Endocannabinoids and stress

Stress. 2011 Jul;14(4):384-97. doi: 10.3109/10253890.2011.586753.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anxiety / etiology
  • Behavior, Animal / physiology
  • Cannabinoid Receptor Modulators / physiology*
  • Depression / etiology
  • Endocannabinoids*
  • Fear / physiology
  • Habituation, Psychophysiologic / physiology
  • Hypothalamo-Hypophyseal System / physiology
  • Memory / physiology
  • Mice
  • Pituitary-Adrenal System / physiology
  • Rats
  • Receptor, Cannabinoid, CB1 / metabolism
  • Signal Transduction / physiology
  • Stress, Physiological / physiology*
  • Stress, Psychological / physiopathology*


  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1