Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence
Condition: Heroin Dependence; Opioid Use Disorder
MeSH terms: Opioid-Related Disorders; Heroin Dependence
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This research deals with behaviors that are part of opioid dependence. The purpose is to
      study how stress and medication dose can affect opioid drug use.
    

Detailed description: 
      If participants meet all the criteria, their involvement in the study (Phases 1 and 2
      described below) will last for 10-13 weeks. Participants will be asked to stay at the
      research site for a minimum of 2 nights on 4 separate weeks and will have 22 office visits
      During that time, participants can't leave the unit unescorted or have visitors.

      Participants will receive a medication called Buprenorphine/Naloxone. Buprenorphine/Naloxone
      is approved by the Food and Drug Administration (FDA) to treat opioid addiction, and is a
      safe and effective alternative to methadone. Participants will receive this medication every
      day. When participants are not living on the inpatient unit they will come to the research
      clinic every day to receive the medication.

      On Day 1, one single 1-mL (0.2 teaspoon) blood sample will be collected to assess the effect
      of the Buprenorphine/Naloxone medication dose on gene expression pattern.

      On each day of admission (once on weeks 3, 5 and 7), a single 1-mL (0.2 teaspoon) blood
      sample will be collected to assess the effect of the buprenorphine/naloxone medication dose
      on the participant's gene expression pattern.

      On the 8 days while participants are an inpatient they will participate in experimental
      sessions that involve drug administration. On some days participants will receive morphine
      and on some days participants will receive oral medications called yohimbine and
      hydrocortisone that will be used to study stress responses. Each afternoon study staff will
      collect one blood sample (10 mL or 2 teaspoons) from a vein in the participant's arm; these
      samples will be used to measure biological signals of stress.

      At the end of the study participants will be detoxified from the Buprenorphine/Naloxone
      medication over a 3-week outpatient period.

      Study participants will be scheduled for one separate in-person visit at 1 month after week
      11. At this follow-up visit participants will be asked to provide a urine sample and to
      complete questionnaires that ask about drug craving and use, withdrawal symptoms, risky
      situations for drug use, coping with stress, and consequences experienced from using drugs or
      being abstinent.
    

Intervention name(s): Extended release morphine; Buprenorphine/Naloxone low dose; Buprenorphine/Naloxone moderate dose; Buprenorphine/Naloxone high dose; Active stressor; Placebo stressor
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Dose (tailored to each participant based on his/her pre-experimental opioid use amount) is administered in 3 divided daily doses.; Buprenorphine/Naloxone dose of 1.4/0.36 mg/day; Buprenorphine/Naloxone dose of 4.2/1.08 mg/day; Buprenorphine/Naloxone dose of 12.8/3.16 mg/day; Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet; Lactose
Other intervention name(s): Zubsolv™ sublingual tablet; Zubsolv™ sublingual tablet; Zubsolv™ sublingual tablet
Intervention MeSH terms: Morphine; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Naloxone
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 4x2 within-subject crossover design: 4 medication conditions (morphine first, then 3 doses of buprenorphine/naloxone), crossed with 2 stress conditions (placebo vs. stress [yohimbine + hydrocortisone], nested within medication conditions)
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science