{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:16:16Z","timestamp":1787505376592,"version":"build-2736575974"},"reference-count":266,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The endocannabinoid system (eCBS) is a versatile neuromodulatory network that orchestrates synaptic plasticity, reward processing, and neuronal homeostasis. Increasing evidence implicates eCBS dysregulation in both addiction and neurodegenerative (ND) disorders, suggesting overlapping molecular and cellular mechanisms underlying these conditions. This review synthesizes recent advances in understanding how eCBS components\u2014cannabinoid receptors (CB1 and CB2), endogenous ligands (anandamide and 2-arachidonoylglycerol), and their metabolic enzymes\u2014modulate dopaminergic and glutamatergic signaling within reward and reinforcement circuits. Chronic exposure to drugs of abuse, including alcohol, opioids, cocaine, and methamphetamine, perturbs eCBS homeostasis, promoting oxidative stress, neuroinflammation, excitotoxicity, mitochondrial dysfunction, and protein aggregation\u2014pathological features common to Alzheimer\u2019s, Parkinson\u2019s, Huntington\u2019s, and amyotrophic lateral sclerosis. These overlapping mechanisms disrupt neuronal integrity and contribute to progressive neurotoxicity, highlighting shared pathogenic pathways between addiction and neurodegeneration. Despite these advances, critical gaps remain in delineating how substance-induced eCBS alterations precipitate neurodegenerative cascades. Addressing these gaps will be essential for harnessing the eCBS as a therapeutic target to mitigate addiction-driven neurotoxicity and age-related cognitive decline.<\/jats:p>","DOI":"10.3390\/ijms262311632","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:13:49Z","timestamp":1764576829000},"page":"11632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["From Synaptic Plasticity to Neurotoxicity: Endocannabinoid Influence on Addiction and Neurodegeneration"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4429-8078","authenticated-orcid":false,"given":"Balapal S.","family":"Basavarajappa","sequence":"first","affiliation":[{"name":"Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA"},{"name":"Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivakumar","family":"Subbanna","sequence":"additional","affiliation":[{"name":"Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(98)00649-9","article-title":"Endocannabinoids","volume":"359","author":"Mechoulam","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0026-895X(25)09876-1","article-title":"Determination and characterization of a cannabinoid receptor in rat brain","volume":"34","author":"Devane","year":"1988","journal-title":"Mol. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/0166-2236(90)90124-S","article-title":"The cannabinoid receptor: Biochemical, anatomical and behavioral characterization","volume":"13","author":"Howlett","year":"1990","journal-title":"Trends Neurosci."},{"key":"ref_5","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_6","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_7","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/cne.903270406","article-title":"Localization of cannabinoid receptor mRNA in rat brain","volume":"327","author":"Matsuda","year":"1993","journal-title":"J. Comp. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0022-3565(25)38122-X","article-title":"Cannabinoid structure-activity relationships: Correlation of receptor binding and in vivo activities","volume":"265","author":"Compton","year":"1993","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/0306-4522(93)90352-G","article-title":"Loss of cannabinoid receptors in the substantia nigra in Huntington\u2019s disease","volume":"56","author":"Glass","year":"1993","journal-title":"Neuroscience"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/S0026-895X(25)13256-2","article-title":"Structure-activity relationships for cannabinoid receptor-binding and analgesic activity: Studies of bicyclic cannabinoid analogs","volume":"44","author":"Melvin","year":"1993","journal-title":"Mol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1016\/0014-2999(94)90666-1","article-title":"The action of synthetic cannabinoids on the induction of long-term potentiation in the rat hippocampal slice","volume":"259","author":"Collins","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0091-3057(94)90110-4","article-title":"Motor behavior and nigrostriatal dopaminergic activity in adult rats perinatally exposed to cannabinoids","volume":"47","author":"Navarro","year":"1994","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/BF02246292","article-title":"Systemic or intrahippocampal cannabinoid administration impairs spatial memory in rats","volume":"119","author":"Lichtman","year":"1995","journal-title":"Psychopharmacology"},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S0022-3565(24)38906-2","article-title":"Cannabinoid agonist signal transduction in rat brain: Comparison of cannabinoid agonists in receptor binding, G-protein activation, and adenylyl cyclase inhibition","volume":"295","author":"Breivogel","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1523\/JNEUROSCI.23-06-02371.2003","article-title":"Regulation of extracellular signal-regulated kinase by cannabinoids in hippocampus","volume":"23","author":"Derkinderen","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1038\/sj.ijo.0803273","article-title":"Mechanisms of CB1 receptor signaling: Endocannabinoid modulation of synaptic strength","volume":"30","author":"Mackie","year":"2006","journal-title":"Int. J. Obes."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev-psych-113011-143739","article-title":"The endocannabinoid system and the brain","volume":"64","author":"Mechoulam","year":"2013","journal-title":"Annu. Rev. Psychol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1146\/annurev.pa.35.040195.003135","article-title":"Pharmacology of cannabinoid receptors","volume":"35","author":"Howlett","year":"1995","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/0006-2952(94)90134-1","article-title":"Effects of anandamide on cannabinoid receptors in rat brain membranes","volume":"47","author":"Childers","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S0026-895X(25)09729-9","article-title":"Cannabinoid receptor binding and agonist activity of amides and esters of arachidonic acid","volume":"46","author":"Pinto","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0009-3084(00)00187-0","article-title":"Cellular signal transduction by anandamide and 2-arachidonoylglycerol","volume":"108","author":"Howlett","year":"2000","journal-title":"Chem. Phys. Lipids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/j.1476-5381.1992.tb14321.x","article-title":"Cannabinoid receptor agonists inhibit Ca current in NG108-15 neuroblastoma cells via a pertussis toxin-sensitive mechanism","volume":"106","author":"Caulfield","year":"1992","journal-title":"Br. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1073\/pnas.89.9.3825","article-title":"Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells","volume":"89","author":"Mackie","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1046\/j.1471-4159.2001.00567.x","article-title":"Cannabinoid receptor agonists inhibit depolarization-induced calcium influx in cerebellar granule neurons","volume":"79","author":"Nogueron","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0026-895X(25)08786-3","article-title":"Rat brain cannabinoid receptor modulates N-type Ca2+ channels in a neuronal expression system","volume":"49","author":"Pan","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0022-3565(24)35181-X","article-title":"Cannabinoid receptors differentially modulate potassium A and D currents in hippocampal neurons in culture","volume":"291","author":"Mu","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1152\/physrev.00004.2003","article-title":"Role of endogenous cannabinoids in synaptic signaling","volume":"83","author":"Freund","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1124\/pr.54.2.161","article-title":"International Union of Pharmacology. XXVII. Classification of cannabinoid receptors","volume":"54","author":"Howlett","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"29085","DOI":"10.1074\/jbc.M602516200","article-title":"Induction of Krox-24 by endogenous cannabinoid type 1 receptors in Neuro2A cells is mediated by the MEK-ERK MAPK pathway and is suppressed by the phosphatidylinositol 3-kinase pathway","volume":"281","author":"Graham","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_31","unstructured":"Kaiser, T.F., and Peters, F.J. (2008). Synaptic Plasticity: Emerging Role for Endocannabinoid system. Synaptic Plasticity: New Research, Nova Science Publishers, Inc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1111\/j.1471-4159.2007.04642.x","article-title":"Regulation of PI3K\/Akt\/GSK-3 pathway by cannabinoids in the brain","volume":"102","author":"Ozaita","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3390\/brainsci5040456","article-title":"Fetal Alcohol Spectrum Disorder: Potential Role of Endocannabinoids Signaling","volume":"5","author":"Basavarajappa","year":"2015","journal-title":"Brain Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/hipo.22213","article-title":"CB1 Receptor-Mediated Signaling Underlies the Hippocampal Synaptic, Learning and Memory Deficits Following Treatment with JWH-081, a New Component of Spice\/K2 Preparations","volume":"24","author":"Basavarajappa","year":"2014","journal-title":"Hippocampus"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0014-5793(95)01207-U","article-title":"The peripheral cannabinoid receptor: Adenylate cyclase inhibition and G protein coupling","volume":"375","author":"Bayewitch","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1098\/rspb.1998.0543","article-title":"A new perspective on cannabinoid signalling: Complementary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain","volume":"265","author":"Egertova","year":"1998","journal-title":"Proc. R. Soc. B Biol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S0306-4522(97)00436-3","article-title":"Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system","volume":"83","author":"Tsou","year":"1998","journal-title":"Neuroscience"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1046\/j.1460-9568.1999.00847.x","article-title":"Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain","volume":"11","author":"Marsicano","year":"1999","journal-title":"Eur. J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1111\/ejn.12561","article-title":"Cannabinoid receptor type 1 receptors on GABAergic vs. glutamatergic neurons differentially gate sex-dependent social interest in mice","volume":"40","author":"Terzian","year":"2014","journal-title":"Eur. J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.neuroscience.2007.02.021","article-title":"Identification of the cannabinoid receptor type 1 in serotonergic cells of raphe nuclei in mice","volume":"146","author":"Haring","year":"2007","journal-title":"Neuroscience"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.brainres.2006.09.110","article-title":"Cannabinoid receptors are localized to noradrenergic axon terminals in the rat frontal cortex","volume":"1127","author":"Oropeza","year":"2007","journal-title":"Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1016\/j.lfs.2005.05.011","article-title":"Cannabinoid receptor homo- and heterodimerization","volume":"77","author":"Mackie","year":"2005","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Navarrete, M., Diez, A., and Araque, A. (2014). Astrocytes in endocannabinoid signalling. Proc. R. Soc. B Biol. Sci., 369.","DOI":"10.1098\/rstb.2013.0599"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1172\/JCI17725","article-title":"The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis","volume":"112","author":"Cota","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S0024-3205(99)00286-6","article-title":"Presence and functional regulation of cannabinoid receptors in immune cells","volume":"65","author":"Parolaro","year":"1999","journal-title":"Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1042\/bj3120637","article-title":"Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1","volume":"312","author":"Bouaboula","year":"1995","journal-title":"Biochem. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.jcmgh.2022.05.015","article-title":"Role of the Endocannabinoid System in the Regulation of Intestinal Homeostasis","volume":"14","author":"Cuddihey","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/bs.apha.2017.03.007","article-title":"CB(1) and CB(2) Receptor Pharmacology","volume":"80","author":"Howlett","year":"2017","journal-title":"Adv. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"108140","DOI":"10.1016\/j.intimp.2021.108140","article-title":"Rimonabant ameliorates hepatic ischemia\/reperfusion injury in rats: Involvement of autophagy via modulating ERK- and PI3K\/AKT-mTOR pathways","volume":"100","author":"Rezq","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/WNR.0000000000002138","article-title":"CB1 receptor coupling to extracellular regulated kinase via multiple Galphai\/o isoforms","volume":"36","author":"Rorabaugh","year":"2025","journal-title":"Neuroreport"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41401-018-0075-x","article-title":"Brain activity of anandamide: A rewarding bliss?","volume":"40","author":"Scherma","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_52","first-page":"2173","article-title":"The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1\/2 phosphorylation in 6-OHDA-lesioned rats","volume":"8","author":"Song","year":"2014","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"pyu028","DOI":"10.1093\/ijnp\/pyu028","article-title":"Ethanol exposure induces neonatal neurodegeneration by enhancing CB1R Exon1 histone H4K8 acetylation and up-regulating CB1R function causing neurobehavioral abnormalities in adult mice","volume":"18","author":"Subbanna","year":"2015","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6350","DOI":"10.1523\/JNEUROSCI.3786-12.2013","article-title":"Anandamide-CB1 Receptor Signaling Contributes to Postnatal Ethanol-Induced Neonatal Neurodegeneration, Adult Synaptic and Memory Deficits","volume":"33","author":"Subbanna","year":"2013","journal-title":"J. Neuosci."},{"key":"ref_55","unstructured":"Murillo-Rodriguez, E. (2017). Cannabinoid Receptors and their Signaling Mechanisms. The Endocannabinoid System, Academic Press."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1111\/jnc.14098","article-title":"Endocannabinoid system in neurodegenerative disorders","volume":"142","author":"Basavarajappa","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/S0026-895X(24)23114-X","article-title":"The CB(1) cannabinoid receptor is coupled to the activation of c-Jun N-terminal kinase","volume":"58","author":"Rueda","year":"2000","journal-title":"Mol. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Di Scala, C., Fantini, J., Yahi, N., Barrantes, F.J., and Chahinian, H. (2018). Anandamide Revisited: How Cholesterol and Ceramides Control Receptor-Dependent and Receptor-Independent Signal Transmission Pathways of a Lipid Neurotransmitter. Biomolecules, 8.","DOI":"10.3390\/biom8020031"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.bjp.0705726","article-title":"Endocannabinoid-mediated short-term synaptic plasticity: Depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE)","volume":"142","author":"Diana","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/385446a0","article-title":"Direct binding of G-protein betagamma complex to voltage-dependent calcium channels","volume":"385","author":"Liu","year":"1997","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.tips.2005.06.008","article-title":"How do G proteins directly control neuronal Ca2+ channel function?","volume":"26","author":"Hering","year":"2005","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.phrs.2016.06.026","article-title":"Gbetagamma subunits-Different spaces, different faces","volume":"111","author":"Khan","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1111\/j.1432-1033.1996.0704p.x","article-title":"Signaling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression","volume":"237","author":"Bouaboula","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1471-4159.2005.03380.x","article-title":"Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli","volume":"95","author":"Maresz","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.brainres.2005.11.035","article-title":"Cannabinoid CB2 receptors: Immunohistochemical localization in rat brain","volume":"1071","author":"Gong","year":"2006","journal-title":"Brain Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1196\/annals.1369.052","article-title":"Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain","volume":"1074","author":"Onaivi","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1038\/s41401-020-00530-2","article-title":"The impact of cannabinoid type 2 receptors (CB2Rs) in neuroprotection against neurological disorders","volume":"41","author":"Xin","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Yu, X., Jia, Y., and Dong, Y. (2023). Research progress on the cannabinoid type-2 receptor and Parkinson\u2019s disease. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1298166"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.neuroscience.2015.10.041","article-title":"Neuronal expression of CB2 cannabinoid receptor mRNAs in the mouse hippocampus","volume":"311","author":"Li","year":"2015","journal-title":"Neuroscience"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.neuron.2016.03.034","article-title":"Cannabinoid Type 2 Receptors Mediate a Cell Type-Specific Plasticity in the Hippocampus","volume":"90","author":"Stempel","year":"2016","journal-title":"Neuron"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1111\/adb.12367","article-title":"Expression of functional cannabinoid CB(2) receptor in VTA dopamine neurons in rats","volume":"22","author":"Zhang","year":"2017","journal-title":"Addict. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/S0026-895X(25)10254-X","article-title":"Activation of the human peripheral cannabinoid receptor results in inhibition of adenylyl cyclase","volume":"48","author":"Slipetz","year":"1995","journal-title":"Mol. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1124\/jpet.105.089474","article-title":"Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors","volume":"315","author":"Shoemaker","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0026-895X(25)10492-6","article-title":"Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors","volume":"48","author":"Felder","year":"1995","journal-title":"Mol. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/oxfordjournals.jbchem.a002904","article-title":"Activation by 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, of p42\/44 mitogen-activated protein kinase in HL-60 cells","volume":"129","author":"Kobayashi","year":"2001","journal-title":"J. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"9742","DOI":"10.1523\/JNEUROSCI.22-22-09742.2002","article-title":"Cannabinoids promote oligodendrocyte progenitor survival: Involvement of cannabinoid receptors and phosphatidylinositol-3 kinase\/Akt signaling","volume":"22","author":"Vela","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1111\/bph.15748","article-title":"Delineating the interactions between the cannabinoid CB(2) receptor and its regulatory effectors; beta-arrestins and GPCR kinases","volume":"179","author":"Patel","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5265","DOI":"10.1038\/s41467-025-60003-0","article-title":"Multiple intramolecular triggers converge to preferential G protein coupling in the CB(2)R","volume":"16","author":"Miljus","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/S0022-3565(24)35147-X","article-title":"Cannabinoid receptors can activate and inhibit G protein-coupled inwardly rectifying potassium channels in a xenopus oocyte expression system","volume":"291","author":"McAllister","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_80","first-page":"363","article-title":"Coupling of the expressed cannabinoid CB1 and CB2 receptors to phospholipase C and G protein-coupled inwardly rectifying K+ channels","volume":"6","author":"Ho","year":"1999","journal-title":"Recept. Channels"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Soobben, M., Sayed, Y., and Achilonu, I. (2024). Exploring the evolutionary trajectory and functional landscape of cannabinoid receptors: A comprehensive bioinformatic analysis. Comput. Biol. Chem., 112.","DOI":"10.1016\/j.compbiolchem.2024.108138"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1007\/s00213-024-06683-w","article-title":"Emerging roles of cannabinoid receptor CB2 receptor in the central nervous system: Therapeutic target for CNS disorders","volume":"241","author":"Bala","year":"2024","journal-title":"Psychopharmacology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0163-7258(97)82001-3","article-title":"Pharmacology of cannabinoid CB1 and CB2 receptors","volume":"74","author":"Pertwee","year":"1997","journal-title":"Pharmacol. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/S0306-4522(97)00348-5","article-title":"Expression of the CB1 and CB2 receptor messenger RNAs during embryonic development in the rat","volume":"82","author":"Buckley","year":"1998","journal-title":"Neuroscience"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6748","DOI":"10.1158\/0008-5472.CAN-06-0169","article-title":"Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes","volume":"66","author":"Carracedo","year":"2006","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ccr.2006.03.005","article-title":"The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells","volume":"9","author":"Carracedo","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1124\/mol.65.4.999","article-title":"Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism","volume":"65","author":"Carrier","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.ajpath.2012.11.024","article-title":"Activation of cannabinoid CB2 receptor-mediated AMPK\/CREB pathway reduces cerebral ischemic injury","volume":"182","author":"Choi","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.febslet.2004.10.064","article-title":"Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways","volume":"577","author":"Gertsch","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5084","DOI":"10.1016\/j.febslet.2005.08.021","article-title":"p38 MAPK is involved in CB2 receptor-induced apoptosis of human leukaemia cells","volume":"579","author":"Herrera","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1096\/fj.06-6164fje","article-title":"Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation","volume":"20","author":"Palazuelos","year":"2006","journal-title":"FASEB J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4953","DOI":"10.4049\/jimmunol.170.10.4953","article-title":"Differential roles of CB1 and CB2 cannabinoid receptors in mast cells","volume":"170","author":"Samson","year":"2003","journal-title":"J. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0006-2952(95)00109-D","article-title":"Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors","volume":"50","author":"Mechoulam","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"ref_94","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_95","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1098\/rstb.2011.0382","article-title":"Why do cannabinoid receptors have more than one endogenous ligand?","volume":"367","year":"2012","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1124\/pr.110.003004","article-title":"International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: Beyond CB(1) and CB(2)","volume":"62","author":"Pertwee","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1016\/j.neuropharm.2012.02.008","article-title":"Differential role of CB1 and TRPV1 receptors on anandamide modulation of defensive responses induced by nitric oxide in the dorsolateral periaqueductal gray","volume":"62","author":"Lisboa","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1111\/bph.13497","article-title":"An update on PPAR activation by cannabinoids","volume":"173","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_99","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_100","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1523\/JNEUROSCI.19-11-04544.1999","article-title":"Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons","volume":"19","author":"Katona","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0301-0082(02)00080-1","article-title":"Retrograde signaling in the regulation of synaptic transmission: Focus on endocannabinoids","volume":"68","author":"Alger","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nrn4036","article-title":"The endocannabinoid system in guarding against fear, anxiety and stress","volume":"16","author":"Lutz","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"13345","DOI":"10.1073\/pnas.0601832103","article-title":"A biosynthetic pathway for anandamide","volume":"103","author":"Liu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_104","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_105","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2174\/092986607780090829","article-title":"Critical Enzymes Involved in Endocannabinoid Metabolism","volume":"14","author":"Basavarajappa","year":"2007","journal-title":"Protein Pept. Lett."},{"key":"ref_106","unstructured":"Dunn, B. (2014). Major Enzymes of Endocannabinoid Metabolism. Frontiers in Protein and Peptide Sciences, Bentham Science Publishers."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5899","DOI":"10.1021\/cr2002799","article-title":"Endocannabinoid oxygenation by cyclooxygenases, lipoxygenases, and cytochromes P450: Cross-talk between the eicosanoid and endocannabinoid signaling pathways","volume":"111","author":"Rouzer","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1152\/physrev.00002.2016","article-title":"From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology","volume":"96","author":"Ligresti","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1073\/pnas.85.14.5274","article-title":"Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats","volume":"85","author":"Imperato","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.neubiorev.2005.04.016","article-title":"The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse?","volume":"30","author":"Pierce","year":"2006","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0031-6997(25)07220-5","article-title":"Demonstration and mapping of central neurons containing dopamine, noradrenaline, and 5-hydroxytryptamine and their reactions to psychopharmaca","volume":"18","author":"Hillarp","year":"1966","journal-title":"Pharmacol. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1523\/JNEUROSCI.3823-03.2004","article-title":"Dopamine operates as a subsecond modulator of food seeking","volume":"24","author":"Roitman","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/nature01476","article-title":"Subsecond dopamine release promotes cocaine seeking","volume":"422","author":"Phillips","year":"2003","journal-title":"Nature"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1523\/JNEUROSCI.4152-06.2007","article-title":"Phasic dopamine release evoked by abused substances requires cannabinoid receptor activation","volume":"27","author":"Cheer","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0165-0173(98)00019-8","article-title":"What is the role of dopamine in reward: Hedonic impact, reward learning, or incentive salience?","volume":"28","author":"Berridge","year":"1998","journal-title":"Brain Res. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1037\/h0025306","article-title":"Neuropsychological interpretation of the effects of drive and incentive-motivation on general and instrumental behavior","volume":"75","author":"Bindra","year":"1968","journal-title":"Psychol. Rev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature09588","article-title":"A selective role for dopamine in stimulus-reward learning","volume":"469","author":"Flagel","year":"2011","journal-title":"Nature"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"16585","DOI":"10.1523\/JNEUROSCI.3958-10.2010","article-title":"The flexible approach hypothesis: Unification of effort and cue-responding hypotheses for the role of nucleus accumbens dopamine in the activation of reward-seeking behavior","volume":"30","author":"Nicola","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1111\/j.1460-9568.2009.06916.x","article-title":"Neural encoding of cocaine-seeking behavior is coincident with phasic dopamine release in the accumbens core and shell","volume":"30","author":"Ariansen","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neuropharm.2008.07.043","article-title":"Neurobiological substrates for the dark side of compulsivity in addiction","volume":"56","author":"Koob","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1749-6632.2001.tb03556.x","article-title":"Compulsive drug-seeking behavior and relapse. Neuroadaptation, stress, and conditioning factors","volume":"937","author":"Weiss","year":"2001","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.cub.2018.03.037","article-title":"Phasic Dopamine Signals in the Nucleus Accumbens that Cause Active Avoidance Require Endocannabinoid Mobilization in the Midbrain","volume":"28","author":"Wenzel","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1523\/JNEUROSCI.0529-04.2004","article-title":"Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats","volume":"24","author":"Cheer","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/BF02245916","article-title":"Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis","volume":"102","author":"Chen","year":"1990","journal-title":"Psychopharmacology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1126\/science.276.5321.2048","article-title":"Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism","volume":"276","author":"Tanda","year":"1997","journal-title":"Science"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0304-3940(97)00278-4","article-title":"delta9-Tetrahydrocannabinol excites rat VTA dopamine neurons through activation of cannabinoid CB1 but not opioid receptors","volume":"226","author":"French","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0014-2999(97)01442-8","article-title":"Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors","volume":"341","author":"Gessa","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.neuron.2017.02.025","article-title":"Cell-Autonomous Excitation of Midbrain Dopamine Neurons by Endocannabinoid-Dependent Lipid Signaling","volume":"93","author":"Gantz","year":"2017","journal-title":"Neuron"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1523\/JNEUROSCI.3884-09.2010","article-title":"Glutamatergic and nonglutamatergic neurons of the ventral tegmental area establish local synaptic contacts with dopaminergic and nondopaminergic neurons","volume":"30","author":"Dobi","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0361-9230(82)90145-9","article-title":"The projections of the ventral tegmental area and adjacent regions: A combined fluorescent retrograde tracer and immunofluorescence study in the rat","volume":"9","author":"Swanson","year":"1982","journal-title":"Brain Res. Bull."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"11070","DOI":"10.1523\/JNEUROSCI.3695-04.2004","article-title":"Independent presynaptic and postsynaptic mechanisms regulate endocannabinoid signaling at multiple synapses in the ventral tegmental area","volume":"24","author":"Riegel","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S0306-4522(00)00241-4","article-title":"Lack of response suppression follows repeated ventral tegmental cannabinoid administration: An in vitro electrophysiological study","volume":"99","author":"Cheer","year":"2000","journal-title":"Neuroscience"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1046\/j.1460-9568.2002.02041.x","article-title":"Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids","volume":"15","author":"Szabo","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.neuropharm.2005.03.016","article-title":"Endocannabinoid release from midbrain dopamine neurons: A potential substrate for cannabinoid receptor antagonist treatment of addiction","volume":"48","author":"Lupica","year":"2005","journal-title":"Neuropharmacology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.neuint.2009.01.017","article-title":"Neurochemical evidence that stimulation of CB1 cannabinoid receptors on GABAergic nerve terminals activates the dopaminergic reward system by increasing dopamine release in the rat nucleus accumbens","volume":"54","author":"Sperlagh","year":"2009","journal-title":"Neurochem. Int."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1523\/JNEUROSCI.21-01-00109.2001","article-title":"Localization and mechanisms of action of cannabinoid receptors at the glutamatergic synapses of the mouse nucleus accumbens","volume":"21","author":"Robbe","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"100951","DOI":"10.1016\/j.isci.2020.100951","article-title":"Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior","volume":"23","author":"Bilbao","year":"2020","journal-title":"iScience"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1369-1600.2011.00432.x","article-title":"Role of mGluR5 neurotransmission in reinstated cocaine-seeking","volume":"18","author":"Wang","year":"2013","journal-title":"Addict. Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2174\/1874473710902010083","article-title":"Metabotropic glutamate receptor ligands as potential therapeutics for addiction","volume":"2","author":"Olive","year":"2009","journal-title":"Curr. Drug Abus. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"8384","DOI":"10.1073\/pnas.122149199","article-title":"Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens","volume":"99","author":"Robbe","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"10230","DOI":"10.1523\/JNEUROSCI.1712-16.2016","article-title":"Drug-Induced Alterations of Endocannabinoid-Mediated Plasticity in Brain Reward Regions","volume":"36","author":"Zlebnik","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"11973","DOI":"10.1523\/JNEUROSCI.2550-10.2010","article-title":"Incentive learning underlying cocaine-seeking requires mGluR5 receptors located on dopamine D1 receptor-expressing neurons","volume":"30","author":"Novak","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/syn.20047","article-title":"Immunolocalization of CB1 receptor in rat striatal neurons: A confocal microscopy study","volume":"53","author":"Fusco","year":"2004","journal-title":"Synapse"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.cell.2018.12.011","article-title":"Crystal Structure of the Human Cannabinoid Receptor CB2","volume":"176","author":"Li","year":"2019","journal-title":"Cell"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1038\/npp.2017.53","article-title":"The GABA(B) Positive Allosteric Modulator ADX71441 Attenuates Alcohol Self-Administration and Relapse to Alcohol Seeking in Rats","volume":"42","author":"Augier","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/adb.12645","article-title":"Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level","volume":"23","author":"Addolorato","year":"2018","journal-title":"Addict. Biol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e09275","DOI":"10.7554\/eLife.09275","article-title":"Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation","volume":"4","author":"Chen","year":"2015","journal-title":"Elife"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuropharm.2010.04.013","article-title":"Delta9-tetrahydrocannabinol is a full agonist at CB1 receptors on GABA neuron axon terminals in the hippocampus","volume":"59","author":"Laaris","year":"2010","journal-title":"Neuropharmacology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0026-895X(24)23149-7","article-title":"Delta9-tetrahydrocannabinol acts as a partial agonist to modulate glutamatergic synaptic transmission between rat hippocampal neurons in culture","volume":"55","author":"Shen","year":"1999","journal-title":"Mol. Pharmacol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"4322","DOI":"10.1523\/JNEUROSCI.16-14-04322.1996","article-title":"Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission in rat hippocampal cultures","volume":"16","author":"Shen","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/npp.2016.275","article-title":"A Feedforward Inhibitory Circuit Mediated by CB1-Expressing Fast-Spiking Interneurons in the Nucleus Accumbens","volume":"42","author":"Wright","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"273","DOI":"10.2174\/156720511795563700","article-title":"FTD and ALS: A tale of two diseases","volume":"8","author":"Ferrari","year":"2011","journal-title":"Curr. Alzheimer Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1212\/01.wnl.0000438219.39061.da","article-title":"Familial clustering of ALS in a population-based resource","volume":"82","author":"Gibson","year":"2014","journal-title":"Neurology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"371","DOI":"10.12688\/f1000research.10476.1","article-title":"What causes amyotrophic lateral sclerosis?","volume":"6","author":"Martin","year":"2017","journal-title":"F1000Research"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/mds.20324","article-title":"Sydney Multicenter Study of Parkinson\u2019s disease: Non-L-dopa-responsive problems dominate at 15 years","volume":"20","author":"Hely","year":"2005","journal-title":"Mov. Disord."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1136\/jnnp.2010.232678","article-title":"Dementia in Parkinson\u2019s disease: A 20-year neuropsychological study (Sydney Multicentre Study)","volume":"82","author":"Reid","year":"2011","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/7854_2025_597","article-title":"Ageing, Neurodegeneration and the Endocannabinoid System","volume":"76","author":"Sagredo","year":"2025","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Meanti, R., Bresciani, E., Rizzi, L., Molteni, L., Coco, S., Omeljaniuk, R.J., and Torsello, A. (2025). Cannabinoid Receptor 2 (CB2R) as potential target for the pharmacological treatment of neurodegenerative diseases. Biomed. Pharmacother., 186.","DOI":"10.1016\/j.biopha.2025.118044"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Oh, T.K., and Song, I.A. (2024). Impact of prescribed opioid use on development of dementia among patients with chronic non-cancer pain. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-53728-3"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Beheshti, I. (2023). Cocaine Destroys Gray Matter Brain Cells and Accelerates Brain Aging. Biology, 12.","DOI":"10.3390\/biology12050752"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Rebolledo-Perez, L., Hernandez-Bello, J., Martinez-Ramos, A., Castaneda-Arellano, R., Fernandez-Quezada, D., Sandoval-Garcia, F., and Aguilar-Garcia, I.G. (2025). Substance Abuse and Cognitive Decline: The Critical Role of Tau Protein as a Potential Biomarker. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157638"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Peng, B., Yang, Q., R, B.J., Liu, Y., Akbar, M., Song, B.J., Zhou, S., and Wang, X. (2020). Role of Alcohol Drinking in Alzheimer\u2019s Disease, Parkinson\u2019s Disease, and Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072316"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"k2927","DOI":"10.1136\/bmj.k2927","article-title":"Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study","volume":"362","author":"Sabia","year":"2018","journal-title":"BMJ"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e1910319","DOI":"10.1001\/jamanetworkopen.2019.10319","article-title":"Alcohol Consumption and Risk of Dementia and Cognitive Decline Among Older Adults With or Without Mild Cognitive Impairment","volume":"2","author":"Koch","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1111\/acer.13256","article-title":"Long-Lasting Effects of Chronic Intermittent Alcohol Exposure in Adolescent Mice on Object Recognition and Hippocampal Neuronal Activity","volume":"40","author":"Beaudet","year":"2016","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1744-9081-8-32","article-title":"Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice","volume":"8","author":"Aguilar","year":"2012","journal-title":"Behav. Brain Funct."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/j.1530-0277.2010.01385.x","article-title":"Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice","volume":"35","author":"Coleman","year":"2011","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/adb.12667","article-title":"Cognitive and neurobehavioral benefits of an enriched environment on young adult mice after chronic ethanol consumption during adolescence","volume":"24","author":"Penasco","year":"2019","journal-title":"Addict. Biol."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Montagud-Romero, S., Daza-Losada, M., Vidal-Infer, A., Maldonado, C., Aguilar, M.A., Minarro, J., and Rodriguez-Arias, M. (2014). The novelty-seeking phenotype modulates the long-lasting effects of intermittent ethanol administration during adolescence. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092576"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.alcohol.2009.10.003","article-title":"Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence","volume":"44","author":"Guerri","year":"2010","journal-title":"Alcohol"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3109\/10408363.2011.580567","article-title":"Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain","volume":"48","author":"Guerri","year":"2011","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/aje\/kwi043","article-title":"Association between reported alcohol intake and cognition: Results from the Women\u2019s Health Initiative Memory Study","volume":"161","author":"Espeland","year":"2005","journal-title":"Am. J. Epidemiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1212\/01.wnl.0000180520.35181.24","article-title":"Alcohol consumption and cognitive function in late life: A longitudinal community study","volume":"65","author":"Ganguli","year":"2005","journal-title":"Neurology"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1056\/NEJMoa041152","article-title":"Effects of moderate alcohol consumption on cognitive function in women","volume":"352","author":"Stampfer","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1111\/j.1532-5415.2008.02007.x","article-title":"Does low to moderate alcohol intake protect against cognitive decline in older people?","volume":"56","author":"Stott","year":"2008","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1093\/aje\/kwq187","article-title":"Is there an association between low-to-moderate alcohol consumption and risk of cognitive decline?","volume":"172","author":"Lobo","year":"2010","journal-title":"Am. J. Epidemiol."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Yen, F.S., Wang, S.I., Lin, S.Y., Chao, Y.H., and Wei, J.C. (2022). The Impact of Alcohol Consumption on Cognitive Impairment in Patients With Diabetes, Hypertension, or Chronic Kidney Disease. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1027146"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1212\/01.wnl.0000453101.10188.87","article-title":"Alcohol consumption and cognitive decline in early old age","volume":"83","author":"Kabai","year":"2014","journal-title":"Neurology"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Kim, J.W., Byun, M.S., Yi, D., Lee, J.H., Ko, K., Jeon, S.Y., Sohn, B.K., Lee, J.Y., Kim, Y.K., and Shin, S.A. (2020). Association of moderate alcohol intake with in vivo amyloid-beta deposition in human brain: A cross-sectional study. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003022"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41398-021-01374-y","article-title":"Imaging beta-amyloid (Abeta) burden in the brains of middle-aged individuals with alcohol-use disorders: A [11C]PIB PET study","volume":"11","author":"Flanigan","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1001\/jama.289.11.1405","article-title":"Prospective study of alcohol consumption and risk of dementia in older adults","volume":"289","author":"Mukamal","year":"2003","journal-title":"JAMA"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/gps.2372","article-title":"The effect of alcohol and tobacco consumption, and apolipoprotein E genotype, on the age of onset in Alzheimer\u2019s disease","volume":"25","author":"Harwood","year":"2010","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1002\/mds.25050","article-title":"Alcohol and risk of Parkinson\u2019s disease in a large, prospective cohort of men and women","volume":"27","author":"Palacios","year":"2012","journal-title":"Mov. Disord."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Eriksson, A.K., Lofving, S., Callaghan, R.C., and Allebeck, P. (2013). Alcohol use disorders and risk of Parkinson\u2019s disease: Findings from a Swedish national cohort study 1972\u20132008. BMC Neurol., 13.","DOI":"10.1186\/1471-2377-13-190"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/jnc.14151","article-title":"Enhanced motivation to alcohol in transgenic mice expressing human alpha-synuclein","volume":"143","author":"Rotermund","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1136\/jnnp-2018-318559","article-title":"Association between alcohol exposure and the risk of amyotrophic lateral sclerosis in the Euro-MOTOR study","volume":"90","author":"Rooney","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"451-a.e2-451.e2","DOI":"10.1176\/jnp.2010.22.4.451.e2","article-title":"Delayed Huntington\u2019s disease diagnosis in two alcoholic patients with a family history of \u201cParkinson\u2019s disease\u201d","volume":"22","author":"Mesquita","year":"2010","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-3-030-21737-2_6","article-title":"Endocannabinoid System and Alcohol Abuse Disorders","volume":"1162","author":"Basavarajappa","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1111\/bph.14780","article-title":"Distinct functions of endogenous cannabinoid system in alcohol abuse disorders","volume":"176","author":"Basavarajappa","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"09","DOI":"10.35946\/arcr.v42.1.09","article-title":"Alcohol-Endocannabinoid Interactions: Implications for Addiction-Related Behavioral Processes","volume":"42","author":"Serrano","year":"2022","journal-title":"Alcohol Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"03","DOI":"10.35946\/arcr.v42.1.03","article-title":"The Synaptic Interactions of Alcohol and the Endogenous Cannabinoid System","volume":"42","author":"Wolfe","year":"2022","journal-title":"Alcohol Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1038\/s41386-018-0055-3","article-title":"Deficient endocannabinoid signaling in the central amygdala contributes to alcohol dependence-related anxiety-like behavior and excessive alcohol intake","volume":"43","author":"Serrano","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Rivera, P., Blanco, E., Bindila, L., Alen, F., Vargas, A., Rubio, L., Pavon, F.J., Serrano, A., Lutz, B., and Rodriguez de Fonseca, F. (2015). Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00379"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"134408","DOI":"10.1016\/j.neulet.2019.134408","article-title":"URB597 ameliorates the deleterious effects induced by binge alcohol consumption in adolescent rats","volume":"711","author":"Bellozi","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Sanchez-Marin, L., Pavon, F.J., Decara, J., Suarez, J., Gavito, A., Castilla-Ortega, E., Rodriguez de Fonseca, F., and Serrano, A. (2017). Effects of Intermittent Alcohol Exposure on Emotion and Cognition: A Potential Role for the Endogenous Cannabinoid System and Neuroinflammation. Front. Behav. Neurosci., 11.","DOI":"10.3389\/fnbeh.2017.00015"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.drugalcdep.2011.02.003","article-title":"Involvement of the endocannabinoid system in alcohol dependence: The biochemical, behavioral and genetic evidence","volume":"117","author":"Erdozain","year":"2011","journal-title":"Drug Alcohol Depend."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s41386-018-0181-y","article-title":"CB1R regulates CDK5 signaling and epigenetically controls Rac1 expression contributing to neurobehavioral abnormalities in mice postnatally exposed to ethanol","volume":"44","author":"Joshi","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/jnc.13006","article-title":"CB1-receptor knockout neonatal mice are protected against ethanol-induced impairments of DNMT1, DNMT3A, and DNA methylation","volume":"132","author":"Nagre","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Subbanna, S., and Basavarajappa, B.S. (2020). Postnatal Ethanol-Induced Neurodegeneration Involves CB1R-Mediated beta-Catenin Degradation in Neonatal Mice. Brain Sci., 10.","DOI":"10.3390\/brainsci10050271"},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Subbanna, S., Nagre, N.N., Shivakumar, M., Joshi, V., Psychoyos, D., Kutlar, A., Umapathy, N.S., and Basavarajappa, B.S. (2018). CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00045"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/jnc.13120","article-title":"Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice","volume":"134","author":"Subbanna","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Ledesma, J.C., Rodriguez-Arias, M., Gavito, A.L., Sanchez-Perez, A.M., Vina, J., Medina Vera, D., Rodriguez de Fonseca, F., and Minarro, J. (2021). Adolescent binge-ethanol accelerates cognitive impairment and beta-amyloid production and dysregulates endocannabinoid signaling in the hippocampus of APP\/PSE mice. Addict. Biol., 26.","DOI":"10.1111\/adb.12883"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12974-023-02792-z","article-title":"Preclinical investigation in FAAH inhibition as a neuroprotective therapy for frontotemporal dementia using TDP-43 transgenic male mice","volume":"20","author":"Villegas","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/glia.24638","article-title":"Fatty acid amide hydrolase gene inactivation induces hetero-cellular potentiation of microglial function in the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"73","author":"Arnanz","year":"2025","journal-title":"Glia"},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Armeli, F., Coccurello, R., Giacovazzo, G., Mengoni, B., Paoletti, I., Oddi, S., Maccarrone, M., and Businaro, R. (2024). FAAH Inhibition Counteracts Neuroinflammation via Autophagy Recovery in AD Models. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212044"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s40478-021-01196-5","article-title":"Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration","volume":"9","author":"Hernandez","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/7854_2022_410","article-title":"Epigenetic Dysregulation in Alcohol-Associated Behaviors: Preclinical and Clinical Evidence","volume":"71","author":"Domi","year":"2025","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Lamb, K.A., Margetts, A.V., Volmar, C.H., Bourgain-Guglielmetti, F., Wahlestedt, C., and Tuesta, L.M. (2025). Dysregulation of Central-Medial Amygdala Histone Modifiers in Preclinical Models of Ethanol Exposure. Addict. Biol., 30.","DOI":"10.1111\/adb.70095"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"e172885","DOI":"10.1172\/JCI172885","article-title":"Human genetics and epigenetics of alcohol use disorder","volume":"134","author":"Zhou","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Basavarajappa, B.S., and Subbanna, S. (2022). Molecular Insights into Epigenetics and Cannabinoid Receptors. Biomolecules, 12.","DOI":"10.3390\/biom12111560"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"NS20220034","DOI":"10.1042\/NS20220034","article-title":"Endocannabinoid signaling and epigenetics modifications in the neurobiology of stress-related disorders","volume":"7","author":"Coelho","year":"2023","journal-title":"Neuronal Signal."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1111\/febs.12125","article-title":"Epigenetic mechanisms and endocannabinoid signalling","volume":"280","author":"Pucci","year":"2013","journal-title":"FEBS J."},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Meccariello, R., Santoro, A., D\u2019Angelo, S., Morrone, R., Fasano, S., Viggiano, A., and Pierantoni, R. (2020). The Epigenetics of the Endocannabinoid System. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031113"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s12640-012-9334-7","article-title":"Psychostimulant abuse and neuroinflammation: Emerging evidence of their interconnection","volume":"23","author":"Clark","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s12640-015-9536-x","article-title":"A Comprehensive View of the Neurotoxicity Mechanisms of Cocaine and Ethanol","volume":"28","author":"Pereira","year":"2015","journal-title":"Neurotox. Res."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"e1582","DOI":"10.1038\/cddis.2014.527","article-title":"Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death","volume":"6","author":"Liu","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1111\/j.1582-4934.2011.01374.x","article-title":"Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders","volume":"15","author":"Doyle","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s11481-013-9438-8","article-title":"Role of endoplasmic reticulum (ER) stress in cocaine-induced microglial cell death","volume":"8","author":"Costa","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1080\/15548627.2016.1183844","article-title":"Cocaine induces astrocytosis through ER stress-mediated activation of autophagy","volume":"12","author":"Periyasamy","year":"2016","journal-title":"Autophagy"},{"key":"ref_220","first-page":"512","article-title":"Alzheimer-like phosphorylation of tau and neurofilament induced by cocaine in vivo","volume":"24","author":"Liu","year":"2003","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1300\/J006v16n01_09","article-title":"Fetal Cocaine Exposure: Neurologic Effects and Sensory-Motor Delays","volume":"16","author":"Arendt","year":"1996","journal-title":"Phys. Occup. Ther. Pediatr."},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Ferreira, C., Almeida, C., Tenreiro, S., and Quintas, A. (2020). Neuroprotection or Neurotoxicity of Illicit Drugs on Parkinson\u2019s Disease. Life, 10.","DOI":"10.3390\/life10060086"},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Wen, S., Aki, T., Funakoshi, T., Unuma, K., and Uemura, K. (2022). Role of Mitochondrial Dynamics in Cocaine\u2019s Neurotoxicity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105418"},{"key":"ref_224","first-page":"916","article-title":"Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis","volume":"15","author":"Lee","year":"2001","journal-title":"FASEB J."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1097\/01.wnr.0000175617.39054.ba","article-title":"Cocaine abuse elevates alpha-synuclein and dopamine transporter levels in the human striatum","volume":"16","author":"Qin","year":"2005","journal-title":"Neuroreport"},{"key":"ref_226","first-page":"66","article-title":"Psychomotor and electroencephalographic sequelae of cocaine dependence","volume":"163","author":"Bauer","year":"1996","journal-title":"NIDA Res. Monogr."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1159\/000318084","article-title":"Cocaine use and abuse triggering sporadic young-onset amyotrophic lateral sclerosis","volume":"8","author":"Argyriou","year":"2011","journal-title":"Neurodegener. Dis."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-3-0348-8833-2_4","article-title":"Glutamatergic involvement in psychomotor stimulant action","volume":"50","author":"Rockhold","year":"1998","journal-title":"Prog. Drug Res."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/mus.10186","article-title":"Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis","volume":"26","author":"Heath","year":"2002","journal-title":"Muscle Nerve"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/jpi.12195","article-title":"Liposomal melatonin rescues methamphetamine-elicited mitochondrial burdens, pro-apoptosis, and dopaminergic degeneration through the inhibition PKCdelta gene","volume":"58","author":"Nguyen","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"101062","DOI":"10.1016\/j.arr.2020.101062","article-title":"The multi-faceted impact of methamphetamine on Alzheimer\u2019s disease: From a triggering role to a possible therapeutic use","volume":"60","author":"Shukla","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_232","first-page":"308052","article-title":"Methamphetamine and Parkinson\u2019s disease","volume":"2013","author":"Granado","year":"2013","journal-title":"Park. Dis."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/joim.12049","article-title":"The role of dopamine receptors in the neurotoxicity of methamphetamine","volume":"273","author":"Granado","year":"2013","journal-title":"J. Intern. Med."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/npp.2013.307","article-title":"Methamphetamine causes degeneration of dopamine cell bodies and terminals of the nigrostriatal pathway evidenced by silver staining","volume":"39","author":"Granado","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2131\/jts.44.493","article-title":"Methamphetamine exposure upregulates the amyloid precursor protein and hyperphosphorylated tau expression: The roles of insulin signaling in SH-SY5Y cell line","volume":"44","author":"Chen","year":"2019","journal-title":"J. Toxicol. Sci."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.drugalcdep.2011.06.013","article-title":"Increased risk of Parkinson\u2019s disease in individuals hospitalized with conditions related to the use of methamphetamine or other amphetamine-type drugs","volume":"120","author":"Callaghan","year":"2012","journal-title":"Drug Alcohol Depend."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.brainres.2019.05.035","article-title":"Methamphetamine persistently increases alpha-synuclein and suppresses gene promoter methylation within striatal neurons","volume":"1719","author":"Biagioni","year":"2019","journal-title":"Brain Res."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"115194","DOI":"10.1016\/j.biopha.2023.115194","article-title":"The FAAH inhibitor URB597 reduces cocaine intake during conditioned punishment and mitigates cocaine seeking during withdrawal","volume":"165","author":"Medrano","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"101597","DOI":"10.1016\/j.molmet.2022.101597","article-title":"Endocannabinoids regulate cocaine-associated memory through brain AEA-CB1R signalling activation","volume":"65","author":"Li","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"8531","DOI":"10.1523\/JNEUROSCI.0726-06.2006","article-title":"Cannabinoid CB1 receptor antagonist AM251 inhibits cocaine-primed relapse in rats: Role of glutamate in the nucleus accumbens","volume":"26","author":"Xi","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/sj.npp.1301552","article-title":"Cannabinoid CB1 receptor antagonists attenuate cocaine\u2019s rewarding effects: Experiments with self-administration and brain-stimulation reward in rats","volume":"33","author":"Xi","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Heinbockel, T., and Csoka, A.B. (2018). Epigenetic Effects of Drugs of Abuse. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15102098"},{"key":"ref_243","doi-asserted-by":"crossref","unstructured":"Anderson, E.M., and Taniguchi, M. (2022). Epigenetic Effects of Addictive Drugs in the Nucleus Accumbens. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.828055"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000544912","article-title":"Epigenetic Insights into Substance Use Disorder and Associated Psychiatric Conditions","volume":"11","author":"Ngo","year":"2025","journal-title":"Complex Psychiatry"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"111401","DOI":"10.1016\/j.drugalcdep.2024.111401","article-title":"Epigenetic effects of cannabis: A systematic scoping review of behavioral and emotional symptoms associated with cannabis use and exocannabinoid exposure","volume":"263","author":"Machado","year":"2024","journal-title":"Drug Alcohol Depend."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s00702-023-02716-4","article-title":"Astrocytic transcriptional and epigenetic mechanisms of drug addiction","volume":"131","author":"Holt","year":"2024","journal-title":"J. Neural Transm."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s13311-015-0381-7","article-title":"Cannabinoids in Neurodegenerative Disorders and Stroke\/Brain Trauma: From Preclinical Models to Clinical Applications","volume":"12","author":"Moro","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/978-3-319-20825-1_8","article-title":"Endocannabinoids and Neurodegenerative Disorders: Parkinson\u2019s Disease, Huntington\u2019s Chorea, Alzheimer\u2019s Disease, and Others","volume":"Volume 231","author":"Romero","year":"2015","journal-title":"Handbook of Experimental Pharmacology"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.1088208","article-title":"CB1 cannabinoid receptors and on-demand defense against excitotoxicity","volume":"302","author":"Marsicano","year":"2003","journal-title":"Science"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1111\/jnc.15922","article-title":"Type-1 cannabinoid receptors and their ever-expanding roles in brain energy processes","volume":"168","author":"Rodrigues","year":"2024","journal-title":"J. Neurochem."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1096\/fj.07-102731","article-title":"Regulation of CB1 cannabinoid receptor trafficking by the adaptor protein AP-3","volume":"22","author":"Rozenfeld","year":"2008","journal-title":"FASEB J."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"29166","DOI":"10.1074\/jbc.M110.217463","article-title":"Intracellular cannabinoid type 1 (CB1) receptors are activated by anandamide","volume":"286","author":"Brailoiu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/sj.bjp.0707466","article-title":"CB2 cannabinoid receptors as an emerging target for demyelinating diseases: From neuroimmune interactions to cell replacement strategies","volume":"153","author":"Gomez","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuint.2011.10.019","article-title":"CB(1) receptor activation inhibits neuronal and astrocytic intermediary metabolism in the rat hippocampus","volume":"60","author":"Duarte","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"6470","DOI":"10.1523\/JNEUROSCI.23-16-06470.2003","article-title":"Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia","volume":"23","author":"Pinteaux","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/glia.20983","article-title":"Cannabinoid and cannabinoid-like receptors in microglia, astrocytes, and astrocytomas","volume":"58","author":"Stella","year":"2010","journal-title":"Glia"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2174\/157015907780866884","article-title":"The cannabinoid CB2 receptor as a target for inflammation-dependent neurodegeneration","volume":"5","author":"Ashton","year":"2007","journal-title":"Curr. Neuropharmacol."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"11136","DOI":"10.1523\/JNEUROSCI.23-35-11136.2003","article-title":"Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer\u2019s disease brains","volume":"23","author":"Benito","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1017\/S1462399409000957","article-title":"Emerging role of the cannabinoid receptor CB2 in immune regulation: Therapeutic prospects for neuroinflammation","volume":"11","author":"Cabral","year":"2009","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_260","doi-asserted-by":"crossref","unstructured":"Cassano, T., Calcagnini, S., Pace, L., De Marco, F., Romano, A., and Gaetani, S. (2017). Cannabinoid Receptor 2 Signaling in Neurodegenerative Disorders: From Pathogenesis to a Promising Therapeutic Target. Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00030"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1111\/bph.12607","article-title":"Regulatory role of the cannabinoid CB2 receptor in stress-induced neuroinflammation in mice","volume":"171","author":"Zoppi","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jns.2014.04.034","article-title":"Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats","volume":"342","author":"Fujii","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1089\/can.2021.0101","article-title":"Endocannabinoid System of the Blood-Brain Barrier: Current Understandings and Therapeutic Potentials","volume":"7","author":"Hagan","year":"2022","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.neuropharm.2011.02.016","article-title":"Modulation of the serotonin system by endocannabinoid signaling","volume":"61","author":"Shen","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s12035-007-8008-6","article-title":"Endocannabinoids and traumatic brain injury","volume":"36","author":"Mechoulam","year":"2007","journal-title":"Mol. Neurobiol."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1007\/s12017-014-8314-x","article-title":"Functions of the CB1 and CB 2 receptors in neuroprotection at the level of the blood-brain barrier","volume":"16","author":"Vendel","year":"2014","journal-title":"NeuroMolecular Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11632\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T05:15:52Z","timestamp":1764738952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,30]]},"references-count":266,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311632"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311632","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,30]]}}}