Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia

Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia

The goal of this study is to compare the abuse potential of low-dose equianalgesic buccal buprenorphine to a commonly used full mu opioid receptor (MOR) agonist in a highly controlled experimental setting. This is a translational study in which healthy participants are phenotyped for psychosocial and Opioid-Use-Disorder-risk-related metrics. In a within-subjects crossover design, 60 participants will receive a standard postoperative oral oxycodone dose (10 mg), placebo, and 3 different doses of buccal buprenorphine across 5 separate sessions. Quantitative Sensory Testing (QST) will be used to evaluate alterations in pain responsiveness relative to placebo across buprenorphine doses and oxycodone, and will compare abuse potential (indexed by the standard FDA drug liking metric) following equianalgesic doses of the two drugs.

Inclusion Criteria:

• Intact cognitive status and ability to provide informed consent
• Ability to read and write in English sufficiently to understand and complete study questionnaires
• Age 18-65
• Opioid-naive status (defined as no use of full mu-opioid receptor (MOR) agonist, partial MOR agonist, or mixed agonist/antagonist medications for the prior 3 months by patient report

Exclusion Criteria:

• Liver/kidney disease
• Chronic pain
• Current/prior substance use disorder
• Pregnancy (to avoid fetal drug exposure, with pregnancy tests conducted to confirm eligibility)
• Seizure disorder
• Certain psychiatric conditions (severe depression, bipolar disorder, psychotic disorders)
• Recent use of medications that may interfere with study drug metabolism
• Recent benzodiazepine or opioid use (confirmed via rapid urine screening prior to each lab session)
• The presence of any medical conditions felt by the study physician to render participant unsafe
• Prior allergic reaction or intolerance to oxycodone, buprenorphine, or their analogs (explicitly including moderate-to-severe nausea or vomiting with prior opioids)
• Recent use of marijuana, delta-8 THC, CBD, and similar products
• Recent use of kratom
• Severe asthma
• Long QT syndrome
• Parkinson disease
• Weight <60 kg