Effects of Ibudilast on Oxycodone Self-administration in Opioid Abusers

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.

Conditions

• Opioid Abuse
• Opioid Dependence

Interventions

DRUG

MN-166 (50 mg) First

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).

DRUG

Placebo First

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).

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA)

  collaborator NIH

• MediciNova

  collaborator INDUSTRY

• New York State Psychiatric Institute

  lead OTHER

Principal Investigators

• Sandra D Comer, PhD · Department of Psychiatry, Columbia University and NYSPI

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

21 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-11-30

Primary Completion

2015-12-31

Completion

2017-05-31

Countries

• United States

Study Locations