Multiple functions of endocannabinoid signaling in the brain

Research output: Contribution to journalReview article

293 Citations (Scopus)


Despite being regarded as a hippie science for decades, cannabinoid research has finally found its well-deserved position in mainstream neuroscience. A series of groundbreaking discoveries revealed that endocannabinoid molecules are as widespread and important as conventional neurotransmitters such as glutamate or GABA, yet they act in profoundly unconventional ways. We aim to illustrate how uncovering the molecular, anatomical, and physiological characteristics of endocannabinoid signaling has revealed new mechanistic insights into several fundamental phenomena in synaptic physiology. First, we summarize unexpected advances in the molecular complexity of biogenesis and inactivation of the two endocannabinoids, anandamide and 2-arachidonoylglycerol. Then, we show how these new metabolic routes are integrated into well-known intracellular signaling pathways. These endocannabinoid-producing signalosomes operate in phasic and tonic modes, thereby differentially governing homeostatic, short-term, and long-term synaptic plasticity throughout the brain. Finally, we discuss how cell type-and synapse-specific refinement of endocannabinoid signalingmay explain the characteristic behavioral effects of cannabinoids.

Original languageEnglish
Pages (from-to)529-558
Number of pages30
JournalAnnual Review of Neuroscience
Publication statusPublished - Jul 1 2012



  • G protein-coupled receptors
  • diacylglycerol lipase
  • feedback inhibition
  • retrograde signaling
  • synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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