Anandamide and 2-arachidonoylglycerol: pharmacological properties, functional features, and emerging specificities of the two major endocannabinoids

Antonio Luchicchi, Marco Pistis

Research output: Contribution to journalReview articleAcademicpeer-review

87 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)374-92
Number of pages19
JournalMolecular neurobiology
Issue number2
Publication statusPublished - Oct 2012
Externally publishedYes


  • Animals
  • Arachidonic Acids
  • Endocannabinoids
  • Glycerides
  • Humans
  • Journal Article
  • Memory
  • Neuronal Plasticity
  • Neuroprotective Agents
  • Nociception
  • Polyunsaturated Alkamides
  • Research Support, Non-U.S. Gov't
  • Review

Cite this