Analgesic Response to Opioid Analgesics in Buprenorphine-Maintained Individuals

Study design is a single-blind examination of the analgesic effects of a single dose of seven test medications provided in an experimental pain paradigm using a cold pressor test (CPT). Test medication conditions include buprenorphine, morphine, hydromorphone, hydrocodone, oxycodone, and two placebo conditions to match test medication formulations (oral tablet, sublingual tablet). Each medication condition will be tested on separate days (seven total days, completing within 12 weeks), with random assignment to order of study medications. After screening, eligible participants will be scheduled for 7 days of testing with test days at least 3 days apart to provide a sufficient medication wash-out period. Pain testing will utilize cold pressor tests (CPT), in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance. Participants will be given a practice trial to provide familiarity with the test and reduce test anxiety. Two CPTs will occur on each test day, and pre- and post-CPT assessments will be administered. Blood samples will be taken on each test day to measure blood levels of buprenorphine. Daily procedures include: (1) A baseline CPT (BL-CPT), (2) Administration of the test medication (active drug or placebo), (3) CPT administered at the time of maximum drug effect (Tmax-CPT) specific to medication (range 30-120 minutes), (4) Pupillometry conducted at baseline (before BL-CPT), and at time of maximum drug effect (before Tmax-CPT). Each participant will be discharged after clinical determination of the participant's safety and well-being. Testing will continue until twelve trials of each medication condition are completed.