The endocannabinoid system in guarding against fear, anxiety and stress

The endocannabinoid (eCB) system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiological and behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus allowing an organism to adapt to its changing environment. eCB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism's long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders. An understanding of the underlying neural cell populations and cellular processes enables the development of therapeutic strategies to mitigate behavioural maladaptation.B.L. was supported by the German Research Foundation (SFB TRR 58, CRC 1080 and FOR 926); G.M. by the Institut national de la santé et de la recherche médicale (INSERM), the European Commission Seventh Framework Programme (REPROBESITY, HEALTH-F2-2008-223713, PAINCAGE and HEALTH-2014-603191), the European Research Council (Endofood, ERC-2010-StG−260515, CannaPreg and ERC-2014-PoC-640923), the Fondation pour la Recherche Medicale (DRM20101220445), the Human Frontiers Science Program, Region Aquitaine, Agence Nationale de la Recherche (ANR Blanc NeuroNutriSens ANR-13-BSV4-0006 and BRAIN ANR-10-LABX-0043); R.M. by the grants SAF2014-59648P, RETICS-RTA#RD12/0028/0023, AGAUR#2014-SGR-1547 and Health-F2-2013-602891; and C.J.H. by the US National Institutes of Health grants DA038663, DA026996 and MH102838