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Age-related changes in the endogenous cannabinoid system could influence the effects of therapies that target the cannabinoid system. At the preclinical level, cannabidiol (CBD) induces anti-amyloidogenic, antioxidative, anti-apoptotic, anti-inflammatory, and neuroprotective effects. These findings suggest a potential therapeutic role of cannabinoids to neurodegenerative disorders such as Parkinson\u2019s disease (PD) and Alzheimer. Emerging evidence suggests that CBD and tetrahydrocannabinol have neuroprotective therapeutic-like effects on dementias. In clinical practice, cannabinoids are being used off-label to relieve symptoms of PD and AD. In fact, patients are using cannabis compounds for the treatment of tremor, non-motor symptoms, anxiety, and sleep assistance in PD, and managing responsive behaviors of dementia such as agitation. However, strong evidence from clinical trials is scarce for most indications. Some clinicians consider cannabinoids an alternative for older adults bearing Parkinson\u2019s disease and Alzheimer\u2019s dementia with a poor response to first-line treatments. In our concept and experience, cannabinoids should never be considered a first-line treatment but could be regarded as an adjuvant therapy in specific situations commonly seen in clinical practice. To mitigate the risk of adverse events, the traditional dogma of geriatric medicine, starting with a low dose and proceeding with a slow titration regime, should also be employed with cannabinoids. In this review, we aimed to address preclinical evidence of cannabinoids in neurodegenerative disorders such as PD and AD and discuss potential off-label use of cannabinoids in clinical practice of these disorders.<\/jats:p>","DOI":"10.3390\/brainsci12121596","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T02:10:54Z","timestamp":1669169454000},"page":"1596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Cannabinoids in Late Life Parkinson\u2019s Disease and Dementia: Biological Pathways and Clinical Challenges"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9832-5860","authenticated-orcid":false,"given":"Alana C.","family":"Costa","sequence":"first","affiliation":[{"name":"Laboratory of Neuroscience (LIM-27), Departamento e Instituto de Psiquiatria, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-903, Brazil"},{"name":"Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN), Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena P. G.","family":"Joaquim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o F. C.","family":"Pedrazzi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, S\u00e3o Paulo 05403-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreia de O.","family":"Pain","sequence":"additional","affiliation":[{"name":"Group of Investigation on Multimorbidity and Mental Health in Aging (GIMMA), Geriatrics Division, Department of Internal Medicine, Jundia\u00ed Medical School, Jundia\u00ed 13202-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8126-0637","authenticated-orcid":false,"given":"Gustavo","family":"Duque","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-7895","authenticated-orcid":false,"given":"Ivan","family":"Aprahamian","sequence":"additional","affiliation":[{"name":"Group of Investigation on Multimorbidity and Mental Health in Aging (GIMMA), Geriatrics Division, Department of Internal Medicine, Jundia\u00ed Medical School, Jundia\u00ed 13202-550, Brazil"},{"name":"Department of Psychiatry, University Medical Center Groningen, University of Groningen, 9712 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/jgs.12148","article-title":"Greater Number of Narcotic Analgesic Prescriptions for Osteoarthritis Is Associated with Falls and Fractures in Elderly Adults","volume":"61","author":"Rolita","year":"2013","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1532-5415.2005.53108.x","article-title":"A 5-Year Prospective Assessment of the Risk Associated with Individual Benzodiazepines and Doses in New Elderly Users","volume":"53","author":"Tamblyn","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"775","DOI":"10.7326\/0003-4819-146-11-200706050-00006","article-title":"Antipsychotic Drug Use and Mortality in Older Adults with Dementia","volume":"146","author":"Gill","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1080\/13607863.2019.1675143","article-title":"Serotonin Receptor Inhibitor Is Associated with Falls Independent of Frailty in Older Adults","volume":"25","author":"Lin","year":"2021","journal-title":"Aging Ment. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s40266-021-00882-2","article-title":"Safety and Tolerability of Natural and Synthetic Cannabinoids in Older Adults: A Systematic Review and Meta-Analysis of Open-Label Trials and Observational Studies","volume":"38","author":"Pisani","year":"2021","journal-title":"Drugs Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s40266-018-0616-5","article-title":"Medical Cannabis for Older Patients","volume":"36","author":"Minerbi","year":"2019","journal-title":"Drugs Aging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101041","DOI":"10.1016\/j.arr.2020.101041","article-title":"The Implications of Late-Life Cannabis Use on Brain Health: A Mapping Review and Implications for Future Research","volume":"59","author":"Weinstein","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173339","DOI":"10.1016\/j.pbb.2022.173339","article-title":"Age-Related Changes in CB1 Receptor Expression and Function and the Behavioral Effects of Cannabinoid Receptor Ligands","volume":"213","author":"Ginsburg","year":"2022","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105990","DOI":"10.1016\/j.clineuro.2020.105990","article-title":"Long-Term Assessment of the Cognitive Effects of Nabiximols in Patients with Multiple Sclerosis: A Pilot Study","volume":"196","author":"Alessandria","year":"2020","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2147\/JPR.S340968","article-title":"Comparison of the Effectiveness and Tolerability of Nabiximols (THC:CBD) Oromucosal Spray versus Oral Dronabinol (THC) as Add-on Treatment for Severe Neuropathic Pain in Real-World Clinical Practice: Retrospective Analysis of the German Pain e-Registry","volume":"15","author":"Ueberall","year":"2022","journal-title":"J. Pain Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ejim.2018.01.019","article-title":"Epidemiological Characteristics, Safety and Efficacy of Medical Cannabis in the Elderly","volume":"49","author":"Abuhasira","year":"2018","journal-title":"Eur. J. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1080\/02791072.2019.1626953","article-title":"Use of Cannabis to Relieve Pain and Promote Sleep by Customers at an Adult Use Dispensary","volume":"51","author":"Bachhuber","year":"2019","journal-title":"J. Psychoact. Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/add.13670","article-title":"Demographic Trends among Older Cannabis Users in the United States, 2006\u20132013","volume":"112","author":"Han","year":"2017","journal-title":"Addiction"},{"key":"ref_14","first-page":"243","article-title":"Medical Cannabinoids for Treatment of Neuropsychiatric Symptoms in Dementia: A Systematic Review","volume":"43","author":"Stella","year":"2021","journal-title":"Trends Psychiatry Psychother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/jgs.16833","article-title":"Cannabis: An Emerging Treatment for Common Symptoms in Older Adults","volume":"69","author":"Yang","year":"2021","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/07317115.2020.1746720","article-title":"Exploring New Use of Cannabis among Older Adults","volume":"44","author":"Baumbusch","year":"2021","journal-title":"Clin. Gerontol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1080\/07317115.2020.1853299","article-title":"Medical Cannabis Use: Exploring the Perceptions and Experiences of Older Adults with Chronic Conditions","volume":"44","author":"Manning","year":"2021","journal-title":"Clin. Gerontol."},{"key":"ref_18","first-page":"e232","article-title":"Measuring Attitudes toward Medical and Recreational Cannabis among Older Adults in Colorado","volume":"60","author":"Arora","year":"2020","journal-title":"Gerontologist"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s40266-019-00665-w","article-title":"Qualitative Analysis of Cannabis Use Among Older Adults in Colorado","volume":"36","author":"Bobitt","year":"2019","journal-title":"Drugs Aging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1111\/jgs.17213","article-title":"Decreasing Perceived Risk Associated with Regular Cannabis Use among Older Adults in the United States from 2015 to 2019","volume":"69","author":"Han","year":"2021","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1021\/cr0782067","article-title":"Enzymatic Pathways That Regulate Endocannabinoid Signaling in the Nervous System","volume":"108","author":"Ahn","year":"2008","journal-title":"Chem. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/346561a0","article-title":"Structure of a Cannabinoid Receptor and Functional Expression of the Cloned CDNA","volume":"346","author":"Matsuda","year":"1990","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/365061a0","article-title":"Molecular Characterization of a Peripheral Receptor for Cannabinoids","volume":"365","author":"Munro","year":"1993","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Silver, R.J. (2019). The Endocannabinoid System of Animals. Animals, 9.","DOI":"10.20944\/preprints201906.0262.v1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1365-2826.2008.01672.x","article-title":"Endocannabinoids and the Brain Immune System: New Neurones at the Horizon?","volume":"20","author":"Wolf","year":"2008","journal-title":"J. Neuroendocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1146\/annurev-neuro-062111-150420","article-title":"Multiple Functions of Endocannabinoid Signaling in the Brain","volume":"35","author":"Katona","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-21737-2_1","article-title":"Endocannabinoid System Components: Overview and Tissue Distribution","volume":"Volume 1162","author":"Joshi","year":"2019","journal-title":"Recent Advances in Cannabinoid Physiology and Pathology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0166-2236(98)01283-1","article-title":"Endocannabinoids: Endogenous Cannabinoid Receptor Ligands with Neuromodulatory Action","volume":"21","author":"Melck","year":"1998","journal-title":"Trends Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1038\/sj.ijo.0803271","article-title":"Endogenous Cannabinoids in the Brain and Peripheral Tissues: Regulation of Their Levels and Control of Food Intake","volume":"30","author":"Matias","year":"2006","journal-title":"Int. J. Obes."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1177\/0269881111408958","article-title":"The Endocannabinoid System in Anxiety, Fear Memory and Habituation","volume":"26","author":"Ruehle","year":"2012","journal-title":"J. Psychopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-pharmtox-030220-112741","article-title":"Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors","volume":"61","author":"Straub","year":"2021","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fpls.2016.00019","article-title":"Cannabis Sativa: The Plant of the Thousand and One Molecules","volume":"7","author":"Andre","year":"2016","journal-title":"Front. Plant Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Onaivi, E.S., Sugiura, T., and Di Marzo, V. (2006). Endocannabinoids: The Brain and Body\u2019s Marijuana and Beyond-Preface, Taylor and Francis.","DOI":"10.1201\/9781420023640"},{"key":"ref_34","first-page":"1","article-title":"Molecular Neurobiological Methods in Marijuana-Cannabinoid Research","volume":"Volume 123","author":"Uhl","year":"2006","journal-title":"Marijuana and Cannabinoid Research"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1126\/science.1470919","article-title":"Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor","volume":"258","author":"Devane","year":"1992","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1089\/can.2018.0057","article-title":"Anandamide Is Related to Clinical and Cardiorespiratory Benefits of Aerobic Exercise Training in Migraine Patients: A Randomized Controlled Clinical Trial","volume":"4","author":"Oliveira","year":"2019","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1021\/cn300015x","article-title":"\u201cRedundancy\u201d of Endocannabinoid Inactivation: New Challenges and Opportunities for Pain Control","volume":"3","author":"Piscitelli","year":"2012","journal-title":"ACS Chem. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.pharmthera.2012.12.002","article-title":"Endocannabinoid System and Mood Disorders: Priming a Target for New Therapies","volume":"138","author":"Micale","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.cmet.2013.03.001","article-title":"The Endocannabinoid System in Energy Homeostasis and the Etiopathology of Metabolic Disorders","volume":"17","author":"Silvestri","year":"2013","journal-title":"Cell Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1006\/bbrc.1995.2437","article-title":"2-Arachidonoylglycerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain","volume":"215","author":"Sugiura","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1111\/bph.12411","article-title":"Parsing the Players: 2-Arachidonoylglycerol Synthesis and Degradation in the CNS","volume":"171","author":"Murataeva","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1152\/physrev.00019.2008","article-title":"Endocannabinoid-Mediated Control of Synaptic Transmission","volume":"89","author":"Kano","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00109-005-0025-1","article-title":"The Marijuana Component Cannabidiol Inhibits Beta-Amyloid-Induced Tau Protein Hyperphosphorylation through Wnt\/Beta-Catenin Pathway Rescue in PC12 Cells","volume":"84","author":"Esposito","year":"2006","journal-title":"J. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Giuliano, C., Francavilla, M., Ongari, G., Petese, A., Ghezzi, C., Rossini, N., Blandini, F., and Cerri, S. (2021). Neuroprotective and Symptomatic Effects of Cannabidiol in an Animal Model of Parkinson\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168920"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Vasincu, A., Rusu, R.-N., Ababei, D.-C., Larion, M., Bild, W., Stanciu, G.D., Solcan, C., and Bild, V. (2022). Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty. Biology, 11.","DOI":"10.3390\/biology11030440"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tadijan, A., Vla\u0161i\u0107, I., Vlaini\u0107, J., \u0110iki\u0107, D., Or\u0161oli\u0107, N., and Jazvin\u0161\u0107ak Jembrek, M. (2022). Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions. Antioxidants, 11.","DOI":"10.3390\/antiox11102049"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"150276","DOI":"10.1098\/rsob.150276","article-title":"Modulation of Cellular Redox Homeostasis by the Endocannabinoid System","volume":"6","author":"Lipina","year":"2016","journal-title":"Open Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/FBP.0000000000000247","article-title":"The Therapeutic Potential of the Phytocannabinoid Cannabidiol for Alzheimer\u2019s Disease","volume":"28","author":"Karl","year":"2017","journal-title":"Behav. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"962922","DOI":"10.3389\/fnins.2022.962922","article-title":"Therapeutic Properties of Multi-Cannabinoid Treatment Strategies for Alzheimer\u2019s Disease","volume":"16","author":"Coles","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4790","DOI":"10.1111\/bph.13250","article-title":"Cannabidiol Is a Negative Allosteric Modulator of the Cannabinoid CB1 Receptor","volume":"172","author":"Laprairie","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2174\/1567202613666160902102007","article-title":"Selective Modulator of Cannabinoid Receptor Type 2 Reduces Memory Impairment and Infarct Size During Cerebral Hypoperfusion and Vascular Dementia","volume":"13","author":"Jayant","year":"2016","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"334","DOI":"10.2174\/1871527319666200708130745","article-title":"Impact of Cannabis-Based Medicine on Alzheimer\u2019s Disease by Focusing on the Amyloid \u03b2-Modifications: A Systematic Study","volume":"19","author":"Farkhondeh","year":"2020","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wu, J., Chen, N., Liu, Y., Godlewski, G., Kaplan, H.J., Shrader, S.H., Song, Z.-H., and Shao, H. (2021). Studies of Involvement of G-Protein Coupled Receptor-3 in Cannabidiol Effects on Inflammatory Responses of Mouse Primary Astrocytes and Microglia. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251677"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Silvestro, S., Schepici, G., Bramanti, P., and Mazzon, E. (2020). Molecular Targets of Cannabidiol in Experimental Models of Neurological Disease. Molecules, 25.","DOI":"10.3390\/molecules25215186"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/abbs\/gmx073","article-title":"Effects of Cannabidiol Interactions with Wnt\/\u03b2-Catenin Pathway and PPAR\u03b3 on Oxidative Stress and Neuroinflammation in Alzheimer\u2019s Disease","volume":"49","author":"Lecarpentier","year":"2017","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Juknat, A., Pietr, M., Kozela, E., Rimmerman, N., Levy, R., Gao, F., Coppola, G., Geschwind, D., and Vogel, Z. (2013). Microarray and Pathway Analysis Reveal Distinct Mechanisms Underlying Cannabinoidmediated Modulation of LPS-Induced Activation of BV-2 Microglial Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061462"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kozela, E., Juknat, A., and Vogel, Z. (2017). Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081669"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fphar.2020.00124","article-title":"From Cannabis Sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases","volume":"11","author":"Cassano","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1002\/ptr.5095","article-title":"Cannabidiol Promotes Amyloid Precursor Protein Ubiquitination and Reduction of Beta Amyloid Expression in SHSY5YAPP+ Cells through PPAR\u03b3 Involvement","volume":"28","author":"Scuderi","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Esposito, G., Scuderi, C., Valenza, M., Togna, G.I., Latina, V., De Filippis, D., Cipriano, M., Carrat\u00f9, M.R., Iuvone, T., and Steardo, L. (2011). Cannabidiol Reduces A\u03b2-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPAR\u03b3 Involvement. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028668"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1523\/JNEUROSCI.4212-08.2009","article-title":"Cannabidiol Targets Mitochondria to Regulate Intracellular Ca2+ Levels","volume":"29","author":"Ryan","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"903","DOI":"10.3233\/JAD-160533","article-title":"Delineating the Efficacy of a Cannabis-Based Medicine at Advanced Stages of Dementia in a Murine Model","volume":"54","author":"Ester","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_63","first-page":"977","article-title":"Cannabis-Based Medicine Reduces Multiple Pathological Processes in A\u03b2PP\/PS1 Mice","volume":"43","author":"Ester","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_64","first-page":"177","article-title":"Effects of Tetrahydrocannabinol Treatment on Brain Metabolism and Neuron Loss in a Mouse Model of Sporadic Alzheimer\u2019s Disease","volume":"58","author":"Franke","year":"2019","journal-title":"Nuklearmedizin"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.euroneuro.2007.11.003","article-title":"Therapeutic Effects of \u03949-\u03949-THC and Modafinil in a Marmoset Parkinson Model","volume":"18","author":"Vanwersch","year":"2008","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1046\/j.0953-816x.2001.01812.x","article-title":"Increased Cannabinoid CB1 Receptor Binding and Activation of GTP-Binding Proteins in the Basal Ganglia of Patients with Parkinson\u2019s Syndrome and of MPTP-Treated Marmosets","volume":"14","author":"Cebeira","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Burgaz, S., Garc\u00eda, C., G\u00f3mez-Ca\u00f1as, M., Rolland, A., Mu\u00f1oz, E., and Fern\u00e1ndez-Ruiz, J. (2021). Neuroprotection with the Cannabidiol Quinone Derivative VCE-004.8 (EHP-101) against 6-Hydroxydopamine in Cell and Murine Models of Parkinson\u2019s Disease. Molecules, 26.","DOI":"10.3390\/molecules26113245"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neuroscience.2022.06.036","article-title":"Cannabidiol Alleviates the Damage to Dopaminergic Neurons in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinson\u2019s Disease Mice via Regulating Neuronal Apoptosis and Neuroinflammation","volume":"498","author":"Wang","year":"2022","journal-title":"Neuroscience"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s007020200064","article-title":"Treatment of Parkinson\u2019s with L-DOPA. The Early Discovery Phase, and a Comment on Current Problems","volume":"109","author":"Carlsson","year":"2002","journal-title":"J. Neural Transm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1136\/jnnp.57.6.672","article-title":"Parkinson\u2019s Disease","volume":"57","author":"Marsden","year":"1994","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.nbd.2016.06.013","article-title":"Co-Administration of Cannabidiol and Capsazepine Reduces L-DOPA-Induced Dyskinesia in Mice: Possible Mechanism of Action","volume":"94","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1002\/mds.10289","article-title":"Stimulation of Cannabinoid Receptors Reduces Levodopa-Induced Dyskinesia in the MPTP-Lesioned Nonhuman Primate Model of Parkinson\u2019s Disease","volume":"17","author":"Fox","year":"2002","journal-title":"Mov. Disord."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1034\/j.1600-0773.2003.930202.x","article-title":"The CB1 Cannabinoid Receptor Agonist, HU-210, Reduces Levodopa-Induced Rotations in 6-Hydroxydopamine-Lesioned Rats","volume":"93","author":"Melamed","year":"2003","journal-title":"Pharmacol. Toxicol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.nbd.2004.11.009","article-title":"Cannabinoids Provide Neuroprotection against 6-Hydroxydopamine Toxicity in Vivo and in Vitro: Relevance to Parkinson\u2019s Disease","volume":"19","author":"Ramos","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1111\/j.1460-9568.2009.06764.x","article-title":"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\u2019s Disease","volume":"29","author":"Price","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s Disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.parkreldis.2022.08.014","article-title":"Cannabinoids in Movement Disorders","volume":"102","author":"Kluger","year":"2022","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/mdc3.13471","article-title":"Effects of Nabilone on Sleep Outcomes in Patients with Parkinson\u2019s Disease: A Post-Hoc Analysis of NMS-Nab Study","volume":"9","author":"Peball","year":"2022","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1089\/can.2016.0034","article-title":"An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies","volume":"2","author":"Iffland","year":"2017","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-022-02073-5","article-title":"The Effect of Medical Cannabis on Cognitive Functions: A Systematic Review","volume":"11","author":"Wieghorst","year":"2022","journal-title":"Syst. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3233\/JPD-212923","article-title":"Effects of Cannabis in Parkinson\u2019s Disease: A Systematic Review and Meta-Analysis","volume":"12","author":"Urbi","year":"2022","journal-title":"J. Parkinson\u2019s Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1007\/s00702-022-02529-x","article-title":"Randomized Controlled Trials on the Use of Cannabis-Based Medicines in Movement Disorders: A Systematic Review","volume":"129","author":"Oikonomou","year":"2022","journal-title":"J. Neural Transm."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1177\/0269881108096519","article-title":"Cannabidiol for the Treatment of Psychosis in Parkinson\u2019s Disease","volume":"23","author":"Zuardi","year":"2009","journal-title":"J. Psychopharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/jcpt.12179","article-title":"Cannabidiol Can Improve Complex Sleep-Related Behaviours Associated with Rapid Eye Movement Sleep Behaviour Disorder in Parkinson\u2019s Disease Patients: A Case Series","volume":"39","author":"Chagas","year":"2014","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1177\/0269881114550355","article-title":"Effects of Cannabidiol in the Treatment of Patients with Parkinson\u2019s Disease: An Exploratory Double-Blind Trial","volume":"28","author":"Chagas","year":"2014","journal-title":"J. Psychopharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Xiong, Y., and Lim, C.-S. (2021). Understanding the Modulatory Effects of Cannabidiol on Alzheimer\u2019s Disease. Brain Sci., 11.","DOI":"10.3390\/brainsci11091211"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Nitzan, K., Ellenbogen, L., Bentulila, Z., David, D., Franko, M., Break, E.P., Zoharetz, M., Shamir, A., Sarne, Y., and Doron, R. (2022). An Ultra-Low Dose of \u22069-Tetrahydrocannabinol Alleviates Alzheimer\u2019s Disease-Related Cognitive Impairments and Modulates TrkB Receptor Expression in a 5XFAD Mouse Model. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169449"},{"key":"ref_88","first-page":"CD012820","article-title":"Cannabinoids for the Treatment of Dementia","volume":"9","author":"Markovic","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00406-019-00984-4","article-title":"How Effective and Safe Is Medical Cannabis as a Treatment of Mental Disorders? A Systematic Review","volume":"269","author":"Hoch","year":"2019","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Bajtel, \u00c1., Kiss, T., T\u00f3th, B., Kiss, S., Hegyi, P., V\u00f6rhendi, N., Csupor-L\u00f6ffler, B., Gede, N., Hohmann, J., and Csupor, D. (2022). The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Pharmaceuticals, 15.","DOI":"10.3390\/ph15010100"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/(SICI)1099-1166(199709)12:9<913::AID-GPS663>3.0.CO;2-D","article-title":"Effects of Dronabinol on Anorexia and Disturbed Behavior in Patients with Alzheimer\u2019s Disease","volume":"12","author":"Volicer","year":"1997","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Abuhasira, R., Ron, A., Sikorin, I., and Novack, V. (2019). Medical Cannabis for Older Patients-Treatment Protocol and Initial Results. J. Clin. Med., 8.","DOI":"10.3390\/jcm8111819"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ejim.2018.01.004","article-title":"Practical Considerations in Medical Cannabis Administration and Dosing","volume":"49","author":"MacCallum","year":"2018","journal-title":"Eur. J. Intern. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ejim.2021.05.002","article-title":"\u201cIs Medical Cannabis Safe for My Patients?\u201d A Practical Review of Cannabis Safety Considerations","volume":"89","author":"MacCallum","year":"2021","journal-title":"Eur. J. Intern. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1111\/bcp.14038","article-title":"A Systematic Review of Cannabidiol Dosing in Clinical Populations","volume":"85","author":"Millar","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.arr.2014.01.007","article-title":"Efficacy and Safety of Medical Cannabinoids in Older Subjects: A Systematic Review","volume":"14","author":"Ahmed","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s42238-021-00073-1","article-title":"Consensus Recommendations on Dosing and Administration of Medical Cannabis to Treat Chronic Pain: Results of a Modified Delphi Process","volume":"3","author":"Bhaskar","year":"2021","journal-title":"J. Cannabis Res."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Velayudhan, L., McGoohan, K., and Bhattacharyya, S. (2021). Safety and Tolerability of Natural and Synthetic Cannabinoids in Adults Aged over 50 Years: A Systematic Review and Meta-Analysis. PLoS Med., 18.","DOI":"10.1371\/journal.pmed.1003524"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.euroneuro.2014.06.007","article-title":"Safety and Pharmacokinetics of Oral Delta-9-Tetrahydrocannabinol in Healthy Older Subjects: A Randomized Controlled Trial","volume":"24","author":"Ahmed","year":"2014","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"294","DOI":"10.2133\/dmpk.DMPK-11-RG-107","article-title":"Comparison in the in Vitro Inhibitory Effects of Major Phytocannabinoids and Polycyclic Aromatic Hydrocarbons Contained in Marijuana Smoke on Cytochrome P450 2C9 Activity","volume":"27","author":"Yamaori","year":"2012","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ebcr.2017.10.001","article-title":"UAB CBD Program An Interaction between Warfarin and Cannabidiol, a Case Report","volume":"9","author":"Grayson","year":"2018","journal-title":"Epilepsy Behav. Case Rep."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/12\/1596\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:24:28Z","timestamp":1760145868000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/12\/1596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,22]]},"references-count":101,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["brainsci12121596"],"URL":"https:\/\/doi.org\/10.3390\/brainsci12121596","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,22]]}}}