The Bridge Device (BD) is a neuromodulator medical device that has been cleared by the FDA for Opioid Use Disorder (OUD) treatment. Importantly, medical devices reviewed by the FDA are cleared (based on safety) rather than approved (based on efficacy), which means the BD did not need to demonstrate efficacy before it became commercially available. As a result, the device was not required to have a sham-controlled trial for FDA clearance and there is no active research, to the investigators' knowledge, that specifically addresses the degree to which opioid withdrawal can be treated through neuromodulation. To rigorously evaluate the efficacy of the BD for treating OUD, the investigators will enroll persons with active OUD, not currently receiving medications for OUD. Participants will be recruited and admitted to the Clinical Research Unit (CRU) for a 2-3 week period. During participants' residential stay, participants will be stabilized for 7-11 days on four times daily morphine (30 mg, SC) and undergo a precipitated withdrawal challenge using the opioid antagonist naloxone, approximately >= 4 days of morphine maintenance. This is a standard practice for the investigators' study and allows the investigators to objectively assess dependence. The BD and study medication will begin following morphine stabilization. Participants will be randomly assigned to one of three conditions (1) active BD with placebo (BD/P), (2) sham BD with lofexidine (SBD/L), or (3) sham BD and placebo (SBD/P). Participants will use the BD for 5 days and will receive study drug for 7 days. Participants will be monitored for an additional 4 days after device removal to determine whether withdrawal resumes. Participants will undergo a second naloxone challenge after removal of the device/capsule completion to verify lack of opioid tolerance and will be encouraged to begin treatment with oral naltrexone followed by extended release naltrexone. Throughout the residential stay, all participants will be given referral to and assisted with engaging in outpatient treatment following study discharge.

Inclusion Criteria:

• Age between 18 and 65 years old
• Meets Diagnostic and Statistical Manual-5 criteria for Opioid Use Disorder (OUD) (moderate or severe) based upon Mini-International Neuropsychiatric Interview (MINI)
• Provides a urine sample that tests positive for opioids during screening or have evidence of opioid withdrawal
• Be in good general health based on a physical examination, medical history, vital signs, and screening urine and blood tests
• No significant psychiatric illnesses besides OUD
• Seeking treatment to stop using illicit opioids
• Willing to comply with the study protocol
• Have no clinically significant chronic medical or surgical disorders or conditions that are judged by the investigators to prevent participation

Exclusion Criteria:

• Pregnant or breast feeding

• Receiving opioid agonist treatment

• Significant medical illness (e.g., insulin dependent diabetes)

• Significant psychiatric illness (e.g., schizophrenia)

• Use of medical cannabis

• Contraindications for use of the Bridge Device, morphine, lofexidine or naloxone (e.g., hemophilia, psoriasis and other skin conditions, a cardiac pacemaker)

• Have evidence of physical dependence on alcohol or benzodiazepines that requires medical detoxification

• Hypotension (diastolic blood pressure of less than 60 mm Hg or systolic blood pressure of less than 90 mm Hg on screening examination)

• Prolonged corrected QT interval interval on screening ECG (defined as >0.44 seconds for males and >0.46 seconds for females)

• Hepatic or renal impairment, as indicated by the following lab results at the screening session:

  • Aspartate aminotransferase or alanine transaminase >3x upper limit of normal (ULN)
  • Total Bilirubin >2x ULN.
  • Creatinine >1.5x ULN.

• Treatment with a strong 2D6 inhibitor (e.g., paroxetine, thioridazine, cinacalcet, bupropion, methotrimeprazine, fluoxetine, midostaurin, propafenone, glycerol phenylbutyrate, halofantrine, cisapride, dacomitinib, orphenadrine, quinidine)

• Have a known allergy to any of the study medications

• Have circumstances that would interfere with study participation (e.g., impending jail)

From the time of randomization up to day 9 (the end of the participant's residential stay)