Send to

Choose Destination
Neuropharmacology. 2017 Sep 15;124:13-24. doi: 10.1016/j.neuropharm.2017.06.017. Epub 2017 Jun 15.

Synaptic functions of endocannabinoid signaling in health and disease.

Author information

Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461, USA. Electronic address:
Institut National de la Santé et et de la Recherche Médicale U901 Marseille, France, Université de la Méditerranée UMR S901 Aix-Marseille Marseille, France, INMED Marseille, France. Electronic address:
Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, Genova, Italy. Electronic address:


Endocannabinoids (eCBs) are a family of lipid molecules that act as key regulators of synaptic transmission and plasticity. They are synthetized "on demand" following physiological and/or pathological stimuli. Once released from postsynaptic neurons, eCBs typically act as retrograde messengers to activate presynaptic type 1 cannabinoid receptors (CB1) and induce short- or long-term depression of neurotransmitter release. Besides this canonical mechanism of action, recent findings have revealed a number of less conventional mechanisms by which eCBs regulate neural activity and synaptic function, suggesting that eCB-mediated plasticity is mechanistically more diverse than anticipated. These mechanisms include non-retrograde signaling, signaling via astrocytes, participation in long-term potentiation, and the involvement of mitochondrial CB1. Focusing on paradigmatic brain areas, such as hippocampus, striatum, and neocortex, we review typical and novel signaling mechanisms, and discuss the functional implications in normal brain function and brain diseases. In summary, eCB signaling may lead to different forms of synaptic plasticity through activation of a plethora of mechanisms, which provide further complexity to the functional consequences of eCB signaling. This article is part of the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology".


Astrocytes; Endocannabinoids; Hippocampus; Prefrontal cortex; Striatum; Synaptic plasticity

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center