Skip to main content
SpringerLink
Log in

Endocannabinoids: Anandamide and 2-Arachidonoylglycerol (2-AG)

  • Chapter
  • First Online:
Cannabinoids and Pain

Abstract

Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are two key players within the endocannabinoid system. Anandamide and 2-AG are lipid neurotransmitters responsible for actions carried out at various receptors, including the cannabinoid receptors. Although these neurotransmitters act within the same system, they differ in biochemical pathways and mechanism of action. Anandamide and 2-AG are both synthesized on demand and have a short-lived transmission. 2-AG is a full agonist at CB1 and CB2 receptors, whereas anandamide is a partial agonist. The endocannabinoid actions at both CB1 and CB2 receptors contribute to the resolution of acute pain. The endocannabinoids also have analgesic benefit to neuropathic, gastrointestinal, inflammatory, and chemotherapy-induced pain. 2-AG has a higher concentration in the nervous tissue and may have a greater role in analgesia and antinociception when compared to anandamide. The endocannabinoid signaling system involving 2-AG and anandamide includes a differential but synergistic role when looking at pharmacological properties.

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. Hillard CJ. Biochemistry and pharmacology of the endocannabinoids arachidonylethanolamide and 2-arachidonylglycerol. Prostaglandins Other Lipid Mediat. 2000;61(1-2):3–18.

    Article  CAS  Google Scholar 

  2. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258(5090):1946–9.

    Article  CAS  Google Scholar 

  3. Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, ALmog S, Martin BR, Compton DR, Pertwee RG, Griffin G, Bayewitch M, Barg J, Vogel Z. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol. 1995;50(1):83–90.

    Article  CAS  Google Scholar 

  4. Luchicch A, Pistis M. Anandamide and 2-arachidonoylglycerol: pharmacological properties, functional features, and emerging specificities of the two major endocannabinoids. Mol Neurobiol. 2012;46:374–92.

    Article  Google Scholar 

  5. Reggio PH. Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown. Curr Med Chem. 2010;17(14):1468–86.

    Article  CAS  Google Scholar 

  6. Mechoulam R, Fride E, Marzo VD. Endocannabinoids. Eur J Pharmacol. 1998;359(1):1–18.

    Article  CAS  Google Scholar 

  7. Ueda N, Tsuboi K, Uyama T. N-acylethanolamine metabolism with special reference to N-acylethanolamine-hydrolyzing acid amidase (NAAA). Prog Lipid Res. 2010;49(4):299–315.

    Article  CAS  Google Scholar 

  8. Yu M, Ives D, Ramesha CS. Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxygenase-2. J Biol Chem. 1997;272(34):21181–6.

    Article  CAS  Google Scholar 

  9. Bornheim LM, Kim KY, Chen B, Correia MA. The effect of cannabidiol on mouse hepatic microsomal cytochrome P450-dependent anandamide metabolism. Biochem Biophys Res Com- mun. 1993;197(2):740–6.

    Article  CAS  Google Scholar 

  10. Iannotti FA, Di Marzo V, Petrosino S. Endocannabinoids and endocannabinoid-related mediators: targets, metabolism and role in neurological disorders. Prog Lipid Res. 2016;62:107–28. https://doi.org/10.1016/j.plipres.2016.02.002.

    Article  CAS  PubMed  Google Scholar 

  11. Woodhams SG, Sagar DR, Burston JJ, Chapman V. The role of the endocannabinoid system in pain. Handb Exp Pharmacol. 2015;227:119–43. https://doi.org/10.1007/978-3-662-46450-2_7.

    Article  CAS  PubMed  Google Scholar 

  12. Manzanares J, Julian MD, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006;4(3):239–57.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ohio Northern University, Ada, OH, USA

    Danielle Despina Pete

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

    Samer N. Narouze

Authors
  1. Danielle Despina Pete
    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

Corresponding author

Correspondence to Danielle Despina Pete .

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

Pete, D.D., Narouze, S.N. (2021). Endocannabinoids: Anandamide and 2-Arachidonoylglycerol (2-AG). In: Narouze, S.N. (eds) Cannabinoids and Pain. Springer, Cham. https://doi.org/10.1007/978-3-030-69186-8_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-69186-8_9

  • 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