NeuroMolecular Medicine

, Volume 7, Issue 1–2, pp 37–50 | Cite as

Cannabinoid receptors and their role in neuroprotection

  • Mario van der Stelt
  • Vincenzo Di MarzoEmail author
Original Article


Two G protein-coupled receptors for marijuana’s psychoactive component, Δ9-tetrahydrocannabinol, have been cloned to date, the cannabinoid CB1 and CB2 receptors. These two proteins, the endogenous lipids that activate them, also known as endocannabinoids, and the proteins for the biosynthesis and inactivation of these ligands constitute the endocannabinoid system. Evidence has accumulated over the last few years suggesting that endocannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. In fact, exogenous and endogenous cannabinoids were 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 cannabinoid CB1-mediated inhibition of glutamatergic transmission, reduction of calcium influx, anti-oxidant activity, activation of the phosphatidylinositol 3-kinase/protein kinase B pathway, induction of phosphorylation of extracellular regulated kinases and the expression of transcription factors and neurotrophins, lowering of cerebrovasoconstriction and induction of hypothermia. The release of endocannabinoids during neuronal injury may constitute a protective response. If this neuroprotective function of cannabinoid receptor activation can be transferred to the clinic, it might represent an interesting target to develop neuroprotective agents.

Index Entries

Endocannabinoid anandamide 2-arachidonoylglycerol cannabinoid-receptor signaling neuromodulatory role of endocannabinoids glutamate excitotoxicity 


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Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  1. 1.Endocannabinoid Research GroupInstitute of Biomolecular Chemistry, Consiglio Nazionale delle RicerchePozzuoli (NA)Italy

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