
[46]
Lacorte, S.; Fernandez-Alba, A.R. Time of flight mass spectrometry applied to the liquid chromatographic analysis of pesticides in water and food. Mass Spectrom. Rev., 2006, 25(6), 866-880.
[http://dx.doi.org/10.1002/mas.20094] [PMID: 16752429]
[47]
Pavlovic, R.; Nenna, G.; Calvi, L.; Panseri, S.; Borgonovo, G.; Giupponi, L.; Cannazza, G.; Giorgi, A. Quality traits of “cannabidiol oils”: cannabinoids content, terpene fingerprint and oxidation stability of european commercially available preparations. Molecules, 2018, 23(5)E1230
[http://dx.doi.org/10.3390/molecules23051230] [PMID: 29783790]
[48]
Bacigalupo, M.A.; Ius, A.; Meroni, G.; Grassi, G.; Moschella, A. Time-resolved fluoroimmunoassay for delta(9)-tetrahydrocannabinol as applied to early discrimination of Cannabis sativa plants. J. Agric. Food Chem., 1999, 47(7), 2743-2745.
[http://dx.doi.org/10.1021/jf981141b] [PMID: 10552557]
[49]
Schwope, D.M.; Milman, G.; Huestis, M.A. Validation of an enzyme immunoassay for detection and semiquantification of cannabinoids in oral fluid. Clin. Chem., 2010, 56(6), 1007-1014.
[http://dx.doi.org/10.1373/clinchem.2009.141754] [PMID: 20360126]
[50]
Castaneto, M.S.; Scheidweiler, K.B.; Gandhi, A.; Wohlfarth, A.; Klette, K.L.; Martin, T.M.; Huestis, M.A. Quantitative urine confirmatory testing for synthetic cannabinoids in randomly collected urine specimens. Drug Test. Anal., 2015, 7(6), 483-493.
[http://dx.doi.org/10.1002/dta.1709] [PMID: 25231213]
[51]
Backstrom, B.; Cole, M.D.; Carrott, M.J.; Jones, D.C.; Davidson, G.; Coleman, K. A preliminary study of the analysis of Cannabis by supercritical fluid chromatography with atmospheric pressure chemical ionisation mass spectroscopic detection. Sci. Just, 1997, 37(2), 91-97.
[http://dx.doi.org/10.1016/s1355-0306(97)72153-1] [PMID: 9206314]
[52]
Mazina, J.; Spiljova, A.; Vaher, M.; Kaljurand, M.; Kulp, M. A rapid capillary electrophoresis method with LED-induced native fluorescence detection for the analysis of cannabinoids in oral fluid. Anal. Methods, 2015, 7(18), 7741-7747.
[http://dx.doi.org/10.1039/C5AY01595B]
[53]
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., 1940, 62(1), 196-200.
[http://dx.doi.org/10.1021/ja01858a058]
[54]
Jacob, A.; Sutcliffe, F.K.; Todd, A.R. 67. Studies on vitamin E. Part VII. Further investigations on homologues of α-tocopherol. J. Chem. Soc., 1940, 0(0), 327-332.
[http://dx.doi.org/10.1039/JR9400000327]
[55]
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]
[56]
Wang, M.; Wang, Y.H.; Avula, B.; Radwan, M.M.; Wanas, A.S.; van Antwerp, J.; Parcher, J.F.; ElSohly, M.A.; Khan, I.A. Decarboxylation study of acidic cannabinoids: a novel approach using ultra-high-performance supercritical fluid chromatography/photodiode array-mass spectrometry. Cannabis Cannabinoid Res., 2016, 1(1), 262-271.
[http://dx.doi.org/10.1089/can.2016.0020] [PMID: 28861498]
[57]
Shani, A.; Mechoulam, R. Cannabielsoic acids. Tetrahedron, 1974, 30(15), 2437-2446.
[http://dx.doi.org/10.1016/S0040-4020(01)97114-5]
[58]
Hazekamp, A.; Peltenburg, A.; Verpoorte, R.; Giroud, C. Chromatographic and spectroscopic data of cannabinoids from Cannabis sativa L. J. Liq. Chromatogr. Relat. Technol., 2005, 28(15), 2361-2382.
[http://dx.doi.org/10.1080/10826070500187558]
[59]
Perrotin-Brunel, H.; Kroon, M.C.; van Roosmalen, M.J.E.; van Spronsen, J.; Peters, C.J.; Witkamp, G-J. Solubility of non-psychoactive cannabinoids in supercritical carbon dioxide and comparison with psychoactive cannabinoids. J. Supercrit. Fluids, 2010, 55(2), 603-608.
[http://dx.doi.org/10.1016/j.supflu.2010.09.011]
[60]
Grijó, R.D.; Vieitez Osorio, I.A.; Cardozo-Filho, L. Supercritical extraction strategies using CO2 and ethanol to obtain cannabinoid compounds from Cannabis hybrid flowers.J. CO2 Util. 2019, 30, 241-248.
[http://dx.doi.org/10.1016/j.jcou.2018.12.014]
[61]
Carcieri, C.; Tomasello, C.; Simiele, M.; De Nicolò, A.; Avataneo, V.; Canzoneri, L.; Cusato, J.; Di Perri, G.; D’Avolio, A. Cannabinoids concentration variability in Cannabis olive oil galenic preparations. J. Pharm. Pharmacol., 2018, 70(1), 143-149.
[http://dx.doi.org/10.1111/jphp.12845] [PMID: 29057480]
[62]
Romano, L.L.; Hazekamp, A. Cannabis Oil: chemical evaluation of an upcoming cannabis-based medicine. Cannabinoids, 2013, 1(1), 1-11.
[63]
Calvi, L.; Pentimalli, D.; Panseri, S.; Giupponi, L.; Gelmini, F.; Beretta, G.; Vitali, D.; Bruno, M.; Zilio, E.; Pavlovic, R.; Giorgi, A. Comprehensive quality evaluation of medical Cannabis sativa L. inflorescence and macerated oils based on HS-SPME coupled to GC-MS and LC-HRMS (q-exactive orbitrap®) approach. J. Pharm. Biomed. Anal., 2018, 150, 208-219.
[http://dx.doi.org/10.1016/j.jpba.2017.11.073] [PMID: 29247961]
[64]
Pacifici, R.; Marchei, E.; Salvatore, F.; Guandalini, L.; Busardò, F.P.; Pichini, S. Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry. Clin. Chem. Lab. Med., 2017, 55(10), 1555-1563.
[http://dx.doi.org/10.1515/cclm-2016-1060] [PMID: 28207408]
[65]
Papaseit, E.; Pérez-Mañá, C.; Pérez-Acevedo, A.P.; Hladun, O.; Torres-Moreno, M.C.; Muga, R.; Torrens, M.; Farré, M. Cannabinoids: from pot to lab. Int. J. Med. Sci., 2018, 15(12), 1286-1295.
[http://dx.doi.org/10.7150/ijms.27087] [PMID: 30275754]
[66]
Merrick, J.; Lane, B.; Sebree, T.; Yaksh, T.; O’Neill, C.; Banks, S.L. Identification of psychoactive degradants of cannabidiol in simulated gastric and physiological fluid. Cannabis Cannabinoid Res., 2016, 1(1), 102-112.
[http://dx.doi.org/10.1089/can.2015.0004] [PMID: 28861485]
[67]
Abrahams, S.; Haylett, W.L.; Johnson, G.; Carr, J.A.; Bardien, S. Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: a review. Neuroscience, 2019, 406, 1-21.
[http://dx.doi.org/10.1016/j.neuroscience.2019.02.020] [PMID: 30825584]
[68]
Bhawana; Basniwal, R.K.; Buttar, H.S.; Jain, V.K.; Jain, N. Curcumin nanoparticles: preparation, characterization, and antimicrobial study. J. Agric. Food Chem., 2011, 59(5), 2056-2061.
[http://dx.doi.org/10.1021/jf104402t] [PMID: 21322563]
[69]
Petrzilka, T.; Haefliger, W.; Sikemeier, C.; Ohloff, G.; Eschenmoser, A. Synthesis and optical rotation of the (-)-cannabidiols. Helv. Chim. Acta, 1967, 50(2), 719-723.
[http://dx.doi.org/10.1002/hlca.19670500235] [PMID: 5587099]
[70]
Mechoulam, R.; Braun, P.; Gaoni, Y. Syntheses of 1-tetrahydrocannabinol and related cannabinoids. J. Am. Chem. Soc., 1972, 94(17), 6159-6165.
[http://dx.doi.org/10.1021/ja00772a038] [PMID: 5054408]
[71]
Petrzilka, T.; Haefliger, W.; Sikemeier, C. Synthese von Haschisch-Inhaltsstoffen. 4. Mitteilung. Helv. Chim. Acta., 1969, 52(4), 1102-1134.
[http://dx.doi.org/10.1002/hlca.19690520427]
[72]
Baek, S-H.; Srebnik, M.; Mechoulam, R. Boron triflouride etherate on alimina - a modified Lewis acid reagent. Tetrahedron Lett., 1985, 26(8), 1083-1086.
[http://dx.doi.org/10.1016/S0040-4039(00)98518-6]
[73]
Vaillancourt, V.; Albizati, K.F. A one-step method for the. alpha.-arylation of camphor. Synthesis of (-)-cannabidiol and (-)-cannabidiol dimethyl ether. J. Org. Chem., 1992, 57(13), 3627-3631.
[http://dx.doi.org/10.1021/jo00039a022]
[74]
Kobayashi, Y.; Takeuchi, A.; Wang, Y.G. Synthesis of cannabidiols via alkenylation of cyclohexenyl monoacetate. Org. Lett., 2006, 8(13), 2699-2702.
[http://dx.doi.org/10.1021/ol060692h] [PMID: 16774235]
[75]
Shultz, Z.P.; Lawrence, G.A.; Jacobson, J.M.; Cruz, E.J.; Leahy, J.W. Enantioselective total synthesis of cannabinoids-a route for analogue development. Org. Lett., 2018, 20(2), 381-384.
[http://dx.doi.org/10.1021/acs.orglett.7b03668] [PMID: 29293352]
[76]
Russo, E.B.; Taming, T.H.C. 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]
[77]
Massimino, L. In silico discovery of terpenoid metabolism in Cannabis sativa. F1000 Res., 2017, 6, 107.
[http://dx.doi.org/10.12688/f1000research.10778.1] [PMID: 28690830]
[78]
Meng, X.Y.; Zhang, H.X.; Mezei, M.; Cui, M. Molecular docking: a powerful approach for structure-based drug discovery. Curr. Comput. Aided Drug Des., 2011, 7(2), 146-157.
[http://dx.doi.org/10.2174/157340911795677602] [PMID: 21534921]
[79]
Huang, S.Y.; Zou, X. Advances and challenges in protein-ligand docking. Int. J. Mol. Sci., 2010, 11(8), 3016-3034.
[http://dx.doi.org/10.3390/ijms11083016] [PMID: 21152288]
[80]
Ferreira, L.G.; Dos Santos, R.N.; Oliva, G.; Andricopulo, A.D. Molecular docking and structure-based drug design strategies. Molecules, 2015, 20(7), 13384-13421.
[http://dx.doi.org/10.3390/molecules200713384] [PMID: 26205061]
[81]
Salsbury, F.R., Jr Molecular dynamics simulations of protein dynamics and their relevance to drug discovery. Curr. Opin. Pharmacol., 2010, 10(6), 738-744.
[http://dx.doi.org/10.1016/j.coph.2010.09.016] [PMID: 20971684]
[82]
Durrant, J.D.; McCammon, J.A. Molecular dynamics simulations and drug discovery. BMC Biol., 2011, 9, 71.
[http://dx.doi.org/10.1186/1741-7007-9-71] [PMID: 22035460]
[83]
Bian, Y.M.; He, X.B.; Jing, Y.K.; Wang, L.R.; Wang, J.M.; Xie, X.Q. Computational systems pharmacology analysis of cannabidiol: a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation. Acta Pharmacol. Sin., 2019, 40(3), 374-386.
[http://dx.doi.org/10.1038/s41401-018-0071-1] [PMID: 30202014]
[84]
Ongaro, A.; Zagotto, G.; Memo, M.; Gianoncelli, A.; Ribaudo, G. Natural phosphodiesterase 5 (PDE5) inhibitors: a computational approach. Nat. Prod. Res., 2019, 1-6.
[http://dx.doi.org/10.1080/14786419.2019.1619726] [PMID: 31140295]
[85]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[86]
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]
[87]
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]
[88]
Devinsky, O. Transition to adult care for children with epilepsy-a call for action. Epilepsia, 2014, 55(Suppl. 3), 54-55.
[http://dx.doi.org/10.1111/epi.12630] [PMID: 25209089]
[89]
Costa, B.; Giagnoni, G.; Franke, C.; Trovato, A.E.; Colleoni, M. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. Br. J. Pharmacol., 2004, 143(2), 247-250.
[http://dx.doi.org/10.1038/sj.bjp.0705920] [PMID: 15313881]
[90]
Singh, D.K.; Karthikeyan, M.; Kirubakaran, P.; Sathya, V.; Nagamani, S. Structure-based drug discovery of ApoE4 inhibitors from the plant compounds. Med. Chem. Res., 2011, 21(6), 825-833.
[http://dx.doi.org/10.1007/s00044-011-9595-3]
[91]
Bales, K.R. Brain lipid metabolism, apolipoprotein E and the pathophysiology of Alzheimer’s disease. Neuropharmacology, 2010, 59(4-5), 295-302.
[http://dx.doi.org/10.1016/j.neuropharm.2010.01.005] [PMID: 20079752]
[92]
Seniya, C.; Khan, G.J.; Uchadia, K. Identification of potential herbal inhibitor of acetylcholinesterase associated Alzheimer’s disorders using molecular docking and molecular dynamics simulation. Biochem. Res. Int., 2014, 2014705451
[http://dx.doi.org/10.1155/2014/705451] [PMID: 25054066]
[93]
Ahmed, A.; van der Marck, M.A.; van den Elsen, G.; Olde Rikkert, M. Cannabinoids in late-onset Alzheimer’s disease. Clin. Pharmacol. Ther., 2015, 97(6), 597-606.
[http://dx.doi.org/10.1002/cpt.117] [PMID: 25788394]
[94]
Kotula, L.; Petniak, A.; Kolodziej, E.; Amarowicz, M.; Urbanczuk, M.; Schab, K.; Gil-Kulik, P.; Karwat, J.; Kotula, J.; Mulawka, P.; Mulawka, D.; Kocki, J. Application of medical cannabis in patients with central nerve system disorders. Mod. Phytomorphol., 2015, 8, 65-70.
[http://dx.doi.org/10.5281/zenodo.159835]
[95]
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]
[96]
Hughes, B.; Herron, C.E. Cannabidiol reverses deficits in hippocampal LTP in a model of Alzheimer’s disease. Neurochem. Res., 2019, 44(3), 703-713.
[http://dx.doi.org/10.1007/s11064-018-2513-z] [PMID: 29574668]
[97]
Weier, M.; Hall, W. The use of cannabinoids in treating dementia. Curr. Neurol. Neurosci. Rep., 2017, 17(8), 56.
[http://dx.doi.org/10.1007/s11910-017-0766-6] [PMID: 28631194]
[98]
Zanforlin, E.; Zagotto, G.; Ribaudo, G. An overview of new possible treatments of Alzheimer’s disease, based on natural products and semi-synthetic compounds. Curr. Med. Chem., 2017, 24(34), 3749-3773.
[http://dx.doi.org/10.2174/0929867324666170712161829] [PMID: 28707586]
[99]
Eubanks, L.M.; Rogers, C.J.; Beuscher, A.E., IV; Koob, G.F.; Olson, A.J.; Dickerson, T.J.; Janda, K.D. A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Mol. Pharm., 2006, 3(6), 773-777.
[http://dx.doi.org/10.1021/mp060066m] [PMID: 17140265]
[100]
Trott, O.; Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[http://dx.doi.org/10.1002/jcc.21334] [PMID: 19499576]
[101]
Elmes, M.W.; Kaczocha, M.; Berger, W.T.; Leung, K.; Ralph, B.P.; Wang, L.; Sweeney, J.M.; Miyauchi, J.T.; Tsirka, S.E.; Ojima, I.; Deutsch, D.G. Fatty acid-binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). J. Biol. Chem., 2015, 290(14), 8711-8721.
[http://dx.doi.org/10.1074/jbc.M114.618447] [PMID: 25666611]
[102]
Zanelati, T.V.; Biojone, C.; Moreira, F.A.; Guimarães, F.S.; Joca, S.R. Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. Br. J. Pharmacol., 2010, 159(1), 122-128.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00521.x] [PMID: 20002102]
[103]
Berger, W.T.; Ralph, B.P.; Kaczocha, M.; Sun, J.; Balius, T.E.; Rizzo, R.C.; Haj-Dahmane, S.; Ojima, I.; Deutsch, D.G. Targeting fatty acid binding protein (FABP) anandamide transporters - a novel strategy for development of anti-inflammatory and anti-nociceptive drugs. PLoS One, 2012, 7(12)e50968
[http://dx.doi.org/10.1371/journal.pone.0050968] [PMID: 23236415]
[104]
Kaczocha, M.; Rebecchi, M.J.; Ralph, B.P.; Teng, Y.H.; Berger, W.T.; Galbavy, W.; Elmes, M.W.; Glaser, S.T.; Wang, L.; Rizzo, R.C.; Deutsch, D.G.; Ojima, I. Inhibition of fatty acid binding proteins elevates brain anandamide levels and produces analgesia. PLoS One, 2014, 9(4)e94200
[http://dx.doi.org/10.1371/journal.pone.0094200] [PMID: 24705380]
[105]
Hassan, S.; Eldeeb, K.; Millns, P.J.; Bennett, A.J.; Alexander, S.P.; Kendall, D.A. Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation. Br. J. Pharmacol., 2014, 171(9), 2426-2439.
[http://dx.doi.org/10.1111/bph.12615] [PMID: 24641282]
[106]
Iannotti, F.A.; Hill, C.L.; Leo, A.; Alhusaini, A.; Soubrane, C.; Mazzarella, E.; Russo, E.; Whalley, B.J.; Di Marzo, V.; Stephens, G.J. Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem. Neurosci., 2014, 5(11), 1131-1141.
[http://dx.doi.org/10.1021/cn5000524] [PMID: 25029033]
[107]
Sanson, B.; Wang, T.; Sun, J.; Wang, L.; Kaczocha, M.; Ojima, I.; Deutsch, D.; Li, H. Crystallographic study of FABP5 as an intracellular endocannabinoid transporter. Acta Crystallogr. D Biol. Crystallogr., 2014, 70(Pt 2), 290-298.
[http://dx.doi.org/10.1107/S1399004713026795] [PMID: 24531463]
[108]
Suzen, S.; Buyukbingol, E. Recent studies of aldose reductase enzyme inhibition for diabetic complications. Curr. Med. Chem., 2003, 10(15), 1329-1352.
[http://dx.doi.org/10.2174/0929867033457377] [PMID: 12871133]
[109]
El-Remessy, A.B.; Al-Shabrawey, M.; Khalifa, Y.; Tsai, N.T.; Caldwell, R.B.; Liou, G.I. Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes. Am. J. Pathol., 2006, 168(1), 235-244.
[http://dx.doi.org/10.2353/ajpath.2006.050500] [PMID: 16400026]
[110]
Smeriglio, A.; Giofrè, S.V.; Galati, E.M.; Monforte, M.T.; Cicero, N.; D’Angelo, V.; Grassi, G.; Circosta, C. Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol. Fitoterapia, 2018, 127, 101-108.
[http://dx.doi.org/10.1016/j.fitote.2018.02.002] [PMID: 29427593]
[111]
D’Aniello, E.; Fellous, T.; Iannotti, F.A.; Gentile, A.; Allarà, M.; Balestrieri, F.; Gray, R.; Amodeo, P.; Vitale, R.M.; Di Marzo, V. Identification and characterization of phytocannabinoids as novel dual PPARα/γ agonists by a computational and in vitro experimental approach. Biochim. Biophys. Acta, Gen. Subj., 2019, 1863(3), 586-597.
[http://dx.doi.org/10.1016/j.bbagen.2019.01.002] [PMID: 30611848]
[112]
Lefebvre, P.; Chinetti, G.; Fruchart, J.C.; Staels, B. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J. Clin. Invest., 2006, 116(3), 571-580.
[http://dx.doi.org/10.1172/JCI27989] [PMID: 16511589]
[113]
van Bakel, H.; Stout, J.M.; Cote, A.G.; Tallon, C.M.; Sharpe, A.G.; Hughes, T.R.; Page, J.E. The draft genome and transcriptome of Cannabis sativa. Genome Biol., 2011, 12(10), R102.
[http://dx.doi.org/10.1186/gb-2011-12-10-r102] [PMID: 22014239]
[114]
Zaka, M.; Sehgal, S.A.; Shafique, S.; Abbasi, B.H. Comparative in silico analyses of Cannabis sativa, Prunella vulgaris and Withania somnifera compounds elucidating the medicinal properties against rheumatoid arthritis. J. Mol. Graph. Model., 2017, 74, 296-304.
[http://dx.doi.org/10.1016/j.jmgm.2017.04.013] [PMID: 28472734]
[115]
Choi, Y.; Arron, J.R.; Townsend, M.J. Promising bone-related therapeutic targets for rheumatoid arthritis. Nat. Rev. Rheumatol., 2009, 5(10), 543-548.
[http://dx.doi.org/10.1038/nrrheum.2009.175] [PMID: 19798028]
[116]
Tian, Z.; Wang, Z.; Han, X.; Wang, N.; Wang, R. Study on the interaction between cannabinol and DNA using acridine orange as a fluorescence probe. J. Mol. Recog, 2018, 31(2)e2682
[http://dx.doi.org/10.1002/jmr.2682] [PMID: 29067762]
[117]
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]
[118]
Montes-Grajales, D.; Martínez-Romero, E.; Olivero-Verbel, J. Phytoestrogens and mycoestrogens interacting with breast cancer proteins. Steroids, 2018, 134, 9-15.
[http://dx.doi.org/10.1016/j.steroids.2018.03.010] [PMID: 29608946]
[119]
Proto, M.C.; Fiore, D.; Piscopo, C.; Franceschelli, S.; Bizzarro, V.; Laezza, C.; Lauro, G.; Feoli, A.; Tosco, A.; Bifulco, G.; Sbardella, G.; Bifulco, M.; Gazzerro, P. Inhibition of Wnt/β-catenin pathway and histone acetyltransferase activity by rimonabant: a therapeutic target for colon cancer. Sci. Rep., 2017, 7(1), 11678.
[http://dx.doi.org/10.1038/s41598-017-11688-x] [PMID: 28916833]
[120]
Rehman, M.T.; AlAjmi, M.F.; Hussain, A.; Rather, G.M.; Khan, M.A. High-throughput virtual screening, molecular dynamics simulation, and enzyme kinetics identified ZINC84525623 as a potential inhibitor of NDM-1. Int. J. Mol. Sci., 2019, 20(4)E819
[http://dx.doi.org/10.3390/ijms20040819] [PMID: 30769822]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy