The Endocannabinoid System and Anxiety

Vitam Horm. 2017;103:193-279. doi: 10.1016/bs.vh.2016.09.006. Epub 2016 Nov 2.


The medical properties of Cannabis sativa is known for centuries. Since the discovery and characterization of the endogenous cannabinoid system, several studies have evaluated how cannabinoid compounds and, particularly, how the modulation of the endocannabinoid (eCB) system influences a wide range of functions, from metabolic to mental disorders. Cannabinoids and eCB system often exert opposite effects on several functions, such as anxiety. Although the mechanisms are not completely understood, evidence points to different factors influencing those effects. In this chapter, the recent advances in research about the relationship between eCB system and anxiety disorders in humans, as well as in animal models, will be discussed. The recent data addressing modulation of the eCBs in specific brain areas, such as the medial prefrontal cortex, amygdaloid complex, bed nucleus of stria terminalis, hippocampus, and dorsal periaqueductal gray, will be summarized. Finally, data from animal models addressing the mechanisms through which the eCB system modulates anxiety-related behavior dependent on stressful situations, such as the involvement of different receptors, distinct eCBs, modulation of neurotransmitters release, HPA axis and immune system activation, and plastic mechanisms, will also be discussed.

Keywords: Amygdala; Animal models; Anxiety; Bed nucleus of the stria terminalis; Endocannabinoids; Hippocampus; Medial prefrontal cortex; Periaqueductal gray.

Publication types

  • Review

MeSH terms

  • Animals
  • Anxiety / genetics
  • Anxiety / immunology
  • Anxiety / metabolism*
  • Anxiety Disorders / genetics
  • Anxiety Disorders / immunology
  • Anxiety Disorders / metabolism*
  • Brain / immunology
  • Brain / metabolism*
  • Endocannabinoids / immunology
  • Endocannabinoids / metabolism*
  • Fear
  • Genetic Predisposition to Disease
  • Humans
  • Hypothalamo-Hypophyseal System / immunology
  • Hypothalamo-Hypophyseal System / metabolism
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity
  • Neurons / immunology
  • Neurons / metabolism*
  • Neuroprotection*
  • Organ Specificity
  • Pituitary-Adrenal System / immunology
  • Pituitary-Adrenal System / metabolism
  • Polymorphism, Single Nucleotide
  • Receptors, Cannabinoid / chemistry
  • Receptors, Cannabinoid / genetics
  • Receptors, Cannabinoid / metabolism*


  • Endocannabinoids
  • Nerve Tissue Proteins
  • Receptors, Cannabinoid