Yet another potential mechanism of relevance for SUDs is the connection to stress. Stress and stress response have long been thought to contribute to SUDs21. One possible mechanism involves the hypothalamic-pituitary-adrenal axis, which is activated by substance use. Circulating glucocorticoids then downregulate hypothalamic-pituitary-adrenal axis activity but also activate extrahypothalamic brain stress systems (for example, the central nucleus of the amygdala and the basolateral amygdala) known to be involved in behavioral responses to stressors.
