This is a human laboratory-based, randomized, cross-over study in which buprenorphine will be administered to healthy volunteers (n=22) in 3 separate inpatient 2-night visits, at least 1 week apart. At each visit, the participant will receive a single dose buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO. Participants will be given naltrexone to produce opioid blockade to eliminate the risk for opioid dependence in individuals without OUD. Timed blood samples will be collected up to 24 hours.

The approach is to conduct a randomized, cross-over trial in a controlled human laboratory setting with healthy volunteers (n=22). After obtaining informed consent, eligible participants will be scheduled for 3 separate two-night test days to receive 0.15mg IV, 8mg PO, or 16mg PO of buprenorphine. The first dose administered will be fixed to an open-label IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO. Visits will be scheduled at least 1 week apart to allow for washout of drug. One hour prior to receipt of the buprenorphine dose, all participants will be fed a standardized light breakfast. The IV dose will be given after establishing IV access, while the PO doses will be swallowed whole. Participants will also receive oral naltrexone 100mg 24 hours prior to each dosing to provide blockade at the mu-receptor, as well as 50mg PO at the study visit itself prior to receipt of buprenorphine. Timed blood samples will be collected in heparinized Vacutainer tubes via a catheter in the antecubital vein at baseline, and at 0.5, 1, 2, 4, 8, and 24 hours. Samples will be centrifuged and frozen until analysis.

Inclusion Criteria:

• English-speaking adults aged 18 and above.
• In good physical health as determined by routine medical screening consisting of a complete physical exam, safety labs and EKG.
• Baseline vital signs with HR between 60 and 100, SBP between 90 and 160mmHg, and respiratory rate between 12 and 20 breaths per minute.
• Prior personal history of opioid use, therapeutic or non-therapeutic in past the 12 months.

Exclusion Criteria:

• DSM-5 diagnosis of any substance use disorder excluding tobacco.
• Presence of any alcohol, cannabis, opioids (including methadone, buprenorphine) or any other illicit substances on urine toxicology at any study visit, including cocaine, amphetamines, and benzodiazepines.
• Receiving treatment with opioid analgesic in last 60 days, or anticipate requiring opioids during the proposed trial, or up to 30 days after the trial completion
• Baseline PHQ-9 or GAD7 > 10 (i.e. moderate depression/anxiety)
• History of chronic pain
• Psychotic disorder, active suicidality or homicidally, or any psychiatric condition that impair ability to provide informed consent.
• History of hypersensitivity or allergy to buprenorphine or naltrexone
• Pregnant or breastfeeding.
• Liver function test greater than 3 times upper normal limit.
• Receiving medications that are strong or moderate CYP34A inducers or inhibitors (including but not limited to ketoconazole, itraconazole, clarithromycin, fluconazole, erythromycin), in the past 30 days.

All portions will be open label