• Aged 21 to 65 years
• Able to read, speak, and understand spoken and written English
• Diagnosis of moderate or severe opioid use disorder (OUD)
• Current opioid misuse, with misuse occurring on at least 10 of the last 30 days. Misuse will be defined as either: 1. Use of illicit opioids, such as heroin or non-prescribed fentanyl; or use of an outpatient prescription opioid (such as oxycodone, morphine, or hydrocodone) through a route other than FDA approved (e.g. nasal, injected), and/or 2. Use of a prescription opioid via a route (e.g. nasal, injected, chewed) or for a purpose (e.g. intoxication, anxiety relief) other than that for which it was prescribed.
• Able to achieve stable daily dose of a buprenorphine-naloxone formulation that controls opioid withdrawal symptoms
• Persons of childbearing potential must agree to practice an effective means of contraception throughout their participation in the study, beginning at screening and throughout follow-up
• Ability and willingness to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and evaluations
• Healthy kidney function
• Able to provide contact information for a local support person. This person must be available during both 24-hour treatment and observation periods, and willing to provide the participant social/emotional support the day after each treatment and as needed during the dosing day and/or overnight observation period.
• Currently prescribed and has taken buprenorphine or buprenorphine formulation (e.g., Suboxone®) for over four weeks immediately prior to initial study contact
• Currently receiving pharmacotherapy of any duration with methadone
• Current participation in a drug treatment court program or other legal supervision. Individuals who are under legal supervision will be advised that participating in this study could potentially violate terms of probation, parole, or extended supervision. Contact information for the individual's community supervision officer must be collected to confirm whether study participation may impact the potential participant's status on probation or parole
• Inadequately treated hypertension
• Current acute coronary syndrome or angina
• Evidence of ischemic disease, cardiac conduction defects, and/or ventricular arrhythmias on screening ECG
• History of heart transplant
• Current insulin dependence, due to Type I or Type II diabetes
• Urine drug test containing non-prescribed drugs of abuse
• Any finding(s), based on the screening process, that the PI feels makes the study unsuitable for the participant

• Alive (per medical record)
• Diagnosed with cancer in the past 3 years
• Received care from a participating oncology clinic in the past year
• Has a current tobacco use status
• Does not have a preferred language other than English (missing language preference will be included).
• Valid address that is not a correctional facility or residential treatment/care facility.
• No flag for patient cognitive impairment, activated health care power of attorney, or other health care agent (e.g., legally authorized representative) in the EHR. The following additional inclusion criteria must be met for inclusion in the CET
• Smoked combustible cigarettes in the past month.
• Able to speak and understand English.
• Willing to set a date to quit smoking in the next 60 days.
• Willing to receive smoking treatment information.
• Willing to complete study activities.
• No current suicidal ideation.
• Suicide attempt in the past year.
• Currently receiving treatment for bipolar disorder, schizophrenia, schizoaffective disorder, or psychotic disorder.
• Incarceration.
• Unable to provide informed consent to treatment (i.e., cannot answer questions about study procedures or risks after hearing about the study).