Skip to content
2000
Volume 22, Issue 2
  • ISSN: 1567-2026
  • E-ISSN: 1875-5739

Abstract

Introduction

An essential component of the endocannabinoid system, cannabinoid receptor type 1 (CB1) is primarily expressed in the central nervous system, where it regulates several neurophysiological activities. Neurotransmitter release, synaptic plasticity, mood modulation, and cognitive processes are all influenced by CB1 receptors. The CB1 receptor is closely linked to a wide range of brain-related disorders, and regulating its activity may be a way to treat several brain-related diseases.

Methods

Literature search across Google Scholar, Scopus, PubMed, and Web of Science, covering publications from 1985 to 2025, aimed to gather extensive information on the pharmacological role of the CB1 receptor in various brain illnesses. Using keywords such as “CB1,” “Brain,” “Epilepsy,” “Alzheimer’s,” “Parkinson’s disease,” “Neuroprotection,” and “Neurodegeneration,” this review consolidates existing knowledge and identifies potential avenues for future research.

Results

This study incorporates pre-clinical evidence and highlights the involvement of the CB1 receptor in etiologies, symptoms, and treatments related to distinct brain-related disorders.

Discussion

Potential treatment strategies that target the endocannabinoid system and the intricate relationship between CB1 receptor activity and its consequences in several brain disorders, including Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, depression, anxiety, ., have been discussed. Additionally, the difficulties and disputes related to CB1 receptor modulation, including the contradictory actions of CB1 receptor agonists and antagonists, are also addressed.

Conclusion

The CB1 receptor is a promising therapeutic target for brain disorders due to its key role in regulating various physiological functions in the CNS, suggesting potential for the treatment of several brain disorders.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cnr/10.2174/0115672026403497250910124233
2025-09-17
2026-03-03

  • From This Site

    /content/journals/cnr/10.2174/0115672026403497250910124233
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. MateiD. TrofinD. IordanD.A. The endocannabinoid system and physical exercise.Int. J. Mol. Sci.2023243198910.3390/ijms24031989 36768332
     [Google Scholar]
  2. HillM.N. HaneyM. HillardC.J. KarhsonD.S. VecchiarelliH.A. The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses.Psychol. Med.202353157006702410.1017/S0033291723002465 37671673
     [Google Scholar]
  3. ChandaD. NeumannD. GlatzJ.F.C. The endocannabinoid system: Overview of an emerging multi-faceted therapeutic target.Prostaglandins Leukot. Essent. Fatty Acids2019140515610.1016/j.plefa.2018.11.016 30553404
     [Google Scholar]
  4. MarzoV.D. BifulcoM. PetrocellisL.D. The endocannabinoid system and its therapeutic exploitation.Nat. Rev. Drug Discov.20043977178410.1038/nrd1495 15340387
     [Google Scholar]
  5. MusellaA. CentonzeD. Electrophysiology of endocannabinoid signaling.Methods Mol. Biol.2023257646147510.1007/978‑1‑0716‑2728‑0_38 36152210
     [Google Scholar]
  6. OyagawaC.R.M. GrimseyN.L. Cannabinoid receptor CB1 and CB2 interacting proteins: Techniques, progress and perspectives.Methods Cell Biol.20211668313210.1016/bs.mcb.2021.06.011 34752341
     [Google Scholar]
  7. Eraso-PichotA. PouvreauS. Olivera-PintoA. Gomez-SotresP. SkupioU. MarsicanoG. Endocannabinoid signaling in astrocytes.Glia2023711445910.1002/glia.24246 35822691
     [Google Scholar]
  8. Martinez RamirezC.E. Ruiz-PérezG. StollenwerkT.M. BehlkeC. DohertyA. HillardC.J. Endocannabinoid signaling in the central nervous system.Glia202371153510.1002/glia.24280 36308424
     [Google Scholar]
  9. MurataevaN. StraikerA. MackieK. Parsing the players: 2‐arachidonoylglycerol synthesis and degradation in the CNS.Br. J. Pharmacol.201417161379139110.1111/bph.12411 24102242
     [Google Scholar]
  10. KatonaI. FreundT.F. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease.Nat. Med.200814992393010.1038/nm.f.1869 18776886
     [Google Scholar]
  11. BorganF. KokkinouM. HowesO. The cannabinoid CB1 receptor in schizophrenia.Biol. Psychiatry Cogn. Neurosci. Neuroimaging202166646659 33077399
     [Google Scholar]
  12. MarsicanoG. LutzB. Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain.Eur. J. Neurosci.199911124213422510.1046/j.1460‑9568.1999.00847.x 10594647
     [Google Scholar]
  13. KatonaI. SperlághB. SíkA. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons.J. Neurosci.199919114544455810.1523/JNEUROSCI.19‑11‑04544.1999 10341254
     [Google Scholar]
  14. MarinelliS. PacioniS. BisognoT. The endocannabinoid 2-arachidonoylglycerol is responsible for the slow self-inhibition in neocortical interneurons.J. Neurosci.20082850135321354110.1523/JNEUROSCI.0847‑08.2008 19074027
     [Google Scholar]
  15. Busquets-GarciaA. BainsJ. MarsicanoG. CB1 Receptor signaling in the brain: Extracting specificity from ubiquity.Neuropsychopharmacology201843142010.1038/npp.2017.206 28862250
     [Google Scholar]
  16. Busquets-GarcíaA. BolañosJ.P. MarsicanoG. Metabolic messengers: endocannabinoids.Nat. Metab.20224784885510.1038/s42255‑022‑00600‑1 35817852
     [Google Scholar]
  17. CristinoL. BisognoT. Di MarzoV. Cannabinoids and the expanded endocannabinoid system in neurological disorders.Nat. Rev. Neurol.202016192910.1038/s41582‑019‑0284‑z 31831863
     [Google Scholar]
  18. VasincuA. RusuR.N. AbabeiD.C. Endocannabinoid modulation in neurodegenerative diseases: In pursuit of certainty.Biology202211344010.3390/biology11030440 35336814
     [Google Scholar]
  19. MishraA. MishraP.S. BandopadhyayR. Neuroprotective potential of chrysin: Mechanistic insights and therapeutic potential for neurological disorders.Molecules20212621645610.3390/molecules26216456 34770864
     [Google Scholar]
  20. GoyalA. SinghG. VermaA. A comprehensive review on therapeutic potential of chrysin in brain related disorders.CNS Neurol. Disord. Drug Targets202322678980010.2174/1871527321666220602111935 35657041
     [Google Scholar]
  21. BalaA. GuptaB.M. Parkinson′s disease in India: An analysis of publications output during 2002-2011.Int. J. Nutr. Pharmacol. Neurol. Dis.20133325426210.4103/2231‑0738.114849
     [Google Scholar]
  22. PanditL. KundapurR. Prevalence and patterns of demyelinating central nervous system disorders in urban Mangalore, South India.Mult. Scler.201420121651165310.1177/1352458514521503 24493471
     [Google Scholar]
  23. MishraA. BandopadhyayR. SinghP.K. MishraP.S. SharmaN. KhuranaN. Neuroinflammation in neurological disorders: pharmacotherapeutic targets from bench to bedside.Metab. Brain Dis.20213671591162610.1007/s11011‑021‑00806‑4 34387831
     [Google Scholar]
  24. AlgerB.E. Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids.Prog. Neurobiol.200268424728610.1016/S0301‑0082(02)00080‑1 12498988
     [Google Scholar]
  25. AraqueA. CastilloP.E. ManzoniO.J. ToniniR. Synaptic functions of endocannabinoid signaling in health and disease.Neuropharmacology2017124132410.1016/j.neuropharm.2017.06.017 28625718
     [Google Scholar]
  26. SerratR. CoveloA. KouskoffV. Astroglial ER-mitochondria calcium transfer mediates endocannabinoid-dependent synaptic integration.Cell Rep.202241211149910.1016/j.celrep.2022.111499 36223755
     [Google Scholar]
  27. HanJ. KesnerP. Metna-LaurentM. Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.Cell201214851039105010.1016/j.cell.2012.01.037 22385967
     [Google Scholar]
  28. MartínR. Bajo-GrañerasR. MoratallaR. PereaG. AraqueA. Circuit-specific signaling in astrocyte-neuron networks in basal ganglia pathways.Science2015349624973073410.1126/science.aaa7945 26273054
     [Google Scholar]
  29. RobinL.M. Oliveira da CruzJ.F. LanglaisV.C. Astroglial CB1 receptors determine synaptic D-serine availability to enable recognition memory.Neuron2018985935944.e510.1016/j.neuron.2018.04.034 29779943
     [Google Scholar]
  30. VarshneyV. GarabaduD. Ang(1–7) exerts Nrf2-mediated neuroprotection against amyloid beta-induced cognitive deficits in rodents.Mol. Biol. Rep.20214854319433110.1007/s11033‑021‑06447‑1 34075536
     [Google Scholar]
  31. GoyalA. VermaA. DubeyN. RaghavJ. AgrawalA. Naringenin: A prospective therapeutic agent for Alzheimer’s and Parkinson’s disease.J. Food Biochem.202246121441510.1111/jfbc.14415 36106706
     [Google Scholar]
  32. VarshneyV. GarabaduD. Ang (1–7)/Mas receptor-axis activation promotes amyloid beta-induced altered mitochondrial bioenergetics in discrete brain regions of Alzheimer’s disease-like rats.Neuropeptides20218610212210.1016/j.npep.2021.102122 33508525
     [Google Scholar]
  33. AsherS. PrieferR. Alzheimer’s disease failed clinical trials.Life Sci.202230612086110.1016/j.lfs.2022.120861 35932841
     [Google Scholar]
  34. HippiusH. NeundörferG. The discovery of Alzheimer’s disease.Dialogues Clin. Neurosci.20035110110810.31887/DCNS.2003.5.1/hhippius 22034141
     [Google Scholar]
  35. BerryA.J. ZubkoO. ReevesS.J. HowardR.J. Endocannabinoid system alterations in Alzheimer’s disease: A systematic review of human studies.Brain Res.2020174914713510.1016/j.brainres.2020.147135 32980333
     [Google Scholar]
  36. PalmisanoM. GarganoA. OlabiyiB.F. LutzB. Bilkei-GorzoA. Hippocampal deletion of CB1 receptor impairs social memory and leads to age-related changes in the hippocampus of adult mice.Int. J. Mol. Sci.20222412610.3390/ijms24010026 36613469
     [Google Scholar]
  37. MarchalantY. CerbaiF. BrothersH.M. WenkG.L. Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats.Neurobiol. Aging200829121894190110.1016/j.neurobiolaging.2007.04.028 17561311
     [Google Scholar]
  38. PrudovaA. BaumanZ. BraunA. VitvitskyV. LuS.C. BanerjeeR. S -adenosylmethionine stabilizes cystathionine β-synthase and modulates redox capacity.Proc. Natl. Acad. Sci. USA2006103176489649410.1073/pnas.0509531103 16614071
     [Google Scholar]
  39. AnelloG. Guéant-RodríguezR.M. BoscoP. Homocysteine and methylenetetrahydrofolate reductase polymorphism in Alzheimer’s disease.Neuroreport200415585986110.1097/00001756‑200404090‑00025 15073531
     [Google Scholar]
  40. DongM. LuY. ZhaY. YangH. Endocannabinoid 2-arachidonylglycerol protects primary cultured neurons against homocysteine-induced impairments in rat caudate nucleus through CB1 receptor.J. Mol. Neurosci.201555250050810.1007/s12031‑014‑0371‑y 25007951
     [Google Scholar]
  41. CrunfliF. VrechiT.A. CostaA.P. TorrãoA.S. Cannabinoid receptor type 1 agonist ACEA improves cognitive deficit on STZ-induced neurotoxicity through apoptosis pathway and NO modulation.Neurotox. Res.201935351652910.1007/s12640‑018‑9991‑2 30607903
     [Google Scholar]
  42. AsoE. PalomerE. JuvésS. MaldonadoR. MuñozF.J. FerrerI. CB1 agonist ACEA protects neurons and reduces the cognitive impairment of AβPP/PS1 mice.J. Alzheimers Dis.201230243945910.3233/JAD‑2012‑111862 22451318
     [Google Scholar]
  43. MoncadaS. HiggsE.A. Endogenous nitric oxide: physiology, pathology and clinical relevance.Eur. J. Clin. Invest.199121436137410.1111/j.1365‑2362.1991.tb01383.x 1718757
     [Google Scholar]
  44. EspositoG. De FilippisD. SteardoL. CB1 receptor selective activation inhibits β-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons.Neurosci. Lett.2006404334234610.1016/j.neulet.2006.06.012 16837132
     [Google Scholar]
  45. Patricio-MartínezA. Sánchez-ZavaletaR. Angulo-CruzI. The acute activation of the CB1 receptor in the hippocampus decreases neurotoxicity and prevents spatial memory impairment in rats lesioned with β-amyloid 25-35.Neuroscience201941623925410.1016/j.neuroscience.2019.08.001 31400487
     [Google Scholar]
  46. AbateG. UbertiD. TambaroS. Potential and limits of cannabinoids in Alzheimer’s disease therapy.Biology202110654210.3390/biology10060542 34204237
     [Google Scholar]
  47. StummC. HiebelC. HansteinR. Cannabinoid receptor 1 deficiency in a mouse model of Alzheimer’s disease leads to enhanced cognitive impairment despite of a reduction in amyloid deposition.Neurobiol. Aging201334112574258410.1016/j.neurobiolaging.2013.05.027 23838176
     [Google Scholar]
  48. AsoE. Andrés-BenitoP. FerrerI. Genetic deletion of CB1 cannabinoid receptors exacerbates the Alzheimer-like symptoms in a transgenic animal model.Biochem. Pharmacol.201815721021610.1016/j.bcp.2018.08.007 30096288
     [Google Scholar]
  49. NedaeiS.E. RezayofA. PourmotabbedA. NasehiM. ZarrindastM.R. Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.Behav. Brain Res.201631118319110.1016/j.bbr.2016.05.043 27230394
     [Google Scholar]
  50. RamírezB.G. BlázquezC. del PulgarT.G. GuzmánM. de CeballosM.L. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation.J. Neurosci.20052581904191310.1523/JNEUROSCI.4540‑04.2005 15728830
     [Google Scholar]
  51. Medina-VeraD. Rosell-ValleC. López-GamberoA.J. Imbalance of endocannabinoid/lysophosphatidylinositol receptors marks the severity of alzheimer’s disease in a preclinical model: A therapeutic opportunity.Biology202091137710.3390/biology9110377 33167441
     [Google Scholar]
  52. González de San RománE. Llorente-OvejeroA. Martínez-GardeazabalJ. Modulation of neurolipid signaling and specific lipid species in the triple transgenic mouse model of Alzheimer’s disease.Int. J. Mol. Sci.202122221225610.3390/ijms222212256 34830150
     [Google Scholar]
  53. BedseG. RomanoA. CianciS. Altered expression of the CB1 cannabinoid receptor in the triple transgenic mouse model of Alzheimer’s disease.J. Alzheimers Dis.201440370171210.3233/JAD‑131910 24496074
     [Google Scholar]
  54. AlbayramO. Bilkei-GorzoA. ZimmerA. Loss of CB1 receptors leads to differential age-related changes in reward-driven learning and memory.Front. Aging Neurosci.201243410.3389/fnagi.2012.00034 23227007
     [Google Scholar]
  55. HasegawaY. KimJ. UrsiniG. Microglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication.Nat. Commun.2023141655910.1038/s41467‑023‑42276‑5 37880248
     [Google Scholar]
  56. TianL. QiangT. LiuS. Cannabinoid receptor 1 ligands: Biased signaling mechanisms driving functionally selective drug discovery.Pharmacol. Ther.202526710879510.1016/j.pharmthera.2025.108795 39828030
     [Google Scholar]
  57. ChiangK.E. HsiaoY.T. Activation of cannabinoid receptor type 1 impairs spatial and temporal aspects of episodic-like memories in rats.J. Integr. Neurosci.2020191111910.31083/j.jin.2020.01.1190 32259882
     [Google Scholar]
  58. BialukI. WinnickaM.M. AM251, cannabinoids receptors ligand, improves recognition memory in rats.Pharmacol. Rep.201163367067910.1016/S1734‑1140(11)70578‑3 21857077
     [Google Scholar]
  59. Peñaloza-SanchoV. Pérez-ValenzuelaC. GonzalezC. JujiharaG. BustosP. Dagnino-SubiabreA. Cannabinoid receptor type 1 modulates the effects of polyunsaturated fatty acids on memory of stressed rats.Nutr. Neurosci.202124858360010.1080/1028415X.2019.1659561 31637966
     [Google Scholar]
  60. LeeJ.H. AgacinskiG. WilliamsJ.H. Intact cannabinoid CB1 receptors in the Alzheimer’s disease cortex.Neurochem. Int.201057898598910.1016/j.neuint.2010.10.010 21034788
     [Google Scholar]
  61. ManuelI. de San RománE.G. GiraltM.T. FerrerI. Rodríguez-PuertasR. Type-1 cannabinoid receptor activity during Alzheimer’s disease progression.J. Alzheimers Dis.201442376176610.3233/JAD‑140492 24946872
     [Google Scholar]
  62. VermaA. GoyalA. Beyond insulin: The Intriguing role of GLP-1 in Parkinson’s disease.Eur. J. Pharmacol.202498217693610.1016/j.ejphar.2024.176936 39182542
     [Google Scholar]
  63. GoyalA. SolankiK. VermaA. Luteolin: Nature’s promising warrior against Alzheimer’s and Parkinson’s disease.J. Biochem. Mol. Toxicol.20243812361910.1002/jbt.23619 38091364
     [Google Scholar]
  64. MoreS.V. ChoiD.K. Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection.Mol. Neurodegener.20151011710.1186/s13024‑015‑0012‑0 25888232
     [Google Scholar]
  65. FoxS.H. BrotchieJ.M. LangA.E. Non-dopaminergic treatments in development for Parkinson’s disease.Lancet Neurol.200871092793810.1016/S1474‑4422(08)70214‑X 18848312
     [Google Scholar]
  66. BenarrochE. Endocannabinoids in basal ganglia circuits.Neurology200769330630910.1212/01.wnl.0000267407.79757.75 17636069
     [Google Scholar]
  67. WilsonR.I. NicollR.A. Endocannabinoid signaling in the brain.Science2002296556867868210.1126/science.1063545 11976437
     [Google Scholar]
  68. Molina-HolgadoE. VelaJ.M. Arévalo-MartínA. Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling.J. Neurosci.200222229742975310.1523/JNEUROSCI.22‑22‑09742.2002 12427829
     [Google Scholar]
  69. BouaboulaM. BourriéB. Rinaldi-CarmonaM. ShireD. FurG.L. CasellasP. Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells.J. Biol. Chem.199527023139731398010.1074/jbc.270.23.13973 7775459
     [Google Scholar]
  70. WalterL. FranklinA. WittingA. Nonpsychotropic cannabinoid receptors regulate microglial cell migration.J. Neurosci.20032341398140510.1523/JNEUROSCI.23‑04‑01398.2003 12598628
     [Google Scholar]
  71. BisognoT. BerrenderoF. AmbrosinoG. Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function.Biochem. Biophys. Res. Commun.1999256237738010.1006/bbrc.1999.0254 10079192
     [Google Scholar]
  72. Van LaereK. CasteelsC. LunskensS. Regional changes in type 1 cannabinoid receptor availability in Parkinson’s disease in vivo.Neurobiol. Aging2012333620.e1620.e810.1016/j.neurobiolaging.2011.02.009 21459482
     [Google Scholar]
  73. CeccariniJ. CasteelsC. AhmadR. Regional changes in the type 1 cannabinoid receptor are associated with cognitive dysfunction in Parkinson’s disease.Eur. J. Nucl. Med. Mol. Imaging201946112348235710.1007/s00259‑019‑04445‑x 31342135
     [Google Scholar]
  74. AjalinR. Al-AbdulrasulH. TuiskuJ.M. Impaired gait, postural instability, and rigidity in relation to CB1 receptor availability in Parkinson’s disease.Mov. Disord.202540116316710.1002/mds.30042 39435606
     [Google Scholar]
  75. Chaves-KirstenG.P. MazucantiC.H.Y. RealC.C. SouzaB.M. BrittoL.R.G. TorrãoA.S. Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible structure-specific plasticity process in 6-OHDA lesioned rats.PLoS One20138107687410.1371/journal.pone.0076874 24116178
     [Google Scholar]
  76. BindaK.H. LandauA.M. ChacurM. BrooksD.J. RealC.C. Treadmill exercise modulates nigral and hippocampal cannabinoid receptor type 1 in the 6-OHDA model of Parkinson’s disease.Brain Res.2023181414843610.1016/j.brainres.2023.148436 37268248
     [Google Scholar]
  77. ChungY.C. BokE. HuhS.H. Cannabinoid receptor type 1 protects nigrostriatal dopaminergic neurons against MPTP neurotoxicity by inhibiting microglial activation.J. Immunol.2011187126508651710.4049/jimmunol.1102435 22079984
     [Google Scholar]
  78. ErustesA.G. AbílioV.C. BincolettoC. PiacentiniM. PereiraG.J.S. SmailiS.S. Cannabidiol induces autophagy via CB1 receptor and reduces α-synuclein cytosolic levels.Brain Res.2025185014941410.1016/j.brainres.2024.149414 39710053
     [Google Scholar]
  79. MorgeseM.G. CassanoT. CuomoV. GiuffridaA. Anti-dyskinetic effects of cannabinoids in a rat model of Parkinson’s disease: Role of CB1 and TRPV1 receptors.Exp. Neurol.2007208111011910.1016/j.expneurol.2007.07.021 17900568
     [Google Scholar]
  80. Di MarzoV. MelckD. BisognoT. De PetrocellisL. Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action.Trends Neurosci.1998211252152810.1016/S0166‑2236(98)01283‑1 9881850
     [Google Scholar]
  81. GerdemanG. LovingerD.M. CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum.J. Neurophysiol.200185146847110.1152/jn.2001.85.1.468 11152748
     [Google Scholar]
  82. ManeufY.P. NashJ.E. CrossmanA.R. BrotchieJ.M. Activation of the cannabinoid receptor by Δ9-tetrahydrocannabinol reduces γ-aminobutyric acid uptake in the globus pallidus.Eur. J. Pharmacol.1996308216116410.1016/0014‑2999(96)00326‑3 8840127
     [Google Scholar]
  83. WallmichrathI. SzaboB. Cannabinoids inhibit striatonigral GABAergic neurotransmission in the mouse.Neuroscience2002113367168210.1016/S0306‑4522(02)00109‑4 12150787
     [Google Scholar]
  84. CaoX. LiangL. HadcockJ.R. Blockade of cannabinoid type 1 receptors augments the antiparkinsonian action of levodopa without affecting dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri] dine-treated rhesus monkeys.J. Pharmacol. Exp. Ther.2007323131832610.1124/jpet.107.125666 17630359
     [Google Scholar]
  85. KelseyJ.E. HarrisO. CassinJ. The CB1 antagonist rimonabant is adjunctively therapeutic as well as monotherapeutic in an animal model of Parkinson’s disease.Behav. Brain Res.2009203230430710.1016/j.bbr.2009.04.035 19414037
     [Google Scholar]
  86. ZuccatoC. ValenzaM. CattaneoE. Molecular mechanisms and potential therapeutical targets in Huntington’s disease.Physiol. Rev.201090390598110.1152/physrev.00041.2009 20664076
     [Google Scholar]
  87. FerranteR.J. KowallN.W. BealM.F. RichardsonE.P. BirdE.D. MartinJ.B. Selective sparing of a class of striatal neurons in Huntington’s disease.Science1985230472556156310.1126/science.2931802 2931802
     [Google Scholar]
  88. GravelandG.A. WilliamsR.S. DiFigliaM. Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington’s disease.Science1985227468877077310.1126/science.3155875 3155875
     [Google Scholar]
  89. BlázquezC. ChiarloneA. SagredoO. Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington’s disease.Brain2011134111913610.1093/brain/awq278 20929960
     [Google Scholar]
  90. ScotterE.L. GoodfellowC.E. GrahamE.S. DragunowM. GlassM. Neuroprotective potential of CB 1 receptor agonists in an in vitro model of Huntington’s disease.Br. J. Pharmacol.2010160374776110.1111/j.1476‑5381.2010.00773.x 20590577
     [Google Scholar]
  91. LaprairieR.B. KellyM.E.M. Denovan-WrightE.M. Cannabinoids increase type 1 cannabinoid receptor expression in a cell culture model of striatal neurons: Implications for Huntington’s disease.Neuropharmacology201372475710.1016/j.neuropharm.2013.04.006 23602984
     [Google Scholar]
  92. SongJ. KimY.K. Animal models for the study of depressive disorder.CNS Neurosci. Ther.202127663364210.1111/cns.13622 33650178
     [Google Scholar]
  93. NemeroffC.B. OwensM.J. Treatment of mood disorders.Nat. Neurosci.20025S111068107010.1038/nn943 12403988
     [Google Scholar]
  94. BoysA. MarsdenJ. StrangJ. Understanding reasons for drug use amongst young people: a functional perspective.Health Educ. Res.200116445746910.1093/her/16.4.457 11525392
     [Google Scholar]
  95. SchlickerE. KathmannM. Modulation of transmitter release via presynaptic cannabinoid receptors.Trends Pharmacol. Sci.2001221156557210.1016/S0165‑6147(00)01805‑8 11698100
     [Google Scholar]
  96. VinodK.Y. ArangoV. XieS. Elevated levels of endocannabinoids and CB1 receptor-mediated G-protein signaling in the prefrontal cortex of alcoholic suicide victims.Biol. Psychiatry200557548048610.1016/j.biopsych.2004.11.033 15737662
     [Google Scholar]
  97. HungundB.L. VinodK.Y. KassirS.A. Upregulation of CB1 receptors and agonist-stimulated [35S]GTPγS binding in the prefrontal cortex of depressed suicide victims.Mol. Psychiatry20049218419010.1038/sj.mp.4001376 14966476
     [Google Scholar]
  98. HillM.N. MillerG.E. CarrierE.J. GorzalkaB.B. HillardC.J. Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress.Psychoneuroendocrinology20093481257126210.1016/j.psyneuen.2009.03.013 19394765
     [Google Scholar]
  99. HillM. MillerG. HoW.S. GorzalkaB. HillardC. Serum endocannabinoid content is altered in females with depressive disorders: a preliminary report.Pharmacopsychiatry2008412485310.1055/s‑2007‑993211 18311684
     [Google Scholar]
  100. KoetheD. LlenosI.C. DulayJ.R. Expression of CB1 cannabinoid receptor in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression.J. Neural Transm. (Vienna)200711481055106310.1007/s00702‑007‑0660‑5 17370106
     [Google Scholar]
  101. TzavaraE.T. DavisR.J. PerryK.W. The CB1 receptor antagonist SR141716A selectively increases monoaminergic neurotransmission in the medial prefrontal cortex: implications for therapeutic actions.Br. J. Pharmacol.2003138454455310.1038/sj.bjp.0705100 12598408
     [Google Scholar]
  102. GriebelG. StemmelinJ. ScattonB. Effects of the cannabinoid CB1 receptor antagonist rimonabant in models of emotional reactivity in rodents.Biol. Psychiatry200557326126710.1016/j.biopsych.2004.10.032 15691527
     [Google Scholar]
  103. ShearmanL.P. RoskoK.M. FleischerR. Antidepressant-like and anorectic effects of the cannabinoid CB1 receptor inverse agonist AM251 in mice.Behav. Pharmacol.200314857358210.1097/00008877‑200312000‑00001 14665974
     [Google Scholar]
  104. BambicoF.R. KatzN. DebonnelG. GobbiG. Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex.J. Neurosci.20072743117001171110.1523/JNEUROSCI.1636‑07.2007 17959812
     [Google Scholar]
  105. HillM.N. GorzalkaB.B. Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the rat forced swim test.Eur. Neuropsychopharmacol.200515659359910.1016/j.euroneuro.2005.03.003 15916883
     [Google Scholar]
  106. GrahamB.M. LangtonJ.M. RichardsonR. Pharmacological enhancement of fear reduction: preclinical models.Br. J. Pharmacol.201116441230124710.1111/j.1476‑5381.2010.01175.x 21175588
     [Google Scholar]
  107. PillayN.S. SteinD.J. Emerging anxiolytics.Expert Opin. Emerg. Drugs200712454155410.1517/14728214.12.4.541 17979598
     [Google Scholar]
  108. ViverosM. MarcoE. FileS. Endocannabinoid system and stress and anxiety responses.Pharmacol. Biochem. Behav.200581233134210.1016/j.pbb.2005.01.029 15927244
     [Google Scholar]
  109. MillanM.J. The neurobiology and control of anxious states.Prog. Neurobiol.20037028324410.1016/S0301‑0082(03)00087‑X 12927745
     [Google Scholar]
  110. ReyA.A. PurrioM. ViverosM.P. LutzB. Biphasic effects of cannabinoids in anxiety responses: CB1 and GABA(B) receptors in the balance of GABAergic and glutamatergic neurotransmission.Neuropsychopharmacology201237122624263410.1038/npp.2012.123 22850737
     [Google Scholar]
  111. Ebrahimi-GhiriM. KhakpaiF. ZarrindastM.R. URB597 abrogates anxiogenic and depressive behaviors in the methamphetamine-withdrawal mice: Role of the cannabinoid receptor type 1, cannabinoid receptor type 2, and transient receptor potential vanilloid 1 channels.J. Psychopharmacol.202135787588410.1177/0269881120965934 33155516
     [Google Scholar]
  112. MicaleV. CristinoL. TamburellaA. Anxiolytic effects in mice of a dual blocker of fatty acid amide hydrolase and transient receptor potential vanilloid type-1 channels.Neuropsychopharmacology200934359360610.1038/npp.2008.98 18580871
     [Google Scholar]
  113. HallerJ. VargaB. LedentC. FreundT.F. CB1 cannabinoid receptors mediate anxiolytic effects: convergent genetic and pharmacological evidence with CB1-specific agents.Behav. Pharmacol.200415429930410.1097/01.fbp.0000135704.56422.40 15252281
     [Google Scholar]
  114. GentileA. FresegnaD. MusellaA. Interaction between interleukin-1β and type-1 cannabinoid receptor is involved in anxiety-like behavior in experimental autoimmune encephalomyelitis.J. Neuroinflammation201613123110.1186/s12974‑016‑0682‑8 27589957
     [Google Scholar]
  115. HouserC.R. Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy.Brain Res.1990535219520410.1016/0006‑8993(90)91601‑C 1705855
     [Google Scholar]
  116. ManfordM. Recent advances in epilepsy.J. Neurol.201726481811182410.1007/s00415‑017‑8394‑2 28120042
     [Google Scholar]
  117. EngelJ. Excitation and inhibition in epilepsy.Can. J. Neurol. Sci.199623316717410.1017/S0317167100038464 8862837
     [Google Scholar]
  118. Lazarini-LopesW. Silva-CardosoG.K. Neuroplastic alterations in cannabinoid receptors type 1 (CB1) in animal models of epileptic seizures.Neurosci. Biobehav. Rev.202213710467510.1016/j.neubiorev.2022.104675 35460705
     [Google Scholar]
  119. FalenskiK.W. BlairR.E. Sim-SelleyL.J. MartinB.R. DeLorenzoR.J. Status epilepticus causes a long-lasting redistribution of hippocampal cannabinoid type 1 receptor expression and function in the rat pilocarpine model of acquired epilepsy.Neuroscience200714631232124410.1016/j.neuroscience.2007.01.065 17433556
     [Google Scholar]
  120. FalenskiK.W. CarterD.S. HarrisonA.J. MartinB.R. BlairR.E. DeLorenzoR.J. Temporal characterization of changes in hippocampal cannabinoid CB1 receptor expression following pilocarpine-induced status epilepticus.Brain Res.20091262647210.1016/j.brainres.2009.01.036 19368833
     [Google Scholar]
  121. RoebuckA.J. GrebaQ. SmolyakovaA.M. Positive allosteric modulation of type 1 cannabinoid receptors reduces spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg.Neuropharmacology202119010855310.1016/j.neuropharm.2021.108553 33845076
     [Google Scholar]
  122. McElroyD.L. RoebuckA.J. GrebaQ. The type 1 cannabinoid receptor positive allosteric modulators GAT591 and GAT593 reduce spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg.IBRO Neuroscience. Reports.20221212113010.1016/j.ibneur.2022.01.006 35128516
     [Google Scholar]
  123. MardaniP. OryanS. SarihiA. AlaeiE. KomakiA. Mirnajafi-ZadehJ. Endocannabinoid CB1 receptors are involved in antiepileptogenic effect of low frequency electrical stimulation during perforant path kindling in rats.Epilepsy Res.2018144718110.1016/j.eplepsyres.2018.05.008 29800824
     [Google Scholar]
  124. Van RijnC.M. GaetaniS. SantoliniI. WAG/Rij rats show a reduced expression of CB 1 receptors in thalamic nuclei and respond to the CB1 receptor agonist, R (+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges.Epilepsia20105181511152110.1111/j.1528‑1167.2009.02510.x 20132294
     [Google Scholar]
  125. BlairR.E. DeshpandeL.S. SombatiS. FalenskiK.W. MartinB.R. DeLorenzoR.J. Activation of the cannabinoid type-1 receptor mediates the anticonvulsant properties of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy and status epilepticus.J. Pharmacol. Exp. Ther.200631731072107810.1124/jpet.105.100354 16469864
     [Google Scholar]
  126. MannaS.S.S. UmatheS.N. Involvement of transient receptor potential vanilloid type 1 channels in the pro-convulsant effect of anandamide in pentylenetetrazole-induced seizures.Epilepsy Res.20121001-211312410.1016/j.eplepsyres.2012.02.003 22386872
     [Google Scholar]
  127. GhanbariM.M. LoronA.G. SayyahM. The ω-3 endocannabinoid docosahexaenoyl ethanolamide reduces seizure susceptibility in mice by activating cannabinoid type 1 receptors.Brain Res. Bull.2021170748010.1016/j.brainresbull.2021.02.011 33581310
     [Google Scholar]
  128. Shirazi-zandZ. Ahmad-MolaeiL. MotamediF. NaderiN. The role of potassium BK channels in anticonvulsant effect of cannabidiol in pentylenetetrazole and maximal electroshock models of seizure in mice.Epilepsy Behav.20132811710.1016/j.yebeh.2013.03.009 23644464
     [Google Scholar]
  129. GuggenhuberS. MonoryK. LutzB. KlugmannM. AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity.PLoS One20105121570710.1371/journal.pone.0015707 21203567
     [Google Scholar]
  130. LutzB. On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures.Biochem. Pharmacol.20046891691169810.1016/j.bcp.2004.07.007 15450934
     [Google Scholar]
  131. MengX.D. WeiD. LiJ. Astrocytic expression of cannabinoid type 1 receptor in rat and human sclerotic hippocampi.Int. J. Clin. Exp. Pathol.20147628252837 25031702
     [Google Scholar]
  132. JohnstonS.C. MendisS. MathersC.D. Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling.Lancet Neurol.20098434535410.1016/S1474‑4422(09)70023‑7 19233730
     [Google Scholar]
  133. XiongL. LuZ. HouL. Pretreatment with repeated electroacupuncture attenuates transient focal cerebral ischemic injury in rats.Chin. Med. J. (Engl.)20031161108111 12667400
     [Google Scholar]
  134. DuJ. WangQ. HuB. Involvement of ERK 1/2 activation in electroacupuncture pretreatment via cannabinoid CB1 receptor in rats.Brain Res.201013601710.1016/j.brainres.2010.07.034 20654595
     [Google Scholar]
  135. ZhaoJ. TianY. XiaoH. HuM. ChenW. Effects of electroacupuncture on hippocampal and cortical apoptosis in a mouse model of cerebral ischemia-reperfusion injury.J. Tradit. Chin. Med.201131434935510.1016/S0254‑6272(12)60017‑X 22462244
     [Google Scholar]
  136. WangQ. PengY. ChenS. Pretreatment with electroacupuncture induces rapid tolerance to focal cerebral ischemia through regulation of endocannabinoid system.Stroke20094062157216410.1161/STROKEAHA.108.541490 19372445
     [Google Scholar]
  137. YangC. LiuJ. WangJ. Activation of astroglial CB1R mediates cerebral ischemic tolerance induced by electroacupuncture.J. Cereb. Blood Flow Metab.20214192295231010.1177/0271678X21994395 33663269
     [Google Scholar]
  138. ZhangH. HeS. HuY. ZhengH. Antagonism of cannabinoid receptor 1 attenuates the anti-inflammatory effects of electroacupuncture in a rodent model of migraine.Acupunct. Med.201634646347010.1136/acupmed‑2016‑011113 27834685
     [Google Scholar]
  139. SilvaniA. BerteottiC. BastianiniS. Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.PLoS One2014928943210.1371/journal.pone.0089432 24586776
     [Google Scholar]
  140. RoserP. HaussleiterI.S. ChongH.J. Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia.Psychopharmacology (Berl.)2011218461162010.1007/s00213‑011‑2352‑y 21590281
     [Google Scholar]
  141. TambaB.I. StanciuG.D. UrîtuC.M. Challenges and opportunities in preclinical research of synthetic cannabinoids for pain therapy.Medicina (Kaunas)20205612410.3390/medicina56010024 31936616
     [Google Scholar]
  142. MurphyT. Le FollB. Targeting the endocannabinoid CB1 receptor to treat body weight disorders: a preclinical and clinical review of the therapeutic potential of past and present CB1 drugs.Biomolecules202010685510.3390/biom10060855 32512776
     [Google Scholar]
  143. MooreN.L.T. GreenleafA.L.R. AchesonS.K. WilsonW.A. SwartzwelderH.S. KuhnC.M. Role of cannabinoid receptor type 1 desensitization in greater tetrahydrocannabinol impairment of memory in adolescent rats.J. Pharmacol. Exp. Ther.2010335229430110.1124/jpet.110.169359 20668056
     [Google Scholar]
/content/journals/cnr/10.2174/0115672026403497250910124233
Loading
Cannabinoid Receptor 1: The Neural Gatekeeper of Health and Disease
Curr Neurovasc Res 22, 100 (2025); https://doi.org/10.2174/0115672026403497250910124233
/content/journals/cnr/10.2174/0115672026403497250910124233
/content/journals/cnr/10.2174/0115672026403497250910124233
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Alzheimer's; brain; cannabinoid; depression; Endocannabinoid; neurodegeneration; neuroprotection

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test