Endocannabinoids and stress

Abstract

Endogenous cannabinoids play an important role in the physiology and behavioral expression of stress responses. Activation of the hypothalamic–pituitary–adrenal (HPA) axis, including the release of glucocorticoids, is the fundamental hormonal response to stress. Endocannabinoid (eCB) signaling serves to maintain HPA-axis homeostasis, by buffering basal activity as well as by mediating glucocorticoid fast feedback mechanisms. Following chronic stressor exposure, eCBs are also involved in physiological and behavioral habituation processes. Behavioral consequences of stress include fear and stress-induced anxiety as well as memory formation in the context of stress, involving contextual fear conditioning and inhibitory avoidance learning. Chronic stress can also lead to depression-like symptoms. Prominent in these behavioral stress responses is the interaction between eCBs and the HPA-axis. Future directions may differentiate among eCB signaling within various brain structures/neuronal subpopulations as well as between the distinct roles of the endogenous cannabinoid ligands. Investigation into the role of the eCB system in allostatic states and recovery processes may give insight into possible therapeutic manipulations of the system in treating chronic stress-related conditions in humans.

Keywords::

• Allostatic state
• CB₁
• endocannabinoid
• habituation
• HPA-axis
• stress

Acknowledgments

This work has been supported by a Natural Sciences and Engineering Research Council of Canada Graduate Scholarship and a doctoral stipend from the Max Planck Society to C. J. R.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.