Molecular Neurobiology

, Volume 26, Issue 2–3, pp 317–346 | Cite as

Acute neuronal injury, excitotoxicity, and the endocannabinoid system

  • Mario van der Stelt
  • Wouter B. Veldhuis
  • Mauro Maccarrone
  • Peter R. Bär
  • Klaas Nicolay
  • Gerrit A. Veldink
  • Vincenzo Di Marzo
  • Johannes F. G. Vliegenthart


The endocannabinoid system is a valuable target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The endocannabinoid system constitutes the endogenous lipids anandamide, 2-arachidonoylglycerol and noladin ether, and the cannabinoid CB1 and CB2 receptors as well as the proteins for their inactivation. It is thought that (endo)cannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. This paper reviews recent developments in the endocannabinoid system and its involvement in neuroprotection.

Exogenous (endo)cannabinoids have been shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms, such as prevention of excitotoxicity by CB1-mediated inhibition of glutamatergic transmission, reduction of calcium influx, and subsequent inhibition of deleterious cascades, TNF-α formation, and anti-oxidant activity. It has been suggested that the release of endogenous endocannabinoids during neuronal injury might be a protective response. However, several observations indicate that the role of the endocannabinoid system as a general endogenous protection system is questionable. The data are critically reviewed and possible explanations are given.

Index Entries

Cannabinoid anandamide 2-arachidonoylglycerol excitotoxicity neuroprotection neurodegeneration 


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Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  • Mario van der Stelt
    • 1
  • Wouter B. Veldhuis
    • 2
    • 3
  • Mauro Maccarrone
    • 4
  • Peter R. Bär
    • 3
  • Klaas Nicolay
    • 2
  • Gerrit A. Veldink
    • 1
  • Vincenzo Di Marzo
    • 5
  • Johannes F. G. Vliegenthart
    • 1
  1. 1.Department of Bio-Organic Chemistry, Bijvoet Center for Biomolecular ResearchUtrecht UniversityCH UtrechtThe Netherlands
  2. 2.Department of Experimental in vivo NMR, Image Sciences Institute, UtrechtUniversity Medical Center UtrechtThe Netherlands
  3. 3.Department of Experimental NeurologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  4. 4.Department of Experimental Medicine and Biochemical SciencesUniversity of Rome “Tor Vergata”RomeItaly
  5. 5.Endocannabinoid Research GroupInstitute of Biomolecular Chemistry—Consiglio Nazionale delle RicerchePozzuoli (Naples)Italy

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