Impact of Lofexidine on Stress, Craving and Opioid Use

Inclusion Criteria 1. Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments. 2. Meet DSM-5 criteria for opioid use disorder (within the past three months). While individuals may also meet criteria for mild use disorders of other substances, they must identify opioids as their primary substance of abuse and must not meet criteria for any other moderate or severe substance use disorder (except tobacco, caffeine, or marijuana) within the last 60 days. 3. On a stable dose of daily buprenorphine or methadone for at least 2 weeks. 4. Age 18-65. 5. Women of childbearing potential must agree to use an effective means of birth control. 6. Consent to remain abstinent from opioids during the 1-week baseline assessment period. 7. Must consent to random assignment. Exclusion Criteria 1. Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control. 2. Evidence or history of major medical illnesses, including liver diseases, abnormal vaginal bleeding, suspected or known malignancy, thrombophlebitis, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders, heart disease, insulin-dependent diabetes, history of stroke or other medical conditions that the investigator deems as contraindicated for the individual to be in the study. 3. History of or current psychotic disorder or bipolar I affective disorder. 4. Current suicidal or homicidal ideation/risk. 5. Taking medications known to act on adrenergic systems (B-blockers; alpha agonists or antagonists) 6. Hypotensive individuals with a sitting blood pressure of \< 90/50 7. QTc interval of \>440 in males and \> 460 in females as the combination of lofexidine plus buprenorphine may increase the QTc interval. 8. Known allergy to lofexidine 9. Unable to comply with study procedures or pose threat to study staff.