Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Efficacy of Cannabis and its Constituents in Disease Management: Insights from Clinical Studies

Author(s): Divya Vimal, Leonard Clinton D’Souza, Vipin Rai, Samridhi Lal, Anurag Sharma* and Subash Chandra Gupta*

Volume 30, Issue 2, 2023

Published on: 26 August, 2022

Page: [178 - 202] Pages: 25

DOI: 10.2174/0929867329666220525124818

Price: $65

Open Access Journals Promotions 2
Abstract

There is a long history of informal use of Cannabis sativa (commonly called cannabis) for many purposes, including treating various ailments worldwide. However, the legalization of cannabis in multiple countries, specifically for medical purposes, has grabbed the researchers' attention to discover the scientific evidence regarding cannabis’s beneficial effects. Among over 500 identified compounds (cannabinoids), Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are two major active cannabinoids derived from cannabis. Cannabinoids exert their effects through cannabinoid receptors (CB1R and CB2R). In the recent past, clinical trials have shown the efficacy of cannabis and cannabinoids for various human ailments, such as cancer, neurological disorders, inflammatory bowel disease, chronic pain, and metabolic disorders. The commonly used constituents and derivatives of cannabis include CBD, THC, THCV, dronabinol, nabilone, and nabiximol. The cannabis constituents have also been used in combination with other agents, such as megestrol acetate, in some clinical trials. The common routes for the administration of cannabis are oral, sublingual, or topical. Cannabis has also been consumed through smoking, inhalation, or with food and tea. A maximum of 572 patients and a minimum of nine patients have participated in a single clinical trial. Cannabis is legalized in some countries with restrictions, such as Belize, Canada, Colombia, Costa Rica, The Czech Republic, Jamaica, Netherlands, South Africa, Spain, and Uruguay. This article provides a compilation of published studies focusing on clinal trials on the therapeutic effects of cannabis. The adverse effects of cannabis and its constituents are also discussed.

Keywords: Cannabinoids, cannabis, chronic disease, clinical trial, inflammation, disease management.

« Previous Next »
[1]
Sirikantaramas, S.; Taura, F.; Morimoto, S.; Shoyama, Y. Recent advances in Cannabis sativa research: Biosynthetic studies and its potential in biotechnology. Curr. Pharm. Biotechnol., 2007, 8(4), 237-243.
[http://dx.doi.org/10.2174/138920107781387456] [PMID: 17691992]
[2]
Bridgeman, M.B.; Abazia, D.T. Medicinal cannabis: history, pharmacology, and implications for the acute care setting. P&T, 2017, 42(3), 180-188.
[PMID: 28250701]
[3]
Cohen, K.; Weinstein, A. The effects of cannabinoids on executive functions: Evidence from cannabis and synthetic cannabinoids-A systematic review. Brain Sci., 2018, 8(3), E40.
[http://dx.doi.org/10.3390/brainsci8030040] [PMID: 29495540]
[4]
Degenhardt, L.; Coffey, C.; Carlin, J.B.; Swift, W.; Moore, E.; Patton, G.C. Outcomes of occasional cannabis use in adolescence: 10-year follow-up study in Victoria, Australia. Br. J. Psychiatry, 2010, 196(4), 290-295.
[http://dx.doi.org/10.1192/bjp.bp.108.056952] [PMID: 20357305]
[5]
Hall, W.; Degenhardt, L. Prevalence and correlates of cannabis use in developed and developing countries. Curr. Opin. Psychiatry, 2007, 20(4), 393-397.
[http://dx.doi.org/10.1097/YCO.0b013e32812144cc] [PMID: 17551355]
[6]
Brenneisen, R. Marijuana and the Cannabinoids, 2007, pp. 17-49.
[7]
Atakan, Z. Cannabis, a complex plant: Different compounds and different effects on individuals. Ther. Adv. Psychopharmacol., 2012, 2(6), 241-254.
[http://dx.doi.org/10.1177/2045125312457586] [PMID: 23983983]
[8]
Meccariello, R.; Battista, N.; Bradshaw, H.B.; Wang, H. Endocannabinoids and reproduction. Int. J. Endocrinol., 2014, 2014, 378069.
[http://dx.doi.org/10.1155/2014/378069] [PMID: 24575130]
[9]
Walker, O.S.; Holloway, A.C.; Raha, S. The role of the endocannabinoid system in female reproductive tissues. J. Ovarian Res., 2019, 12(1), 3.
[http://dx.doi.org/10.1186/s13048-018-0478-9] [PMID: 30646937]
[10]
Pamplona, F.A.; Takahashi, R.N. Psychopharmacology of the endocannabinoids: Far beyond anandamide. J. Psychopharmacol., 2012, 26(1), 7-22.
[http://dx.doi.org/10.1177/0269881111405357] [PMID: 21652605]
[11]
Whiting, P.F.; Wolff, R.F.; Deshpande, S.; Di Nisio, M.; Duffy, S.; Hernandez, A.V.; Keurentjes, J.C.; Lang, S.; Misso, K.; Ryder, S.; Schmidlkofer, S.; Westwood, M.; Kleijnen, J. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA, 2015, 313(24), 2456-2473.
[http://dx.doi.org/10.1001/jama.2015.6358] [PMID: 26103030]
[12]
Hazekamp, A.; Ware, M.A.; Muller-Vahl, K.R.; Abrams, D.; Grotenhermen, F. The medicinal use of cannabis and cannabinoids-an international cross-sectional survey on administration forms. J. Psychoactive Drugs, 2013, 45(3), 199-210.
[http://dx.doi.org/10.1080/02791072.2013.805976] [PMID: 24175484]
[13]
Vasudevan, K.; Stahl, V. CBD-supplemented polishing powder enhances tooth polishing by inhibiting dental plaque bacteria. J. Int. Soc. Prev. Community Dent., 2020, 10(6), 766-770.
[PMID: 33437711]
[14]
Anis, O.; Vinayaka, A.C.; Shalev, N.; Namdar, D.; Nadarajan, S.; Anil, S.M.; Cohen, O.; Belausov, E.; Ramon, J.; Mayzlish Gati, E.; Koltai, H. Cannabis-derived compounds cannabichromene and Δ9-tetrahydrocannabinol interact and exhibit cytotoxic activity against urothelial cell carcinoma correlated with inhibition of cell migration and cytoskeleton organization. Molecules, 2021, 26(2), 465.
[http://dx.doi.org/10.3390/molecules26020465] [PMID: 33477303]
[15]
Raja, A.; Ahmadi, S.; de Costa, F.; Li, N.; Kerman, K. Attenuation of oxidative stress by cannabinoids and cannabis extracts in differentiated neuronal cells. Pharmaceuticals (Basel), 2020, 13(11), E328.
[http://dx.doi.org/10.3390/ph13110328] [PMID: 33105840]
[16]
Anil, S.M.; Shalev, N.; Vinayaka, A.C.; Nadarajan, S.; Namdar, D.; Belausov, E.; Shoval, I.; Mani, K.A.; Mechrez, G.; Koltai, H. Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages. Sci. Rep., 2021, 11(1), 1462.
[http://dx.doi.org/10.1038/s41598-021-81049-2] [PMID: 33446817]
[17]
Li, H-L. An archaeological and historical account of cannabis in China. Econ. Bot., 1973, 28(4), 437-448.
[http://dx.doi.org/10.1007/BF02862859]
[18]
Mikuriya, T.H. Marijuana in medicine: Past, present and future. Calif. Med., 1969, 110(1), 34-40.
[PMID: 4883504]
[19]
Touw, M. The religious and medicinal uses of cannabis in China, India and Tibet. J. Psychoactive Drugs, 1981, 13(1), 23-34.
[http://dx.doi.org/10.1080/02791072.1981.10471447] [PMID: 7024492]
[20]
Kalant, H. Medicinal use of cannabis: History and current status. Pain Res. Manag., 2001, 6(2), 80-91.
[http://dx.doi.org/10.1155/2001/469629] [PMID: 11854770]
[21]
Pinho, A.R.D. Social and medical aspects of the use of cannabis in Brazil. 1975, 293-302.
[http://dx.doi.org/10.1515/9783110812060.293]
[22]
Carter, A. A north American history of cannabis use in the treatment of epilepsy. J. Clin. Neurophysiol., 2020, 37(1), 35-38.
[http://dx.doi.org/10.1097/WNP.0000000000000644] [PMID: 31895188]
[23]
Elsohly, M.A.; Slade, D. Chemical constituents of marijuana: The complex mixture of natural cannabinoids. Life Sci., 2005, 78(5), 539-548.
[http://dx.doi.org/10.1016/j.lfs.2005.09.011] [PMID: 16199061]
[24]
Radwan, M.M.; Chandra, S.; Gul, S.; ElSohly, M.A. Cannabinoids, phenolics, terpenes and alkaloids of cannabis. Molecules, 2021, 26(9), 2774.
[http://dx.doi.org/10.3390/molecules26092774] [PMID: 34066753]
[25]
Turner, C.E.; Elsohly, M.A.; Boeren, E.G. Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J. Nat. Prod., 1980, 43(2), 169-234.
[http://dx.doi.org/10.1021/np50008a001] [PMID: 6991645]
[26]
Alves, P.; Amaral, C.; Teixeira, N.; Correia-da-Silva, G. Cannabis sativa: Much more beyond Δ9-tetrahydrocannabinol. Pharmacol. Res., 2020, 157, 104822.
[http://dx.doi.org/10.1016/j.phrs.2020.104822] [PMID: 32335286]
[27]
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]
[28]
Cristino, L.; Bisogno, T.; Di Marzo, V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat. Rev. Neurol., 2020, 16(1), 9-29.
[http://dx.doi.org/10.1038/s41582-019-0284-z] [PMID: 31831863]
[29]
Hazekamp, A.; Fischedick, J.T.; Díez, M.L.; Lubbe, A.; Ruhaak, R.L. Chemistry of Cannabis. Elsevier, 2010; pp. 1033-1084.
[http://dx.doi.org/10.1016/B978-008045382-8.00091-5]
[30]
Tournebize, J.; Gibaja, V.; Kahn, J.P. Acute effects of synthetic cannabinoids: Update 2015. Subst. Abus., 2017, 38(3), 344-366.
[http://dx.doi.org/10.1080/08897077.2016.1219438] [PMID: 27715709]
[31]
Schifano, F.; Papanti, G.D.; Orsolini, L.; Corkery, J.M. Novel psychoactive substances: The pharmacology of stimulants and hallucinogens. Expert Rev. Clin. Pharmacol., 2016, 9(7), 943-954.
[http://dx.doi.org/10.1586/17512433.2016.1167597] [PMID: 26985969]
[32]
De Luca, M.A.; Bimpisidis, Z.; Melis, M.; Marti, M.; Caboni, P.; Valentini, V.; Margiani, G.; Pintori, N.; Polis, I.; Marsicano, G.; Parsons, L.H.; Di Chiara, G. Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a Spice cannabinoid. Neuropharmacology, 2015, 99, 705-714.
[http://dx.doi.org/10.1016/j.neuropharm.2015.08.041] [PMID: 26327678]
[33]
Antoniou, T.; Juurlink, D.N. Synthetic cannabinoids. CMAJ, 2014, 186(3), 210.
[http://dx.doi.org/10.1503/cmaj.130510] [PMID: 24101614]
[34]
Mills, B.; Yepes, A.; Nugent, K. Synthetic cannabinoids. Am. J. Med. Sci., 2015, 350(1), 59-62.
[http://dx.doi.org/10.1097/MAJ.0000000000000466] [PMID: 26132518]
[35]
Klahn, P. Cannabinoids-promising antimicrobial drugs or intoxicants with benefits? Antibiotics (Basel), 2020, 9(6), E297.
[http://dx.doi.org/10.3390/antibiotics9060297] [PMID: 32498408]
[36]
Devane, W.A.; Dysarz, F.A., III; Johnson, M.R.; Melvin, L.S.; Howlett, A.C. Determination and characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol., 1988, 34(5), 605-613.
[PMID: 2848184]
[37]
Matsuda, L.A.; Lolait, S.J.; Brownstein, M.J.; Young, A.C.; Bonner, T.I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 1990, 346(6284), 561-564.
[http://dx.doi.org/10.1038/346561a0] [PMID: 2165569]
[38]
Munro, S.; Thomas, K.L.; Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature, 1993, 365(6441), 61-65.
[http://dx.doi.org/10.1038/365061a0] [PMID: 7689702]
[39]
Nocerino, E.; Amato, M.; Izzo, A.A. Cannabis and cannabinoid receptors. Fitoterapia, 2000, 71(Suppl. 1), S6-S12.
[http://dx.doi.org/10.1016/S0367-326X(00)00171-4] [PMID: 10930707]
[40]
Pertwee, R.G.; Howlett, A.C.; Abood, M.E.; Alexander, S.P.; Di Marzo, V.; Elphick, M.R.; Greasley, P.J.; Hansen, H.S.; Kunos, G.; Mackie, K.; Mechoulam, R.; Ross, R.A. International union of basic and clinical pharmacology. LXXIX. Cannabinoid receptors and their ligands: Beyond CB1 and CB2. Pharmacol. Rev., 2010, 62(4), 588-631.
[http://dx.doi.org/10.1124/pr.110.003004] [PMID: 21079038]
[41]
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]
[42]
Kendall, D.A.; Yudowski, G.A. Cannabinoid receptors in the central nervous system: Their signaling and roles in disease. Front. Cell. Neurosci., 2017, 10, 294.
[http://dx.doi.org/10.3389/fncel.2016.00294] [PMID: 28101004]
[43]
Krishna Kumar, K.; Shalev-Benami, M.; Robertson, M.J.; Hu, H.; Banister, S.D.; Hollingsworth, S.A.; Latorraca, N.R.; Kato, H.E.; Hilger, D.; Maeda, S.; Weis, W.I.; Farrens, D.L.; Dror, R.O.; Malhotra, S.V.; Kobilka, B.K.; Skiniotis, G. Structure of a signaling cannabinoid receptor 1-G protein complex. Cell, 2019, 176(3), 448-458.e12.
[http://dx.doi.org/10.1016/j.cell.2018.11.040] [PMID: 30639101]
[44]
Spiller, K.J.; Bi, G.H.; He, Y.; Galaj, E.; Gardner, E.L.; Xi, Z.X. Cannabinoid CB1 and CB2 receptor mechanisms underlie cannabis reward and aversion in rats. Br. J. Pharmacol., 2019, 176(9), 1268-1281.
[http://dx.doi.org/10.1111/bph.14625] [PMID: 30767215]
[45]
Mackie, K. Cannabinoid receptors: Where they are and what they do. J. Neuroendocrinol., 2008, 20(Suppl. 1), 10-14.
[http://dx.doi.org/10.1111/j.1365-2826.2008.01671.x] [PMID: 18426493]
[46]
Fernández-Ruiz, J.; Moreno-Martet, M.; Rodríguez-Cueto, C.; Palomo-Garo, C.; Gómez-Cañas, M.; Valdeolivas, S.; Guaza, C.; Romero, J.; Guzmán, M.; Mechoulam, R.; Ramos, J.A. Prospects for cannabinoid therapies in basal ganglia disorders. Br. J. Pharmacol., 2011, 163(7), 1365-1378.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01365.x] [PMID: 21545415]
[47]
Maresz, K.; Pryce, G.; Ponomarev, E.D.; Marsicano, G.; Croxford, J.L.; Shriver, L.P.; Ledent, C.; Cheng, X.; Carrier, E.J.; Mann, M.K.; Giovannoni, G.; Pertwee, R.G.; Yamamura, T.; Buckley, N.E.; Hillard, C.J.; Lutz, B.; Baker, D.; Dittel, B.N. Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat. Med., 2007, 13(4), 492-497.
[http://dx.doi.org/10.1038/nm1561] [PMID: 17401376]
[48]
McCaw, E.A.; Hu, H.; Gomez, G.T.; Hebb, A.L.; Kelly, M.E.; Denovan-Wright, E.M. Structure, expression and regulation of the cannabinoid receptor gene (CB1) in Huntington’s disease transgenic mice. Eur. J. Biochem., 2004, 271(23-24), 4909-4920.
[http://dx.doi.org/10.1111/j.1432-1033.2004.04460.x] [PMID: 15606779]
[49]
Shahbazi, F.; Grandi, V.; Banerjee, A.; Trant, J.F. Cannabinoids and cannabinoid receptors: The story so far. iScience, 2020, 23(7), 101301.
[http://dx.doi.org/10.1016/j.isci.2020.101301] [PMID: 32629422]
[50]
An, D.; Peigneur, S.; Hendrickx, L.A.; Tytgat, J. Targeting cannabinoid receptors: current status and prospects of natural products. Int. J. Mol. Sci., 2020, 21(14), E5064.
[http://dx.doi.org/10.3390/ijms21145064] [PMID: 32709050]
[51]
Khatoon, E.; Banik, K.; Harsha, C.; Sailo, B.L.; Thakur, K.K.; Khwairakpam, A.D.; Vikkurthi, R.; Devi, T.B.; Gupta, S.C.; Kunnumakkara, A.B. Phytochemicals in cancer cell chemosensitization: Current knowledge and future perspectives. Semin. Cancer Biol., 2020.
[PMID: 32610149]
[52]
Choudhari, A.S.; Mandave, P.C.; Deshpande, M.; Ranjekar, P.; Prakash, O. Phytochemicals in cancer treatment: From preclinical dtudies to clinical practice. Front. Pharmacol., 2020, 10, 1614.
[http://dx.doi.org/10.3389/fphar.2019.01614] [PMID: 32116665]
[53]
Hosseini, A.; Ghorbani, A. Cancer therapy with phytochemicals: Evidence from clinical studies. Avicenna J. Phytomed., 2015, 5(2), 84-97.
[PMID: 25949949]
[54]
Kirtonia, A.; Gala, K.; Fernandes, S.G.; Pandya, G.; Pandey, A.K.; Sethi, G.; Khattar, E.; Garg, M. Repurposing of drugs: An attractive pharmacological strategy for cancer therapeutics. Semin. Cancer Biol., 2021, 68, 258-278.
[http://dx.doi.org/10.1016/j.semcancer.2020.04.006] [PMID: 32380233]
[55]
Afrin, F.; Chi, M.; Eamens, A.L.; Duchatel, R.J.; Douglas, A.M.; Schneider, J.; Gedye, C.; Woldu, A.S.; Dun, M.D. Can hemp help? low-thc cannabis and non-thc cannabinoids for the treatment of cancer. Cancers (Basel), 2020, 12(4), E1033.
[http://dx.doi.org/10.3390/cancers12041033] [PMID: 32340151]
[56]
Morales, P.; Vara, D.; Goméz-Cañas, M.; Zúñiga, M.C.; Olea-Azar, C.; Goya, P.; Fernández-Ruiz, J.; Díaz-Laviada, I.; Jagerovic, N. Synthetic cannabinoid quinones: Preparation, in vitro antiproliferative effects and in vivo prostate antitumor activity. Eur. J. Med. Chem., 2013, 70, 111-119.
[http://dx.doi.org/10.1016/j.ejmech.2013.09.043] [PMID: 24141201]
[57]
Roberto, D.; Klotz, L.H.; Venkateswaran, V. Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner. Prostate, 2019, 79(2), 151-159.
[http://dx.doi.org/10.1002/pros.23720] [PMID: 30242861]
[58]
Elbaz, M.; Nasser, M.W.; Ravi, J.; Wani, N.A.; Ahirwar, D.K.; Zhao, H.; Oghumu, S.; Satoskar, A.R.; Shilo, K.; Carson, W.E., III; Ganju, R.K. Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of Cannabidiol in breast cancer. Mol. Oncol., 2015, 9(4), 906-919.
[http://dx.doi.org/10.1016/j.molonc.2014.12.010] [PMID: 25660577]
[59]
Milian, L.; Mata, M.; Alcacer, J.; Oliver, M.; Sancho-Tello, M.; Martín de Llano, J.J.; Camps, C.; Galbis, J.; Carretero, J.; Carda, C. Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro. PLoS One, 2020, 15(2), e0228909.
[http://dx.doi.org/10.1371/journal.pone.0228909] [PMID: 32049991]
[60]
Preet, A.; Ganju, R.K.; Groopman, J.E. Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene, 2008, 27(3), 339-346.
[http://dx.doi.org/10.1038/sj.onc.1210641] [PMID: 17621270]
[61]
Gómez del Pulgar, T.; Velasco, G.; Sánchez, C.; Haro, A.; Guzmán, M. De novo-synthesized ceramide is involved in cannabinoid-induced apoptosis. Biochem. J., 2002, 363(Pt 1), 183-188.
[http://dx.doi.org/10.1042/bj3630183] [PMID: 11903061]
[62]
Velasco, G.; Sánchez, C.; Guzmán, M. Anticancer mechanisms of cannabinoids. Curr. Oncol., 2016, 23(2), S23-S32.
[http://dx.doi.org/10.3747/co.23.3080] [PMID: 27022311]
[63]
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 Delta9-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]
[64]
Turcott, J.G.; Del Rocío Guillen Núñez, M.; Flores-Estrada, D.; Oñate-Ocaña, L.F.; Zatarain-Barrón, Z.L.; Barrón, F.; Arrieta, O. The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: A randomized, double-blind clinical trial. Support. Care Cancer, 2018, 26(9), 3029-3038.
[http://dx.doi.org/10.1007/s00520-018-4154-9] [PMID: 29550881]
[65]
Nelson, K.; Walsh, D.; Deeter, P.; Sheehan, F. A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J. Palliat. Care, 1994, 10(1), 14-18.
[http://dx.doi.org/10.1177/082585979401000105] [PMID: 8035251]
[66]
Brisbois, T.D.; de Kock, I.H.; Watanabe, S.M.; Mirhosseini, M.; Lamoureux, D.C.; Chasen, M.; MacDonald, N.; Baracos, V.E.; Wismer, W.V. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: Results of a randomized, double-blind, placebo-controlled pilot trial. Ann. Oncol., 2011, 22(9), 2086-2093.
[http://dx.doi.org/10.1093/annonc/mdq727] [PMID: 21343383]
[67]
Jatoi, A.; Windschitl, H.E.; Loprinzi, C.L.; Sloan, J.A.; Dakhil, S.R.; Mailliard, J.A.; Pundaleeka, S.; Kardinal, C.G.; Fitch, T.R.; Krook, J.E.; Novotny, P.J.; Christensen, B. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: A North Central Cancer Treatment Group study. J. Clin. Oncol., 2002, 20(2), 567-573.
[http://dx.doi.org/10.1200/JCO.2002.20.2.567] [PMID: 11786587]
[68]
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]
[69]
Johnson, J.R.; Lossignol, D.; Burnell-Nugent, M.; Fallon, M.T. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J. Pain Symptom Manage., 2013, 46(2), 207-218.
[http://dx.doi.org/10.1016/j.jpainsymman.2012.07.014] [PMID: 23141881]
[70]
Lichtman, A.H.; Lux, E.A.; McQuade, R.; Rossetti, S.; Sanchez, R.; Sun, W.; Wright, S.; Kornyeyeva, E.; Fallon, M.T. Results of a double-blind, randomized, placebo-controlled study of nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain. J. Pain Symptom Manage., 2018, 55(2), 179-188.e1.
[http://dx.doi.org/10.1016/j.jpainsymman.2017.09.001] [PMID: 28923526]
[71]
Lynch, M.E.; Cesar-Rittenberg, P.; Hohmann, A.G. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J. Pain Symptom Manage., 2014, 47(1), 166-173.
[http://dx.doi.org/10.1016/j.jpainsymman.2013.02.018] [PMID: 23742737]
[72]
Kaplan, G.G.; Ng, S.C. Understanding and preventing the global increase of inflammatory bowel disease. Gastroenterology, 2017, 152(2), 313-321.e2.
[http://dx.doi.org/10.1053/j.gastro.2016.10.020] [PMID: 27793607]
[73]
Molodecky, N.A.; Soon, I.S.; Rabi, D.M.; Ghali, W.A.; Ferris, M.; Chernoff, G.; Benchimol, E.I.; Panaccione, R.; Ghosh, S.; Barkema, H.W.; Kaplan, G.G. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology, 2012, 142(1), 46-54.e42.
[http://dx.doi.org/10.1053/j.gastro.2011.10.001] [PMID: 22001864]
[74]
Baron, J.A.; Folan, R.D.; Kelley, M.L., Jr. Ulcerative colitis and marijuana. Ann. Intern. Med., 1990, 112(6), 471.
[http://dx.doi.org/10.7326/0003-4819-76-3-112-6-471_1] [PMID: 2310110]
[75]
Herkenham, M.; Lynn, A.B.; Little, M.D.; Johnson, M.R.; Melvin, L.S.; de Costa, B.R.; Rice, K.C. Cannabinoid receptor localization in brain. Proc. Natl. Acad. Sci. USA, 1990, 87(5), 1932-1936.
[http://dx.doi.org/10.1073/pnas.87.5.1932] [PMID: 2308954]
[76]
Naftali, T.; Mechulam, R.; Lev, L.B.; Konikoff, F.M. Cannabis for inflammatory bowel disease. Dig. Dis., 2014, 32(4), 468-474.
[http://dx.doi.org/10.1159/000358155] [PMID: 24969296]
[77]
Swaminath, A.; Berlin, E.P.; Cheifetz, A.; Hoffenberg, E.; Kinnucan, J.; Wingate, L.; Buchanan, S.; Zmeter, N.; Rubin, D.T. The role of cannabis in the management of inflammatory bowel disease: A review of clinical, scientific, and regulatory information. Inflamm. Bowel Dis., 2019, 25(3), 427-435.
[http://dx.doi.org/10.1093/ibd/izy319] [PMID: 30358848]
[78]
Becker, W.; Alrafas, H.R.; Busbee, P.B.; Walla, M.D.; Wilson, K.; Miranda, K.; Cai, G.; Putluri, V.; Putluri, N.; Nagarkatti, M.; Nagarkatti, P.S. Cannabinoid receptor activation on haematopoietic cells and enterocytes protects against colitis. J. Crohn’s Colitis, 2021, 15(6), 1032-1048.
[http://dx.doi.org/10.1093/ecco-jcc/jjaa253] [PMID: 33331878]
[79]
Wright, K.; Rooney, N.; Feeney, M.; Tate, J.; Robertson, D.; Welham, M.; Ward, S. Differential expression of cannabinoid receptors in the human colon: Cannabinoids promote epithelial wound healing. Gastroenterology, 2005, 129(2), 437-453.
[http://dx.doi.org/10.1016/j.gastro.2005.05.026] [PMID: 16083701]
[80]
Singh, U.P.; Singh, N.P.; Singh, B.; Price, R.L.; Nagarkatti, M.; Nagarkatti, P.S. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10(-/-) mice by attenuating the activation of T cells and promoting their apoptosis. Toxicol. Appl. Pharmacol., 2012, 258(2), 256-267.
[http://dx.doi.org/10.1016/j.taap.2011.11.005] [PMID: 22119709]
[81]
Castañeda Cardona, C.; Lasalvia, P.; Ferreriros, A.; Pantoja Ruiz, C.; Restrepo Jimenez, P.; Rosselli, D. Cannabis in inflammatory bowel disease: A narrative summary. Rev. Colomb. Gastroenterol., 2020, 35(1), 104-113.
[http://dx.doi.org/10.22516/25007440.407]
[82]
Goyal, H.; Singla, U.; Gupta, U.; May, E. Role of cannabis in digestive disorders. Eur. J. Gastroenterol. Hepatol., 2017, 29(2), 135-143.
[http://dx.doi.org/10.1097/MEG.0000000000000779] [PMID: 27792038]
[83]
García-Planella, E.; Marín, L.; Domènech, E.; Bernal, I.; Mañosa, M.; Zabana, Y.; Gassull, M.A. Use of complementary and alternative medicine and drug abuse in patients with inflammatory bowel disease. Med. Clin. (Barc.), 2007, 128(2), 45-48.
[PMID: 17266900]
[84]
Ravikoff Allegretti, J.; Courtwright, A.; Lucci, M.; Korzenik, J.R.; Levine, J. Marijuana use patterns among patients with inflammatory bowel disease. Inflamm. Bowel Dis., 2013, 19(13), 2809-2814.
[http://dx.doi.org/10.1097/01.MIB.0000435851.94391.37] [PMID: 24185313]
[85]
Storr, M.; Devlin, S.; Kaplan, G.G.; Panaccione, R.; Andrews, C.N. Cannabis use provides symptom relief in patients with inflammatory bowel disease but is associated with worse disease prognosis in patients with Crohn’s disease. Inflamm. Bowel Dis., 2014, 20(3), 472-480.
[http://dx.doi.org/10.1097/01.MIB.0000440982.79036.d6] [PMID: 24407485]
[86]
Lal, S.; Prasad, N.; Ryan, M.; Tangri, S.; Silverberg, M.S.; Gordon, A.; Steinhart, H. Cannabis use amongst patients with inflammatory bowel disease. Eur. J. Gastroenterol. Hepatol., 2011, 23(10), 891-896.
[http://dx.doi.org/10.1097/MEG.0b013e328349bb4c] [PMID: 21795981]
[87]
Phatak, U.P.; Rojas-Velasquez, D.; Porto, A.; Pashankar, D.S. Prevalence and patterns of marijuana use in young adults with inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr., 2017, 64(2), 261-264.
[http://dx.doi.org/10.1097/MPG.0000000000001474] [PMID: 27846066]
[88]
Hoffenberg, E.J.; McWilliams, S.K.; Mikulich-Gilbertson, S.K.; Murphy, B.V.; Lagueux, M.; Robbins, K.; Hoffenberg, A.S.; de Zoeten, E.; Hopfer, C.J. Marijuana use by adolescents and young adults with inflammatory bowel disease. J. Pediatr., 2018, 199, 99-105.
[http://dx.doi.org/10.1016/j.jpeds.2018.03.041] [PMID: 29673723]
[89]
Naftali, T.; Lev, L.B.; Yablecovitch, D.; Half, E.; Konikoff, F.M. Treatment of Crohn’s disease with cannabis: An observational study. Isr. Med. Assoc. J., 2011, 13(8), 455-458.
[PMID: 21910367]
[90]
Lahat, A.; Lang, A.; Ben-Horin, S. Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: A pilot prospective study. Digestion, 2012, 85(1), 1-8.
[http://dx.doi.org/10.1159/000332079] [PMID: 22095142]
[91]
Naftali, T.; Mechulam, R.; Marii, A.; Gabay, G.; Stein, A.; Bronshtain, M.; Laish, I.; Benjaminov, F.; Konikoff, F.M. Low-dose cannabidiol is safe but not effective in the treatment for Crohn’s disease, a randomized controlled trial. Dig. Dis. Sci., 2017, 62(6), 1615-1620.
[http://dx.doi.org/10.1007/s10620-017-4540-z] [PMID: 28349233]
[92]
Naftali, T.; Bar-Lev Schleider, L.; Dotan, I.; Lansky, E.P.; Sklerovsky Benjaminov, F.; Konikoff, F.M. Cannabis induces a clinical response in patients with Crohn’s disease: A prospective placebo-controlled study. Clin. Gastroenterol. Hepatol., 2013, 11(10), 1276-1280.e1.
[http://dx.doi.org/10.1016/j.cgh.2013.04.034] [PMID: 23648372]
[93]
Weiss, A.; Friedenberg, F. Patterns of cannabis use in patients with inflammatory bowel disease: A population based analysis. Drug Alcohol Depend., 2015, 156, 84-89.
[http://dx.doi.org/10.1016/j.drugalcdep.2015.08.035] [PMID: 26422462]
[94]
Koning, M.; Ailabouni, R.; Gearry, R.B.; Frampton, C.M.; Barclay, M.L. Use and predictors of oral complementary and alternative medicine by patients with inflammatory bowel disease: A population-based, case-control study. Inflamm. Bowel Dis., 2013, 19(4), 767-778.
[http://dx.doi.org/10.1097/MIB.0b013e31827f27c8] [PMID: 23429459]
[95]
Vučković, S.; Srebro, D.; Vujović, K.S.; Vučetić, Č.; Prostran, M. Cannabinoids and pain: New insights from old molecules. Front. Pharmacol., 2018, 9, 1259.
[http://dx.doi.org/10.3389/fphar.2018.01259] [PMID: 30542280]
[96]
Huang, S.M.; Bisogno, T.; Petros, T.J.; Chang, S.Y.; Zavitsanos, P.A.; Zipkin, R.E.; Sivakumar, R.; Coop, A.; Maeda, D.Y.; De Petrocellis, L.; Burstein, S.; Di Marzo, V.; Walker, J.M. Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain. J. Biol. Chem., 2001, 276(46), 42639-42644.
[http://dx.doi.org/10.1074/jbc.M107351200] [PMID: 11518719]
[97]
Russo, E.B.; Burnett, A.; Hall, B.; Parker, K.K. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem. Res., 2005, 30(8), 1037-1043.
[http://dx.doi.org/10.1007/s11064-005-6978-1] [PMID: 16258853]
[98]
Staton, P.C.; Hatcher, J.P.; Walker, D.J.; Morrison, A.D.; Shapland, E.M.; Hughes, J.P.; Chong, E.; Mander, P.K.; Green, P.J.; Billinton, A.; Fulleylove, M.; Lancaster, H.C.; Smith, J.C.; Bailey, L.T.; Wise, A.; Brown, A.J.; Richardson, J.C.; Chessell, I.P. The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain, 2008, 139(1), 225-236.
[http://dx.doi.org/10.1016/j.pain.2008.04.006] [PMID: 18502582]
[99]
Grim, T.W.; Ghosh, S.; Hsu, K.L.; Cravatt, B.F.; Kinsey, S.G.; Lichtman, A.H. Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in mouse neuropathic and inflammatory pain models. Pharmacol. Biochem. Behav., 2014, 124, 405-411.
[http://dx.doi.org/10.1016/j.pbb.2014.07.008] [PMID: 25058512]
[100]
Ware, M.A.; Wang, T.; Shapiro, S.; Robinson, A.; Ducruet, T.; Huynh, T.; Gamsa, A.; Bennett, G.J.; Collet, J.P. Smoked cannabis for chronic neuropathic pain: A randomized controlled trial. CMAJ, 2010, 182(14), E694-E701.
[http://dx.doi.org/10.1503/cmaj.091414] [PMID: 20805210]
[101]
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(1-3), 210-220.
[http://dx.doi.org/10.1016/j.pain.2007.08.028] [PMID: 17997224]
[102]
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]
[103]
Serpell, M.; Ratcliffe, S.; Hovorka, J.; Schofield, M.; Taylor, L.; Lauder, H.; Ehler, E. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur. J. Pain, 2014, 18(7), 999-1012.
[http://dx.doi.org/10.1002/j.1532-2149.2013.00445.x] [PMID: 24420962]
[104]
Wilsey, B.; Marcotte, T.; Deutsch, R.; Gouaux, B.; Sakai, S.; Donaghe, H. Low-dose vaporized cannabis significantly improves neuropathic pain. J. Pain, 2013, 14(2), 136-148.
[http://dx.doi.org/10.1016/j.jpain.2012.10.009] [PMID: 23237736]
[105]
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]
[106]
Poli, P.; Crestani, F.; Salvadori, C.; Valenti, I.; Sannino, C. Medical cannabis in patients with chronic pain: effect on pain relief, pain disability, and psychological aspects. A prospective non randomized single arm clinical trial. Clin. Ter., 2018, 169(3), e102-e107.
[PMID: 29938740]
[107]
Nyakudya, T.T.; Tshabalala, T.; Dangarembizi, R.; Erlwanger, K.H.; Ndhlala, A.R. The potential therapeutic value of medicinal plants in the management of metabolic disorders. Molecules, 2020, 25(11), E2669.
[http://dx.doi.org/10.3390/molecules25112669] [PMID: 32526850]
[108]
Altemimi, A.; Lakhssassi, N.; Baharlouei, A.; Watson, D.G.; Lightfoot, D.A. Phytochemicals: Extraction, isolation, and identification of bioactive compounds from plant extracts. Plants, 2017, 6(4), E42.
[http://dx.doi.org/10.3390/plants6040042] [PMID: 28937585]
[109]
Rodriguez-Casado, A. The health potential of fruits and vegetables phytochemicals: Notable examples. Crit. Rev. Food Sci. Nutr., 2016, 56(7), 1097-1107.
[http://dx.doi.org/10.1080/10408398.2012.755149] [PMID: 25225771]
[110]
Bielawiec, P.; Harasim-Symbor, E.; Chabowski, A. Phytocannabinoids: Useful drugs for the treatment of obesity? special focus on cannabidiol. Front. Endocrinol. (Lausanne), 2020, 11, 114.
[http://dx.doi.org/10.3389/fendo.2020.00114] [PMID: 32194509]
[111]
Veilleux, A.; Di Marzo, V.; Silvestri, C. The expanded endocannabinoid system/endocannabinoidome as a potential target for treating diabetes mellitus. Curr. Diab. Rep., 2019, 19(11), 117.
[http://dx.doi.org/10.1007/s11892-019-1248-9] [PMID: 31686231]
[112]
Bermúdez-Silva, F.J.; Suárez, J.; Baixeras, E.; Cobo, N.; Bautista, D.; Cuesta-Muñoz, A.L.; Fuentes, E.; Juan-Pico, P.; Castro, M.J.; Milman, G.; Mechoulam, R.; Nadal, A.; Rodríguez de Fonseca, F. Presence of functional cannabinoid receptors in human endocrine pancreas. Diabetologia, 2008, 51(3), 476-487.
[http://dx.doi.org/10.1007/s00125-007-0890-y] [PMID: 18092149]
[113]
Li, C.; Bowe, J.E.; Jones, P.M.; Persaud, S.J. Expression and function of cannabinoid receptors in mouse islets. Islets, 2010, 2(5), 293-302.
[http://dx.doi.org/10.4161/isl.2.5.12729] [PMID: 21099327]
[114]
Vilches-Flores, A.; Delgado-Buenrostro, N.L.; Navarrete-Vázquez, G.; Villalobos-Molina, R. CB1 cannabinoid receptor expression is regulated by glucose and feeding in rat pancreatic islets. Regul. Pept., 2010, 163(1-3), 81-87.
[http://dx.doi.org/10.1016/j.regpep.2010.04.013] [PMID: 20451564]
[115]
Scherer, T.; Buettner, C. The dysregulation of the endocannabinoid system in diabesity-a tricky problem. J. Mol. Med. (Berl.), 2009, 87(7), 663-668.
[http://dx.doi.org/10.1007/s00109-009-0459-y] [PMID: 19290485]
[116]
Frisher, M.; White, S.; Varbiro, G.; Voisey, C.; Perumal, D.; Crome, I.; Khideja, N.; Bashford, J. The role of cannabis and cannabinoids in diabetes. Br. J. Diabetes Vasc. Dis., 2010, 10(6), 267-273.
[http://dx.doi.org/10.1177/1474651410385860]
[117]
Li, X.; Kaminski, N.E.; Fischer, L.J. Examination of the immunosuppressive effect of delta9-tetrahydrocannabinol in streptozotocin-induced autoimmune diabetes. Int. Immunopharmacol., 2001, 1(4), 699-712.
[http://dx.doi.org/10.1016/S1567-5769(01)00003-0] [PMID: 11357882]
[118]
Horváth, B.; Mukhopadhyay, P.; Haskó, G.; Pacher, P. The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications. Am. J. Pathol., 2012, 180(2), 432-442.
[http://dx.doi.org/10.1016/j.ajpath.2011.11.003] [PMID: 22155112]
[119]
Jadoon, K.A.; Ratcliffe, S.H.; Barrett, D.A.; Thomas, E.L.; Stott, C.; Bell, J.D.; O’Sullivan, S.E.; Tan, G.D. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care, 2016, 39(10), 1777-1786.
[http://dx.doi.org/10.2337/dc16-0650] [PMID: 27573936]
[120]
Hoggart, B.; Ratcliffe, S.; Ehler, E.; Simpson, K.H.; Hovorka, J.; Lejčko, J.; Taylor, L.; Lauder, H.; Serpell, M. A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain. J. Neurol., 2015, 262(1), 27-40.
[http://dx.doi.org/10.1007/s00415-014-7502-9] [PMID: 25270679]
[121]
Wallace, M.S.; Marcotte, T.D.; Umlauf, A.; Gouaux, B.; Atkinson, J.H. Efficacy of inhaled cannabis on painful diabetic neuropathy. J. Pain, 2015, 16(7), 616-627.
[http://dx.doi.org/10.1016/j.jpain.2015.03.008] [PMID: 25843054]
[122]
Xu, D.H.; Cullen, B.D.; Tang, M.; Fang, Y. The Effectiveness of topical cannabidiol oil in symptomatic relief of peripheral neuropathy of the lower extremities. Curr. Pharm. Biotechnol., 2020, 21(5), 390-402.
[http://dx.doi.org/10.2174/1389201020666191202111534] [PMID: 31793418]
[123]
Toth, C.; Mawani, S.; Brady, S.; Chan, C.; Liu, C.; Mehina, E.; Garven, A.; Bestard, J.; Korngut, L. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain, 2012, 153(10), 2073-2082.
[http://dx.doi.org/10.1016/j.pain.2012.06.024] [PMID: 22921260]
[124]
Solinas, M.; Goldberg, S.R.; Piomelli, D. The endocannabinoid system in brain reward processes. Br. J. Pharmacol., 2008, 154(2), 369-383.
[http://dx.doi.org/10.1038/bjp.2008.130] [PMID: 18414385]
[125]
Scheen, A.J.; Finer, N.; Hollander, P.; Jensen, M.D.; Van Gaal, L.F. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: A randomised controlled study. Lancet, 2006, 368(9548), 1660-1672.
[http://dx.doi.org/10.1016/S0140-6736(06)69571-8] [PMID: 17098084]
[126]
Christensen, R.; Kristensen, P.K.; Bartels, E.M.; Bliddal, H.; Astrup, A. Efficacy and safety of the weight-loss drug rimonabant: A meta-analysis of randomised trials. Lancet, 2007, 370(9600), 1706-1713.
[http://dx.doi.org/10.1016/S0140-6736(07)61721-8] [PMID: 18022033]
[127]
Tudge, L.; Williams, C.; Cowen, P.J.; McCabe, C. Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin on food reward and aversion in healthy volunteers. Int. J. Neuropsychopharmacol., 2014, 18(6), pyu094.
[PMID: 25542687]
[128]
Soto, C.; Estrada, L.D. Protein misfolding and neurodegeneration. Arch. Neurol., 2008, 65(2), 184-189.
[http://dx.doi.org/10.1001/archneurol.2007.56] [PMID: 18268186]
[129]
Yankner, B.A.; Lu, T.; Loerch, P. The aging brain. Annu. Rev. Pathol., 2008, 3, 41-66.
[http://dx.doi.org/10.1146/annurev.pathmechdis.2.010506.092044] [PMID: 18039130]
[130]
Iuvone, T.; Esposito, G.; De Filippis, D.; Scuderi, C.; Steardo, L. Cannabidiol: A promising drug for neurodegenerative disorders? CNS Neurosci. Ther., 2009, 15(1), 65-75.
[http://dx.doi.org/10.1111/j.1755-5949.2008.00065.x] [PMID: 19228180]
[131]
Skaper, S.D. The brain as a target for inflammatory processes and neuroprotective strategies. Ann. N. Y. Acad. Sci., 2007, 1122, 23-34.
[http://dx.doi.org/10.1196/annals.1403.002] [PMID: 18077562]
[132]
Zuardi, A.W. Cannabidiol: From an inactive cannabinoid to a drug with wide spectrum of action. Rev. Bras. Psiquiatr., 2008, 30(3), 271-280.
[http://dx.doi.org/10.1590/S1516-44462008000300015] [PMID: 18833429]
[133]
Oberbarnscheidt, T.; Miller, N.S. The impact of cannabidiol on psychiatric and medical conditions. J. Clin. Med. Res., 2020, 12(7), 393-403.
[http://dx.doi.org/10.14740/jocmr4159] [PMID: 32655732]
[134]
Pertwee, R.G. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br. J. Pharmacol., 2008, 153(2), 199-215.
[http://dx.doi.org/10.1038/sj.bjp.0707442] [PMID: 17828291]
[135]
Venderová, K.; Růzicka, E.; Vorísek, V.; Visnovský, P. Survey on cannabis use in Parkinson’s disease: subjective improvement of motor symptoms. Mov. Disord., 2004, 19(9), 1102-1106.
[http://dx.doi.org/10.1002/mds.20111] [PMID: 15372606]
[136]
Castillo, P.E.; Younts, T.J.; Chávez, A.E.; Hashimotodani, Y. Endocannabinoid signaling and synaptic function. Neuron, 2012, 76(1), 70-81.
[http://dx.doi.org/10.1016/j.neuron.2012.09.020] [PMID: 23040807]
[137]
Kluger, B.; Triolo, P.; Jones, W.; Jankovic, J. The therapeutic potential of cannabinoids for movement disorders. Mov. Disord., 2015, 30(3), 313-327.
[http://dx.doi.org/10.1002/mds.26142] [PMID: 25649017]
[138]
Bilsland, L.G.; Dick, J.R.; Pryce, G.; Petrosino, S.; Di Marzo, V.; Baker, D.; Greensmith, L. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. FASEB J., 2006, 20(7), 1003-1005.
[http://dx.doi.org/10.1096/fj.05-4743fje] [PMID: 16571781]
[139]
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]
[140]
Trapp, B.D.; Nave, K.A. Multiple sclerosis: An immune or neurodegenerative disorder? Annu. Rev. Neurosci., 2008, 31, 247-269.
[http://dx.doi.org/10.1146/annurev.neuro.30.051606.094313] [PMID: 18558855]
[141]
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]
[142]
Booz, G.W. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic. Biol. Med., 2011, 51(5), 1054-1061.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.01.007] [PMID: 21238581]
[143]
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]
[144]
de Almeida, D.L.; Devi, L.A. Diversity of molecular targets and signaling pathways for CBD. Pharmacol. Res. Perspect., 2020, 8(6), e00682.
[http://dx.doi.org/10.1002/prp2.682] [PMID: 33169541]
[145]
Basavarajappa, B.S.; Shivakumar, M.; Joshi, V.; Subbanna, S. Endocannabinoid system in neurodegenerative disorders. J. Neurochem., 2017, 142(5), 624-648.
[http://dx.doi.org/10.1111/jnc.14098] [PMID: 28608560]
[146]
Fernández-Ruiz, J.; Sagredo, O.; Pazos, M.R.; García, C.; Pertwee, R.; Mechoulam, R.; Martínez-Orgado, J. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? Br. J. Clin. Pharmacol., 2013, 75(2), 323-333.
[http://dx.doi.org/10.1111/j.1365-2125.2012.04341.x] [PMID: 22625422]
[147]
Riva, N.; Mora, G.; Sorarù, G.; Lunetta, C.; Ferraro, O.E.; Falzone, Y.; Leocani, L.; Fazio, R.; Comola, M.; Comi, G.; Group, C.S. Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): A multicentre, double-blind, randomised, placebo- controlled, phase 2 trial. Lancet Neurol., 2019, 18(2), 155-164.
[http://dx.doi.org/10.1016/S1474-4422(18)30406-X] [PMID: 30554828]
[148]
Bowling, A. Cannabinoids in MS-are we any closer to knowing how best to use them? Mult. Scler., 2006, 12(5), 523-525.
[http://dx.doi.org/10.1177/1352458506072514] [PMID: 17086895]
[149]
Rudroff, T.; Honce, J.M. Cannabis and multiple sclerosis-the way forward. Front. Neurol., 2017, 8, 299.
[http://dx.doi.org/10.3389/fneur.2017.00299] [PMID: 28690588]
[150]
Chong, M.S.; Wolff, K.; Wise, K.; Tanton, C.; Winstock, A.; Silber, E. Cannabis use in patients with multiple sclerosis. Mult. Scler., 2006, 12(5), 646-651.
[http://dx.doi.org/10.1177/1352458506070947] [PMID: 17086912]
[151]
Vaney, C.; Heinzel-Gutenbrunner, M.; Jobin, P.; Tschopp, F.; Gattlen, B.; Hagen, U.; Schnelle, M.; Reif, M. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled, crossover study. Mult. Scler., 2004, 10(4), 417-424.
[http://dx.doi.org/10.1191/1352458504ms1048oa] [PMID: 15327040]
[152]
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]
[153]
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]
[154]
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]
[155]
Perras, C. Sativex for the management of multiple sclerosis symptoms. Issues Emerg. Health Technol., 2005, (72), 1-4.
[PMID: 16317825]
[156]
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. Sativex Spasticity Study, G., A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex(R)), 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]
[157]
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]
[158]
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]
[159]
Kavia, R.B.; 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]
[160]
Kano, M.; Ohno-Shosaku, T.; Hashimotodani, Y.; Uchigashima, M.; Watanabe, M. Endocannabinoid-mediated control of synaptic transmission. Physiol. Rev., 2009, 89(1), 309-380.
[http://dx.doi.org/10.1152/physrev.00019.2008] [PMID: 19126760]
[161]
Marsicano, G.; Goodenough, S.; Monory, K.; Hermann, H.; Eder, M.; Cannich, A.; Azad, S.C.; Cascio, M.G.; Gutiérrez, S.O.; van der Stelt, M.; López-Rodriguez, M.L.; Casanova, E.; Schütz, G.; Zieglgänsberger, W.; Di Marzo, V.; Behl, C.; Lutz, B. CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science, 2003, 302(5642), 84-88.
[http://dx.doi.org/10.1126/science.1088208] [PMID: 14526074]
[162]
López-Sendón Moreno, J.L.; García Caldentey, J.; Trigo Cubillo, P.; Ruiz Romero, C.; García Ribas, G.; Alonso Arias, M.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]
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]
[164]
Balash, Y.; Bar-Lev Schleider, L.; Korczyn, A.D.; Shabtai, H.; Knaani, J.; Rosenberg, A.; Baruch, Y.; Djaldetti, R.; Giladi, N.; Gurevich, T. Medical cannabis in parkinson disease: Real-life patients’ experience. Clin. Neuropharmacol., 2017, 40(6), 268-272.
[http://dx.doi.org/10.1097/WNF.0000000000000246] [PMID: 29059132]
[165]
Lotan, I.; Treves, T.A.; Roditi, Y.; Djaldetti, R. Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: An open-label observational study. Clin. Neuropharmacol., 2014, 37(2), 41-44.
[http://dx.doi.org/10.1097/WNF.0000000000000016] [PMID: 24614667]
[166]
Sieradzan, K.A.; Fox, S.H.; Hill, M.; Dick, J.P.; Crossman, A.R.; Brotchie, J.M. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: A pilot study. Neurology, 2001, 57(11), 2108-2111.
[http://dx.doi.org/10.1212/WNL.57.11.2108] [PMID: 11739835]
[167]
Karila, L.; Roux, P.; Rolland, B.; Benyamina, A.; Reynaud, M.; Aubin, H.J.; Lançon, C. Acute and long-term effects of cannabis use: A review. Curr. Pharm. Des., 2014, 20(25), 4112-4118.
[http://dx.doi.org/10.2174/13816128113199990620] [PMID: 24001294]
[168]
Bergamaschi, M.M.; Queiroz, R.H.; Zuardi, A.W.; Crippa, J.A. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr. Drug Saf., 2011, 6(4), 237-249.
[http://dx.doi.org/10.2174/157488611798280924] [PMID: 22129319]
[169]
Crocker, C.E.; Carter, A.J.E.; Emsley, J.G.; Magee, K.; Atkinson, P.; Tibbo, P.G. When cannabis use goes wrong: Mental health side effects of cannabis use that present to emergency services. Front. Psychiatry, 2021, 12, 640222.
[http://dx.doi.org/10.3389/fpsyt.2021.640222] [PMID: 33658953]
[170]
Hall, W. European Monitoring centre for drugs and drug addiction; EMCDDA: Luxembourg, 2018.

Rights & Permissions Print Cite
Article Metrics
84
2
2
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy