The purpose of this study is to determine if personalized (adaptive) Deep Brain Stimulation (DBS) based upon invasive brain mapping is safe and can lead to better outcomes like reductions in craving and opioid use.

This study will enroll individuals with severe Opioid Use Disorder (OUD) who have not responded to standard treatments. The devices used in this study are investigational, which means they are not approved by the Food and Drug Administration (FDA) to treat OUD. The information we obtain in this study will be used to better understand the mechanisms of OUD in the brain.

Inclusion Criteria:

• Adults (all genders) 22 to 75 years old.
• Current diagnosis of severe primary opioid use disorder (OUD) (>= 6 on DSM-5 OUD criteria) (any form of opioid use).
• History of opioid use for more than 5 years.
• Participants are seeking treatment for their OUD.
• Participants have insight into their opioid use disorder (score > 26 on the recognition subscale of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES V.8))
• OUD is treatment refractory: unable to achieve sustained remission over the past 5 years, despite at least three treatment attempts (outpatient, residential, inpatient), with at least one treatment attempt involving taking a first-line medication for OUD (MOUD) such as buprenorphine, methadone, or extended-release naltrexone. Treatment failure is defined as continued opioid use or relapse during or after completion of treatment. Sustained remission is defined per DSM-5 as not meeting any OUD criteria except craving for > 12 months. Documented adherence: participants must have documented adherence to the failed first-line MOUD for at least 8 weeks (PMID: 29083570).
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Social support system and stable living arrangement to provide assurances that the subject will adhere to study requirements: family or friends who live with or near the subject, and can provide collateral information, monitor the subject's behavior, support, and encourage the subject to participate in follow-up visits and evaluations.
• For individuals of reproductive potential: use of highly effective contraception for at least 4 weeks prior to sEEG surgery and agreement to use such a method during study participation.

Exclusion Criteria:

• Pregnancy or lactation.
• Non-English speaking.
• Participants are not willing to start MOUD treatment with buprenorphine or to switch MOUD to buprenorphine if they are already on other MOUD, for the duration of the study.
• OUD treatment with another investigational drug or other intervention within 3 months.
• History of primary psychosis or Bipolar I disorder per the medical interview.
• History of severe personality disorder that could interfere with study participation (e.g., antisocial personality disorder) per the medical interview.
• History of traumatic brain injury with loss of consciousness greater than 5 minutes.
• Clinically significant cognitive impairment per neuropsychological testing.
• History of suicidal attempts in the past 3 years or current suicidal thoughts per psychiatric evaluation.
• Coagulopathy: INR > 1.4, aPTT > 40 s, platelets < 100,000.
• Current clinically significant medical or neurologic disease that affects brain function (e.g., recent stroke, myocardial infarction, seizures not due to alcohol withdrawal).
• Clinically significant abnormality on structural brain MRI scan.
• Life expectancy less than 24 months per the clinical judgment of study investigators (e.g., terminal cancers).
• Any labeled DBS contraindication or inability to have brain MRI: certain pacemakers, metal in body, inability to undergo awake operation, significant cardiac or other medical risk factors for surgery, infection, and coagulopathy.
• Exclusion for early remission: participants who achieve early remission after initiating buprenorphine during the screening phase (prior to the sEEG phase) will be excluded from the study.

All study participants and study personnel involved in clinical outcomes collection and analysis will be blinded. Study personnel overseeing participant safety, randomization, and DBS optimization will not be blinded and will not be involved in assessing the clinical outcome measures.