Abstract
Three prevalent neurodegenerative diseases, Parkinson’s, Alzheimer’s, and Huntington’s are in need of symptomatic relief of slowing disease progression or both. This chapter focuses on the potential of cannabinoids to afford neuroprotection, i.e. avoid or retard neuronal death. The neuroprotective potential of cannabinoids is known from the work in animal models and is mediated by the two cannabinoid receptors (CB1/CB2) and eventually, by their heteromers, GPR55, orphan receptors (GPR3/GPR6/GPR12/GPR18), or PPARγ. Now, there is the time to translate the findings into patients. The chapter takes primarily into account advances since 2016 and addresses the issue of proving neuroprotection in humans. One recent discovery is the existence of activated microglia with neuroprotective phenotype; cannabinoids are good candidates to skew phenotype, especially via glial CB2 receptors (CB2R), whose targeting has, a priori, less side effects those targeting the CBs1 receptor (CB1R), which are expressed in both neurons and glia. The fact that a cannabis extract (SativexTM) is approved for human therapy, such that cannabis use will likely be legalized in many countries and different possibilities that cannabinoid pharmacology suggests a successful route of cannabinoids (natural or synthetic) all the way to be approved and used in the treatment of neurodegeneration.
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Abbreviations
- AD:
-
Alzheimer’s disease
- CB1R:
-
cannabinoid CB1 receptor
- CB2R:
-
cannabinoid CB2 receptor
- CBD:
-
cannabidiol
- CNS:
-
central nervous system
- FAAH:
-
fatty acid amide hydrolase
- GPCR:
-
G-protein-coupled receptor
- GPRn:
-
orphan GPCR number “n”
- MDS-UPDRS:
-
Scale for non-motor symptoms in parkinsonian patients
- PD:
-
Parkinson’s disease
- PET:
-
positron emission tomography
- PPARγ:
-
peroxisome proliferator-activated receptor γ
- THC:
-
Δ9-tetrahydrocannabinol
References
Aso E, Andrés-Benito P, Ferrer I (2016) Delineating the efficacy of a cannabis-based medicine at advanced stages of dementia in a murine model. J Alzheimers Dis 54:903–912. https://doi.org/10.3233/JAD-160533
Attili B, Celen S, Ahamed M, Koole M, Van Den Haute C, Vanduffel W, Bormans G (2019) Preclinical evaluation of [18 F]MA3: a CB2 receptor agonist radiotracer for PET. Br J Pharmacol 176:1481–1491. https://doi.org/10.1111/bph.14564
Bagher AM, Laprairie RB, Kelly MEM, Denovan-Wright EM (2018) Methods to quantify cell signaling and GPCR receptor ligand bias: characterization of drugs that target the Endocannabinoid receptors in Huntington’s disease. In: Methods in molecular biology. Humana Press, Clifton, N.J, pp 549–571. https://doi.org/10.1007/978-1-4939-7825-0_25
Balenga NA, Martínez-Pinilla E, Kargl J, Schröder R, Peinhaupt M, Platzer W, Bálint Z, Zamarbide M, Dopeso-Reyes IG, Ricobaraza A et al (2014) Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signalling. Br J Pharmacol 171:1–64. https://doi.org/10.1111/bph.12850
Benito C, Núñez E, Tolón RM, Carrier EJ, Rábano A, Hillard CJ, Romero J (2003) Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains. J Neurosci 23:11136–11141
Çakır M, Tekin S, Doğanyiğit Z, Erden Y, Soytürk M, Çiğremiş Y, Sandal S (2019) Cannabinoid type 2 receptor agonist JWH-133, attenuates Okadaic acid induced spatial memory impairment and neurodegeneration in rats. Life Sci 217:25–33. https://doi.org/10.1016/j.lfs.2018.11.058
Calabrese EJ, Baldwin LA (2002) Defining hormesis. Hum Exp Toxicol 21:91–97. https://doi.org/10.1191/0960327102ht217oa
Calabrese EJ, Rubio-Casillas A (2018) Biphasic effects of THC in memory and cognition. Eur J Clin Investig 48:e12920. https://doi.org/10.1111/eci.12920
Callén L, Moreno E, Barroso-Chinea P, Moreno-Delgado D, Cortés A, Mallol J, Casadó V, Lanciego JL, Franco R, Lluis C et al (2012) Cannabinoid receptors CB1 and CB2 form functional heteromers in brain. J Biol Chem 287:20851–20865. https://doi.org/10.1074/jbc.M111.335273
Carai MAM, Colombo G, Maccioni P, Gessa GL (2006) Efficacy of rimonabant and other cannabinoid CB1 receptor antagonists in reducing food intake and body weight: preclinical and clinical data. CNS Drug Rev 12:91–99. https://doi.org/10.1111/j.1527-3458.2006.00091.x
Celorrio M, Fernández-Suárez D, Rojo-Bustamante E, Echeverry-Alzate V, Ramírez MJ, Hillard CJ, López-Moreno JA, Maldonado R, Oyarzábal J, Franco R et al (2016) Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinson’s disease. Brain Behav Immun 57:94–105. https://doi.org/10.1016/j.bbi.2016.06.010
Celorrio M, Rojo-Bustamante E, Fernández-Suárez D, Sáez E, Estella-Hermoso de Mendoza A, Müller CE, Ramírez MJ, Oyarzábal J, Franco R, Aymerich MS (2017) GPR55: a therapeutic target for Parkinson’s disease? Neuropharmacology 125:319–332. https://doi.org/10.1016/j.neuropharm.2017.08.017
Cilia R (2018) Molecular imaging of the cannabinoid system in idiopathic Parkinson’s disease. Int Rev Neurobiol 141:305–345. https://doi.org/10.1016/bs.irn.2018.08.004
Díaz-Alonso J, Paraíso-Luna J, Navarrete C, del Río C, Cantarero I, Palomares B, Aguareles J, Fernández-Ruiz J, Bellido ML, Pollastro F et al (2016) VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease. Sci Rep 6:29789. https://doi.org/10.1038/srep29789
Fernández-Ruiz J, Romero J, Ramos JA (2015) Endocannabinoids and neurodegenerative disorders: Parkinson’s disease, Huntington’s chorea, Alzheimer’s disease, and others. Handb Exp Pharmacol 231:233–259. https://doi.org/10.1007/978-3-319-20825-1_8
Fraguas-Sánchez AI, Torres-Suárez AI (2018) Medical use of cannabinoids. Drugs 78:1665–1703. https://doi.org/10.1007/s40265-018-0996-1
Franco R, Aguinaga D, Jiménez J, Lillo J, Martínez-Pinilla E, Navarro G (2018) Biased receptor functionality versus biased agonism in G-protein-coupled receptors. Biomol Concepts 9:143–154. https://doi.org/10.1515/bmc-2018-0013
Franco R, Cedazo-Minguez A (2014) Successful therapies for Alzheimer’s disease: why so many in animal models and none in humans? Front Pharmacol 5:146. https://doi.org/10.3389/fphar.2014.00146
Franco R, Fernández-Suárez D (2015) Alternatively activated microglia and macrophages in the central nervous system. Prog Neurobiol 131:65–86. https://doi.org/10.1016/j.pneurobio.2015.05.003
Franco R, Martínez-Pinilla E, Navarro G (2019) Why have transgenic rodent models failed to successfully mimic Alzheimer’s disease. How can we develop effective drugs without them? Expert Opin Drug Discovery 14:327–330. https://doi.org/10.1080/17460441.2019.1581169
Franco R, Navarro G (2018) Adenosine A2A receptor antagonists in neurodegenerative diseases: huge potential and huge challenges. Front Psych 9:1–5. https://doi.org/10.3389/fpsyt.2018.00068
Gajardo-Gómez R, Labra VC, Maturana CJ, Shoji KF, Santibañez CA, Sáez JC, Giaume C, Orellana JA (2017) Cannabinoids prevent the amyloid β-induced activation of astroglial hemichannels: a neuroprotective mechanism. Glia 65:122–137. https://doi.org/10.1002/glia.23080
Gaoni Y, Mechoulam R (1964) Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 86:1646–1647. https://doi.org/10.1021/ja01062a046
García C, Gómez-Cañas M, Burgaz S, Palomares B, Gómez-Gálvez Y, Palomo-Garo C, Campo S, Ferrer-Hernández J, Pavicic C, Navarrete C et al (2018) Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation-driven neuronal deterioration in experimental Parkinson’s disease: possible involvement of different binding sites at the PPARγ receptor. J Neuroinflammation 15:19. https://doi.org/10.1186/s12974-018-1060-5
García-Gutiérrez MS, Navarrete F, Navarro G, Reyes-Resina I, Franco R, Lanciego JL, Giner S, Manzanares J (2018) Alterations in gene and Protein expression of cannabinoid CB2 and GPR55 receptors in the dorsolateral prefrontal cortex of suicide victims. Neurotherapeutics 15:796–806. https://doi.org/10.1007/s13311-018-0610-y
Gómez-Gálvez Y, Palomo-Garo C, Fernández-Ruiz J, García C (2016) Potential of the cannabinoid CB2 receptor as a pharmacological target against inflammation in Parkinson’s disease. Prog Neuro-Psychopharmacol Biol Psychiatry 64:200–208. https://doi.org/10.1016/j.pnpbp.2015.03.017
Gómez-Ruiz M, Rodríguez-Cueto C, Luna-Piñel E, Hernández-Gálvez M, Fernández-Ruiz J (2019) Endocannabinoid system in Spinocerebellar ataxia Type-3 and other autosomal-dominant cerebellar ataxias: potential role in pathogenesis and expected relevance as Neuroprotective targets. Front Mol Neurosci 12:94. https://doi.org/10.3389/fnmol.2019.00094
Goncalves MB, Suetterlin P, Yip P, Molina-Holgado F, Walker DJ, Oudin MJ, Zentar MP, Pollard S, Yáñez-Muñoz RJ, Williams G et al (2008) A diacylglycerol lipase-CB2 cannabinoid pathway regulates adult subventricular zone neurogenesis in an age-dependent manner. Mol Cell Neurosci 38:526–536. https://doi.org/10.1016/j.mcn.2008.05.001
González-Naranjo P, Pérez-Macias N, Pérez C, Roca C, Vaca G, Girón R, Sánchez-Robles E, Martín-Fontelles MI, de Ceballos ML, Martin-Requero A et al (2019) Indazolylketones as new multitarget cannabinoid drugs. Eur J Med Chem 166:90–107. https://doi.org/10.1016/j.ejmech.2019.01.030
Janssen B, Vugts D, Windhorst A, Mach R (2018) PET imaging of microglial activation—beyond targeting TSPO. Molecules 23:607. https://doi.org/10.3390/molecules23030607
Kallinen A, Boyd R, Lane S, Bhalla R, Mardon K, Stimson DHR, Werry EL, Fulton R, Connor M, Kassiou M (2019) Synthesis and in vitro evaluation of fluorine-18 benzimidazole sulfones as CB2 PET-radioligands. Org Biomol Chem 17:5086–5098. https://doi.org/10.1039/c9ob00656g
Kargl J, Balenga N, Parzmair GP, Brown AJ, Heinemann A, Waldhoer M (2012) The cannabinoid receptor CB1 modulates the signaling properties of the lysophosphatidylinositol receptor GPR55. J Biol Chem 287:44234–44248. https://doi.org/10.1074/jbc.M112.364109
Katz I, Katz D, Shoenfeld Y, Porat-Katz BS (2017) Clinical evidence for utilizing cannabinoids in the elderly. Isr Med Assoc J IMAJ 19:71–75
Kaur RJ, Singh S, Sidhu P, Sharma PK (2018) TGN-1412 and BIA-2474 trials with tragic end: lessons learnt to make clinical trials safer. Rev Recent Clin Trials 13:252–256. https://doi.org/10.2174/1574887113666180521093529
Kho DT, Glass M, Graham ES (2017) Is the cannabinoid CB 2 receptor a major regulator of the Neuroinflammatory Axis of the neurovascular unit in humans? Adv Pharmacol 80:367–396. https://doi.org/10.1016/bs.apha.2017.03.009
Laprairie RB, Bagher AM, Kelly MEM, Denovan-Wright EM (2015) Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol 172:4790–4805. https://doi.org/10.1111/bph.13250
Laprairie RB, Bagher AM, Kelly MEM, Denovan-Wright EM (2016) Biased type 1 cannabinoid receptor signaling influences neuronal viability in a cell culture model of Huntington disease. Mol Pharmacol 89:364–375. https://doi.org/10.1124/mol.115.101980
Laun AS, Shrader SH, Brown KJ, Song Z-H (2019) GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and interaction with cannabidiol. Acta Pharmacol Sin 40:300–308. https://doi.org/10.1038/s41401-018-0031-9
Laun AS, Song Z-H (2017) GPR3 and GPR6, novel molecular targets for cannabidiol. Biochem Biophys Res Commun 490:17–21. https://doi.org/10.1016/j.bbrc.2017.05.165
Libro R, Diomede F, Scionti D, Piattelli A, Grassi G, Pollastro F, Bramanti P, Mazzon E, Trubiani O (2016) Cannabidiol modulates the expression of Alzheimer’s disease-related genes in Mesenchymal stem cells. Int J Mol Sci 18:26. https://doi.org/10.3390/ijms18010026
Lim K, See YM, Lee J (2017) A systematic review of the effectiveness of medical cannabis for psychiatric, movement and neurodegenerative disorders. Clin Psychopharmacol Neurosci 15:301–312. https://doi.org/10.9758/cpn.2017.15.4.301
Liu CS, Chau SA, Ruthirakuhan M, Lanctôt KL, Herrmann N (2015) Cannabinoids for the treatment of agitation and aggression in Alzheimer’s disease. CNS Drugs 29:615–623. https://doi.org/10.1007/s40263-015-0270-y
Llorente-Ovejero A, Manuel I, Lombardero L, Giralt MT, Ledent C, Giménez-Llort L, Rodríguez-Puertas R (2018) Endocannabinoid and muscarinic signaling crosstalk in the 3xTg-AD mouse model of Alzheimer’s disease. J Alzheimers Dis 64:117–136. https://doi.org/10.3233/JAD-180137
López-Sendón Moreno JL, García Caldentey J, Trigo Cubillo P, Ruiz Romero C, García Ribas G, Alonso Arias MAA, García de Yébenes MJ, Tolón RM, Galve-Roperh I, Sagredo O et al (2016) A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease. J Neurol 263:1390–1400. https://doi.org/10.1007/s00415-016-8145-9
MacCallum CA, Russo EB (2018) Practical considerations in medical cannabis administration and dosing. Eur J Intern Med 49:12–19. https://doi.org/10.1016/j.ejim.2018.01.004
Maccarrone M, Maldonado R, Casas M, Henze T, Centonze D (2017) Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others? Expert Rev Clin Pharmacol 10:443–455. https://doi.org/10.1080/17512433.2017.1292849
Madeo G, Schirinzi T, Maltese M, Martella G, Rapino C, Fezza F, Mastrangelo N, Bonsi P, Maccarrone M, Pisani A (2016) Dopamine-dependent CB 1 receptor dysfunction at corticostriatal synapses in homozygous PINK1 knockout mice. Neuropharmacology 101:460–470. https://doi.org/10.1016/j.neuropharm.2015.10.021
Mannucci C, Navarra M, Calapai F, Spagnolo EV, Busardò FP, Cas RD, Ippolito FM, Calapai G (2017) Neurological aspects of medical use of Cannabidiol. CNS Neurol Disord Drug Targets 16:541–553. https://doi.org/10.2174/1871527316666170413114210
Martínez-Pinilla E, Reyes-Resina I, Oñatibia-Astibia A, Zamarbide M, Ricobaraza A, Navarro G, Moreno E, Dopeso-Reyes IGG, Sierra S, Rico AJJ et al (2014) CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum. Exp Neurol 261:44–52. https://doi.org/10.1016/j.expneurol.2014.06.017
Martínez-Pinilla E, Varani K, Reyes-Resina I, Angelats E, Vincenzi F, Ferreiro-Vera C, Oyarzabal J, Canela EI, Lanciego JL, Nadal X et al (2017) Binding and signaling studies disclose a potential allosteric site for cannabidiol in cannabinoid CB2receptors. Front Pharmacol 8:744. https://doi.org/10.3389/fphar.2017.00744
McCarthy RC, Lu D-Y, Alkhateeb A, Gardeck AM, Lee C-H, Wessling-Resnick M (2016) Characterization of a novel adult murine immortalized microglial cell line and its activation by amyloid-beta. J Neuroinflammation 13:21. https://doi.org/10.1186/s12974-016-0484-z
Mechoulam R, Parker LA (2013) The Endocannabinoid system and the brain. Annu Rev Psychol 64:21–47. https://doi.org/10.1146/annurev-psych-113011-143739
Mechoulam R, Shani A, Edery H, Grunfeld Y (1970) Chemical basis of hashish activity. Science (New York, NY) 169:611–612. https://doi.org/10.1126/science.169.3945.611
Morales P, Isawi I, Reggio PH (2018) Towards a better understanding of the cannabinoid-related orphan receptors GPR3, GPR6, and GPR12. Drug Metab Rev 50:74–93. https://doi.org/10.1080/03602532.2018.1428616
Nadal X, del Río C, Casano S, Palomares B, Ferreiro-Vera C, Navarrete C, Sánchez-Carnerero C, Cantarero I, Bellido ML, Meyer S et al (2017) Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity. Br J Pharmacol 174:4263–4276. https://doi.org/10.1111/bph.14019
Navarro G, Borroto-Escuela D, Angelats E, Etayo I, Reyes-Resina I, Pulido-Salgado M, Rodríguez-Pérez A, Canela E, Saura J, Lanciego JL et al (2018) Receptor-heteromer mediated regulation of endocannabinoid signaling in activated microglia. Role of CB1 and CB2 receptors and relevance for Alzheimer’s disease and levodopa-induced dyskinesia. Brain Behav Immun 67:139–151. https://doi.org/10.1016/j.bbi.2017.08.015
Navarro G, Reyes-Resina I, Rivas-Santisteban R, Sánchez de Medina V, Morales P, Casano S, Ferreiro-Vera C, Lillo A, Aguinaga D, Jagerovic N et al (2018) Cannabidiol skews biased agonism at cannabinoid CB1 and CB2 receptors with smaller effect in CB1-CB2 heteroreceptor complexes. Biochem Pharmacol 157:148–158. https://doi.org/10.1016/j.bcp.2018.08.046
Navarro G, Varani K, Reyes-Resina I, Sánchez de Medina V, Rivas-Santisteban R, Sánchez-Carnerero Callado C, Vincenzi F, Casano S, Ferreiro-Vera C, Canela EI et al (2018) Cannabigerol action at cannabinoid CB1 and CB2 receptors and at CB1-CB2 Heteroreceptor complexes. Front Pharmacol 9:632. https://doi.org/10.3389/fphar.2018.00632
Navarro-Dorado J, Villalba N, Prieto D, Brera B, Martín-Moreno AM, Tejerina T, de Ceballos ML (2016) Vascular dysfunction in a transgenic model of Alzheimer’s disease: effects of CB1R and CB2R cannabinoid agonists. Front Neurosci 10:422. https://doi.org/10.3389/fnins.2016.00422
Noel C (2017) Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders. Ment Health Clin 7:29–38. https://doi.org/10.9740/mhc.2017.01.029
Ojha S, Javed H, Azimullah S, Haque ME (2016) β-Caryophyllene, a phytocannabinoid attenuates oxidative stress, neuroinflammation, glial activation, and salvages dopaminergic neurons in a rat model of Parkinson disease. Mol Cell Biochem 418:59–70. https://doi.org/10.1007/s11010-016-2733-y
Palomo-Garo C, Gómez-Gálvez Y, García C, Fernández-Ruiz J (2016) Targeting the cannabinoid CB 2 receptor to attenuate the progression of motor deficits in LRRK2-transgenic mice. Pharmacol Res 110:181–192. https://doi.org/10.1016/j.phrs.2016.04.004
Pascual AC, Gaveglio VL, Giusto NM, Pasquaré SJ (2017) 2-Arachidonoylglycerol metabolism is differently modulated by oligomeric and fibrillar conformations of amyloid beta in synaptic terminals. Neuroscience 362:168–180. https://doi.org/10.1016/j.neuroscience.2017.08.042
Peball M, Werkmann M, Ellmerer P, Stolz R, Valent D, Knaus H-G, Ulmer H, Djamshidian A, Poewe W, Seppi K (2019) Nabilone for non-motor symptoms of Parkinson’s disease: a randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study (the NMS-nab study). J Neural Transm 126:1061–1072. https://doi.org/10.1007/s00702-019-02021-z
Qureshi AR, Rana AQ, Malik SH, Rizvi SFH, Akhter S, Vannabouathong C, Sarfraz Z, Rana R (2018) Comprehensive examination of therapies for pain in Parkinson’s disease: a systematic review and meta-analysis. Neuroepidemiology 51:190–206. https://doi.org/10.1159/000492221
Reyes-Resina I, Navarro G, Aguinaga D, Canela EI, Schoeder CT, Załuski M, Kieć-Kononowicz K, Saura CA, Müller CE, Franco R (2018) Molecular and functional interaction between GPR18 and cannabinoid CB2G-protein-coupled receptors. Relevance in neurodegenerative diseases. Biochem Pharmacol 157:169–179. https://doi.org/10.1016/j.bcp.2018.06.001
Rojo-Bustamante E, Abellanas MA, Clavero P, Thiolat ML, Qin L, Luquin MR, Bezard E, Aymerich MS (2018) The expression of cannabinoid type 1 receptor and 2-arachidonoyl glycerol synthesizing/degrading enzymes is altered in basal ganglia during the active phase of levodopa-induced dyskinesia. Neurobiol Dis 118:64–75. https://doi.org/10.1016/j.nbd.2018.06.019
Ruiz-Calvo A, Bajo-Grañeras R, Maroto IB, Zian D, Grabner GF, García-Taboada E, Resel E, Zechner R, Zimmermann R, Ortega-Gutiérrez S et al (2019) Astroglial monoacylglycerol lipase controls mutant huntingtin-induced damage of striatal neurons. Neuropharmacology 150:134–144. https://doi.org/10.1016/j.neuropharm.2019.03.027
Ruthirakuhan MT, Herrmann N, Gallagher D, Andreazza AC, Kiss A, Verhoeff NPLG, Black SE, Lanctôt KL (2019) Investigating the safety and efficacy of nabilone for the treatment of agitation in patients with moderate-to-severe Alzheimer’s disease: study protocol for a cross-over randomized controlled trial. Contemporary Clin Trial Comm 15:100385. https://doi.org/10.1016/j.conctc.2019.100385
Ruthirakuhan M, Lanctôt KL, Vieira D, Herrmann N (2019) Natural and synthetic cannabinoids for agitation and aggression in Alzheimer’s disease. J Clin Psychiatry 80:18r12617. https://doi.org/10.4088/JCP.18r12617
Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson N-O, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101. https://doi.org/10.1038/sj.bjp.0707460
Saft C, von Hein SM, Lücke T, Thiels C, Peball M, Djamshidian A, Heim B, Seppi K (2018) Cannabinoids for treatment of dystonia in Huntington’s disease. J Huntington’s Disease 7:167–173. https://doi.org/10.3233/JHD-170283
Sam AH, Salem V, Ghatei MA (2011) Rimonabant: from RIO to ban. J Obes 2011:432607. https://doi.org/10.1155/2011/432607
Schubert D, Kepchia D, Liang Z, Dargusch R, Goldberg J, Maher P (2019) Efficacy of cannabinoids in a pre-clinical drug-screening platform for Alzheimer’s disease. Mol Neurobiol 56(11):7719–7730. https://doi.org/10.1007/s12035-019-1637-8
Sierra S, Luquin N, Rico AJ, Gómez-Bautista V, Roda E, Dopeso-Reyes IG, Vázquez A, Martínez-Pinilla E, Labandeira-García JL, Franco R et al (2015) Detection of cannabinoid receptors CB1 and CB2 within basal ganglia output neurons in macaques: changes following experimental parkinsonism. Brain Struct Funct 220:2721–2738. https://doi.org/10.1007/s00429-014-0823-8
Simard O, Niavarani SR, Gaudreault V, Boissonneault G (2017) Torsional stress promotes trinucleotidic expansion in spermatids. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 800–802:1–7. https://doi.org/10.1016/j.mrfmmm.2017.04.001
Spinelli F, Capparelli E, Abate C, Colabufo NA, Contino M (2017) Perspectives of cannabinoid type 2 receptor (CB2R) ligands in neurodegenerative disorders: structure–affinity relationship (SAfiR) and structure–activity relationship (SAR) studies. J Med Chem 60:9913–9931. https://doi.org/10.1021/acs.jmedchem.7b00155
Udow SJ, Freitas ME, Fox SH, Lang AE (2018) Exacerbation of psychosis triggered by a synthetic cannabinoid in a 70-year-old woman with Parkinson disease. Can Med Assoc J 190:E50–E52. https://doi.org/10.1503/cmaj.170361
Valdeolivas S, Sagredo O, Delgado M, Pozo MA, Fernández-Ruiz J (2017) Effects of a Sativex-like combination of Phytocannabinoids on disease progression in R6/2 mice, an experimental model of Huntington’s disease. Int J Mol Sci 18:684. https://doi.org/10.3390/ijms18040684
Vallée A, Lecarpentier Y, Guillevin R, Vallée J-N (2017) Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer’s disease. Acta Biochim Biophys Sin 49:853–866. https://doi.org/10.1093/abbs/gmx073
van Esbroeck ACM, Janssen APA, Cognetta AB, Ogasawara D, Shpak G, van der Kroeg M, Kantae V, Baggelaar MP, de Vrij FMS, Deng H et al (2017) Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474. Science 356:1084–1087. https://doi.org/10.1126/science.aaf7497
Wang L, Liu B-J, Cao Y, Xu W-Q, Sun D-S, Li M-Z, Shi F-X, Li M, Tian Q, Wang J-Z et al (2018) Deletion of Type-2 cannabinoid receptor induces Alzheimer’s disease-like tau pathology and memory impairment through AMPK/GSK3β pathway. Mol Neurobiol 55:4731–4744. https://doi.org/10.1007/s12035-017-0676-2
Zeissler M-L, Eastwood J, McCorry K, Hanemann OC, Zajicek JP, Carroll CB (2016) Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis. Oncotarget 7:46603–46614. https://doi.org/10.18632/oncotarget.10314
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Pérez-Olives, C., Rivas-Santisteban, R., Lillo, J., Navarro, G., Franco, R. (2021). Recent Advances in the Potential of Cannabinoids for Neuroprotection in Alzheimer’s, Parkinson’s, and Huntington’s Diseases. In: Murillo-Rodriguez, E., Pandi-Perumal, S.R., Monti, J.M. (eds) Cannabinoids and Neuropsychiatric Disorders. Advances in Experimental Medicine and Biology, vol 1264. Springer, Cham. https://doi.org/10.1007/978-3-030-57369-0_6
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DOI: https://doi.org/10.1007/978-3-030-57369-0_6
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