Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Systematic Review Article

Impact of Cannabis-Based Medicine on Alzheimer’s Disease by Focusing on the Amyloid β-Modifications: A Systematic Study

Author(s): Tahereh Farkhondeh, Haroon Khan, Michael Aschner, Fariborz Samini, Ali M. Pourbagher-Shahri, Hamed Aramjoo, Babak Roshanravan, Christopher Hoyte, Omid Mehrpour and Saeed Samarghandian*

Volume 19, Issue 5, 2020

Page: [334 - 343] Pages: 10

DOI: 10.2174/1871527319666200708130745

Price: $65

conference banner
Abstract

Deposition of Amyloid-beta (Aβ) peptide in the brain is the leading source of the onset and progression of Alzheimer’s Disease (AD). Recent studies have suggested that anti-amyloidogenic agents may be a suitable therapeutic strategy for AD. The current review was proposed to address the beneficial effects of cannabis-based drugs for the treatment of AD, focusing primarily on Aβ modifications. Keywords related to AD, Aβ, and cannabis-based on MeSH were identified and were searched in PubMed, Google Scholar, Scopus, Ovid-Medline, and Web of Science from inception until 15 March 2020. The full text of identified papers was obtained and assessed based on exclusion and inclusion criteria. The review is based on articles that have focused on AD and the amyloidogenic pathway. A total of 17 studies were identified based on the inclusion criteria; however, nine studies qualified for this systematic review. The maximum and minimum cannabis dosages, mostly CBD and THC in animal studies, were 0.75 and 50 mg/kg, respectively. Cannabis (CBD and THC) was injected for 10 to 21 days. The findings of the 9 articles indicated that cannabis-based drugs might modulate Aβ modifications in several AD models. Our findings establish that cannabis-based drugs inhibited the progression of AD by modulating Aβ modifications.

Keywords: Amyloid-beta, Alzheimer's disease, cannabis, cannabinoids, cannabidiol, molecular assays.

Graphical Abstract
[1]
Gómez-Gómez ME, Zapico SC. Frailty, cognitive decline, neurodegenerative diseases and nutrition interventions. Int J Mol Sci 2019; 20(11): 2842.
[http://dx.doi.org/10.3390/ijms20112842 ] [PMID: 31212645]
[2]
Mayeux R, Stern Y. Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2(8)a006239
[http://dx.doi.org/10.1101/cshperspect.a006239 ] [PMID: 22908189]
[3]
Organization WH. The epidemiology and impact of dementia current state and future trends Available from: https://www.who.int/mental_health/neurology/dementia/dementia_thematicbrief_epidemiology.pdf
[4]
Prince M, Guerchet M, Prina M. The global impact of dementia 2013-2050: Alzheimer's Disease International 2013 Available form: https://www.researchgate.net/publication/259193075_The_Global_Impact_of_Dementia_2013-2050
[6]
Murphy MP, LeVine M H III. TAlzheimer’s disease and the amyloidbeta peptide. J Alzheimers Dis 2010; 19(1): 311-23.
[http://dx.doi.org/10.3233/JAD-2010-1221] [PMID: 20061647]
[7]
[5] Farlow MR. Etiology and pathogenesis of Alzheimer’s disease. Am J Health Promot 1998; 55(Suppl. 2): S5-S10.
[http://dx.doi.org/10.1093/ajhp/55.suppl_2.S5]
[8]
[6] Murphy MP, LeVine H III. Alzheimer’s disease and the amyloid-beta peptide. J Alzheimers Dis 2010; 19(1): 311-23.
[http://dx.doi.org/10.3233/JAD-2010-1221 ] [PMID: 20061647]
[9]
[7] Chow VW, Mattson MP, Wong PC, Gleichmann M. An overview of APP processing enzymes and products. Neuromolecular Med 2010; 12(1): 1-12.
[http://dx.doi.org/10.1007/s12017-009-8104-z] [PMID: 20232515]
[10]
[8] Zhang X, Fu Z, Meng L, He M, Zhang Z. The early events that initiate β-amyloid aggregation in Alzheimer’s disease. Front Aging Neurosci 2018; 10: 359.
[http://dx.doi.org/10.3389/fnagi.2018.00359 ] [PMID: 30542277]
[11]
2019.
[12]
[10] Huang L-K, Chao S-P, Hu C-J. Clinical trials of new drugs for Alzheimer disease. J Biomed Sci 2020; 27(1): 18.
[http://dx.doi.org/10.1186/s12929-019-0609-7 ] [PMID: 31906949]
[13]
[11] Neugroschl J, Sano M. Current treatment and recent clinical research in Alzheimer’s disease. Mt Sinai J Med 2010; 77(1): 3-16.
[http://dx.doi.org/10.1002/msj.20165 ] [PMID: 20101716]
[14]
[12] Yager D, Watson M, Healy B, Eckman EA, Eckman CB. Natural product extracts that reduce accumulation of the Alzheimer’s amyloid beta peptide: selective reduction in A beta42. J Mol Neurosci 2002; 19(1-2): 129-33.
[15]
[13] Kuruuzum-Uz A, Suleyman H, Cadirci E, Guvenalp Z. Demirezer LOJZfNC. Investigation on anti-inflammatory and antiulcer activities of Anchusa azurea extracts and their major constituent rosmarinic acid. Z Naturforsch C 2012; 67(7-8): 360-6.
[16]
2010.
[17]
2015.
[18]
[16] McPartland JM. Cannabis systematics at the levels of family, genus, and species. Cannabis Cannabinoid Res 2018; 3(1): 203-12.
[http://dx.doi.org/10.1089/can.2018.0039 ] [PMID: 30426073]
[19]
[17] Piluzza G, Delogu G, Cabras A, Marceddu S, Bullitta S. Differentiation between fiber and drug types of hemp (Cannabis sativa L.) from a collection of wild and domesticated accessions. Genet Resour Crop Evol 2013; 60: 2331-42.
[http://dx.doi.org/10.1007/s10722-013-0001-5]
[20]
[18] Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol 2012; 2(6): 241-54.
[http://dx.doi.org/10.1177/2045125312457586 ] [PMID: 23983983]
[21]
[19] DeLong GT, Wolf CE, Poklis A, Lichtman AH. Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol. Drug Alcohol Depend 2010; 112(1-2): 126-33.
[http://dx.doi.org/10.1016/j.drugalcdep.2010.05.019] [PMID: 20619971]
[22]
[20] Niesink RJ, Rigter S, Koeter MW, Brunt TMJA. Potency trends of Δ9‐tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005-15. Addiction 2015; 110(12): 1941-50.
[23]
[21] Harvey DJ. Cyclic alkylboronates as derivatives for the characterization of cannabinolic acids by combined gas chromatography and mass spectrometry. Biomed Mass Spectrom 1977; 4(2): 88-93.
[24]
2005.
[25]
[23] Morimoto S, Komatsu K, Taura F, Shoyama Y. Purification and characterization of cannabichromenic acid synthase from Cannabis sativa. Phytochemistry 1998; 49(6): 1525-9.
[http://dx.doi.org/10.1016/S0031-9422(98)00278-7] [PMID: 9862135]
[26]
[24] Amouzeshi A, Pourbagher-Shahri AM. Effects of endocannabinoid system, synthetic and nonsynthetic cannabinoid drugs on traumatic brain injury outcome: a narrative review. J Surgery Trauma 2019; 7(1): 3-14.
[27]
2009.
[28]
2008.
[29]
[27] Collin C, Davies P, Mutiboko I, Ratcliffe S. Randomized controlled trial of cannabis‐based medicine in spasticity caused by multiple sclerosis. Eur J Neurol 2007; 14(3): 290-6.
[30]
[28] Aso E, Sánchez-Pla A, Vegas-Lozano E, Maldonado R. Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice. J Alzheimers Dis 2015; 43(3): 977-91.
[31]
2016.
[32]
[30] Chen B, Bromley-Brits K, He G, Cai F, Zhang X, Song WJCAR. Effect of synthetic cannabinoid HU210 on memory deficits and neuropathology in Alzheimer’s disease mouse model. Curr Alzheimer Res 2010; 7(3): 255-61.
[33]
2020.
[34]
[32] Janefjord E, Mååg JL, Harvey BS, Smid SDJC. Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cell Mol Neurobiol 2014; 34(1): 31-42.
[35]
[33] Scuderi C, Steardo L, Esposito GJPr. Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPAR involvement. Phytother Res 2014; 28(7): 1007-13.
[36]
2014.
[37]
2019.
[38]
2016.
[39]
[37] Cai Z, Zhao B. Ratka AJNm. Oxidative stress and β-amyloid protein in Alzheimer’s disease. Redox Biol 2018; 14: 450-64.
[40]
2017.
[41]
[39] Pugazhenthi S, Wang M, Pham S, Sze C-I. Eckman CB. Downregulation of CREB expression in Alzheimer’s brain and in Aβ-treated rat hippocampal neurons. Mol Neurodegener 2011; 6(1): 60.
[42]
[40] Varnum MM, Ikezu TJAiete. The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain. Arch Immunol Ther Exp (Warsz) 2012; 60(4): 251-66.
[43]
2009.
[44]
[42] Perry VH, Cunningham C, Holmes CJNRI. Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 2007; 7(2): 161-7.
[http://dx.doi.org/10.1038/nri2015]
[45]
[43] Ramírez BG, Blázquez C, del Pulgar TG, Guzmán M. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 2005; 25(8): 1904-13.
[46]
[44] Waksman Y, Olson JM, Carlisle SJ. Therapeutics E The central cannabinoid receptor (CB1) mediates inhibition of nitric oxide production by rat microglial cells. J Pharmacol Exp Ther 1999; 288(3): 1357-66.
[47]
[45] Facchinetti F, Del Giudice E, Furegato S, Passarotto M, Leon AJG. Cannabinoids ablate release of TNFα in rat microglial cells stimulated with lipopolysaccharide. Glia 2003; 41(2): 161-8.
[48]
2011.
[49]
2005.
[50]
2009.
[51]
[49] Esposito G, De Filippis D, Maiuri MC, De Stefano D, Carnuccio R. Iuvone TJNl. Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in β-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-κB involvement. Neurosci Lett 2006; 399(1-2): 91-5.
[52]
[50] Iuvone T, Esposito G, Esposito R, Santamaria Rita, Rosa MD, Izzo AA. Neuroprotective effect of cannabidiol, a non‐psychoactive component from Cannabis sativa, on β‐amyloid‐induced toxicity in PC12 cells. J Neurochem 2004; 89(1): 134-41.
[53]
[51] Chauhan V, Chauhan AJP. Oxidative stress in Alzheimer’s disease. Pathophysiology 2006; 13(3): 195-208.
[http://dx.doi.org/10.1016/j.pathophys.2006.05.004]
[54]
2010.
[55]
[53] Agostinho P, Cunha RA, Oliveira C. Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer’s disease. Curr Pharm Des 2010; 16(25): 2766-78.
[56]
[54] Kurata S. Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress. J Biol Chem 2000; 275(31): 23413-6.
[57]
[55] Kefaloyianni E, Gaitanaki C, Isidoros B. ERK1/2 and p38-MAPK signalling pathways, through MSK1, are involved in NF-κB transactivation during oxidative stress in skeletal myoblasts. Cell Signal 2006; 18(12): 2238-51.
[58]
[56] Munoz L, Ammit AJJN. Targeting p38 MAPK pathway for the treatment of Alzheimer’s disease. Neuropharmacology 2010; 58(3): 561-8.
[http://dx.doi.org/10.1016/j.neuropharm.2009.11.010]
[59]
2006.
[60]
[58] Markesbery WR. Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 1997; 23(1): 134-47.
[http://dx.doi.org/10.1016/S0891-5849(96)00629-6] [PMID: 9165306]
[61]
[59] Onoue S, Endo K, Ohshima K, Yajima T, Kashimoto KJP. The neuropeptide PACAP attenuates β-amyloid (1–42)-induced toxicity in PC12 cells. Peptides 2002; 23(8): 1471-8.
[62]
[60] Guan Z-Z, Yu W-F. Nordberg AJNi. Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Neurochem Int 2003; 43(3): 243-9.
[63]
[61] Cash AD, Perry G. Smith MA. Therapeutic potential in Alzheimer disease. Curr Med Chem 2002; 9(17): 1605-10.
[64]
[62] Chen Y, Buck J. Therapeutics E Cannabinoids protect cells from oxidative cell death: a receptor-independent mechanism. J Pharmacol Exp Ther 2000; 293(3): 807-12.
[65]
[63] Hampson A, Grimaldi M, Axelrod J. Wink DJPotNAoS. Cannabidiol and (−) Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA 1998; 95(14): 8268-73.
[66]
2001.
[67]
[65] Esposito G, Izzo AA, Di Rosa M. Iuvone T. Selective cannabinoid CB1 receptor‐mediated inhibition of inducible nitric oxide synthase protein expression in C6 rat glioma cells. J Neurochem 2001; 78(4): 835-41.
[68]
2002.
[69]
[67] Milton NGN. Anandamide and noladin ether prevent neurotoxicity of the human amyloid-β peptide. Neurosci Lett 2002; 332(2): 127-30.
[http://dx.doi.org/10.1016/S0304-3940(02)00936-9]
[70]
[68] Zhou Y, Gopalakrishnan V, Richardson JS. Actions of neurotoxic β‐amyloid on calcium homeostasis and viability of PC12 cells are blocked by antioxidants but not by calcium channel antagonists. J Neurochem 1996; 67(4): 1419-25.
[71]
[69] Nicholson DW. Thornberry NA. Caspases: killer proteases. Trends Biochem Sci 1997; 22(8): 299-306.
[72]
[70] Gschwind M. Huber G. Apoptotic cell death induced by β‐Amyloid1-42 peptide is cell type dependent. J Neurochem 1995; 65(1): 292-300.
[73]
1999.
[74]
2005.
[75]
[73] Camacho IE, Serneels L, Spittaels K, Merchiers P, Dominguez D. De Strooper B. Peroxisome proliferator-activated receptor induces a clearance mechanism for the amyloid-β peptide. J Neurosci 2004; 24(48): 10908-17.
[76]
[74] Heneka MT. Landreth GE. PPARs in the brain. Biochim Biophys Acta 2007; 1771(8): 1031-45.
[77]
[75] O’Sullivan SE, Sun Y, Bennett AJ, Randall MD. Kendall DA. Time-dependent vascular actions of cannabidiol in the rat aorta. Eur J Pharmacol 2009; 612(1-3): 61-8.
[78]
2011.
[79]
[77] Costello DA, O’Leary DM, Herron CEJN. Agonists of peroxisome proliferator-activated receptor- attenuate the Aβ-mediated impairment of LTP in the hippocampus in vitro. Neuropharmacology 2005; 49(3): 359-66.
[http://dx.doi.org/10.1016/j.neuropharm.2005.03.009]
[80]
2011.
[81]
2014.
[82]
[80] Esposito G, De Filippis D, Carnuccio R, Izzo AA, Iuvone T. The marijuana component cannabidiol inhibits β-amyloid-induced tau protein hyperphosphorylation through Wnt/β-catenin pathway rescue in PC12 cells. J Mol Med (Berl) 2006; 84(3): 253-8.
[83]
[81] Inestrosa NC, Godoy JA, Quintanilla RA, Koenig CS, Bronfman M. Peroxisome proliferator-activated receptor is expressed in hippocampal neurons and its activation prevents β-amyloid neurodegeneration: role of Wnt signaling. Exp Cell Res 2005; 304(1): 91-104.
[84]
[82] Vallée A, Lecarpentier Y, Guillevin R. Vallée JN. Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPAR on oxidative stress and neuroinflammation in Alzheimer’s disease. Acta Biochim Biophys Sin (Shanghai) 2017; 49(10): 853-66.
[85]
[83] Boonen RA, van Tijn P, Zivkovic D. Wnt signaling in Alzheimer’s disease: up or down, that is the question. Ageing Res Rev 2009; 8(2): 71-82.
[http://dx.doi.org/10.1016/j.arr.2008.11.003 ] [PMID: 19101658]
[86]
[84] Hernández F, de Barreda EG, Fuster-Matanzo A, Lucas J. GSK3: a possible link between beta amyloid peptide and tau protein. Exp Neurol 2010; 223(2): 322-5.
[87]
[85] Trazzi S, Steger M, Mitrugno VM, Bartesaghi R, Ciani E. CB1 cannabinoid receptors increase neuronal precursor proliferation through AKT/glycogen synthase kinase-3beta/beta-catenin signaling. J Biol Chem 2010; 285(13): 10098-109.
[http://dx.doi.org/10.1074/jbc.M109.043711 ] [PMID: 20083607]
[88]
Khaspekov LG, Brenz Verca MS, Frumkina LE, Hermann H, Marsicano Lutz B. Involvement of brain-derived neurotrophic factor in cannabinoid receptor-dependent protection against excitotoxicity. Eur J Neurosci 2004; 19(7): 1691-8.
[http://dx.doi.org/10.1111/j.1460-9568.2004.03285.x] [PMID: 15078543]
[89]
GSK-3 pathway by cannabinoids in the brain. J Neurochem 2007; 102(4): 1105-14.
[http://dx.doi.org/10.1111/j.1471-4159.2007.04642.x] [PMID: 17484726]
[90]
[87] Hassan S, Eldeeb K, Millns PJ, Bennett AJ, Alexander SP, Kendall DA. Cannabidiol enhances microglial phagocytosis via Transient Receptor Potential (TRP) channel activation. Br J Pharmacol 2014; 171(9): 2426-39.
[http://dx.doi.org/10.1111/bph.12615 ] [PMID: 24641282]
[91]
[88] Khaspekov LG, Brenz Verca MS, Frumkina LE, Hermann H, Marsicano G, Lutz B. Involvement of brain-derived neurotrophic factor in cannabinoid receptor-dependent protection against excitotoxicity. Eur J Neurosci 2004; 19(7): 1691-8.
[http://dx.doi.org/10.1111/j.1460-9568.2004.03285.x] [PMID: 15078543]
[92]
2005.
[93]
2009.
[94]
[91] Scharfman H, Goodman J, Macleod A, Phani S, Antonelli C, Croll S. Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats. Exp Neurol 2005; 192(2): 348-56.
[http://dx.doi.org/10.1016/j.expneurol.2004.11.016] [PMID: 15755552]
[95]
2013.
[96]
[93] Wagner JA, Járai Z, Bátkai S, Kunos G. Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors. Eur J Pharmacol 2001; 423(2-3): 203-10.
[http://dx.doi.org/10.1016/S0014-2999(01)01112-8] [PMID: 11448486]
[97]
[94] Pacher P, Bátkai S, Kunos G. Cardiovascular pharmacology of cannabinoids. Handb Exp Pharmacol 2005; (168): 599-625.
[http://dx.doi.org/10.1007/3-540-26573-2_20 ] [PMID: 16596789]
[98]
2013.
[99]
[96] Maldonado R, Berrendero F, Ozaita A, Robledo P. Neurochemical basis of cannabis addiction. Neuroscience 2011; 5181: 1-17.
[http://dx.doi.org/10.1016/j.neuroscience.2011.02.035]
[100]
[97] Fadda P, Robinson L, Fratta W, Pertwee RG, Riedel G. Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats. Neuropharmacology 2004; 47(8): 1170-9.
[http://dx.doi.org/10.1016/j.neuropharm.2004.08.009] [PMID: 15567426]

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