The HPA axis is a neuroendocrine system involved in stress response by regulating ACTH and cortisol secretion (Hernandez-Avila et al. 2003). Disruption of stress pathways is considered to be one of the causes of addictive disorders (Koob and Kreek 2007; Kreek and Koob 1998). The mu opioid system plays an important role in stress response by regulating the HPA axis. Studies have shown that the mu opioid receptor is involved in modulation of the HPA axis by tonic inhibition of corticotropin-releasing hormone (CRH, also called CRF) in the hypothalamus and POMC in the anterior pituitary. The PDYN/OPRK1 system may also modulate the HPA axis by activation. Naloxone, nalmefene or naltrexone challenge in healthy subjects caused transient increase in plasma levels of ACTH and cortisol by disinhibition of the hypothalamic-pituitary part, indicating activation of the HPA axis (King et al. 2002; Schluger et al. 1998). HPA-axis stimulation plays an important role in the neurobiology of AD, CD and OD. Clinical studies and studies of animal models have shown that modest stimulation of the HPA axis is sought or desired by alcohol-
