biostudies-literatureGuille COffice of Research on Womens HealthNIDA NIH HHSNational Institute on Drug Abuse106616https://www.ebi.ac.uk/biostudies/studies/S-EPMC8761253biostudies-literatureUnknown111Opioid Use Disorders (OUDs) and drug overdose deaths are increasing at alarmingly high rates in the United States. Stress and dysregulation in biologic stress response systems such as the hypothalamic-pituitary-adrenal axis and noradrenergic system appear to play an important role in the pathophysiology of substance use disorders and relapse to drug use, particularly for women. Alpha-2 adrenergic agonist medications effectively decrease noradrenergic activity and have demonstrated benefit in preventing relapse to substance use and decreasing stress-reactivity and craving in cocaine- and nicotine-dependent women, compared to men. Alpha-2 adrenergic agonists may help decrease stress reactivity in individuals with OUDs and prevent relapse to drug use, but gender differences have yet to be sysContemporary clinical trialsThe impact of lofexidine on stress-related opioid craving and relapse: Design and methodology of a randomized clinical trial.PMC8761253U54 DA016511Guille CCortese BBaker NBrady KMcRae-Clark AKing CRogers TNunn LRamakrishnan VfalseThe impact of lofexidine on stress-related opioid craving and relapse: Design and methodology of a randomized clinical trial.Opioid Use Disorders (OUDs) and drug overdose deaths are increasing at alarmingly high rates in the United States. Stress and dysregulation in biologic stress response systems such as the hypothalamic-pituitary-adrenal axis and noradrenergic system appear to play an important role in the pathophysiology of substance use disorders and relapse to drug use, particularly for women. Alpha-2 adrenergic agonist medications effectively decrease noradrenergic activity and have demonstrated benefit in preventing relapse to substance use and decreasing stress-reactivity and craving in cocaine- and nicotine-dependent women, compared to men. Alpha-2 adrenergic agonists may help decrease stress reactivity in individuals with OUDs and prevent relapse to drug use, but gender differences have yet to be sys2021-01-01T00:00:00Z2021 Dec2025-04-19T15:39:57.773Z2025-04-19T15:39:57.773ZS-EPMC87612533473709110.1016/j.cct.2021.106616