Molecular Neurobiology

, Volume 46, Issue 2, pp 374-392

First online:

Anandamide and 2-arachidonoylglycerol: Pharmacological Properties, Functional Features, and Emerging Specificities of the Two Major Endocannabinoids

  • Antonio LuchicchiAffiliated withDepartment of Biomedical Sciences, University of Cagliari
  • , Marco PistisAffiliated withDepartment of Biomedical Sciences, University of CagliariCNR Neuroscience InstituteCenter of Excellence for the Neurobiology of Addiction, University of CagliariDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria Email author 

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Since the discovery of endocannabinoids and their receptors, two major members of the endocannabinoid family, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), have been regarded almost as twin brothers. Pharmacological properties were initially considered to be similar, as these molecules were believed mutually exchangeable and almost indistinguishable in the regulation of synaptic functions, such as long- and short-term synaptic plasticity, and in behavioral aspects, such as learning and memory, reward and addiction, antinociception, and anxiety. In recent years, however, endocannabinoid signaling specificity began to emerge, in particular, due to the production of genetically engineered mice lacking key enzymes in endocannabinoid synthesis or degradation, together with the development of selective inhibitors of AEA or 2-AG catabolic enzymes. Evidence now suggests that AEA and 2-AG possess specific pharmacological properties, are engaged in different forms of synaptic plasticity, and take part in different behavioral functions. In this review, we provide an overview on similarities and specificities of the two endocannabinoids in the CNS and on the unresolved questions concerning their role in synaptic signaling.


Anandamide 2-Arachidonoylglycerol Cannabinoids Cannabinoid receptors Synaptic plasticity