Effects of Ibudilast on Oxycodone Self-administration in Opioid Abusers
Condition: Opioid Abuse; Opioid Dependence
MeSH terms: Opioid-Related Disorders
Intervention: MN-166 (50 mg) First; Placebo First
Intervention description: In this arm of the study participants were first maintained on 50 mg MN-166 BID for approximately 14 days, and were then switched onto placebo maintenance. The subjective and analgesic effects of Oxycodone (0 mg, 15 mg and 30 mg) were tested under each of the two maintenance conditions (Placebo & MN-166).; This arm of the study participants were first maintained on placebo for approximately 14 days, and were then switched onto 50mg MN-166 BID maintenance. . The subjective and analgesic effects of Oxycodone (0 mg, 15 mg and 30 mg) were tested under each of the two maintenance conditions (Placebo & MN-166).
Intervention MeSH terms: Ibudilast
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 28.0
Sex: All
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: prescription opioid abuse; pain; opioid withdrawal; oxycodone; ibudilast

Summary:

      Opioid drugs increase glial cell activation which may be related to the abuse liability of
      opioid drugs. Data supporting this hypothesis have demonstrated that glial cell attenuators
      decrease the positive rewarding aspect of opioids in laboratory animals. Ibudilast (MN-166,
      formerly AV411) is a compound that inhibits the activation of glia. Recent preclinical
      studies demonstrate that while ibudilast increases the analgesic effects of opioids, it
      decreases the rewarding effects of such drugs. It has also been shown that ibudilast
      suppresses morphine-induced release of dopamine, a primary neurotransmitter involved in the
      rewarding and reinforcing effects of abused drugs. Additionally, we recently found that
      ibudilast decreases subjective symptoms of opioid withdrawal in opioid dependent humans
      during detoxification.

      Therefore, the primary aim of this 6-7 week inpatient study is to investigate the ability of
      MN-166 to dose-dependently alter the reinforcing, analgesic, subjective, performance, and
      physiological effects of oxycodone, a commonly abused prescription opioid.

      This study includes a 10-day morphine taper phase, followed by two study phases
      (approximately 18 days each) with daily active ibudilast and placebo administration,
      respectively. After the detoxification phase, participants are randomized to receive placebo
      or MN-166, and then be stabilized on the medication. Thereafter, participants will complete
      laboratory sessions. Subsequently, during Phase 2, participants will cross over to the other
      treatment arm, stabilize, and complete laboratory sessions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults between the ages of 21 and 55

          -  Current opioid dependence according to DSM-IV criteria

          -  currently not seeking treatment

        Exclusion Criteria:

          -  Female patients that are currently pregnant, or breastfeeding. Lack of effective birth
             control.

          -  Participants who have a positive history of neurological illness (including epilepsy)
             or those who have received anticonvulsant therapy during the past 5 years.

          -  Liver disease requiring medication or medical treatment, and/or aspartate or alanine
             aminotransferase levels greater than 3 times the upper limit of normal.

          -  Gastrointestinal or renal disease that would significantly impair absorption,
             metabolism or excretion of study drug, or require medication or medical treatment.

          -  Neurological or psychiatric disorders including psychosis, bipolar disorder, organic
             brain disease, any seizure history or other disorders that require treatment or that
             could make study compliance difficult.

          -  Positive tuberculosis (PPD) TB skin test, clinical history, and chest X-ray indicative
             of active tuberculosis. (Individuals with a positive PPD test and negative chest X-ray
             who are not symptomatic for tuberculosis, and do not require antituberculosis therapy
             will be eligible to participate. Participants will be asked if they ever tested
             positive for tuberculosis. If so, they will not be given a PPD and chest X-ray and
             clinical history will be used for evaluation purposes).

          -  Presence or positive history of severe medical illness or cardiovascular disease or
             heart abnormality, such as low hemoglobin (Hb < 13 gm/dL in males, Hb < 11 gm/dL in
             females) with evidence of acute or chronic blood loss, or BP > 140/90.

          -  Participants on any current psychoactive prescription medications that may interfere
             with the study measures.

          -  Current physical dependence on any substance, other than opioids, nicotine or caffeine
             (ex., methadone, benzodiazepines, LAAM, marijuana, alcohol, etc.).

          -  Participants for whom detoxification is not "clinically recommended" such as those
             with a significant history of overdose following detoxification.

          -  Participation in an investigational drug study within the past 3 months.

          -  Hypersensitivity to any of the medications used in this study.

          -  Current (within the last 3 months) chronic pain.

          -  Platelet and white blood cell count that are not within the normal range (platelet =
             120 x103/μl -400 x103/μl; WBC= 3.5 x106/μl -10.8x106/μl).

          -  Use of Theophylline (PDE-3 inhibitor) or Roflumilast (PDE-4 inhibitor).