Skip to main content
SpringerLink
Log in

Cannabinoid Receptor 2 (CB2)

  • Chapter
  • First Online:
Cannabinoids and Pain

Abstract

CB2 receptor was once considered to be the “peripheral cannabinoid receptor.” This label was based on its discovery and abundant expression in the immune system and, until recently, absence from the central nervous system. It is now accepted that CB2 receptors are expressed in the central nervous system as well. CB2 receptors have been expressed in the brain microglia during neuronal inflammation. Dorsal root ganglion upregulation of CB2 receptors plays a major role in the antinociceptive effects.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zhang HY, Bi GH, Li X, Li J, Qu H, Zhang SJ, Li CY, Onaivi ES, Gardner EL, Xi ZX, Liu QR. Species differences in Cannabinoid receptor 2 and receptor responses to cocaine self-administration in mice and rats. Neuropsychopharmacology. 2015r;40(4):1037–51. https://doi.org/10.1038/npp.2014.297.

    Article  CAS  PubMed  Google Scholar 

  2. Chen DJ, Gao M, Gao FF, Su QX, Wu J. Brain cannabinoid receptor 2: expression, function and modulation. Acta Pharmacol Sin. 2017\;38(3):312–6. https://doi.org/10.1038/aps.2016.149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Miller LK, Devi LA. The highs and lows of cannabinoid receptor expression in disease: mechanisms and their therapeutic implications. Pharmacol Rev. 2011;63(3):461–70. https://doi.org/10.1124/pr.110.003491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Atwood BK, Wager-Miller J, Haskins C, Straiker A, Mackie K. Functional selectivity in CB(2) cannabinoid receptor signaling and regulation: implications for the therapeutic potential of CB(2) ligands. Mol Pharmacol. 2012;81(2):250–63. https://doi.org/10.1124/mol.111.074013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Ma AL, Mitchell RL. Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol. 1995;48(3):443–50.

    CAS  PubMed  Google Scholar 

  6. Mukherjee S, Adams M, Whiteaker K, Daza A, Kage K, Cassar S, Meyer M, Yao BB. Species comparison and pharmacological characterization of rat and human CB2 cannabinoid receptors. Eur J Pharmacol. 2004;505(1–3):1–9. https://doi.org/10.1016/j.ejphar.2004.09.058.

    Article  CAS  PubMed  Google Scholar 

  7. Dhopeshwarkar A, Mackie K. CB2 Cannabinoid receptors as a therapeutic target. What does the future hold? Mol Pharmacol. 2014;86(4):430–7. https://doi.org/10.1124/mol.114.094649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu QR, Pan CH, Hishimoto A, Li CY, Xi ZX, Llorente-Berzal A, Viveros MP, Ishiguro H, Arinami T, Onaivi ES, Uhl GR. 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(5):519–30. https://doi.org/10.1111/j.1601-183X.2009.00498.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365(6441):61–5. https://doi.org/10.1038/365061a0.

    Article  CAS  PubMed  Google Scholar 

  10. Atwood BK, Mackie K. 2010. CB2: a cannabinoid receptor with an identity crisis. Br J Pharmacol. 2010;160(3):467–79. https://doi.org/10.1111/j.1476-5381.2010.00729.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cabral GA, Raborn ES, Griffin L, Dennis J, Marciano-Cabral F. CB2 receptors in the brain: role in central immune function. Br J Pharmacol. 2008;153(2):240–51. https://doi.org/10.1038/sj.bjp.0707584.

    Article  CAS  PubMed  Google Scholar 

  12. Stempel AV, Stumpf A, Zhang HY, Özdoğan T, Pannasch U, Theis AK, Otte DM, Wojtalla A, Rácz I, Ponomarenko A, Xi ZX, Zimmer A, Schmitz D. Cannabinoid type 2 receptors mediate a cell type-specific plasticity in the Hippocampus. Neuron. 2016;90(4):795–809. https://doi.org/10.1016/j.neuron.2016.03.034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shoemaker JL, Ruckle MB, Mayeux PR, Prather PL. Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors. J Pharmacol Exp Ther. 2005;315(2):828–38. https://doi.org/10.1124/jpet.105.089474.

    Article  CAS  PubMed  Google Scholar 

  14. Pertwee RG, Howlett AC, Abood ME, Alexander SPH, DiMarzo V, Elphick MR, Greasley PJ, et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev. 2010;62:588–631.

    Google Scholar 

  15. Donvito G, Nass SR, Wilkerson JL, Curry ZA, Schurman LD, Kinsey SG, Lichtman AH. The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain. Neuropsychopharmacology. 2018;43(1):52–79. https://doi.org/10.1038/npp.2017.204.

    Article  CAS  PubMed  Google Scholar 

  16. Hsieh GC, Pai M, Chandran P, Hooker BA, Zhu CZ, Salyers AK, et al. Central and peripheral sites of action for CB2 receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats. Br J Pharmacol. 2011;162:428–40.

    Article  CAS  Google Scholar 

  17. Burston JJ, Sagar DR, Shao P, Bai M, King E, Brailsford L, Turner JM, Hathway GJ, Bennett AJ, Walsh DA, Kendall DA, Lichtman A, Chapman V. Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint. PLoS One. 2013;8(11):e80440. https://doi.org/10.1371/journal.pone.0080440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Austin PJ, Moalem-Taylor G. The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. J Neuroimmunol. 2010;229(1–2):26–50. https://doi.org/10.1016/j.jneuroim.2010.08.013.

    Article  CAS  PubMed  Google Scholar 

  19. Bouaboula M, Dussossoy D, Casellas P. Regulation of peripheral cannabinoid receptor CB2 phosphorylation by the inverse agonist SR 144528. Implications for receptor biological responses. J Biol Chem. 1999;274(29):20397–405.

    Article  CAS  Google Scholar 

  20. Carrier EJ, Kearn CS, Barkmeier AJ, Breese NM, Yang W, Nithipatikom K, Pfister SL, Campbell WB, Hillard CJ. Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Mol Pharmacol. 2004;65(4):999–1007.

    Article  CAS  Google Scholar 

  21. Howlett AC, Abood ME. CB1 and CB2 receptor pharmacology. Adv Pharmacol. 2017;80:169–206. https://doi.org/10.1016/bs.apha.2017.03.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Deng L, 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(5):475–87. https://doi.org/10.1016/j.biopsych.2014.04.009.

    Article  CAS  PubMed  Google Scholar 

  23. Li X, Hua T, Vemuri K, Ho JH, Wu Y, Wu L, Popov P, Benchama O, Zvonok N, Locke K, Qu L, Han GW, Iyer MR, Cinar R, Coffey NJ, Wang J, Wu M, Katritch V, Zhao S, Kunos G, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ. Crystal structure of the human Cannabinoid receptor CB2. Cell. 2019;176(3):459–467.e13. https://doi.org/10.1016/j.cell.2018.12.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Petrucci V, Chicca A, Glasmacher S, Paloczi J, Cao Z, Pacher P, Gertsch J. Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage. Sci Rep. 2017;7(1):9560. https://doi.org/10.1038/s41598-017-09808-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Western Reserve Hospital, Cuyahoga Falls, OH, USA

    Glenn R. Rech

  2. Western Reserve Hospital, Center For Pain Medicine, Cuyahoga Falls, OH, USA

    Samer N. Narouze

Authors
  1. Glenn R. Rech
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samer N. Narouze
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Western Reserve Hospital, Center For Pain Medicine, Cuyahoga Falls, OH, USA

    Samer N. Narouze

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rech, G.R., Narouze, S.N. (2021). Cannabinoid Receptor 2 (CB2). In: Narouze, S.N. (eds) Cannabinoids and Pain. Springer, Cham. https://doi.org/10.1007/978-3-030-69186-8_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-69186-8_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-69185-1

  • Online ISBN: 978-3-030-69186-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation