Effects of Buprenorphine on Mood in Adults With a Range of Depressive Symptomatology
Condition: Depression
MeSH terms: Depression
Study type: Interventional

Summary: 
      This study seeks to to study the effects of buprenorphine, a partial mu-opioid agonist, on
      depressed mood in a healthy young adults with a range of depressive symptomatology.
    

Detailed description: 
      It has been shown that opioid analgesics, particularly the mu-opioid partial agonist
      buprenorphine, have anti-depressant properties in laboratory animal models. In humans, rates
      of prescription opioid abuse are significantly higher in patients with depression. This
      suggests that individuals with negative mood states (e.g., depressive states) may respond
      more positively to opioid drugs. A handful of small studies in in humans have suggested that
      buprenorphine reduces symptoms of depression in patients who did not respond to standard
      anti-depressants, and laboratory studies have shown buprenorphine may reduce responses to
      some types of negative stimuli and enhance responses to positive stimuli. However, a
      controlled laboratory study assessing potential anti-depressant effects of an opioid
      medication has never been conducted. In this project, the investigators propose to examine
      depressive symptomatology as a predictor of subjective mood responses to buprenorphine, using
      two measures; i) self-reported depressive symptomatology as measured by the Beck Depression
      Inventory (BDI-II), and ii) physiological indices of depressive symptomatology as measured by
      heart rate variability. Reduced heart rate variability has been shown to be associated with
      depression, and such a physiological measure may allow for the detection of more subtle
      effects than would a self-report questionnaire alone. Healthy volunteers (N=60) will first
      complete the BDI and provide baseline measures of heart rate variability. Then they will
      attend two laboratory sessions, at which they will receive placebo or 0.2mg buprenorphine.
      The investigators have tested these low doses of buprenorphine in previous studies, and they
      produce measurable changes in mood and behavior in healthy volunteers. The investigators will
      collect measures of mood and physiological drug response (pupillometry, heart rate, and blood
      pressure) at regular intervals throughout each session, and will then examine their baseline
      indices of depressive symptomatology in relation to responses to the drug. The central
      hypothesis is that individuals with greater self-reported depressive symptoms and lower heart
      rate variability will experience the greatest enhancement of mood in response to
      buprenorphine. It is expected that this work will provide a better understanding of which
      individuals are most likely to experience positive mood effects in response to opioid drugs,
      and may therefore be at-risk for developing an opioid use disorder. Furthermore, it may lay
      the foundation for future research in the development of novel opioid-based treatments for
      depression.

      Design: The study will use a 3-session within-subjects double-blind design in which
      participants will receive single doses of buprenorphine (0, 0.2 mg sublingual) in randomized
      order. All screening, orientation, and study session procedures will take place in the Human
      Behavioral Pharmacology Laboratory suite in the L4 wing of 5841 S. Maryland Ave.

      Drug and Doses: Investigators will administer placebo, 0.2 mg buprenorphine (Temgesic) via
      sublingual tablet in counterbalanced order under double-blind conditions. These tablets
      dissolve within 5-8 minutes. This drug has been approved for treatment of severe pain. The
      onset of action after sublingual administration is 30 minutes, with a peak plasma
      concentration at 1/5-2 hours and a half-life of 5 hours. The dose of buprenorphine are very
      low, and the average maintenance dose for opioid abusers is 8 mg. Doses will be separated by
      at least 72 hours.
    

Intervention name(s): 0.2mg Buprenorphine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Sublingual buprenorphine tablets (0.2mg); Placebo
Intervention MeSH terms: Buprenorphine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science