The role of the endocannabinoid system in the regulation of hypothalamic-pituitary-adrenal axis activity.

D. Cota
J Neuroendocrinol. 2008-05-01; 20(s1): 35-38
DOI: 10.1111/j.1365-2826.2008.01673.x

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The endocannabinoid system (ECS) is a recently identified neuromodulatory system,
which is involved in several physiological processes and in disease. For example,
the ECS not only represents the biological substrate of marijuana’s effects, but
also is known to modulate several neuroendocrine axes, including the
hypothalamic-pituitary-adrenal (HPA) axis. Although previous pharmacological
studies using plant-derived or synthetic cannabinoids have implied a stimulating
action on the HPA axis, more recent findings have led to the conclusion that an
endogenous cannabinoid tone might exist, which is actually inhibiting the release
of both adrenocorticotrophic hormone and glucocorticoids. Studies using mice
lacking cannabinoid receptor CB(1) have demonstrated that presence and activity
of these receptors is essential for the regulation of HPA axis activity.
Interestingly, the effects of endocannabinoids on the HPA axis are consistent
with their neuromodulatory action on brain neurotransmitter systems.
Endocannabinoids have been found to mediate the nongenomic glucocorticoid-induced
inhibition of the release of corticotrophin-releasing factor within the
paraventricular nucleus of the hypothalamus. Altogether, these observations
suggest that alterations of the endocannabinoid tone might be associated with the
development of stress-related diseases, including anxiety, depression and

Auteurs Bordeaux Neurocampus