Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The impact of cannabinoid type 2 receptors (CB2Rs) in neuroprotection against neurological disorders

Abstract

Cannabinoids have long been used for their psychotropic and possible medical properties of symptom relief. In the past few years, a vast literature shows that cannabinoids are neuroprotective under different pathological situations. Most of the effects of cannabinoids are mediated by the well-characterized cannabinoid receptors, the cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R). Even though CB1Rs are highly expressed in the central nervous system (CNS), the adverse central side effects and the development of tolerance resulting from CB1R activation may ultimately limit the clinical utility of CB1R agonists. In contrast to the ubiquitous presence of CB1Rs, CB2Rs are less commonly expressed in the healthy CNS but highly upregulated in glial cells under neuropathological conditions. Experimental studies have provided robust evidence that CB2Rs seem to be involved in the modulation of different neurological disorders. In this paper, we summarize the current knowledge regarding the protective effects of CB2R activation against the development of neurological diseases and provide a perspective on the future of this field. A better understanding of the fundamental pharmacology of CB2R activation is essential for the development of clinical applications and the design of novel therapeutic strategies.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Activation of CB2Rs after neurological disorders.

References

  1. 1.

    Di Marzo V, Piscitelli F. The endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics. 2015;12:692–8.

    PubMed  PubMed Central  Google Scholar 

  2. 2.

    Huang WJ, Chen WW, Zhang X. Endocannabinoid system: role in depression, reward and pain control (Review). Mol Med Rep. 2016;14:2899–903.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Basavarajappa BS, Shivakumar M, Joshi V, Subbanna S. Endocannabinoid system in neurodegenerative disorders. J Neurochem. 2017;142:624–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol. 2020;16:9–29.

    PubMed  Google Scholar 

  5. 5.

    Nguyen T, Thomas BF, Zhang Y. Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: current approaches for therapeutics development. Curr Top medicinal Chem. 2019;19:1418–35.

    CAS  Google Scholar 

  6. 6.

    Moreira FA, Grieb M, Lutz B. Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: focus on anxiety and depression. Best Pr Res Clin Endocrinol Metab. 2009;23:133–44.

    CAS  Google Scholar 

  7. 7.

    Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365:61–5.

    CAS  PubMed  Google Scholar 

  8. 8.

    Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem. 1995;232:54–61.

    CAS  PubMed  Google Scholar 

  9. 9.

    Schatz AR, Lee M, Condie RB, Pulaski JT, Kaminski NE. Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system. Toxicol Appl Pharmacol. 1997;142:278–87.

    CAS  PubMed  Google Scholar 

  10. 10.

    McCoy KL, Matveyeva M, Carlisle SJ, Cabral GA. Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation. J Pharmacol Exp Ther. 1999;289:1620–5.

    CAS  PubMed  Google Scholar 

  11. 11.

    Burdyga G, Lal S, Varro A, Dimaline R, Thompson DG, Dockray GJ. Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. J Neurosci. 2004;24:2708–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Atwood BK, Mackie K. CB2: a cannabinoid receptor with an identity crisis. Br J Pharmacol. 2010;160:467–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Jordan CJ, Xi ZX. Progress in brain cannabinoid CB2 receptor research: From genes to behavior. Neurosci Biobehav Rev. 2019;98:208–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Reddy V, Grogan D, Ahluwalia M, Salles EL, Ahluwalia P, Khodadadi H, et al. Targeting the endocannabinoid system: a predictive, preventive, and personalized medicine-directed approach to the management of brain pathologies. EPMA J. 2020;11:217–50.

    PubMed  Google Scholar 

  15. 15.

    Miller LK, Devi LA. The highs and lows of cannabinoid receptor expression in disease: mechanisms and their therapeutic implications. Pharmacol Rev. 2011;63:461–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Onaivi ES, Ishiguro H, Gong JP, Patel S, Meozzi PA, Myers L, et al. Functional expression of brain neuronal CB2 cannabinoid receptors are involved in the effects of drugs of abuse and in depression. Ann N Y Acad Sci. 2008;1139:434–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Onaivi ES, Ishiguro H, Gu S, Liu QR. CNS effects of CB2 cannabinoid receptors: beyond neuro-immuno-cannabinoid activity. J Psychopharmacol. 2012;26:92–103.

    CAS  PubMed  Google Scholar 

  18. 18.

    Pacher P, Mechoulam R. Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog Lipid Res. 2011;50:193–211.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Fernandez-Ruiz J, Pazos MR, Garcia-Arencibia M, Sagredo O, Ramos JA. Role of CB2 receptors in neuroprotective effects of cannabinoids. Mol Cell Endocrinol. 2008;286:S91–6.

    CAS  PubMed  Google Scholar 

  20. 20.

    Hryhorowicz S, Kaczmarek-Rys M, Andrzejewska A, Staszak K, Hryhorowicz M, Korcz A, et al. Allosteric modulation of cannabinoid receptor 1-current challenges and future opportunities. Int J Mol Sci. 2019;20:5874.

    CAS  PubMed Central  Google Scholar 

  21. 21.

    Xi ZX, Peng XQ, Li X, Song R, Zhang HY, Liu QR, et al. Brain cannabinoid CB(2) receptors modulate cocaine’s actions in mice. Nat Neurosci. 2011;14:1160–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Navarrete F, Rodriguez-Arias M, Martin-Garcia E, Navarro D, Garcia-Gutierrez MS, Aguilar MA, et al. Role of CB2 cannabinoid receptors in the rewarding, reinforcing, and physical effects of nicotine. Neuropsychopharmacology. 2013;38:2515–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Ortega‐Álvaro A, Ternianov A, Aracil‐Fernández A, Navarrete F, García‐Gutiérrez MS, Manzanares J. Role of cannabinoid CB receptor in the reinforcing actions of ethanol. Addict Biol 2013;20:43–55.

  24. 24.

    Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Philos Trans R Soc Lond B Biol Sci. 2012;367:3353–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Gong JP, Onaivi ES, Ishiguro H, Liu QR, Tagliaferro PA, Brusco A, et al. Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res. 2006;1071:10–23.

    CAS  PubMed  Google Scholar 

  26. 26.

    Brusco A, Tagliaferro PA, Saez T, Onaivi ES. Ultrastructural localization of neuronal brain CB2 cannabinoid receptors. Ann N Y Acad Sci. 2008;1139:450–7.

    CAS  PubMed  Google Scholar 

  27. 27.

    Ashton JC, Friberg D, Darlington CL, Smith PF. Expression of the cannabinoid CB2 receptor in the rat cerebellum: an immunohistochemical study. Neurosci Lett. 2006;396:113–6.

    CAS  PubMed  Google Scholar 

  28. 28.

    Baek JH, Zheng Y, Darlington CL, Smith PF. Cannabinoid CB2 receptor expression in the rat brainstem cochlear and vestibular nuclei. Acta Otolaryngol. 2008;128:961–7.

    CAS  PubMed  Google Scholar 

  29. 29.

    Brusco A, Tagliaferro P, Saez T, Onaivi ES. Postsynaptic localization of CB2 cannabinoid receptors in the rat hippocampus. Synapse. 2008;62:944–9.

    CAS  PubMed  Google Scholar 

  30. 30.

    Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science. 2005;310:329–32.

    PubMed  Google Scholar 

  31. 31.

    Núñez E, Benito C, Pazos MR, Barbachano A, Fajardo O, González S, et al. Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study. Synapse. 2004;53:208–13.

    PubMed  Google Scholar 

  32. 32.

    Zhang HY, Gao M, Liu QR, Bi GH, Li X, Yang HJ, et al. Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. Proc Natl Acad Sci U S A. 2014;111:E5007–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Stempel AV, Stumpf A, Zhang HY, Ozdogan T, Pannasch U, Theis AK, et al. Cannabinoid type 2 receptors mediate a cell type-specific plasticity in the hippocampus. Neuron. 2016;90:795–809.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Joshi N, Onaivi ES. Endocannabinoid system components: overview and tissue distribution. Adv Exp Med Biol. 2019;1162:1–12.

    CAS  PubMed  Google Scholar 

  35. 35.

    Liu QR, Pan CH, Hishimoto A, Li CY, Xi ZX, Llorente-Berzal A, et al. Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression and regulation by cannabinoid receptor ligands. Genes Brain Behav. 2009;8:519–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Maccarone R, Rapino C, Zerti D, di Tommaso M, Battista N, Di Marco S, et al. Modulation of type-1 and type-2 cannabinoid receptors by saffron in a rat model of retinal neurodegeneration. PLoS ONE. 2016;11:e0166827.

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Zhang HY, Bi GH, Li X, Li J, Qu H, Zhang SJ, et al. Species differences in cannabinoid receptor 2 and receptor responses to cocaine self-administration in mice and rats. Neuropsychopharmacology. 2015;40:1037–51.

    CAS  PubMed  Google Scholar 

  38. 38.

    Li Y, Kim J. Neuronal expression of CB2 cannabinoid receptor mRNAs in the mouse hippocampus. Neuroscience. 2015;311:253–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Gómez-Gálvez Y, Palomo-Garo C, Fernández-Ruiz J, García C. Potential of the cannabinoid CB(2) receptor as a pharmacological target against inflammation in Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:200–8.

    PubMed  Google Scholar 

  40. 40.

    Chung YC, Shin WH, Baek JY, Cho EJ, Baik HH, Kim SR, et al. CB2 receptor activation prevents glial-derived neurotoxic mediator production, BBB leakage and peripheral immune cell infiltration and rescues dopamine neurons in the MPTP model of Parkinson’s disease. Exp Mol Med. 2016;48:e205.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Lu Q, Straiker A, Maguire G. Expression of CB2 cannabinoid receptor mRNA in adult rat retina. Vis Neurosci. 2000;17:91–5.

    CAS  PubMed  Google Scholar 

  42. 42.

    Palazuelos J, Ortega Z, Díaz-Alonso J, Guzmán M, Galve-Roperh I. CB2 cannabinoid receptors promote neural progenitor cell proliferation via mTORC1 signaling. J Biol Chem. 2012;287:1198–209.

    CAS  PubMed  Google Scholar 

  43. 43.

    Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation. 2018;137:e67–e492.

    Google Scholar 

  44. 44.

    Webb RL, Kaiser EE, Jurgielewicz BJ, Spellicy S, Scoville SL, Thompson TA, et al. Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke. Stroke. 2018;49:1248–56.

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Hosoya T, Fukumoto D, Kakiuchi T, Nishiyama S, Yamamoto S, Ohba H, et al. In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study. J Neuroinflammation. 2017;14:69.

    PubMed  PubMed Central  Google Scholar 

  46. 46.

    Zhang M, Martin BR, Adler MW, Razdan RK, Jallo JI, Tuma RF, et al. Cannabinoid CB(2) receptor activation decreases cerebral infarction in a mouse focal ischemia/reperfusion model. J Cereb Blood Flow Metab. 2007;27:1387–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Zhang M, Adler MW, Abood ME, Ganea D, Jallo J, Tuma RF. CB2 receptor activation attenuates microcirculatory dysfunction during cerebral ischemic/reperfusion injury. Microvasc Res. 2009;78:86–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Murikinati S, Juttler E, Keinert T, Ridder DA, Muhammad S, Waibler Z, et al. Activation of cannabinoid 2 receptors protects against cerebral ischemia by inhibiting neutrophil recruitment. FASEB J. 2010;24:788–98.

    CAS  PubMed  Google Scholar 

  49. 49.

    Choi IY, Ju C, Anthony Jalin AM, Lee DI, Prather PL, Kim WK. Activation of cannabinoid CB2 receptor-mediated AMPK/CREB pathway reduces cerebral ischemic injury. Am J Pathol. 2013;182:928–39.

    CAS  PubMed  Google Scholar 

  50. 50.

    Guo K, Mou X, Huang J, Xiong N, Li H. Trans-caryophyllene suppresses hypoxia-induced neuroinflammatory responses by inhibiting NF-kappaB activation in microglia. J Mol Neurosci. 2014;54:41–8.

    CAS  PubMed  Google Scholar 

  51. 51.

    Cheng L, Li J, Zhou Y, Zheng Q, Ming X, Liu S. N-linoleyltyrosine protects against transient cerebral ischemia in gerbil via CB2 receptor involvement in PI3K/Akt signaling pathway. Biol Pharm Bull. 2019;42:1867–76.

    CAS  PubMed  Google Scholar 

  52. 52.

    Yu SJ, Reiner D, Shen H, Wu KJ, Liu QR, Wang Y. Time-Dependent Protection of CB2 Receptor Agonist in Stroke. PLoS ONE. 2015;10:e0132487.

    PubMed  PubMed Central  Google Scholar 

  53. 53.

    Ronca RD, Myers AM, Ganea D, Tuma RF, Walker EA, Ward SJ. A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice. Life Sci. 2015;138:72–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Kossatz E, Maldonado R, Robledo P. CB2 cannabinoid receptors modulate HIF-1alpha and TIM-3 expression in a hypoxia-ischemia mouse model. Eur Neuropsychopharmacol. 2016;26:1972–88.

    CAS  PubMed  Google Scholar 

  55. 55.

    Bravo-Ferrer I, Cuartero MI, Zarruk JG, Pradillo JM, Hurtado O, Romera VG, et al. Cannabinoid type-2 receptor drives neurogenesis and improves functional outcome after stroke. Stroke. 2017;48:204–12.

    CAS  PubMed  Google Scholar 

  56. 56.

    Ahmad A, Ali T, Park HY, Badshah H, Rehman SU, Kim MO. Neuroprotective effect of fisetin against amyloid-beta-induced cognitive/synaptic dysfunction, neuroinflammation, and neurodegeneration in adult mice. Mol Neurobiol. 2017;54:2269–85.

    CAS  PubMed  Google Scholar 

  57. 57.

    Lopez A, Aparicio N, Pazos MR, Grande MT, Barreda-Manso MA, Benito-Cuesta I, et al. Cannabinoid CB2 receptors in the mouse brain: relevance for Alzheimer’s disease. J Neuroinflammation. 2018;15:158.

    PubMed  PubMed Central  Google Scholar 

  58. 58.

    Schmöle AC, Lundt R, Toporowski G, Hansen JN, Beins E, Halle A, et al. Cannabinoid receptor 2-deficiency ameliorates disease symptoms in a mouse model with Alzheimer’s disease-like pathology. J Alzheimers Dis. 2018;64:379–92.

    PubMed  Google Scholar 

  59. 59.

    Benito C, Nunez E, Tolon RM, Carrier EJ, Rabano A, Hillard CJ, et al. Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains. J Neurosci. 2003;23:11136–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci. 2005;25:1904–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Solas M, Francis PT, Franco R, Ramirez MJ. CB2 receptor and amyloid pathology in frontal cortex of Alzheimer’s disease patients. Neurobiol Aging. 2013;34:805–8.

    CAS  PubMed  Google Scholar 

  62. 62.

    Savonenko AV, Melnikova T, Wang Y, Ravert H, Gao Y, Koppel J, et al. Cannabinoid CB2 receptors in a mouse model of abeta amyloidosis: immunohistochemical analysis and suitability as a PET biomarker of neuroinflammation. PLoS ONE. 2015;10:e0129618.

    PubMed  PubMed Central  Google Scholar 

  63. 63.

    Koppel J, Vingtdeux V, Marambaud P, d’Abramo C, Jimenez H, Stauber M, et al. CB2 receptor deficiency increases amyloid pathology and alters tau processing in a transgenic mouse model of Alzheimer’s disease. Mol Med. 2014;20:29–36.

    PubMed  PubMed Central  Google Scholar 

  64. 64.

    Klegeris A, Bissonnette CJ, McGeer PL. Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor. Br J Pharmacol. 2003;139:775–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Aso E, Juves S, Maldonado R, Ferrer I. CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AbetaPP/PS1 mice. J Alzheimers Dis. 2013;35:847–58.

    PubMed  Google Scholar 

  66. 66.

    Navarro-Dorado J, Villalba N, Prieto D, Brera B, Martín-Moreno AM, Tejerina T, et al. Vascular dysfunction in a transgenic model of Alzheimer’s disease: effects of CB1R and CB2R cannabinoid agonists. Front Neurosci. 2016;10:422.

    PubMed  PubMed Central  Google Scholar 

  67. 67.

    Wu J, Bie B, Yang H, Xu JJ, Brown DL, Naguib M. Activation of the CB2 receptor system reverses amyloid-induced memory deficiency. Neurobiol Aging. 2013;34:791–804.

    CAS  PubMed  Google Scholar 

  68. 68.

    Wu J, Hocevar M, Foss JF, Bie B, Naguib M. Activation of CB2 receptor system restores cognitive capacity and hippocampal Sox2 expression in a transgenic mouse model of Alzheimer’s disease. Eur J Pharmacol. 2017;811:12–20.

    CAS  PubMed  Google Scholar 

  69. 69.

    Kofalvi A, Lemos C, Martin-Moreno AM, Pinheiro BS, Garcia-Garcia L, Pozo MA, et al. Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer’s disease. Neuropharmacology. 2016;110:519–29.

    CAS  PubMed  Google Scholar 

  70. 70.

    Li C, Shi J, Wang B, Li J, Jia H. CB2 cannabinoid receptor agonist ameliorates novel object recognition but not spatial memory in transgenic APP/PS1 mice. Neurosci Lett. 2019;707:134286.

    CAS  PubMed  Google Scholar 

  71. 71.

    Zhang J, Chen C. Alleviation of neuropathology by inhibition of monoacylglycerol lipase in APP transgenic mice lacking CB2 receptors. Mol Neurobiol. 2018;55:4802–10.

    CAS  PubMed  Google Scholar 

  72. 72.

    Chen R, Zhang J, Wu Y, Wang D, Feng G, Tang YP, et al. Monoacylglycerol lipase is a therapeutic target for Alzheimer’s disease. Cell Rep. 2012;2:1329–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Aso E, Andrés-Benito P, Carmona M, Maldonado R, Ferrer I. Cannabinoid receptor 2 participates in amyloid-β processing in a mouse model of Alzheimer’s disease but plays a minor role in the therapeutic properties of a cannabis-based medicine. J Alzheimers Dis. 2016;51:489–500.

    CAS  PubMed  Google Scholar 

  74. 74.

    Schmöle AC, Lundt R, Ternes S, Albayram Ö, Ulas T, Schultze JL, et al. Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer’s disease mouse model. Neurobiol Aging. 2015;36:710–9.

    PubMed  Google Scholar 

  75. 75.

    Mhyre TR, Boyd JT, Hamill RW, Maguire-Zeiss KA. Parkinson’s disease. Sub-Cell Biochem. 2012;65:389–455.

    CAS  Google Scholar 

  76. 76.

    Concannon RM, Okine BN, Finn DP, Dowd E. Differential upregulation of the cannabinoid CB(2) receptor in neurotoxic and inflammation-driven rat models of Parkinson’s disease. Exp Neurol. 2015;269:133–41.

    CAS  PubMed  Google Scholar 

  77. 77.

    García MC, Cinquina V, Palomo-Garo C, Rábano A, Fernández-Ruiz J. Identification of CB2 receptors in human nigral neurons that degenerate in Parkinson’s disease. Neurosci Lett. 2015;587:1–4.

    PubMed  Google Scholar 

  78. 78.

    Shi J, Cai Q, Zhang J, He X, Liu Y, Zhu R, et al. AM1241 alleviates MPTP-induced Parkinson’s disease and promotes the regeneration of DA neurons in PD mice. Oncotarget. 2017;8:67837–50.

    PubMed  PubMed Central  Google Scholar 

  79. 79.

    Price DA, Martinez AA, Seillier A, Koek W, Acosta Y, Fernandez E, et al. WIN55,212-2, a cannabinoid receptor agonist, protects against nigrostriatal cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Eur J Neurosci. 2009;29:2177–86.

    PubMed  PubMed Central  Google Scholar 

  80. 80.

    Javed H, Azimullah S, Haque ME, Ojha SK. Cannabinoid type 2 (CB2) receptors activation protects against oxidative stress and neuroinflammation associated dopaminergic neurodegeneration in rotenone model of Parkinson’s disease. Front Neurosci. 2016;10:321.

    PubMed  PubMed Central  Google Scholar 

  81. 81.

    Viveros-Paredes JM, Gonzalez-Castaneda RE, Gertsch J, Chaparro-Huerta V, Lopez-Roa RI, Vazquez-Valls E, et al. Neuroprotective effects of beta-caryophyllene against dopaminergic neuron injury in a murine model of parkinson’s disease induced by MPTP. Pharmaceuticals (Basel, Switz). 2017;10:60.

    Google Scholar 

  82. 82.

    Wang G, Ma W, Du J. beta-Caryophyllene (BCP) ameliorates MPP+ induced cytotoxicity. Biomed Pharmacother. 2018;103:1086–91.

    CAS  PubMed  Google Scholar 

  83. 83.

    Eddings CR, Arbez N, Akimov S, Geva M, Hayden MR, Ross CA. Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor. Neurobiol Dis. 2019;129:118–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Spinelli F, Capparelli E, Abate C, Colabufo NA, Contino M. Perspectives of Cannabinoid type 2 receptor (CB2R) ligands in neurodegenerative disorders: structure-affinity relationship (SAfiR) and structure-activity relationship (SAR) studies. J Med Chem. 2017;60:9913–31.

    CAS  PubMed  Google Scholar 

  85. 85.

    Haider A, Spinelli F, Herde AM, Mu B, Keller C, Margelisch M, et al. Evaluation of 4-oxo-quinoline-based CB2 PET radioligands in R6/2 chorea huntington mouse model and human ALS spinal cord tissue. Eur J Med Chem. 2018;145:746–59.

    CAS  PubMed  Google Scholar 

  86. 86.

    Palazuelos J, Aguado T, Pazos MR, Julien B, Carrasco C, Resel E, et al. Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain. 2009;132:3152–64.

    PubMed  Google Scholar 

  87. 87.

    Sagredo O, Gonzalez S, Aroyo I, Pazos MR, Benito C, Lastres-Becker I, et al. Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease. Glia. 2009;57:1154–67.

    PubMed  PubMed Central  Google Scholar 

  88. 88.

    Bouchard J, Truong J, Bouchard K, Dunkelberger D, Desrayaud S, Moussaoui S, et al. Cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of Huntington’s disease. J Neurosci. 2012;32:18259–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Dowie MJ, Grimsey NL, Hoffman T, Faull RL, Glass M. Cannabinoid receptor CB2 is expressed on vascular cells, but not astroglial cells in the post-mortem human Huntington’s disease brain. J Chem Neuroanat. 2014;59-60:62–71.

    CAS  PubMed  Google Scholar 

  90. 90.

    Jafarzadeh Bejargafshe M, Hedayati M, Zahabiasli S, Tahmasbpour E, Rahmanzadeh S, Nejad-Moghaddam A. Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosis. Stem Cell Investig. 2019;6:44.

    PubMed  PubMed Central  Google Scholar 

  91. 91.

    Gonçalves ED, Dutra RC. Cannabinoid receptors as therapeutic targets for autoimmune diseases: where do we stand? Drug Disco Today. 2019;24:1845–53.

    Google Scholar 

  92. 92.

    Tahamtan A, Rezaiy S, Samadizadeh S, Moradi A, Tabarraei A, Javid N, et al. Cannabinoid CB2 receptor functional variation (Q63R) is associated with multiple sclerosis in iranian subjects. J Mol Neurosci. 2020;70:26–31.

  93. 93.

    Maresz K, Carrier EJ, Ponomarev ED, Hillard CJ, Dittel BN. Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem. 2005;95:437–45.

    CAS  PubMed  Google Scholar 

  94. 94.

    Yiangou Y, Facer P, Durrenberger P, Chessell IP, Naylor A, Bountra C, et al. COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol. 2006;6:12.

    PubMed  PubMed Central  Google Scholar 

  95. 95.

    Benito C, Romero JP, Tolon RM, Clemente D, Docagne F, Hillard CJ, et al. Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. J Neurosci. 2007;27:2396–402.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Palazuelos J, Davoust N, Julien B, Hatterer E, Aguado T, Mechoulam R, et al. The CB(2) cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of an animal model of multiple sclerosis. J Biol Chem. 2008;283:13320–9.

    CAS  PubMed  Google Scholar 

  97. 97.

    Zhang M, Martin BR, Adler MW, Razdan RJ, Kong W, Ganea D, et al. Modulation of cannabinoid receptor activation as a neuroprotective strategy for EAE and stroke. J NeuroImmune Pharmacol. 2009;4:249–59.

    PubMed  PubMed Central  Google Scholar 

  98. 98.

    Lourbopoulos A, Grigoriadis N, Lagoudaki R, Touloumi O, Polyzoidou E, Mavromatis I, et al. Administration of 2-arachidonoylglycerol ameliorates both acute and chronic experimental autoimmune encephalomyelitis. Brain Res. 2011;1390:126–41.

    CAS  PubMed  Google Scholar 

  99. 99.

    Correa F, Docagne F, Mestre L, Clemente D, Hernangomez M, Loria F, et al. A role for CB2 receptors in anandamide signalling pathways involved in the regulation of IL-12 and IL-23 in microglial cells. Biochem Pharmacol. 2009;77:86–100.

    CAS  PubMed  Google Scholar 

  100. 100.

    Fu W, Taylor BK. Activation of cannabinoid CB2 receptors reduces hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Neurosci Lett. 2015;595:1–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Alberti TB, Barbosa WL, Vieira JL, Raposo NR, Dutra RC. (−)-β-Caryophyllene, a CB2 receptor-selective phytocannabinoid, suppresses motor paralysis and neuroinflammation in a murine model of multiple sclerosis. Int J Mol Sci. 2017;18:691.

    PubMed Central  Google Scholar 

  102. 102.

    Sirabella R, Valsecchi V, Anzilotti S, Cuomo O, Vinciguerra A, Cepparulo P, et al. Ionic homeostasis maintenance in ALS: focus on new therapeutic targets. Front Neurosci. 2018;12:510.

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Habib AA, Mitsumoto H. Emerging drugs for amyotrophic lateral sclerosis. Expert Opin Emerg Drugs. 2011;16:537–58.

    PubMed  Google Scholar 

  104. 104.

    Shoemaker JL, Seely KA, Reed RL, Crow JP, Prather PL. The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. J Neurochem. 2007;101:87–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Kim K, Moore DH, Makriyannis A, Abood ME. AM1241, a cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis. Eur J Pharmacol. 2006;542:100–5.

    CAS  PubMed  Google Scholar 

  106. 106.

    Espejo-Porras F, García-Toscano L, Rodríguez-Cueto C, Santos-García I, de Lago E, Fernandez-Ruiz J. Targeting glial cannabinoid CB. Br J Pharmacol. 2019;176:1585–600.

    CAS  PubMed  Google Scholar 

  107. 107.

    Espejo-Porras F, Piscitelli F, Verde R, Ramos JA, Di Marzo V, de Lago E, et al. Changes in the endocannabinoid signaling system in CNS structures of TDP-43 transgenic mice: relevance for a neuroprotective therapy in TDP-43-related disorders. J Neuroimmune Pharmacol. 2015;10:233–44.

    PubMed  Google Scholar 

  108. 108.

    Fernández-Trapero M, Espejo-Porras F, Rodríguez-Cueto C, Coates JR, Pérez-Díaz C, de Lago E, et al. Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis. Dis Model Mech. 2017;10:551–8.

    PubMed  PubMed Central  Google Scholar 

  109. 109.

    Espejo-Porras F, Fernández-Ruiz J, de Lago E. Analysis of endocannabinoid receptors and enzymes in the post-mortem motor cortex and spinal cord of amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener. 2018;19:377–86.

    CAS  PubMed  Google Scholar 

  110. 110.

    Mu L, Bieri D, Slavik R, Drandarov K, Müller A, Cermak S, et al. Radiolabeling and in vitro /in vivo evaluation of N-(1-adamantyl)-8-methoxy-4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxamide as a PET probe for imaging cannabinoid type 2 receptor. J Neurochem. 2013;126:616–24.

    CAS  PubMed  Google Scholar 

  111. 111.

    Wei F, Yan LM, Su T, He N, Lin ZJ, Wang J, et al. Ion channel genes and epilepsy: functional alteration, pathogenic potential, and mechanism of epilepsy. Neurosci Bull. 2017;33:455–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. 112.

    Tang F, Hartz AMS, Bauer B. Drug-resistant epilepsy: multiple hypotheses, few answers. Front Neurol. 2017;8:301.

    PubMed  PubMed Central  Google Scholar 

  113. 113.

    Deshpande LS, Sombati S, Blair RE, Carter DS, Martin BR, DeLorenzo RJ. Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy. Neurosci Lett. 2007;411:11–6.

    CAS  PubMed  Google Scholar 

  114. 114.

    Kozan R, Ayyildiz M, Agar E. The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats. Epilepsia. 2009;50:1760–7.

    CAS  PubMed  Google Scholar 

  115. 115.

    Cakil D, Yildirim M, Ayyildiz M, Agar E. The effect of co-administration of the NMDA blocker with agonist and antagonist of CB1-receptor on penicillin-induced epileptiform activity in rats. Epilepsy Res. 2011;93:128–37.

    CAS  PubMed  Google Scholar 

  116. 116.

    Wallace MJ, Blair RE, Falenski KW, Martin BR, DeLorenzo RJ. The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther. 2003;307:129–37.

    CAS  PubMed  Google Scholar 

  117. 117.

    Capasso A. Do Cannabinoids confer neuroprotection against epilepsy? An overview. Open Neurol J. 2017;11:61–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. 118.

    Neale M. Efficacy and safety of cannabis for treating children with refractory epilepsy. Nurs Child Young People. 2017;29:32–7.

    PubMed  Google Scholar 

  119. 119.

    De Caro C, Leo A, Citraro R, De Sarro C, Russo R, Calignano A, et al. The potential role of cannabinoids in epilepsy treatment. Expert Rev Neurother. 2017;17:1069–79.

    PubMed  Google Scholar 

  120. 120.

    Sugaya Y, Yamazaki M, Uchigashima M, Kobayashi K, Watanabe M, Sakimura K, et al. Crucial roles of the endocannabinoid 2-arachidonoylglycerol in the suppression of epileptic seizures. Cell Rep. 2016;16:1405–15.

    CAS  PubMed  Google Scholar 

  121. 121.

    Deadwyler SA, Hampson RE, Mu J, Whyte A, Childers S. Cannabinoids modulate voltage sensitive potassium A-current in hippocampal neurons via a cAMP-dependent process. J Pharmacol Exp Ther. 1995;273:734–43.

    CAS  PubMed  Google Scholar 

  122. 122.

    Pan X, Ikeda SR, Lewis DL. Rat brain cannabinoid receptor modulates N-type Ca2+ channels in a neuronal expression system. Mol Pharmacol. 1996;49:707–14.

    CAS  PubMed  Google Scholar 

  123. 123.

    Kreitzer AC, Regehr WG. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron. 2001;29:717–27.

    CAS  PubMed  Google Scholar 

  124. 124.

    Wilson RI, Nicoll RA. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature. 2001;410:588–92.

    CAS  PubMed  Google Scholar 

  125. 125.

    Wilson RI, Kunos G, Nicoll RA. Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron. 2001;31:453–62.

    CAS  PubMed  Google Scholar 

  126. 126.

    Arslan G, Ayyildiz M, Agar E. The interaction between ghrelin and cannabinoid systems in penicillin-induced epileptiform activity in rats. Neuropeptides. 2014;48:345–52.

    CAS  PubMed  Google Scholar 

  127. 127.

    Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15:270–8.

    CAS  PubMed  Google Scholar 

  128. 128.

    Devinsky O, Cross JH, Wright S. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;377:699–700.

    PubMed  Google Scholar 

  129. 129.

    Szaflarski M, Hansen B, Bebin EM, Szaflarski JP. Social correlates of health status, quality of life, and mood states in patients treated with cannabidiol for epilepsy. Epilepsy Behav. 2017;70:364–9.

    PubMed  Google Scholar 

  130. 130.

    Aghaei I, Rostampour M, Shabani M, Naderi N, Motamedi F, Babaei P, et al. Palmitoylethanolamide attenuates PTZ-induced seizures through CB1 and CB2 receptors. Epilepsy Res. 2015;117:23–8.

    CAS  PubMed  Google Scholar 

  131. 131.

    Huizenga MN, Wicker E, Beck VC, Forcelli PA. Anticonvulsant effect of cannabinoid receptor agonists in models of seizures in developing rats. Epilepsia. 2017;58:1593–602.

    CAS  PubMed  Google Scholar 

  132. 132.

    Rowley S, Sun X, Lima IV, Tavenier A, de Oliveira ACP, Dey SK, et al. Cannabinoid receptor 1/2 double-knockout mice develop epilepsy. Epilepsia. 2017;58:e162–e6.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. 133.

    Xin Q, Bai B, Liu W. The analgesic effects of oxytocin in the peripheral and central nervous system. Neurochem Int. 2017;103:57–64.

    CAS  PubMed  Google Scholar 

  134. 134.

    Guerrero-Alba R, Barragan-Iglesias P, Gonzalez-Hernandez A, Valdez-Morales EE, Granados-Soto V, Condes-Lara M, et al. Some prospective alternatives for treating pain: the endocannabinoid system and its putative receptors GPR18 and GPR55. Front Pharmacol. 2018;9:1496.

    CAS  PubMed  Google Scholar 

  135. 135.

    Svizenska IH, Brazda V, Klusakova I, Dubovy P. Bilateral changes of cannabinoid receptor type 2 protein and mRNA in the dorsal root ganglia of a rat neuropathic pain model. J Histochem Cytochem. 2013;61:529–47.

    PubMed  PubMed Central  Google Scholar 

  136. 136.

    Lotsch J, Weyer-Menkhoff I, Tegeder I. Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings. Eur J Pain. 2018;22:471–84.

    CAS  PubMed  Google Scholar 

  137. 137.

    Racz I, Nadal X, Alferink J, Banos JE, Rehnelt J, Martin M, et al. Crucial role of CB2 cannabinoid receptor in the regulation of central immune responses during neuropathic pain. J Neurosci. 2008;28:12125–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. 138.

    Liu QR, Canseco-Alba A, Zhang HY, Tagliaferro P, Chung M, Dennis E, et al. Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference. Sci Rep. 2017;7:17410.

    PubMed  PubMed Central  Google Scholar 

  139. 139.

    Hossain MZ, Ando H, Unno S, Kitagawa J. Targeting peripherally restricted cannabinoid receptor 1, cannabinoid receptor 2, and endocannabinoid-degrading enzymes for the treatment of neuropathic pain including neuropathic orofacial pain. Int J Mol Sci. 2020;21:1423.

    CAS  PubMed Central  Google Scholar 

  140. 140.

    Sanchez-Aparicio P, Floran B, Velazquez DR, Ibancovichi JA, Guerrero JAV, Recillas S. Cannabinoids CB2 receptors, one new promising drug target for chronic and degenerative pain conditions in equine veterinary patients. J Equine Vet Sci. 2020;85:102880.

    PubMed  Google Scholar 

  141. 141.

    Deng LT, Guindon J, Cornett BL, Makriyannis A, Mackie K, Hohmann AG. Chronic cannabinoid receptor 2 Activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal. Biol Psychiatry. 2015;77:475–87.

    CAS  PubMed  Google Scholar 

  142. 142.

    Watkins LR, Hutchinson MR, Rice KC, Maier SF. The “toll” of opioid-induced glial activation: improving the clinical efficacy of opioids by targeting glia. Trends Pharmacol Sci. 2009;30:581–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  143. 143.

    Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, et al. CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sci USA. 2005;102:3093–8.

    CAS  PubMed  Google Scholar 

  144. 144.

    Li AL, Lin XY, Dhopeshwarkar AS, Thomaz AC, Carey LM, Liu YP, et al. Cannabinoid CB2 agonist AM1710 differentially suppresses distinct pathological pain states and attenuates morphine tolerance and withdrawal. Mol Pharmacol. 2019;95:155–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  145. 145.

    Lin XY, Dhopeshwarkar AS, Huibregtse M, Mackie K, Hohmann AG. Slowly signaling G protein-biased CB2 cannabinoid receptor agonist LY2828360 suppresses neuropathic pain with sustained efficacy and attenuates morphine tolerance and dependence. Mol Pharmacol. 2018;93:49–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. 146.

    Zhang MY, Wang K, Ma M, Tian SY, Wei N, Wang GN. Low-dose cannabinoid type 2 receptor agonist attenuates tolerance to repeated morphine administration via regulating mu-opioid receptor expression in walker 256 tumor-bearing rats. Anesth Analg. 2016;122:1031–7.

    CAS  PubMed  Google Scholar 

  147. 147.

    Wouters E, Walraed J, Banister SD, Stove CP. Insights into biased signaling at cannabinoid receptors: synthetic cannabinoid receptor agonists. Biochem Pharmacol. 2019;169:113623.

    CAS  PubMed  Google Scholar 

  148. 148.

    Ye L, Cao Z, Wang W, Zhou N. New insights in cannabinoid receptor structure and signaling. Curr Mol Pharmacol. 2019;12:239–48.

    CAS  PubMed  Google Scholar 

  149. 149.

    An D, Peigneur S, Hendrickx LA, Tytgat J. Targeting cannabinoid receptors: current status and prospects of natural products. Int J Mol Sci. 2020;21:5064.

    CAS  PubMed Central  Google Scholar 

  150. 150.

    Cécyre B, Zabouri N, Huppé-Gourgues F, Bouchard JF, Casanova C. Roles of cannabinoid receptors type 1 and 2 on the retinal function of adult mice. Invest Ophthalmol Vis Sci. 2013;54:8079.

    PubMed  Google Scholar 

  151. 151.

    Yang W, Li Q, Wang SY, Gao F, Qian WJ, Li F, et al. Cannabinoid receptor agonists modulate calcium channels in rat retinal müller cells. Neuroscience. 2016;313:213–24.

    CAS  PubMed  Google Scholar 

  152. 152.

    Bouskila J, Javadi P, Casanova C, Ptito M, Bouchard JF. Müller cells express the cannabinoid CB2 receptor in the vervet monkey retina. J Comp Neurol. 2013;521:2399–415.

    CAS  PubMed  Google Scholar 

  153. 153.

    Lanciego JL, Barroso-Chinea P, Rico AJ, Conte-Perales L, Callén L, Roda E, et al. Expression of the mRNA coding the cannabinoid receptor 2 in the pallidal complex of. J Psychopharmacol. 2020;25:97–104.

    Google Scholar 

  154. 154.

    Sierra S, Luquin N, Rico AJ, Gómez-Bautista V, Roda E, Dopeso-Reyes IG, et al. Detection of cannabinoid receptors CB1 and CB2 within basal ganglia output neurons in macaques: changes following experimental parkinsonism. Brain Struct Funct. 2015;220:2721–38.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr. Jing Chen and Bai-liu Ya, at the Institute of Neurobiology in Jining Medical University, for their critical discussions and valuable comments for this article. The present work was supported by National Natural Science Foundation of China (81371437, 81703490), Shandong Province Medical and Health Technology Development Project (No. 2018WSB33004), Scientific Research Funds for young teachers of Jining Medical University (No. JYFC2019FKJ016), Research Fund for Academician Lin He New Medicine (JYHL2019MS17), Key Research and Development Project of Jining (2019SMNS018).

Author information

Affiliations

Authors

Contributions

Both QX and FX equally contributed to writing the manuscript and sourcing references for the review. DHT and JFZ contributed to discussions and editing of the manuscript. JW conceived the outline of this paper and participated in critical review and further revision of the manuscript. All authors contributed to critical discussions and finalizing the manuscript before submission. They have all given approval to the final form of the manuscript.

Corresponding author

Correspondence to Jie Wu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Xin, Q., Xu, F., Taylor, D.H. et al. The impact of cannabinoid type 2 receptors (CB2Rs) in neuroprotection against neurological disorders. Acta Pharmacol Sin 41, 1507–1518 (2020). https://doi.org/10.1038/s41401-020-00530-2

Download citation

Keywords

  • cannabinoid
  • cannabinoid type 2 receptor
  • neuroprotection
  • ischemic stroke
  • Alzheimer’s disease
  • Parkinson disease

Search

Quick links