Weeding out bad waves: Towards selective cannabinoid circuit control in epilepsy

Ivan Soltesz, Bradley E. Alger, Masanobu Kano, Sang Hun Lee, David M. Lovinger, Takako Ohno-Shosaku, Masahiko Watanabe

Research output: Contribution to journalReview articlepeer-review

113 Scopus citations


Endocannabinoids are lipid-derived messengers, and both their synthesis and breakdown are under tight spatiotemporal regulation. As retrograde signalling molecules, endocannabinoids are synthesized postsynaptically but activate presynaptic cannabinoid receptor 1 (CB1) receptors to inhibit neurotransmitter release. In turn, CB1-expressing inhibitory and excitatory synapses act as strategically placed control points for activity-dependent regulation of dynamically changing normal and pathological oscillatory network activity. Here, we highlight emerging principles of cannabinoid circuit control and plasticity, and discuss their relevance for epilepsy and related comorbidities. New insights into cannabinoid signalling may facilitate the translation of the recent interest in cannabis-related substances as antiseizure medications to evidence-based treatment strategies.

Original languageEnglish
Pages (from-to)264-277
Number of pages14
JournalNature Reviews Neuroscience
Issue number5
StatePublished - Apr 20 2015

Bibliographical note

Funding Information:
The authors thank J. G. Malpeli for comments on the manuscript and M. Uchigashima for Figure 1c. This work was supported by a US National Institutes of Health grant (NS74432 to I.S.) and Grants-in-Aid for Scientific Research (23500466 to T.O.-S. and 25000015 to M.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.

ASJC Scopus subject areas

  • Neuroscience (all)


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