• 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 (at least 5 of last 30 days if already on buprenorphine/naloxene. See exclusion #1). Misuse will be defined as either:

‣ Use of illicit opioids, such as heroin or street fentanyl; or use of a prescription opioid (such as oxycodone, morphine, or hydrocodone) through a route (e.g. nasal, injected) other than FDA approved , and/or

⁃ Use of a prescription opioid 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.