Targeting Treatment-Resistant OUD With Ketamine-Assisted Mindfulness Oriented Recovery Enhancement

The goal of this clinical trial is to examine the usefulness of Mindfulness-Oriented Recovery Enhancement combined with Ketamine-Assisted Psychotherapy (KetaMORE) for individuals with opioid use disorder who are receiving medication treatment. The main question it aims to answer is whether individuals with opioid use disorder who receive Mindfulness-Oriented Recovery Enhancement in combination with Ketamine-Assisted Psychotherapy will demonstrate greater reductions in opioid use and craving than individuals who receive Ketamine-Assisted Psychotherapy with a non-mindfulness support group. Participants will be randomly assigned to receive either Mindfulness-Oriented Recovery Enhancement combined with Ketamine-Assisted Psychotherapy or Ketamine-Assisted Psychotherapy combined with a support group control condition. Researchers will compare these groups on days of opioid use, time to first opioid use lapse, craving, and mood, assessed using ecological momentary assessments and standardized measures collected during treatment and follow-up.

Inclusion Criteria: 1. English-speaking . 2. DSM-5 criteria for Opioid Use Disorder (OUD). 3. Documented evidence (by urine toxicology) of current illicit drug use (upon screening) or by self-report on the Addiction Severity Index (ASI). 4. Men/Women \>/= 18 5. Current prescription of a buprenorphine-containing product. 6. Have a support person that would be able to escort the subject home on the evening of the ketamine dosing session. The use of ride services will not be permitted (e.g., Uber, Lift, taxi, etc.). 7. Agreement to adhere to Lifestyle Considerations Exclusion Criteria: * 1\. A primary DSM-5 Axis I diagnosis of schizophrenia, schizoaffective disorder, dissociative identity disorder, or bipolar I/II disorder as determined by psychiatric evaluation. 2\. Has baseline hypertension (≥160 SBP or ≥100 DBP), after repeated measurements. Note: Participants with hypertension that has been controlled by medication down to \= 2x ULN. 4. AST/ALT \>3 upper limit of normal (ULN) 5. Total bilirubin \> 1.5x ULN (Gilbert syndrome is allowed). 6. Alkaline phosphatase (ALP) \>2x ULN. 7. Renal insufficiency (i.e., estimated glomerular filtration rate (eGFR) \< 30 milliliter/minute (mL/min) /1.73 m\^2 (using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation), Creatinine Clearance (CrCl) \< 30 mL/min (using the Cockcroft-Gault Equation), or current dialysis)). 16\. Currently pregnant or breastfeeding. 17. Has uncontrolled insulin-dependent diabetes and has had a hospitalization for diabetes-related complication within 6 months of signing ICF. 18\. Diagnosed cognitive impairments, including dementia, mild cognitive impairment, traumatic brain injury, or developmental delays, that would prevent the participant from completing the study protocol, as identified by self-disclosure when asked in eligibility screening question. 19\. Individuals prescribed monoamine oxidase inhibitors.(see Appendix 1) 20. Individuals prescribed medications that are CYP2B6 inhibitors or inducers (see Appendix 1) 21. Patients taking \>2 mg of lorazepam-equivalents per day.