Neurodegenerative diseases are characterized by progressive degeneration and/or death of neuronal cells and results in a wide array of cognitive impairments and other serious neurological defects. The signaling pathways and definite cause underlying the development of neurodegenerative nerve diseases have not been well defined. There is evidence of mechanisms within the endocannabinoid system that may suggest important pathways involved the progression of neurodegenerative diseases as well as some cancers. The endocannabinoid system is an endogenous ubiquitous neuromodulatory system that plays a critical in the development of the central nervous system (CNS), synaptic plasticity, as well as other primary neuronal functions. The recent identification of various cannabinoid receptors and their endogenous lipid ligands has generated an interest and significant increase in research of the endocannabinoid system and its role in human health and diseases. The Endocannabinoid system possesses essential endogenous receptors—cannabinoid receptors type 1 (CB1R) and type 2 (CB2R)—which are involved in mechanisms that contribute to the progression of neurodegenerative diseases and some cancers. In this review, we discuss the role of the endocannabinoid system in various neurodegenerative diseases as well as some cancers, and its promise as a targeted pharmacological therapy for patients of neurodegenerative diseases.
Brenneisen, R. (2007) Chemistry and Analysis of Phytocannabinoids and Other Cannabis Constituents. In: El Sohly, M.A., Ed., Marijuana and the Cannabinoids, Humana Press, Cliftong, 17-49. https://doi.org/10.1007/978-1-59259-947-9_2
Mannucci, C., Navarra, M., Calapai, F., Spagnolo, E., Busardo, F., Cas, R., Calapai, G., et al. (2017) Neurological Aspects of Medical Use of Cannabidiol. CNS & Neurological Disorders-Drug Targets, 16, 541-553. https://doi.org/10.2174/1871527316666170413114210
Morales, P., Reggio, P.H. and Jagerovic, N. (2017) An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol. Frontiers in Pharmacology, 8, 422. https://doi.org/10.3389/fphar.2017.00422
Chanda, D., Neumann, D. and Glatz, J.F.C. (2016) The Endocannabinoid System: Overview of an Emerging Multi-Faceted Therapeutic Target. Prostaglandins, Leukotrienes & Essential Fatty Acids, 140, 51-56. https://doi.org/10.1016/j.plefa.2018.11.016
Basavarajappa, B.S., Shivakumar, M., Joshi, V. and Subbanna, S. (2017) Endocannabinoid System in Neurodegenerative Disorders. Journal of Neurochemistry, 142, 624-648. https://doi.org/10.1111/jnc.14098
Katona, I., Urbán, G.M., Wallace, M., Ledent, C., Jung, K.M., Piomelli, D., Freund, T.F., et al. (2006) Molecular Composition of the Endocannabinoid System at Glutamatergic Synapses. Journal of Neuroscience, 26, 5628-5637. https://doi.org/10.1523/JNEUROSCI.0309-06.2006
Campion, D., Dumanchin, C., Hannequin, D., Dubois, B., Belliard, S., Puel, M., Frebourg, T., et al. (1999) Early-Onset Autosomal Dominant Alzheimer Disease: Prevalence, Genetic Heterogeneity, and Mutation Spectrum. The American Journal of Human Genetics, 65, 664-670. https://doi.org/10.1086/302553
Smith, L.A., Azariah, F., Lavender, V.T., Stoner, N.S. and Bettiol, S. (2015) Cannabinoids for Nausea and Vomiting in Adults with Cancer Receiving Chemotherapy. Cochrane Database of Systematic Reviews, No. 11, CD009464. https://doi.org/10.1002/14651858.CD009464.pub2
Reddy, D.S. and Golub, V.M. (2016) The Pharmacological Basis of Cannabis Therapy for Epilepsy. Journal of Pharmacology and Experimental Therapeutics, 357, 45-55. https://doi.org/10.1124/jpet.115.230151
Ostendorf, A.P. and Ng, Y.T. (2017) Treatment-Resistant Lennox-Gastaut Syndrome: Therapeutic Trends, Challenges and Future Directions. Neuropsychiatric Disease and Treatment, 13, 1131-1140. https://doi.org/10.2147/NDT.S115996
Devinsky, O., Cilio, M.R., Cross, H., Fernandez-Ruiz, J., French, J., Hill, C., Friedman, D., et al. (2014) Cannabidiol: Pharmacology and Potential Therapeutic Role in Epilepsy and Other Neuropsychiatric Disorders. Epilepsia, 55, 791-802. https://doi.org/10.1111/epi.12631
Gaston, T.E. and Friedman, D. (2017) Pharmacology of Cannabinoids in the Treatment of Epilepsy. Epilepsy & Behavior, 70, 313-318. https://doi.org/10.1016/j.yebeh.2016.11.016
Huang, W.J., Chen, W.W. and Zhang, X. (2016) Endocannabinoid System: Role in Depression, Reward and Pain Control (Review). Molecular Medicine Reports, 14, 2899-2903. https://doi.org/10.3892/mmr.2016.5585
Nelson, P.T., Alafuzoff, I., Bigio, E.H., Bouras, C., Braak, H., Cairns, N.J., Beach, T.G., et al. (2012) Correlation of Alzheimer Disease Neuropathologic Changes with Cognitive Status: A Review of the Literature. Journal of Neuropathology & Experimental Neurology, 71, 362-381. https://doi.org/10.1097/NEN.0b013e31825018f7
Milton, N.G. (2002) Anandamide and Noladin Ether Prevent Neurotoxicity of the Human Amyloid-Beta Peptide. Neuroscience Letters, 332, 127-130. https://doi.org/10.1016/S0304-3940(02)00936-9
Ramirez, B.G., Blazquez, C., del Pulgar, T.G., Guzman, M. and de Ceballos, M.L. (2005) Prevention of Alzheimer’s Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation. Journal of Neuroscience, 25, 1904-1913. https://doi.org/10.1523/JNEUROSCI.4540-04.2005
Solas, M., Francis, P.T., Franco, R. and Ramirez, M.J. (2013) CB2 Receptor and Amyloid Pathology in Frontal Cortex of Alzheimer’s Disease Patients. Neurobiology of Aging, 34, 805-808. https://doi.org/10.1016/j.neurobiolaging.2012.06.005
Ehrhart, J., Obregon, D., Mori, T., Hou, H., Sun, N., Shytle, R.D., et al. (2005) Stimulation of Cannabinoid Receptor 2 (CB2) Suppresses Microglial Activation. Journal of Neuroinflammation, 2, 29. https://doi.org/10.1186/1742-2094-2-29
Soderstrom, K., Soliman, E. and Van Dross, R. (2017) Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms. Frontiers in Pharmacology, 8, 72. https://doi.org/10.3389/fphar.2017.00720
Sreevalsan, S., Joseph, S., Jutooru, I., Chadalapaka, G. and Safe, S.H. (2011) Induction of Apoptosis by Cannabinoids in Prostate and Colon Cancer Cells Is Phosphatase Dependent. Anticancer Research, 31, 3799-3807.
Sreevalsan, S. and Safe, S. (2013) The Cannabinoid WIN 55,212-2 Decreases Specificity Protein Transcription Factors and the Oncogenic Cap Protein eIF4E in Colon Cancer Cells. Molecular Cancer Therapeutics, 12, 2483-2493. https://doi.org/10.1158/1535-7163.MCT-13-0486
Borrelli, F., Pagano, E., Romano, B., Panzera, S., Maiello, F., Coppola, D., Izzo, A.A., et al. (2014) Colon Carcinogenesis Is Inhibited by the TRPM8 Antagonist Cannabigerol, a Cannabis-Derived Non-Psychotropic Cannabinoid. Carcinogenesis, 35, 2787-2797. https://doi.org/10.1093/carcin/bgu205
Nabissi, M., Morelli, M.B., Amantini, C., Liberati, S., Santoni, M., Ricci-Vitiani, L., Santoni, G., et al. (2015) Cannabidiol Stimulates Aml-1a-Dependent Glial Differentiation and Inhibits Glioma Stem-Like Cells Proliferation by Inducing Autophagy in a TRPV2-Dependent Manner. International Journal of Cancer, 137, 1855-1869. https://doi.org/10.1002/ijc.29573
Eichele, K., Weinzierl, U., Ramer, R., Brune, K. and Hinz, B. (2006) R(+)-Methanandamide Elicits a Cyclooxygenase-2-Dependent Mitochondrial Apoptosis Signaling Pathway in Human Neuroglioma Cells. Pharmaceutical Research, 23, 90-94. https://doi.org/10.1007/s11095-005-8815-2
Ramer, R., Heinemann, K., Merkord, J., Rohde, H., Salamon, A., Linnebacher, M. and Hinz, B. (2013) COX-2 and PPAR-γ Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells. Molecular Cancer Therapeutics, 12, 69-82. https://doi.org/10.1158/1535-7163.MCT-12-0335
Gardner, B., Zhu, L.X., Sharma, S., Tashkin, D.P. and Dubinett, S.M. (2003) Methanandamide Increases COX-2 Expression and Tumor Growth in Murine Lung Cancer. The FASEB Journal, 17, 2157-2159. https://doi.org/10.1096/fj.03-0254fje
Contassot, E., Wilmotte, R., Tenan, M., Belkouch, M.C., Schnuriger, V., de Tribolet, N., Dietrich, P.Y., et al. (2004) Arachidonylethanolamide Induces Apoptosis of Human Glioma Cells through Vanilloid Receptor-1. Journal of Neuropathology & Experimental Neurology, 63, 956-963. https://doi.org/10.1093/jnen/63.9.956
Morelli, M.B., Offidani, M., Alesiani, F., Discepoli, G., Liberati, S., Olivieri, A., Nabissi, M., et al. (2014) The Effects of Cannabidiol and Its Synergism with Bortezomib in Multiple Myeloma Cell Lines. A Role for Transient Receptor Potential Vanilloid Type-2. International Journal of Cancer, 134, 2534-2546. https://doi.org/10.1002/ijc.28591
Patsos, H.A., Hicks, D.J., Dobson, R.R., Greenhough, A., Woodman, N., Lane, J.D., Paraskeva, C., et al. (2005) The Endogenous Cannabinoid, Anandamide, Induces Cell Death in Colorectal Carcinoma Cells: A Possible Role for Cyclooxygenase 2. Gut, 54, 1741-1750. https://doi.org/10.1136/gut.2005.073403
Contassot, E., Tenan, M., Schnüriger, V., Pelte, M.-F. and Dietrich, P.-Y. (2004) Arachidonylethanolamide Induces Apoptosis of Uterine Cervix Cancer Cells via Aberrantly Expressed Vanilloid Receptor-1. Gynecologic Oncology, 93, 182-188. https://doi.org/10.1016/j.ygyno.2003.12.040
Hamtiaux, L., Hansoulle, L., Dauguet, N., Muccioli, G.G., Gallez, B. and Lambert, D.M. (2011) Increasing Antiproliferative Properties of Endocannabinoids in N1E-115 Neuroblastoma Cells through Inhibition of Their Metabolism. PLoS ONE, 6, e26823. https://doi.org/10.1371/journal.pone.0026823
Kuc, C., Jenkins, A. and Van Dross, R.T. (2012) Arachidonoyl Ethanolamide (AEA)-Induced Apoptosis Is Mediated by J-Series Prostaglandins and Is Enhanced by Fatty Acid Amide Hydrolase (FAAH) Blockade. Molecular Carcinogenesis, 51, 139-149. https://doi.org/10.1002/mc.20770
Eichele, K., Ramer, R. and Hinz, B. (2009) R(+)-Methanandamide-Induced Apoptosis of Human Cervical Carcinoma Cells Involves a Cyclooxygenase-2-Dependent Pathway. Pharmaceutical Research, 26, 346-355. https://doi.org/10.1007/s11095-008-9748-3
DeMorrow, S., Glaser, S., Francis, H., Venter, J., Vaculin, B., Vaculin, S. and Alpini, G. (2007) Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth Recruitment of Fas and Fas Ligand to Lipid Rafts. The Journal of Biological Chemistry, 282, 13098-13113. https://doi.org/10.1074/jbc.M608238200
Mulder, J., Zilberter, M., Pasquare, S.J., Alpar, A., Schulte, G., Ferreira, S.G., Harkany, T., et al. (2011) Molecular Reorganization of Endo-1284 Cannabinoid Signalling in Alzheimer’s Disease. Brain, 134, 1041-1060. https://doi.org/10.1093/brain/awr046
Tanveer, R., Gowran, A., Noonan, J., Keating, S.E., Bowie, A.G. and Campbell, V.A. (2012) The Endocannabinoid, Anandamide, Augments Notch-1 Signaling in Cultured Cortical Neurons Exposed to Amyloid-Beta and in the Cortex of Aged Rats. The Journal of Biological Chemistry, 287, 34709-34721. https://doi.org/10.1074/jbc.M112.350678
Iuvone, T., Esposito, G., Esposito, R., Santamaria, R., Di Rosa, M. and Izzo, A.A. (2004) Neuroprotective Effect of Cannabidiol, a Non-Psychoactive Component from Cannabis sativa, on Beta Amyloid-Induced Toxicity in PC12 Cells. Journal of Neurochemistry, 89, 134-141. https://doi.org/10.1111/j.1471-4159.2003.02327.x
Loewenstein, D., Curiel, R. and Raffo, A. (2018) PTSD and Neurodegenerative Disorders. Post-Traumatic Stress Disorder, 93. https://doi.org/10.1093/med/9780190259440.003.0006
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders. 5th Edition, Author, Arlington. https://doi.org/10.1176/appi.books.9780890425596
Arnsten, A., Raskind, M., Taylor, F. and Connor, D. (2015) The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder. Neurobiology of Stress, 1, 89-99. https://doi.org/10.1016/j.ynstr.2014.10.002
Almli, L.M., Fani, N., Smith, A.K. and Ressler, K.J. (2014) Genetic Approaches to Understanding Post-Traumatic Stress Disorder. International Journal of Neuropsychopharmacology, 17, 355-370. https://doi.org/10.1017/S1461145713001090
Lupien, S., Maheul, F. and Weekes, N. (2005) Glucocorticoids: Effects on Human Cognition. In: Steckler, T., Kalin, N.H. and Reul, J.M.H.M., Eds., Handbook of Stress and the Brain Part 1: The Neurobiology of Stress Techniques in the Behavioral and Neural Sciences, Elsevier Science, Amsterdam, 387-402. https://doi.org/10.1016/S0921-0709(05)80022-7
Koenigs, M., Huey, E.D., Raymont, V., Cheon, B., Solomon, J., Wassermann, E.M. and Grafman, J. (2008) Focal Brain Damage Protects against Post-Traumatic Stress Disorder in Combat Veterans. Nature Neuroscience, 11, 232-237. https://doi.org/10.1038/nn2032
Logue, M.W., van Rooij, S., Dennis, E.L., Davis, S.L., Hayes, J.P., Stevens, J.S., Morey, R.A., et al. (2018) Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results from Posttraumatic Stress Disorder Consortia. Biological Psychiatry, 83, 244-253. https://doi.org/10.1016/j.biopsych.2017.09.006
Pitman, R., Rasmusson, A., Koenen, K., Shin, L., Orr, S., Gilbertson, M., Liberzon, I., et al. (2012) Biological Studies of Post-Traumatic Stress Disorder. Nature Reviews Neuroscience, 13, 769-787. https://doi.org/10.1038/nrn3339
Eiland, L. and McEwen, B. (2012) Early Life Stress Followed by Subsequent Adult Chronic Stress Potentiates Anxiety and Blunts Hippocampal Structural Remodeling. Hippocampus, 22, 82-91. https://doi.org/10.1002/hipo.20862
Katona, I. and Freund, T. (2012) Multiple Functions of Endocannabinoid Signaling in the Brain. Annual Review of Neuroscience, 35, 529-558. https://doi.org/10.1146/annurev-neuro-062111-150420
Ohno-Shosaku, T. and Kano, M. (2014) Endocannabinoid-Mediated Retrograde Modulation of Synaptic Transmission. Current Opinion in Neurobiology, 29, 1-8. https://doi.org/10.1016/j.conb.2014.03.017
Hill, M.N., Eiland, L., Lee, T.T.Y., Hillard, C.J. and McEwen, B.S. (2019) Early Life Stress Alters the Developmental Trajectory of Corticolimbic Endocannabinoid Signaling in Male Rats. Neuropharmacology, 146, 154-162. https://doi.org/10.1016/j.neuropharm.2018.11.036
Hill, M.N., Campolongo, P., Yehuda, R. and Patel, S. (2018) Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder. Neuropsychopharmacology, 43, 80-102. https://doi.org/10.1038/npp.2017.162
Hill, M. and Patel, S. (2013) Translational Evidence for the Involvement of the Endocannabinoid System in Stress-Related Psychiatric Illnesses. Biology of Mood and Anxiety Disorders, 3, 19. https://doi.org/10.1186/2045-5380-3-19
Hillard, C., Weinlander, K. and Stuhr, K. (2012) Contributions of Endocannabinoid Signaling to Psychiatric Disorders in Humans: Genetic and Biochemical Evidence. Neuroscience, 204, 207-229. https://doi.org/10.1016/j.neuroscience.2011.11.020
McEwen, B. (2007) Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain. Physiological Reviews, 87, 873-904. https://doi.org/10.1152/physrev.00041.2006
Bluett, R.J., Báldi, R., Haymer, A., Gaulden, A.D., Hartley, N.D., Parrish, W.P., Patel, S., et al. (2017) Endocannabinoid Signalling Modulates Susceptibility to Traumatic Stress Exposure. Nature Communications, 8, Article No. 14782. https://doi.org/10.1038/ncomms14782
Liu, P. and Nusslock, R. (2018) How Stress Gets under the Skin: Early Life Adversity and Glucocorticoid Receptor Epigenetic Regulation. Current Genomics, 19, 653-664. https://doi.org/10.2174/1389202919666171228164350
Turecki, G. and Meaney, M. (2016) Effects of the Social Environment and Stress on Glucocorticoid Receptor Gene Methylation: A Systematic Review. Biological Psychiatry, 79, 87-96. https://doi.org/10.1016/j.biopsych.2014.11.022
Andersen, S. and Teicher, M. (2004) Delayed Effects of Early Stress on Hippocampal Development. Neuropsychopharmacology, 29, 1988-1993. https://doi.org/10.1038/sj.npp.1300528
Brunson, K.L., Kramár, E., Lin, B., Chen, Y., Colgin, L.L., Yanagihara, T.K., Baram, T.Z., et al. (2005) Mechanisms of Late-Onset Cognitive Decline after Early-Life Stress. Journal of Neuroscience, 25, 9328-9338. https://doi.org/10.1523/JNEUROSCI.2281-05.2005
Ivy, A., Rex, C., Chen, Y., Dubé, C., Maras, P.M., Grigoriadis, D.E., Baram, T.Z., et al. (2010) Hippocampal Dysfunction and Cognitive Impairments Provoked by Chronic Early-Life Stress Involve Excessive Activation of CRH Receptors. Journal of Neuroscience, 30, 13005-13015. https://doi.org/10.1523/JNEUROSCI.1784-10.2010
Karten, Y.J., Olariu, A. and Cameron, H.A. (2005) Stress in Early Life Inhibits Neurogenesis in Adulthood. Trends in Neurosciences, 28, 171-172. https://doi.org/10.1016/j.tins.2005.01.009
Leslie, A.T., Akers, K.G., Krakowski, A.D., Stone, S.S., Sakaguchi, M., Arruda-Carvalho, M. and Frankland, P.W. (2011) Impact of Early Adverse Experience on Complexity of Adult-Generated Neurons. Translational Psychiatry, 1, e35. https://doi.org/10.1038/tp.2011.38
Wang, X.D., Su, Y.A., Wagner, K.V., Avrabos, C., Scharf, S.H., Hartmann, J., Schmidt, M.V., et al. (2013) Nectin-3 Links CRHR1 Signaling to Stress-Induced Memory Deficits and Spine Loss. Nature Neuroscience, 16, 706-713. https://doi.org/10.1038/nn.3395
Rubin, M., Shvil, E., Papini, S., Chhetry, B.T., Helpman, L., Markowitz, J.C., Neria, Y., et al. (2016) Greater Hippocampal Volume Is Associated with PTSD Treatment Response. Psychiatry Research. Neuroimaging, 252, 36-39. https://doi.org/10.1016/j.pscychresns.2016.05.001
Spagnolo, P.A., Ramchandani, V.A., Schwandt, M.L., Kwako, L.E., George, D.T., Mayo, L.M., Heilig, M., et al. (2016) FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence. Alcoholism, Clinical and Experimental Research, 40, 2426-2434. https://doi.org/10.1111/acer.13210
Gray, J.M., Vecchiarelli, H.A., Morena, M., Lee, T.T., Hermanson, D.J., Kim, A.B., Hill, M.N., et al. (2015) Corticotropin-Releasing Hormone Drives Anandamide Hydrolysis in the Amygdala to Promote Anxiety. Journal of Neuroscience, 35, 3879-3892. https://doi.org/10.1523/JNEUROSCI.2737-14.2015
Hill, M.N., McLaughlin, R.J., Morrish, A.C., Viau, V., Floresco, S.B., Hillard, C.J. and Gorzalka, B.B. (2009) Suppression of Amygdalar Endocannabinoid Signaling by Stress Contributes to Activation of the Hypothalamic-Pituitary-Adrenal Axis. Neuropsychopharmacology, 34, 2733-2745. https://doi.org/10.1038/npp.2009.114
Anderson, K.E., van Duijn, E., Craufurd, D., Drazinic, C., Edmondson, M., Goodman, N., Goodman, L.V., et al. (2018) Clinical Management of Neuropsychiatric Symptoms of Huntington Disease: Expert-Based Consensus Guidelines on Agitation, Anxiety, Apathy, Psychosis and Sleep Disorders. Journal of Huntington’s Disease, 7, 355-366. https://doi.org/10.3233/JHD-180293
Maya-López, M., Colín-González, A.L., Aguilera, G., de Lima, M.E., Colpo-Ceolin, A., Rangel-López, E., Santamaría, A., et al. (2017) Neuroprotective Effect of WIN55,212-2 against 3-Nitropropionic Acid-Induced Toxicity in the Rat Brain: Involvement of CB1 and NMDA Receptors. American Journal of Translational Research, 9, 261-274.
Díaz-Alonso, J., Paraíso-Luna, J., Navarrete, C., Del Río, C., Cantarero, I., Palomares, B., Munoz, E., 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. Scientific Reports, 6, Article No. 29789. https://doi.org/10.1038/srep29789
Kalia, L.V. and Lang, A.E. (2015) Parkinson’s Disease. The Lancet, 386, 896-912. https://doi.org/10.1016/S0140-6736(14)61393-3
Schneider, R.B., Iourinets, J. and Richard, I.H. (2017) Parkinson’s Disease Psychosis: Presentation, Diagnosis and Management. Neurodegenerative Disease Management, 7, 365-376. https://doi.org/10.2217/nmt-2017-0028
Cao, X., Liang, L., Hadcock, J.R., Iredale, P.A., Griffith, D.A., Menniti, F.S., Papa, S.M., et al. (2007) Blockade of Cannabinoid Type 1 Receptors Augments the Antiparkinsonian Action of Levodopa without Affecting Dyskinesias in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Rhesus Monkeys. Journal of Pharmacology and Experimental Therapeutics, 323, 318-326. https://doi.org/10.1124/jpet.107.125666
González, S., Scorticati, C., García-Arencibia, M., de Miguel, R., Ramos, J.A. and Fernández-Ruiz, J. (2006) Effects of Rimonabant, a Selective Cannabinoid CB1 Receptor Antagonist, in a Rat Model of Parkinson’s Disease. Brain Research, 1073-1074, 209-219. https://doi.org/10.1016/j.brainres.2005.12.014
Fernandez-Espejo, E., Caraballo, I., de Fonseca, F.R., El Banoua, F., Ferrer, B., Flores, J.A. and Galan-Rodriguez, B. (2005) Cannabinoid CB1 Antagonists Possess Antiparkinsonian Efficacy Only in Rats with Very Severe Nigral Lesion in Experimental Parkinsonism. Neurobiology of Disease, 18, 591-601. https://doi.org/10.1016/j.nbd.2004.10.015
Tambasco, N., Romoli, M. and Calabresi, P. (2018) Levodopa in Parkinson’s Disease: Current Status and Future Developments. Current Neuropharmacology, 16, 1239-1252. https://doi.org/10.2174/1570159X15666170510143821
Maccarrone, M., Gubellini, P., Bari, M., Picconi, B., Battista, N., Centonze, D., Calabresi, P., et al. (2003) Levodopa Treatment Reverses Endocannabinoid System Abnormalities in Experimental Parkinsonism. Journal of Neurochemistry, 85, 1018-1025. https://doi.org/10.1046/j.1471-4159.2003.01759.x
El-Banoua, F., Caraballo, I., Flores, J.A., Galan-Rodriguez, B. and Fernandez-Espejo, E. (2004) Effects on Turning of Microinjections into Basal Ganglia of D(1) and D(2) Dopamine Receptors Agonists and the Cannabinoid CB(1) Antagonist SR141716A in a Rat Parkinson’s Model. Neurobiology of Disease, 16, 377-385. https://doi.org/10.1016/j.nbd.2004.03.002
Raup-Konsavage, W.M., Johnson, M., Legare, C.A., Yochum, G.S., Morgan, D.J. and Vrana, K. (2018) Synthetic Cannabinoid Activity against Colorectal Cancer Cells. Cannabis and Cannabinoid Research, 3, 272-281. https://doi.org/10.1089/can.2018.0065
Fearon, E.R. (2011) Molecular Genetics of Colorectal Cancer. Annual Review of Pathology, 6, 479-507. https://doi.org/10.1146/annurev-pathol-011110-130235
Greenhough, A., Patsos, H.A., Williams, A.C. and Paraskeva, C. (2007) The Cannabinoid Delta(9)-Tetrahydrocannabinol Inhibits RAS-MAPK and PI3K-AKT Survival Signalling and Induces BAD-Mediated Apoptosis in Colorectal Cancer Cells. International Journal of Cancer, 121, 2172-2180. https://doi.org/10.1002/ijc.22917
Martínez-Martínez, E., Gómez, I., Martín, P., Sánchez, A., Román, L., Tejerina, E., García, J.M., et al. (2015) Cannabinoids Receptor Type 2, CB2, Expression Correlates with Human Colon Cancer Progression and Predicts Patient Survival. Oncoscience, 2, 131-141. https://doi.org/10.18632/oncoscience.119
Martínez-Martínez, E., Martín-ruiz, A., Martín, P., Calvo, V., Provencio, M. and García, J.M. (2016) CB2 Cannabinoid Receptor Activation Promotes Colon Cancer Progression via AKT/GSK3β Signaling Pathway. Oncotarget, 7, 68781-68791. https://doi.org/10.18632/oncotarget.11968
Keresztes, A. and Streicher, J.M. (2017) Synergistic Interaction of the Cannabinoid and Death Receptor Systems: A Potential Target for Future Cancer Therapies? FEBS Letters, 591, 3235-3251. https://doi.org/10.1002/1873-3468.12863
Ramos-González, J., López-Sánchez, D., Castellanos-Garzón, J.A., de Paz, J.F. and Corchado, J.M. (2017) A CBR Framework with Gradient Boosting Based Feature Selection for Lung Cancer Subtype Classification. Computers in Biology and Medicine, 86, 98-106. https://doi.org/10.1016/j.compbiomed.2017.05.010