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Central Nervous System Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

Review Article

The Neuroprotective Properties, Functions, and Roles of Cannabis sativa in Selected Diseases Related to the Nervous System

Author(s): Onesimus Mahdi, Mohamad T.H. Baharuldin, Nurul Huda M. Nor, Samaila M. Chiroma, Saravanan Jagadeesan and Mohamad A.M. Moklas*

Volume 21, Issue 1, 2021

Published on: 27 January, 2021

Page: [20 - 38] Pages: 19

DOI: 10.2174/1871524921666210127110028

Price: $65

Abstract

Background: Cannabis and its extracts are now being explored due to their huge health benefits. Although, the effect they elicit, whether on humans or rodents, may vary based on the age of the animal/subject and or the time in which the extract is administered. However, several debates exist concerning the various medical applications of these compounds. Nonetheless, their applicability as therapeutics should not be clouded based on their perceived negative biological actions.

Methods: Articles from reliable databases such as Science Direct, PubMed, Google Scholar, Scopus, and Ovid were searched. Specific search methods were employed using multiple keywords: ‘‘Medicinal Cannabis; endocannabinoid system; cannabinoids receptors; cannabinoids and cognition; brain disorders; neurodegenerative diseases’’. For the inclusion/exclusion criteria, only relevant articles related to medicinal Cannabis and its various compounds were considered.

Results: The current review highlights the role, effects, and involvement of Cannabis, cannabinoids, and endocannabinoids in preventing selected neurodegenerative diseases and possible amelioration of cognitive impairments. Furthermore, it also focuses on Cannabis utilization in many disease conditions such as Alzheimer’s and Parkinson’s disease among others.

Conclusion: In conclusion, the usage of Cannabis should be further explored as accumulating evidence suggests that it could be effective and somewhat safe, especially when adhered to the recommended dosage. Furthermore, in-depth studies should be conducted in order to unravel the specific mechanism underpinning the involvement of cannabinoids at the cellular level and their therapeutic applications.

Keywords: Medicinal cannabis, endocannabinoid system, cannabinoids receptors, cannabinoids and cognition, brain disorders, neurodegenerative diseases.

Graphical Abstract

[1]
Maurya N, Velmurugan BK. Therapeutic applications of cannabinoids. Chem Biol Interact 2018; 293: 77-88.
[http://dx.doi.org/10.1016/j.cbi.2018.07.018] [PMID: 30040916]
[2]
Pollio A. The name of cannabis: A short guide for nonbotanists. Cannabis Cannabinoid Res 2016; 1(1): 234-8.
[http://dx.doi.org/10.1089/can.2016.0027] [PMID: 28861494]
[3]
Sirikantaramas S, Taura F, Morimoto S, et al. Recent advances in Cannabis sativa research: Biosynthetic studies and its potential in biotechnology. Curr Pharm Biotechnol 2007; 8(4): 237-43.
[http://dx.doi.org/10.2174/138920107781387456] [PMID: 17691992]
[4]
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]
[5]
Andre CM, Hausman J-F, Guerriero G. Cannabis sativa: The plant of the thousand and one molecules. Front Plant Sci 2016; 7: 19.
[http://dx.doi.org/10.3389/fpls.2016.00019] [PMID: 26870049]
[6]
Bernstein N, Gorelick J, Koch S. Interplay between chemistry and morphology in medical cannabis. Ind Crops Prod 2018; 185-94.
[7]
Brand EJ, Zhao Z. Cannabis in Chinese medicine: Are some traditional indications referenced in ancient literature related to cannabinoids? Front Pharmacol 2017; 8: 108.
[http://dx.doi.org/10.3389/fphar.2017.00108] [PMID: 28344554]
[8]
Maroon J, Bost J. Review of the neurological benefits of phytocannabinoids. Surg Neurol Int 2018; 9(1): 91.
[http://dx.doi.org/10.4103/sni.sni_45_18] [PMID: 29770251]
[9]
United Nations. World Drug Report. Drug use and health consequences. 2020.
[10]
Ghosh T, Van Dyke M, Maffey A, Whitley E, Gillim-Ross L, Wolk L. The public health framework of legalized marijuana in Colorado. Am J Public Health 2016; 106(1): 21-7.
[http://dx.doi.org/10.2105/AJPH.2015.302875] [PMID: 26562117]
[11]
Kerai A, Sim TF, Emmerton L. Medical cannabis: A needs analysis for people with epilepsy. Complement Ther Clin Pract 2018; 33: 43-8.
[http://dx.doi.org/10.1016/j.ctcp.2018.08.003] [PMID: 30396625]
[12]
Gonçalves J, Rosado T, Soares S, et al. Cannabis and its secondary metabolites: Their use as therapeutic drugs, toxicological aspects, and analytical determination. Medicines (Basel) 2019; 6(1): 31.
[http://dx.doi.org/10.3390/medicines6010031] [PMID: 30813390]
[13]
Kim YE, Hwang CJ, Lee HP, et al. Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB. Neuropharmacology 2017; 117: 21-32.
[http://dx.doi.org/10.1016/j.neuropharm.2017.01.025] [PMID: 28132781]
[14]
Fairman BJ. Trends in registered medical marijuana participation across 13 US states and District of Columbia. Drug Alcohol Depend 2016; 159: 72-9.
[http://dx.doi.org/10.1016/j.drugalcdep.2015.11.015] [PMID: 26686277]
[15]
Hamilton HA, Brands B, Ialomiteanu AR, Mann RE. Therapeutic use of cannabis: Prevalence and characteristics among adults in Ontario, Canada. Can J Public Health 2017; 108(3): e282-7.
[http://dx.doi.org/10.17269/CJPH.108.6130] [PMID: 28910251]
[16]
Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA 2015; 313(24): 2456-73.
[http://dx.doi.org/10.1001/jama.2015.6358] [PMID: 26103030]
[17]
Lim K, See YM, Lee J. A systematic review of the effectiveness of medical Cannabis for psychiatric, movement and neurodegenerative disorders. Clin Psychopharmacol Neurosci 2017; 15(4): 301-12.
[http://dx.doi.org/10.9758/cpn.2017.15.4.301] [PMID: 29073741]
[18]
Dow-Edwards D, Silva L. Endocannabinoids in brain plasticity: Cortical maturation, HPA axis function and behavior. Brain Res 2017; 1654(Pt B): 157-64.
[http://dx.doi.org/10.1016/j.brainres.2016.08.037] [PMID: 27569586]
[19]
Lu HC, Mackie K. An introduction to the endogenous cannabinoid system. Biol Psychiatry 2016; 79(7): 516-25.
[http://dx.doi.org/10.1016/j.biopsych.2015.07.028] [PMID: 26698193]
[20]
Moreno E, Cavic M, Krivokuca A, Casadó V, Canela E. The endocannabinoid system as a target in cancer diseases: Are we there yet? Front Pharmacol 2019; 10(APR): 339.
[http://dx.doi.org/10.3389/fphar.2019.00339] [PMID: 31024307]
[21]
Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 1988; 34(5): 605-13.
[22]
Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346(6284): 561-4.
[http://dx.doi.org/10.1038/346561a0] [PMID: 2165569]
[23]
Savinainen JR, Saario SM, Laitinen JT. The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoyl-glycerol signalling through cannabinoid receptors. Acta Physiol (Oxf) 2012; 204(2): 267-76.
[http://dx.doi.org/10.1111/j.1748-1716.2011.02280.x] [PMID: 21418147]
[24]
Soderstrom K, Soliman E, Van Dross R. Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-In-dependent Mechanisms. Front Pharmacol 2017; 8: 720.
[http://dx.doi.org/10.3389/fphar.2017.00720] [PMID: 29066974]
[25]
Castillo PE, Younts TJ, Chávez AE, 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]
[26]
Jiang W, Zhang Y, Xiao L, et al. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest 2005; 115(11): 3104-16.
[http://dx.doi.org/10.1172/JCI25509] [PMID: 16224541]
[27]
Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. Int J Mol Sci 2018; 19(3): E833.
[http://dx.doi.org/10.3390/ijms19030833] [PMID: 29533978]
[28]
Scotter EL, Abood ME, Glass M. The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br J Pharmacol 2010; 160(3): 480-98.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00735.x] [PMID: 20590559]
[29]
Bilkei-Gorzo A. The endocannabinoid system in normal and pathological brain ageing. Philos Trans R Soc Lond B Biol Sci 2012; 367(1607): 3326-41.
[http://dx.doi.org/10.1098/rstb.2011.0388] [PMID: 23108550]
[30]
Preedy VR. Handbook of Cannabis and Related Pathologies BT - Biology, Pharmacology, Diagnosis, and Treatment. Elsevier 2016.
[31]
Gould J. The Cannabis crop. Nature 2015; 525(7570): S2-3.
[http://dx.doi.org/10.1038/525S2a] [PMID: 26398736]
[32]
Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86(8): 1646-7.
[http://dx.doi.org/10.1021/ja01062a046]
[33]
El-Alfy AT, Ivey K, Robinson K, et al. Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacol Biochem Behav 2010; 95(4): 434-42.
[http://dx.doi.org/10.1016/j.pbb.2010.03.004] [PMID: 20332000]
[34]
Hanuš LO, Meyer SM, Muñoz E, Taglialatela-Scafati O, Appendino G. Phytocannabinoids: A unified critical inventory. 2016; 33(12)
[35]
Aggarwal SK, Carter GT, Sullivan MD, ZumBrunnen C, Morrill R, Mayer JD. Medicinal use of Cannabis in the United States: historical perspectives, current trends, and future directions. J Opioid Manag 2009; 5(3): 153-68.
[http://dx.doi.org/10.5055/jom.2009.0016] [PMID: 19662925]
[36]
Khan MI, Sobocińska AA, Czarnecka AM, Król M, Botta B, Szczylik C. The therapeutic aspects of the Endocannabinoid System (ECS) for cancer and their development: From nature to laboratory. Curr Pharm Des 2016; 22(12): 1756-66.
[http://dx.doi.org/10.2174/1381612822666151211094901] [PMID: 26654588]
[37]
United Nations. World Drug Report. Analysis of drug markets. 2018.
[38]
Volkow ND, Swanson JM, Evins AE, et al. Effects of Cannabis use on human behavior, including cognition, motivation, and psychosis: A review. JAMA Psychiatry 2016; 73(3): 292-7.
[http://dx.doi.org/10.1001/jamapsychiatry.2015.3278] [PMID: 26842658]
[39]
Levine A, Clemenza K, Rynn M, Lieberman J. Evidence for the risks and consequences of adolescent cannabis exposure. J Am Acad Child Adolesc Psychiatry 2017; 56(3): 214-25.
[http://dx.doi.org/10.1016/j.jaac.2016.12.014] [PMID: 28219487]
[40]
Lepousez G, Nissant A, Lledo P-M. Adult neurogenesis and the future of the rejuvenating brain circuits. Neuron 2015; 86(2): 387-401.
[http://dx.doi.org/10.1016/j.neuron.2015.01.002] [PMID: 25905812]
[41]
Deng W, Aimone JB, Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 2010; 11(5): 339-50.
[http://dx.doi.org/10.1038/nrn2822] [PMID: 20354534]
[42]
Sahay A, Hen R. Adult hippocampal neurogenesis in depression. Nat Neurosci 2007; 10(9): 1110-5.
[http://dx.doi.org/10.1038/nn1969] [PMID: 17726477]
[43]
Kempermann G, Gast D, Kronenberg G, Yamaguchi M, Gage FH. Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 2003; 130(2): 391-9.
[http://dx.doi.org/10.1242/dev.00203] [PMID: 12466205]
[44]
Yau SY, Li A, So KF. Involvement of adult hippocampal neurogenesis in learning and forgetting. Neural Plast 2015; 2015: 717958.
[http://dx.doi.org/10.1155/2015/717958] [PMID: 26380120]
[45]
Spalding KL, Bergmann O, Alkass K, et al. Dynamics of hippocampal neurogenesis in adult humans. Cell 2013; 153(6): 1219-27.
[http://dx.doi.org/10.1016/j.cell.2013.05.002] [PMID: 23746839]
[46]
Dupret D, Revest JM, Koehl M, et al. Spatial relational memory requires hippocampal adult neurogenesis. PLoS One 2008; 3(4): e1959.
[http://dx.doi.org/10.1371/journal.pone.0001959] [PMID: 18509506]
[47]
Shors TJ, Townsend DA, Zhao M, Kozorovitskiy Y, Gould E. Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 2002; 12(5): 578-84.
[http://dx.doi.org/10.1002/hipo.10103] [PMID: 12440573]
[48]
Kozareva DA, Cryan JF, Nolan YM. Born this way: Hippocampal neurogenesis across the lifespan. Aging Cell 2019; 18(5): e13007.
[http://dx.doi.org/10.1111/acel.13007] [PMID: 31298475]
[49]
Jin X. The role of neurogenesis during development and in the adult brain. Eur J Neurosci 2016; 44(6): 2291-9.
[http://dx.doi.org/10.1111/ejn.13251] [PMID: 27062253]
[50]
Semënov MV. Adult hippocampal neurogenesis is a developmental process involved in cognitive development. Front Neurosci 2019; 13: 159.
[http://dx.doi.org/10.3389/fnins.2019.00159] [PMID: 30894797]
[51]
Prenderville JA, Kelly ÁM, Downer EJ. The role of cannabinoids in adult neurogenesis. Br J Pharmacol 2015; 172(16): 3950-63.
[http://dx.doi.org/10.1111/bph.13186] [PMID: 25951750]
[52]
Eriksson PS, Perfilieva E, Björk-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med 1998; 4(11): 1313-7.
[http://dx.doi.org/10.1038/3305] [PMID: 9809557]
[53]
Sanai N, Tramontin AD, Quiñones-Hinojosa A, et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 2004; 427(6976): 740-4.
[http://dx.doi.org/10.1038/nature02301] [PMID: 14973487]
[54]
Ernst A, Alkass K, Bernard S, et al. Neurogenesis in the striatum of the adult human brain. Cell 2014; 156(5): 1072-83.
[http://dx.doi.org/10.1016/j.cell.2014.01.044] [PMID: 24561062]
[55]
Dokter M. von Bohlen und Halbach O. Neurogenesis within the adult hippocampus under physiological conditions and in depression. Neural Regen Res 2012; 7(7): 552-9.
[PMID: 25745444]
[56]
Noonan MA, Bulin S, Fuller DC, Eisch AJ. Reduction of adult hippocampal neurogenesis confers vulnerability in an animal model of cocaine addiction. J Neurosci 2010; 30(1): 304-15.
[http://dx.doi.org/10.1523/JNEUROSCI.4256-09.2010.Reduction]
[57]
Bayer R, Franke H, Ficker C, et al. Alterations of neuronal precursor cells in stages of human adult neurogenesis in heroin addicts. Drug Alcohol Depend 2015; 156: 139-49.
[http://dx.doi.org/10.1016/j.drugalcdep.2015.09.005] [PMID: 26416695]
[58]
Nyffeler M, Yee BK, Feldon J, Knuesel I. Abnormal differentiation of newborn granule cells in age-related working memory impairments. Neurobiol Aging 2010; 31(11): 1956-74.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.10.014] [PMID: 19100662]
[59]
Barnea A, Nottebohm F. Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees. Proc Natl Acad Sci USA 1994; 91(23): 11217-21.
[http://dx.doi.org/10.1073/pnas.91.23.11217] [PMID: 7972037]
[60]
Suliman NA, Taib CNM, Moklas MAM, Basir R. Delta-9-Tetrahydrocannabinol (∆9-THC) induce neurogenesis and improve cognitive performances of male Sprague Dawley rats. Neurotox Res 2018; 33(2): 402-11.
[http://dx.doi.org/10.1007/s12640-017-9806-x] [PMID: 28933048]
[61]
Barnea A, Nottebohm F. Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees. Proc Natl Acad Sci USA 1994; 91(23): 11217-21.
[http://dx.doi.org/10.1073/pnas.91.23.11217]
[62]
Bilkei-Gorzo A, Albayram O, Draffehn A, et al. A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat Med 2017; 23(6): 782-7.
[http://dx.doi.org/10.1038/nm.4311] [PMID: 28481360]
[63]
Steel RWJ, Miller JH, Sim DA, Day DJ. Delta-9-tetrahydro-cannabinol disrupts hippocampal neuroplasticity and neurogenesis in trained, but not untrained adolescent Sprague-Dawley rats. Brain Res 2014; 1548: 12-9.
[http://dx.doi.org/10.1016/j.brainres.2013.12.034] [PMID: 24398456]
[64]
Niaz K, Khan F, Maqbool F, et al. Endo-cannabinoids system and the toxicity of cannabinoids with a biotechnological approach. EXCLI J 2017; 16: 688-711.
[PMID: 28827985]
[65]
D’Addario C, Di Bonaventura MV, Pucci M, et al. Endocannabinoid signaling and food addiction. Neurosci Biobehav Rev 2014; 47: 203-24.
[http://dx.doi.org/10.1016/j.neubiorev.2014.08.008] [PMID: 25173635]
[66]
Bonnet AE, Marchalant Y. Potential therapeutical contributions of the endocannabinoid system towards aging and Alzheimer’s disease. Aging Dis 2015; 6(5): 400-5.
[http://dx.doi.org/10.14336/AD.2015.0617] [PMID: 26425394]
[67]
Gowran A, Noonan J, Campbell VA. The multiplicity of action of cannabinoids: implications for treating neurodegeneration. CNS Neurosci Ther 2011; 17(6): 637-44.
[http://dx.doi.org/10.1111/j.1755-5949.2010.00195.x] [PMID: 20875047]
[68]
Nuutinen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. Eur J Med Chem 2018; 157: 198-228.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.076] [PMID: 30096653]
[69]
Rapino C, Tortolani D, Scipioni L, Maccarrone M. Neuroprotection by (endo)cannabinoids in glaucoma and retinal neurodegenerative diseases. Curr Neuropharmacol 2018; 16(7): 959-70.
[http://dx.doi.org/10.2174/1570159X15666170724104305] [PMID: 28738764]
[70]
Serviddio G, Romano AD, Cassano T, Bellanti F, Altomare E, Vendemiale G. Principles and therapeutic relevance for targeting mitochondria in aging and neurodegenerative diseases. Curr Pharm Des 2011; 17(20): 2036-55.
[http://dx.doi.org/10.1016/j.intimp.2016.05.002]
[71]
Rodrigues RS, Lourenço DM, Paulo SL, et al. Cannabinoid actions on neural stem cells: Implications for pathophysiology. 2019; 24(7): 1350.
[72]
Mulder J, Zilberter M, Pasquaré SJ, et al. Molecular reorganization of endocannabinoid signalling in Alzheimer’s disease. Brain 2011; 134(Pt 4): 1041-60.
[http://dx.doi.org/10.1093/brain/awr046] [PMID: 21459826]
[73]
Basavarajappa BS, Shivakumar M, Joshi V, Subbanna S. Endocannabinoid system in neurodegenerative disorders. J Neurochem 2017; 142(5): 624-48.
[http://dx.doi.org/10.1111/jnc.14098] [PMID: 28608560]
[74]
Schatz AR, Lee M, Condie RB, Pulaski JT, Kaminski NE. Cannabinoid receptors CB1 and CB2: A characterization of expression and adenylate cyclase modulation within the immune system. Toxicol Appl Pharmacol 1997; 142(2): 278-87.
[http://dx.doi.org/10.1006/taap.1996.8034] [PMID: 9070350]
[75]
Rom S, Persidsky Y. Cannabinoid receptor 2: Potential role in immunomodulation and neuroinflammation. J Neuroimmune Pharmacol 2013; 8(3): 608-20.
[http://dx.doi.org/10.1007/s11481-013-9445-9] [PMID: 23471521]
[76]
Ashton CH, Moore PB. Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatr Scand 2011; 124(4): 250-61.
[http://dx.doi.org/10.1111/j.1600-0447.2011.01687.x] [PMID: 21916860]
[77]
Howlett AC. The cannabinoid receptors. Prostaglandins Other Lipid Mediat 2002; 68-69: 619-31.
[http://dx.doi.org/10.1016/S0090-6980(02)00060-6] [PMID: 12432948]
[78]
Pellati F, Borgonetti V, Brighenti V, Biagi M, Benvenuti S, Corsi L. Cannabis sativa L. and nonpsychoactive cannabinoids: Their chemistry and role against oxidative stress, inflammation, and cancer. BioMed Res Int 2018; 2018: 1691428.
[http://dx.doi.org/10.1155/2018/1691428] [PMID: 30627539]
[79]
Presburger G, Robinson JK. Spatial signal detection in rats is differentially disrupted by delta-9-tetrahydrocannabinol, scopolamine, and MK-801. Behav Brain Res 1999; 99(1): 27-34.
[http://dx.doi.org/10.1016/S0166-4328(98)00065-5] [PMID: 10512569]
[80]
Calignano A, Kátona I, Désarnaud F, et al. Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature 2000; 408(6808): 96-101.
[http://dx.doi.org/10.1038/35040576] [PMID: 11081515]
[81]
Mechoulam R, Parker L. The endocannabinoid system and the brain. Annu Rev Psychol 2013; 64: 21-47.
[http://dx.doi.org/10.1146/annurev-psych-113011-143739]]
[82]
Hua T, Vemuri K, Nikas SP, et al. Crystal structures of agonist-bound human cannabinoid receptor CB1. Nature 2017; 547(7664): 468-71.
[http://dx.doi.org/10.1038/nature23272] [PMID: 28678776]
[83]
Mecha M, Carrillo-Salinas FJ, Feliú A, Mestre L, Guaza C. Microglia activation states and cannabinoid system: Therapeutic implications. Pharmacol Ther 2016; 166: 40-55.
[http://dx.doi.org/10.1016/j.pharmthera.2016.06.011] [PMID: 27373505]
[84]
Turcotte C, Blanchet MR, Laviolette M, Flamand N. The CB2 receptor and its role as a regulator of inflammation. Cell Mol Life Sci 2016; 73(23): 4449-70.
[http://dx.doi.org/10.1007/s00018-016-2300-4] [PMID: 27402121]
[85]
Calignano A, La Rana G, Giuffrida A, Piomelli D. Control of pain initiation by endogenous cannabinoids. Nature 1998; 394(6690): 277-81.
[http://dx.doi.org/10.1038/28393] [PMID: 9685157]
[86]
Maresz K, Carrier EJ, Ponomarev ED, Hillard CJ, Dittel BN. Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 2005; 95(2): 437-45.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03380.x] [PMID: 16086683]
[87]
Ehrhart J, Obregon D, Mori T, et al. Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation. J Neuroinflammation 2005; 2: 29.
[http://dx.doi.org/10.1186/1742-2094-2-29] [PMID: 16343349]
[88]
Kong W, Li H, Tuma RF, Ganea D. Selective CB2 receptor activation ameliorates EAE by reducing Th17 differentiation and immune cell accumulation in the CNS. Cell Immunol 2014; 287(1): 1-17.
[http://dx.doi.org/10.1016/j.cellimm.2013.11.002] [PMID: 24342422]
[89]
Benito C, Tolón RM, Pazos MR, Núñez E, Castillo AI, Romero J. Cannabinoid CB2 receptors in human brain inflammation. Br J Pharmacol 2008; 153(2): 277-85.
[http://dx.doi.org/10.1038/sj.bjp.0707505] [PMID: 17934510]
[90]
Cabral GA, Griffin-Thomas L. Emerging role of the CB2 cannabinoid receptor in immune regulation and therapeutic prospects. Expert Rev Mol Med 2009; 11(804): 1-31.
[http://dx.doi.org/10.1017/S1462399409000957] [PMID: 19152719]
[91]
Vendel E, de Lange ECM. Functions of the CB1 and CB 2 receptors in neuroprotection at the level of the blood-brain barrier. Neuromolecular Med 2014; 16(3): 620-42.
[http://dx.doi.org/10.1007/s12017-014-8314-x] [PMID: 24929655]
[92]
Bedse G, Romano A, Lavecchia AM, Cassano T, Gaetani S. The role of endocannabinoid signaling in the molecular mechanisms of neurodegeneration in Alzheimer’s disease. J Alzheimers Dis 2015; 43(4): 1115-36.
[http://dx.doi.org/10.3233/JAD-141635] [PMID: 25147120]
[93]
Di Marzo V, Piscitelli F. The Endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics 2015; 12(4): 692-8.
[http://dx.doi.org/10.1007/s13311-015-0374-6] [PMID: 26271952]
[94]
de Lago E, Fernández-Ruiz J. Cannabinoids and neuroprotection in motor-related disorders. CNS Neurol Disord Drug Targets 2007; 6(6): 377-87.
[http://dx.doi.org/10.2174/187152707783399210] [PMID: 18220777]
[95]
Manuel I, González de San Román E, Giralt MT, Ferrer I, Rodríguez-Puertas R. Type-1 cannabinoid receptor activity during Alzheimer’s disease progression. J Alzheimers Dis 2014; 42(3): 761-6.
[http://dx.doi.org/10.3233/JAD-140492] [PMID: 24946872]
[96]
Rodríguez-Cueto C, Benito C, Fernández-Ruiz J, Romero J, Hernández-Gálvez M, Gómez-Ruiz M. Changes in CB(1) and CB(2) receptors in the post-mortem cerebellum of humans affected by spinocerebellar ataxias. Br J Pharmacol 2014; 171(6): 1472-89.
[http://dx.doi.org/10.1111/bph.12283] [PMID: 23808969]
[97]
Solas M, Francis PT, Franco R, Ramirez MJ. CB2 receptor and amyloid pathology in frontal cortex of Alzheimer’s disease patients. Neurobiol Aging 2013; 34(3): 805-8.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.06.005] [PMID: 22763024]
[98]
Ramírez BG, Blázquez C, Gómez del Pulgar T, Guzmán M, de Ceballos ML. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 2005; 25(8): 1904-13.
[http://dx.doi.org/10.1523/JNEUROSCI.4540-04.2005] [PMID: 15728830]
[99]
Kalifa S, Polston EK, Allard JS, Manaye KF. Distribution patterns of cannabinoid CB1 receptors in the hippocampus of APPswe/PS1ΔE9 double transgenic mice. Brain Res 2011; 1376: 94-100.
[http://dx.doi.org/10.1016/j.brainres.2010.12.061] [PMID: 21192920]
[100]
Fernández-Ruiz J, Moro MA, Martínez-Orgado J. Cannabinoids in neurodegenerative disorders and stroke/brain trauma: From preclinical models to clinical applications. Neurotherapeutics 2015; 12(4): 793-806.
[http://dx.doi.org/10.1007/s13311-015-0381-7] [PMID: 26260390]
[101]
Kumar K, Kumar A, Keegan RM, Deshmukh R. Recent advances in the neurobiology and neuropharmacology of Alzheimer’s disease. Biomed Pharmacother 2018; 98: 297-307.
[http://dx.doi.org/10.1016/j.biopha.2017.12.053] [PMID: 29274586]
[102]
Hayakawa K, Mishima K, Nozako M, et al. Repeated treatment with cannabidiol but not Δ9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance. Neuropharmacology 2007; 52(4): 1079-87.
[http://dx.doi.org/10.1016/j.neuropharm.2006.11.005] [PMID: 17320118]
[103]
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.
[http://dx.doi.org/10.1007/s00109-005-0025-1] [PMID: 16389547]
[104]
Aso E, Ferrer I. Cannabinoids for treatment of alzheimer’s disease: Moving toward the clinic. Front Pharmacol 2014; 5: 1-11.
[105]
Hampson AJ, Grimaldi M. Cannabinoid receptor activation and elevated cyclic AMP reduce glutamate neurotoxicity. Eur J Neurosci 2001; 13(8): 1529-36.
[http://dx.doi.org/10.1046/j.0953-816x.2001.01536.x] [PMID: 11328347]
[106]
Sohre S, Moosmann B. The pathological hallmarks of Alzheimer’s disease derive from compensatory responses to NMDA receptor insufficiency. bioRxiv 2018; Available from: https://www.biorxiv.org/content/10.1101/41856 6v1.full.pdf
[107]
Anstey KJ, Cherbuin N, Herath PM, et al. A self-report risk index to predict occurrence of dementia in three independent cohorts of older adults: the ANU-ADRI. PLoS One 2014; 9(1): e86141.
[http://dx.doi.org/10.1371/journal.pone.0086141] [PMID: 24465922]
[108]
Alzheimer’s & Dementia, “Basics of Alzheimer’S Disease”. Alzheimer's Association Annual Report 2015; available from: https://www.alz.org/media/documents/annual-report-2015.pdf
[109]
Aso E, Andrés-Benito P, Carmona M, Maldonado R, Ferrer I. Cannabinoid receptor 2 participates in amyloid-β processing in a mouse model of Alzheimer’s disease but plays a minor role in the therapeutic properties of a Cannabis-based medicine. J Alzheimers Dis 2016; 51(2): 489-500.
[http://dx.doi.org/10.3233/JAD-150913] [PMID: 26890764]
[110]
Westlake TM, Howlett AC, Bonner TI, Matsuda LA, Herkenham M. Cannabinoid receptor binding and messenger RNA expression in human brain: An in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer’s brains. Neuroscience 1994; 63(3): 637-52.
[http://dx.doi.org/10.1016/0306-4522(94)90511-8] [PMID: 7898667]
[111]
Grünblatt E, Bartl J, Zehetmayer S, et al. Gene expression as peripheral biomarkers for sporadic Alzheimer’s disease. J Alzheimers Dis 2009; 16(3): 627-34.
[http://dx.doi.org/10.3233/JAD-2009-0996] [PMID: 19276557]
[112]
Shen M, Thayer SA. Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity. Mol Pharmacol 1998; 54(3): 459-62.
[http://dx.doi.org/10.1124/mol.54.3.459] [PMID: 9730904]
[113]
Bedse G, Romano A, Cianci S, et al. Altered expression of the CB1 cannabinoid receptor in the triple transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 2014; 40(3): 701-12.
[http://dx.doi.org/10.3233/JAD-131910] [PMID: 24496074]
[114]
Nagayama T, et al. Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures. J Neurosci 1999; 19(8): 2987-95.
[http://dx.doi.org/10.1523/JNEUROSCI.19-08-02987.1999]
[115]
Panikashvili D, Simeonidou C, Ben-Shabat S, et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001; 413(6855): 527-31.
[http://dx.doi.org/10.1038/35097089] [PMID: 11586361]
[116]
Kendall DA, Yudowski GA. 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]
[117]
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): 977-91.
[http://dx.doi.org/10.3233/JAD-141014] [PMID: 25125475]
[118]
Chen R, et al. Erratum: Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling (Cell (2013) 155 (1154-1165)). Cell 2014; 156(3): 618.
[http://dx.doi.org/10.1016/j.cell.2014.01.034] [PMID: 22541432]
[119]
Walther S, Mahlberg R, Eichmann U, Kunz D. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology (Berl) 2006; 185(4): 524-8.
[http://dx.doi.org/10.1007/s00213-006-0343-1] [PMID: 16521031]
[120]
Aso E, Juvés S, Maldonado R, Ferrer I. CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 mice. J Alzheimers Dis 2013; 35(4): 847-58.
[http://dx.doi.org/10.3233/JAD-130137] [PMID: 23515018]
[121]
Ahmed A, van der Marck MA, 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]
[122]
Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 1997; 12(9): 913-9.
[http://dx.doi.org/10.1002/(SICI)1099-1166(199709)12:9<913:AID-GPS663>3.0.CO;2-D] [PMID: 9309469]
[123]
Woodward MR, Harper DG, Stolyar A, Forester BP, Ellison JM. Dronabinol for the treatment of agitation and aggressive behavior in acutely hospitalized severely demented patients with noncognitive behavioral symptoms. Am J Geriatr Psychiatry 2014; 22(4): 415-9.
[http://dx.doi.org/10.1016/j.jagp.2012.11.022] [PMID: 23597932]
[124]
Cabral GA, Jamerson M. Marijuana use and brain immune mechanisms. Int Rev Neurobiol 2014; 118: 199-230.
[125]
Iuvone T, Esposito G, Esposito R, Santamaria R, Di Rosa M, 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.
[http://dx.doi.org/10.1111/j.1471-4159.2003.02327.x] [PMID: 15030397]
[126]
Janefjord E, Mååg JLV, Harvey BS, Smid SD. Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cell Mol Neurobiol 2014; 34(1): 31-42.
[http://dx.doi.org/10.1007/s10571-013-9984-x] [PMID: 24030360]
[127]
Martín-Moreno AM, Brera B, Spuch C, et al. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice. J Neuroinflammation 2012; 9(1): 8.
[http://dx.doi.org/10.1186/1742-2094-9-8] [PMID: 22248049]
[128]
Esposito G, De Filippis D, Steardo L, et al. CB1 receptor selective activation inhibits β-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons. Neurosci Lett 2006; 404(3): 342-6.
[http://dx.doi.org/10.1016/j.neulet.2006.06.012] [PMID: 16837132]
[129]
Esposito G, Scuderi C, Valenza M, et al. Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement. PLoS One 2011; 6(12): e28668.
[http://dx.doi.org/10.1371/journal.pone.0028668] [PMID: 22163051]
[130]
Martín-Moreno AM, Reigada D, Ramírez BG, et al. Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer’s disease. Mol Pharmacol 2011; 79(6): 964-73.
[http://dx.doi.org/10.1124/mol.111.071290] [PMID: 21350020]
[131]
Eubanks LM, Rogers CJ, Beuscher AE IV, et al. A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Mol Pharm 2006; 3(6): 773-7.
[http://dx.doi.org/10.1021/mp060066m] [PMID: 17140265]
[132]
Currais A, Quehenberger OM, Armando A, Daugherty D, Maher P, Schubert D. Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. NPJ Aging Mech Dis 2016; 2: 16012.
[http://dx.doi.org/10.1038/npjamd.2016.12] [PMID: 28721267]
[133]
Casarejos MJ, Perucho J, Gomez A, et al. Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy. J Alzheimers Dis 2013; 35(3): 525-39.
[http://dx.doi.org/10.3233/JAD-130050] [PMID: 23478312]
[134]
de Lau LML, Breteler MMB. Epidemiology of Parkinson’s disease. Lancet Neurol 2006; 5(6): 525-35.
[http://dx.doi.org/10.1016/S1474-4422(06)70471-9] [PMID: 16713924]
[135]
Magrinelli F, Picelli A, Tocco P, et al. Pathophysiology of motor dysfunction in Parkinson’s disease as the rationale for drug treatment and rehabilitation. Park Dis 2016; 2016: 9832839.
[136]
Bartels AL, Leenders KL. Parkinson’s disease: The syndrome, the pathogenesis and pathophysiology. Cortex 2009; 45(8): 915-21.
[137]
Bugalho P, Lampreia T, Miguel R, Mendonça MD, Caetano A, Barbosa R. Non-motor symptoms in Portuguese Parkinson’s disease patients: Correlation and impact on quality of life and activities of daily living. Sci Rep 2016; 6: 32267.
[http://dx.doi.org/10.1038/srep32267] [PMID: 27573215]
[138]
Trapani A, De Giglio E, Cafagna D, et al. Characterization and evaluation of chitosan nanoparticles for dopamine brain delivery. Int J Pharm 2011; 419(1-2): 296-307.
[http://dx.doi.org/10.1016/j.ijpharm.2011.07.036] [PMID: 21821107]
[139]
Denora N, Cassano T, Laquintana V, et al. Novel codrugs with GABAergic activity for dopamine delivery in the brain. Int J Pharm 2012; 437(1-2): 221-31.
[http://dx.doi.org/10.1016/j.ijpharm.2012.08.023] [PMID: 22940209]
[140]
Di Gioia S, Trapani A, Mandracchia D, et al. Intranasal delivery of dopamine to the striatum using glycol chitosan/sulfobutylether-β-cyclodextrin based nanoparticles. Eur J Pharm Biopharm 2015; 94: 180-93.
[http://dx.doi.org/10.1016/j.ejpb.2015.05.019] [PMID: 26032293]
[141]
Palomo-Garo C, Gómez-Gálvez Y, García C, Fernández-Ruiz J. Targeting the cannabinoid CB2 receptor to attenuate the progression of motor deficits in LRRK2-transgenic mice. Pharmacol Res 2016; 110: 181-92.
[http://dx.doi.org/10.1016/j.phrs.2016.04.004] [PMID: 27063942]
[142]
Price DA, Martinez AA, Seillier A, et al. WIN55,212-2, a cannabinoid receptor agonist, protects against nigrostriatal cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Eur J Neurosci 2009; 29(11): 2177-86.
[http://dx.doi.org/10.1111/j.1460-9568.2009.06764.x] [PMID: 19490092]
[143]
Molina-Holgado F, Molina-Holgado E, Guaza C, Rothwell NJ. Role of CB1 and CB2 receptors in the inhibitory effects of cannabinoids on lipopolysaccharide-induced nitric oxide release in astrocyte cultures. J Neurosci Res 2002; 67(6): 829-36.
[http://dx.doi.org/10.1002/jnr.10165] [PMID: 11891798]
[144]
Molina-Holgado F, Pinteaux E, Moore JD, et al. Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia. J Neurosci 2003; 23(16): 6470-4.
[http://dx.doi.org/10.1523/JNEUROSCI.23-16-06470.2003] [PMID: 12878687]
[145]
Lotan I, Treves TA, 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): 41-4.
[http://dx.doi.org/10.1097/WNF.0000000000000016] [PMID: 24614667]
[146]
van Vliet SAM, Vanwersch RAP, Jongsma MJ, Olivier B, Philippens IH. Therapeutic effects of Δ9-THC and modafinil in a marmoset Parkinson model. Eur Neuropsychopharmacol 2008; 18(5): 383-9.
[http://dx.doi.org/10.1016/j.euroneuro.2007.11.003] [PMID: 18222654]
[147]
García C, Palomo-Garo C, García-Arencibia M, Ramos J, Pertwee R, Fernández-Ruiz J. Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson’s disease. Br J Pharmacol 2011; 163(7): 1495-506.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01278.x] [PMID: 21323909]
[148]
Lastres-Becker I, Molina-Holgado F, Ramos JA, Mechoulam R, Fernández-Ruiz J. Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: Relevance to Parkinson’s disease. Neurobiol Dis 2005; 19(1-2): 96-107.
[http://dx.doi.org/10.1016/j.nbd.2004.11.009] [PMID: 15837565]
[149]
Fernandez-Espejo E, Caraballo I, Rodriguez de Fonseca F, et al. Experimental parkinsonism alters anandamide precursor synthesis, and functional deficits are improved by AM404: A modulator of endocannabinoid function. Neuropsychopharmacology 2004; 29(6): 1134-42.
[http://dx.doi.org/10.1038/sj.npp.1300407] [PMID: 15010694]
[150]
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): 1102-6.
[http://dx.doi.org/10.1002/mds.20111] [PMID: 15372606]
[151]
Sieradzan KA, Fox SH, Hill M, Dick JPR, Crossman AR, Brotchie JM. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: A pilot study. Neurology 2001; 57(11): 2108-11.
[http://dx.doi.org/10.1212/WNL.57.11.2108] [PMID: 11739835]
[152]
Suryadevara U, Bruijnzeel DM, Nuthi M, Jagnarine DA, Tandon R, Bruijnzeel AW. Pros and cons of medical cannabis use by People with chronic brain disorders. Curr Neuropharmacol 2017; 15(6): 800-14.
[http://dx.doi.org/10.2174/1570159X14666161101095325] [PMID: 27804883]
[153]
Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med 2017; 377(2): 162-72.
[http://dx.doi.org/10.1056/NEJMra1603471] [PMID: 28700839]
[154]
Lomen-Hoerth C, Murphy J, Langmore S, Kramer JH, Olney RK, Miller B. Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 2003; 60(7): 1094-7.
[http://dx.doi.org/10.1212/01.WNL.0000055861.95202.8D] [PMID: 12682312]
[155]
Ringholz GM, Appel SH, Bradshaw M, et al. Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology 2005; 65(4): 586-90.
[http://dx.doi.org/10.1212/01.wnl.0000172911.39167.b6] [PMID: 16116120]
[156]
Logroscino G, Traynor BJ, Hardiman O, et al. Incidence of amyotrophic lateral sclerosis in Europe. J Neurol 2011; 81(4): 385-90.
[http://dx.doi.org/10.1136/jnnp.2009.183525.Incidence]
[157]
Cleveland DW, Rothstein JD. From Charcot to Lou Gehrig: Deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2001; 2(11): 806-19.
[http://dx.doi.org/10.1038/35097565] [PMID: 11715057]
[158]
Wosiski-Kuhn M, Lyon MS, Caress J, et al. Inflammation, immunity, and amyotrophic lateral sclerosis: Etiology and pathology. Muscle Nerve 2018; 59(1): 23-33.
[PMID: 29979478]
[159]
Witting A, Weydt P, Hong S, Kliot M, Moller T, Stella N. Endocannabinoids accumulate in spinal cord of SOD1 G93A transgenic mice. J Neurochem 2004; 89(6): 1555-7.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02544.x] [PMID: 15189359]
[160]
Shoemaker JL, Seely KA, Reed RL, Crow JP, Prather PL. 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]
[161]
Espejo-Porras F, Piscitelli F, Verde R, et al. Changes in the endocannabinoid signaling system in CNS structures of TDP-43 transgenic mice: Relevance for a neuroprotective therapy in TDP-43-related disorders. J Neuroimmune Pharmacol 2015; 10(2): 233-44.
[http://dx.doi.org/10.1007/s11481-015-9602-4] [PMID: 25819934]
[162]
Tsao W, Jeong YH, Lin S, et al. Rodent models of TDP-43: recent advances. Brain Res 2012; 1462: 26-39.
[http://dx.doi.org/10.1016/j.brainres.2012.04.031] [PMID: 22608070]
[163]
Yang C, Wang H, Qiao T, et al. Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 2014; 111(12): E1121-9.
[http://dx.doi.org/10.1073/pnas.1322641111] [PMID: 24616503]
[164]
Abood ME, Rizvi G, Sallapudi N, McAllister SD. Activation of the CB1 cannabinoid receptor protects cultured mouse spinal neurons against excitotoxicity. Neurosci Lett 2001; 309(3): 197-201.
[http://dx.doi.org/10.1016/S0304-3940(01)02065-1] [PMID: 11514075]
[165]
Chiurchiù V, Leuti A, Maccarrone M. cannabinoid signaling and neuroinflammatory diseases: A melting pot for the regulation of brain immune responses. J Neuroimmune Pharmacol 2015; 10(2): 268-80.
[http://dx.doi.org/10.1007/s11481-015-9584-2] [PMID: 25601726]
[166]
Giacoppo S, Mazzon E. Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis? Neural Regen Res 2016; 11(12): 1896-9.
[http://dx.doi.org/10.4103/1673-5374.197125] [PMID: 28197175]
[167]
Raman C, McAllister SD, Rizvi G, Patel SG, Moore DH, Abood ME. Amyotrophic lateral sclerosis: Delayed disease progression in mice by treatment with a cannabinoid. Amyotroph Lateral Scler Other Motor Neuron Disord 2004; 5(1): 33-9.
[http://dx.doi.org/10.1080/14660820310016813] [PMID: 15204022]
[168]
Lisboa SF, Gomes FV, Guimaraes FS, Campos AC. Microglial cells as a link between cannabinoids and the immune hypothesis of psychiatric disorders. Front Neurol 2016; 7: 5.
[http://dx.doi.org/10.3389/fneur.2016.00005] [PMID: 26858686]
[169]
Carter GT, Abood ME, Aggarwal SK, Weiss MD. Cannabis and amyotrophic lateral sclerosis: Hypothetical and practical applications, and a call for clinical trials. Am J Hosp Palliat Care 2010; 27(5): 347-56.
[http://dx.doi.org/10.1177/1049909110369531] [PMID: 20439484]
[170]
Amtmann D, Weydt P, Johnson KL, Jensen MP, Carter GT. Survey of Cannabis use in patients with amyotrophic lateral sclerosis. Am J Hosp Palliat Care 2004; 21(2): 95-104.
[http://dx.doi.org/10.1177/104990910402100206] [PMID: 15055508]
[171]
Cui SQ, Wang Q, Zheng Y, et al. Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning. Braz J Med Biol Res 2015; 48(6): 515-22.
[http://dx.doi.org/10.1590/1414-431x20144250] [PMID: 25831201]
[172]
Rabkin JG, Albert SM, Del Bene ML, et al. Prevalence of depressive disorders and change over time in late-stage ALS. Neurology 2005; 65(1): 62-7.
[http://dx.doi.org/10.1212/01.wnl.0000167187.14501.0c] [PMID: 16009886]
[173]
Lutz B, Marsicano G, Maldonado R, Hillard CJ. The endocannabinoid system in guarding against fear, anxiety and stress. Nat Rev Neurosci 2015; 16(12): 705-18.
[http://dx.doi.org/10.1038/nrn4036] [PMID: 26585799]
[174]
Kobelt G, Thompson A, Berg J, Gannedahl M, Eriksson J. MSCOI Study Group. European Multiple Sclerosis Platform. New insights into the burden and costs of multiple sclerosis in Europe. Mult Scler 2017; 23(8): 1123-36.
[http://dx.doi.org/10.1177/1352458517694432] [PMID: 28273775]
[175]
Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 2015; 14(2): 183-93.
[http://dx.doi.org/10.1016/S1474-4422(14)70256-X] [PMID: 25772897]
[176]
Nielsen S, Germanos R, Weier M, et al. The use of cannabis and cannabinoids in treating symptoms of multiple sclerosis: A systematic review of reviews. Curr Neurol Neurosci Rep 2018; 18(2): 8.
[http://dx.doi.org/10.1007/s11910-018-0814-x] [PMID: 29442178]
[177]
Goldenberg MM. Multiple sclerosis review. Pharmacol Ther 2012; 37(3): 175-84.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC335 1877/
[178]
Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists: Pharmacological strategies and therapeutic possibilities. Philos Trans R Soc Lond B Biol Sci 2012; 367(1607): 3353-63.
[http://dx.doi.org/10.1098/rstb.2011.0381] [PMID: 23108552]
[179]
Ungerleider JT, Andyrsiak T, Fairbanks L, Ellison GW, Myers LW. Delta-9-THC in the treatment of spasticity associated with multiple sclerosis. Adv Alcohol Subst Abuse 1987; 7(1): 39-50.
[http://dx.doi.org/10.1300/J251v07n01_04] [PMID: 2831701]
[180]
Meinck H-M, Schönle PW, Conrad B. Effect of cannabinoids on spasticity and ataxia in multiple sclerosis. J Neurol 1989; 236(2): 120-2.
[http://dx.doi.org/10.1007/BF00314410] [PMID: 2709054]
[181]
Consroe P, Musty R, Rein J, Tillery W, Pertwee R. The perceived effects of smoked Cannabis on patients with multiple sclerosis. Eur Neurol 1997; 38(1): 44-8.
[http://dx.doi.org/10.1159/000112901] [PMID: 9252798]
[182]
Koppel BS, Brust JC, Fife T, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014; 82(17): 1556-63.
[http://dx.doi.org/10.1212/WNL.0000000000000363] [PMID: 24778283]
[183]
Keating GM. Delta-9-tetrahydrocannabinol/cannabidiol oromucosal spray (Sativex®): A review in multiple sclerosis-related spasticity. Drugs 2017; 77(5): 563-74.
[http://dx.doi.org/10.1007/s40265-017-0720-6] [PMID: 28293911]
[184]
Baker D, Pryce G, Giovannoni G, Thompson AJ. The therapeutic potential of Cannabis. Lancet Neurol 2003; 2(5): 291-8.
[http://dx.doi.org/10.1016/S1474-4422(03)00381-8] [PMID: 12849183]
[185]
Pryce G, Baker D. Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors. Br J Pharmacol 2007; 150(4): 519-25.
[http://dx.doi.org/10.1038/sj.bjp.0707003] [PMID: 17220914]
[186]
Docagne F, Muñetón V, Clemente D, et al. Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation. Mol Cell Neurosci 2007; 34(4): 551-61.
[http://dx.doi.org/10.1016/j.mcn.2006.12.005] [PMID: 17229577]
[187]
Croxford JL. Therapeutic potential of cannabinoids in CNS disease. CNS Drugs 2003; 17(3): 179-202.
[http://dx.doi.org/10.2165/00023210-200317030-00004] [PMID: 12617697]
[188]
Corey-Bloom J, Wolfson T, Gamst A, et al. Smoked Cannabis for spasticity in multiple sclerosis: A randomized, placebo-controlled trial. CMAJ 2012; 184(10): 1143-50.
[http://dx.doi.org/10.1503/cmaj.110837] [PMID: 22586334]
[189]
Greenberg HS, Werness SAS, Pugh JE, Andrus RO, Anderson DJ, Domino EF. Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers. Clin Pharmacol Ther 1994; 55(3): 324-8.
[http://dx.doi.org/10.1038/clpt.1994.33] [PMID: 8143398]
[190]
Lorente Fernández L, Monte Boquet E, Pérez-Miralles F, et al. Clinical experiences with cannabinoids in spasticity management in multiple sclerosis. Neurologia 2014; 29(5): 257-60.
[http://dx.doi.org/10.1016/j.nrleng.2013.06.007] [PMID: 24035293]
[191]
Zajicek J, Fox P, Sanders H, et al. UK MS Research Group. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): Multicentre randomised placebo-controlled trial. Lancet 2003; 362(9395): 1517-26.
[http://dx.doi.org/10.1016/S0140-6736(03)14738-1] [PMID: 14615106]
[192]
Kavia RBC, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler 2010; 16(11): 1349-59.
[http://dx.doi.org/10.1177/1352458510378020] [PMID: 20829244]
[193]
Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991; 41(5): 685-91.
[http://dx.doi.org/10.1212/WNL.41.5.685] [PMID: 2027484]
[194]
Minden SL, Feinstein A, Kalb RC, et al. Guideline Development Subcommittee of the American Academy of Neurology. Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014; 82(2): 174-81.
[http://dx.doi.org/10.1212/WNL.0000000000000013] [PMID: 24376275]
[195]
Pavisian B, MacIntosh BJ, Szilagyi G, Staines RW, O’Connor P, Feinstein A. Effects of Cannabis on cognition in patients with MS: A psychometric and MRI study. Neurology 2014; 82(21): 1879-87.
[http://dx.doi.org/10.1212/WNL.0000000000000446] [PMID: 24789863]
[196]
Honarmand K, Tierney MC, Psych C, O’Connor P, Feinstein A. Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurology 2011; 76(13): 1153-60.
[197]
Romero K, Pavisian B, Staines WR, Feinstein A. Multiple sclerosis, cannabis, and cognition: A structural MRI study. Neuroimage Clin 2015; 8: 140-7.
[http://dx.doi.org/10.1016/j.nicl.2015.04.006] [PMID: 26106538]
[198]
American Psychatric Association Diagnostic and Statistical Manual of Mental Disorders. 2013.
[199]
Ashton CH, Moore PB, Gallagher P, Young AH. Cannabinoids in bipolar affective disorder: A review and discussion of their therapeutic potential. J Psychopharmacol 2005; 19(3): 293-300.
[http://dx.doi.org/10.1177/0269881105051541] [PMID: 15888515]
[200]
Marrie RA, Reingold S, Cohen J, et al. The incidence and prevalence of psychiatric disorders in multiple sclerosis: A systematic review. Mult Scler 2015; 21(3): 305-17.
[http://dx.doi.org/10.1177/1352458514564487] [PMID: 25583845]
[201]
Silveira C, Guedes R, Maia D, Curral R, Coelho R. Neuropsychiatric symptoms of multiple sclerosis: State of the art. Psychiatry Investig 2019; 16(12): 877-88.
[http://dx.doi.org/10.30773/pi.2019.0106] [PMID: 31805761]
[202]
de G. R Henquet C, Krabbendam L. Cannabis use and expression of mania in the general population. J Affect Disord 2006; 95(1-3): 103-10.
[203]
Kvitland LR, Melle I, Aminoff SR, et al. Continued cannabis use at one year follow up is associated with elevated mood and lower global functioning in bipolar I disorder. BMC Psychiatry 2015; 15(11): 11.
[http://dx.doi.org/10.1186/s12888-015-0389-x] [PMID: 25651990]
[204]
Iseger TA, Bossong MG. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr Res 2015; 162(1-3): 153-61.
[http://dx.doi.org/10.1016/j.schres.2015.01.033] [PMID: 25667194]
[205]
Pfister EL, DiNardo N, Mondo E, et al. Artificial miRNAs reduce human mutant huntingtin throughout the striatum in a transgenic sheep model of Huntington’s disease. Hum Gene Ther 2018; 29(6): 663-73.
[http://dx.doi.org/10.1089/hum.2017.199] [PMID: 29207890]
[206]
Zuccato C, Valenza M, Cattaneo E. Molecular mechanisms and potential therapeutical targets in Huntington’s disease. Physiol Rev 2010; 90(3): 905-81.
[http://dx.doi.org/10.1152/physrev.00041.2009] [PMID: 20664076]
[207]
Burgunder J-M, Guttman M, Perlman S, Goodman N, van Kammen DP, Goodman L. An international survey-based algorithm for the pharmacologic treatment of chorea in Huntington’s disease. PLoS Curr 2011; 3.
[208]
Coppen EM, Roos RAC. Current pharmacological approaches to reduce chorea in Huntington’s disease. Drugs 2017; 77(1): 29-46.
[http://dx.doi.org/10.1007/s40265-016-0670-4] [PMID: 27988871]
[209]
Bisogno T, Oddi S, Piccoli A, Fazio D, Maccarrone M. Type-2 cannabinoid receptors in neurodegeneration. Pharmacol Res 2016; 111: 721-30.
[http://dx.doi.org/10.1016/j.phrs.2016.07.021] [PMID: 27450295]
[210]
Valdeolivas S, Navarrete C, Cantarero I, Bellido ML, Muñoz E, Sagredo O. Neuroprotective properties of cannabigerol in Huntington’s disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice. Neurotherapeutics 2015; 12(1): 185-99.
[http://dx.doi.org/10.1007/s13311-014-0304-z] [PMID: 25252936]
[211]
Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 2012; 133(1): 79-97.
[http://dx.doi.org/10.1016/j.pharmthera.2011.09.002] [PMID: 21924288]
[212]
Valdeolivas S, Satta V, Pertwee RG, Fernández-Ruiz J, Sagredo O. Sativex-like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington’s disease: role of CB1 and CB2 receptors. ACS Chem Neurosci 2012; 3(5): 400-6.
[http://dx.doi.org/10.1021/cn200114w] [PMID: 22860209]
[213]
Blázquez C, Chiarlone A, Sagredo O, et al. Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington’s disease. Brain 2011; 134(Pt 1): 119-36.
[http://dx.doi.org/10.1093/brain/awq278] [PMID: 20929960]
[214]
Palazuelos J, Aguado T, Pazos MR, et al. Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain 2009; 132(Pt 11): 3152-64.
[http://dx.doi.org/10.1093/brain/awp239] [PMID: 19805493]
[215]
Pintor A, Tebano MT, Martire A, et al. The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum. Neuropharmacology 2006; 51(5): 1004-12.
[http://dx.doi.org/10.1016/j.neuropharm.2006.06.013] [PMID: 16895732]
[216]
Dowie MJ, Howard ML, Nicholson LFB, Faull RLM, Hannan AJ, Glass M. Behavioural and molecular consequences of chronic cannabinoid treatment in Huntington’s disease transgenic mice. Neuroscience 2010; 170(1): 324-36.
[http://dx.doi.org/10.1016/j.neuroscience.2010.06.056] [PMID: 20600638]
[217]
O’Shaughnessy WB. On the Preparations of the Indian Hemp, or Gunjah: Cannabis indica, their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. BMJ 1843; 1-5: 363-9.
[218]
Fiest KM, Sauro KM, Wiebe S, et al. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies. Neurology 2017; 88(3): 296-303.
[http://dx.doi.org/10.1212/WNL.0000000000003509] [PMID: 27986877]
[219]
Devinsky O, Patel AD, Cross JH, et al. GWPCARE3 Study Group. Effect of cannabidiol on drop seizures in the lennox–gastaut syndrome. N Engl J Med 2018; 378(20): 1888-97.
[http://dx.doi.org/10.1056/NEJMoa1714631] [PMID: 29768152]
[220]
Devinsky O, Nabbout R, Miller I, et al. Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial. Epilepsia 2019; 60(2): 294-302.
[http://dx.doi.org/10.1111/epi.14628] [PMID: 30582156]
[221]
Szaflarski JP, Bebin EM, Comi AM, et al. CBD EAP study group. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. Epilepsia 2018; 59(8): 1540-8.
[http://dx.doi.org/10.1111/epi.14477] [PMID: 29998598]
[222]
Thiele EA, Marsh ED, French JA, et al. GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018; 391(10125): 1085-96.
[http://dx.doi.org/10.1016/S0140-6736(18)30136-3] [PMID: 29395273]
[223]
Brodie MJ, Barry SJE, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology 2012; 78(20): 1548-54.
[http://dx.doi.org/10.1212/WNL.0b013e3182563b19] [PMID: 22573629]
[224]
Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: An open-label interventional trial. Lancet Neurol 2016; 15(3): 270-8.
[http://dx.doi.org/10.1016/S1474-4422(15)00379-8] [PMID: 26724101]
[225]
Soltesz I, Alger BE, Kano M, et al. Weeding out bad waves: Towards selective cannabinoid circuit control in epilepsy. Nat Rev Neurosci 2015; 16(5): 264-77.
[http://dx.doi.org/10.1038/nrn3937] [PMID: 25891509]
[226]
Sugaya Y, Kano M. Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling. Cell Mol Life Sci 2018; 75(15): 2793-811.
[http://dx.doi.org/10.1007/s00018-018-2834-8] [PMID: 29737364]
[227]
Lupica CR, Hu Y, Devinsky O, Hoffman AF. Cannabinoids as hippocampal network administrators. Neuropharmacology 2017; 124: 25-37.
[http://dx.doi.org/10.1016/j.neuropharm.2017.04.003] [PMID: 28392266]
[228]
Huntsman JR, Tang-Wai R. Cannabis for pediatric and adult epilepsy. Recent Adv Cannabinoid Res 2019; 2019: 202-19.
[229]
Feeney DM. Marihuana and epilepsy: Paradoxical anticonvulsant and convulsant effects. Pergamon Press Ltd. 1978; pp. 22-3.
[230]
Ligresti A, De Petrocellis L, Di Marzo V. From phytocannabinoids to cannabinoid receptors and endocannabinoids: Pleiotropic physiological and pathological roles through complex pharmacology. Physiol Rev 2016; 96(4): 1593-659.
[http://dx.doi.org/10.1152/physrev.00002.2016] [PMID: 27630175]
[231]
Consroe P, Benedito MAC, Leite JR, Carlini EA, Mechoulam R. Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice. Eur J Pharmacol 1982; 83(3-4): 293-8.
[http://dx.doi.org/10.1016/0014-2999(82)90264-3] [PMID: 6129147]
[232]
Tsuboi K, Uyama T, Okamoto Y, Ueda N. Endocannabinoids and related N-acylethanolamines: Biological activities and metabolism. Inflamm Regen 2018; 38(1): 28.
[http://dx.doi.org/10.1186/s41232-018-0086-5] [PMID: 30288203]
[233]
Jones NA, Glyn SE, Akiyama S, et al. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure 2012; 21(5): 344-52.
[http://dx.doi.org/10.1016/j.seizure.2012.03.001] [PMID: 22520455]
[234]
Jones NA, Hill AJ, Smith I, et al. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J Pharmacol Exp Ther 2010; 332(2): 569-77.
[http://dx.doi.org/10.1124/jpet.109.159145] [PMID: 19906779]
[235]
Pitman A, Suleman S, Hyde N, Hodgkiss A. Depression and anxiety in patients with cancer. BMJ 2018; 361: k1415.
[http://dx.doi.org/10.1136/bmj.k1415] [PMID: 29695476]
[236]
Kramer JL. Medical marijuana for cancer. CA Cancer J Clin 2015; 65(2): 109-22.
[http://dx.doi.org/10.3322/caac.21260] [PMID: 25503438]
[237]
Pergam SA, Woodfield MC, Lee CM, et al. Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use. Cancer 2017; 123(22): 4488-97.
[http://dx.doi.org/10.1002/cncr.30879] [PMID: 28944449]
[238]
Gruber SA, Sagar KA, Dahlgren MK, et al. The grass might be greener: Medical marijuana patients exhibit altered brain activity and improved executive function after 3 months of treatment. Front Pharmacol 2018; 8: 983.
[http://dx.doi.org/10.3389/fphar.2017.00983] [PMID: 29387010]
[239]
Rocha FCM, Dos Santos Júnior JG, Stefano SC, da Silveira DX. Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas. J Neurooncol 2014; 116(1): 11-24.
[http://dx.doi.org/10.1007/s11060-013-1277-1] [PMID: 24142199]
[240]
Tervo-Clemmens B, Simmonds D, Calabro FJ, Day NL, Richardson GA, Luna B. Adolescent Cannabis use and brain systems supporting adult working memory encoding, maintenance, and retrieval. Neuroimage 2018; 169: 496-509.
[http://dx.doi.org/10.1016/j.neuroimage.2017.12.041]

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