Cortisol/DHEA-S Ratio Normalization by Buprenorphine: Associations with Stress, Coping, and Social Support in Youth with Opioid Use Disorder.

Opioid use disrupts the hypothalamic-pituitary-adrenal (HPA) axis, altering stress responses depending on the stage of use. A higher cortisol/DHEA-S ratio may indicate relapse risk in substance use disorders. This study aimed to explore differences in serum cortisol/DHEA-S ratio and its association with proximal and perceived stress, social support, and coping strategies in opioid-dependent youth. In this study, we assessed 51 males aged 15-24 with opioid (heroin) use disorder from an Indian treatment center, categorized into three groups: recently admitted patients with opioid use, buprenorphine-maintained patients, and healthy controls (n = 17 each). Serum cortisol and DHEA-S levels were analyzed using ELISA. We found significant differences in cortisol (p < .001), DHEA-S (p < .001), and cortisol/DHEA-S ratio (p < .001) across groups. Recently admitted patients with opioid use had elevated cortisol/DHEA-S ratios (0.37), whereas buprenorphine maintenance with active coping strategies showed reduced ratios (0.22), indicating potential normalization of HPA axis function. Cortisol levels correlated positively with past-year stress in recent users, whereas the cortisol/DHEA-S ratio correlated negatively with social support. These findings suggest that buprenorphine maintenance, combined with effective coping and social support, may help normalize HPA axis imbalance, potentially reducing relapse risk in opioid-dependent youth. Further research is needed to confirm these findings and their implications for treatment strategies.