[THE ROLE OF THE ENDOGENOUS CANNABINOID SYSTEM IN THE FORMATION OF THE GENERAL ADAPTATION SYNDROME]

Nonopioid stress-induced analgesia is the consequence of activation of CB1 receptors by the increased level of 2-arachidonoyl glycerol, anandamide in the periaqueductal gray matter in the midbrain. The activation of cannabinoid CB1 receptors inhibits stress-induced ulcerogenesis due to the strengthening of the antioxidant defense of the gastric mucosa. CB1 receptor antagonists promote an increase in ACTH and corticosterone concentrations in the blood of intact animals, the knockout of the gene encoding the CB1 receptor exhibits the same effect. Antagonists of CB1 receptors enhance the stressor elevation of ACTH and corticosterone levels in the blood of experimental animals. It was found an increase in stress-induced elevation of corticosterone and ACTH levels in the blood of mice with a knockout of the gene encoding the CB1 receptor. An increase in the endogenous anandamide level or disturbance of the reuptake of endogenous cannabi-noids after application of pharmacological agents promotes reducing corticosterone level in stressed animals. Consequently, endogenous cannabinoids inhibit basal and suppress stress-induced activity of the hypothalamic-pituitary-adrenal axis. The indicated regulation is carried out on the level of the hypothalamus, pituitary and adrenal cortex. Stimulation of central cannabinoid receptors leads to an activation of the sympathetic system. The activation of peripheral CB1 receptors leads to inhibition of norepinephrine release from sympathetic terminals and epinephrine release from the adrenal glands. The endogenous CB1 receptor agonists play an anxiolytic role and prevent the occurrence of pathological anxiety.