Study for Naltrexone on the Abuse Potential of Methylphenidate
Condition: Naltrexone; Methylphenidate Abuse
Study type: Interventional
Phase: Phase 1

Summary: 
      The current abuse liability study aims to assess the potential for co-administration of
      naltrexone (NTX) to reduce the abuse potential of methylphenidate (MPH).
    

Detailed description: 
      The abuse of MPH, as a Schedule II substance, is a well-documented problem. Studies in animal
      models, including primates, show that high-dose MPH can produce reinforcement or reward. A
      number of studies suggest that the rapid elevation of MPH levels in the blood and brain that
      occurs following intranasal or oral administration of supra-therapeutic doses is a key
      requirement for development of MPH-associated euphoria, reinforcement, and addiction. The
      concerns about MPH abuse potential and addiction often play a role in the decision of
      patients, parents, or physicians who opt against treatment with MPH, despite its
      effectiveness. This provides an imperative for development of MPH formulations that are
      therapeutically potent but with lower abuse potential. Methylphenidate acts mainly through
      the dopaminergic system. At sufficiently high doses, MPH can also activate the mu opioid
      receptors (MOPR) in the brain. Recent data indicate that blockade of MOPRs by naltrexone
      (NTX) blocks the rewarding effects of MPH in mice. Clinical studies on the modulatory effect
      of NTX on dopamine release following chronic amphetamine use also support the involvement of
      opioid-dopamine interactions in the reinforcing and rewarding effects of amphetamine. These
      data support the hypothesis that NTX will block the reinforcing effect of MPH in humans.
    

Intervention name(s): Placebo; Methylphenidate 60 mg; Treatment Phase Sequence 4213; Treatment Phase Sequence 2134; Treatment Phase Sequence 1342; Treatment Phase Sequence 3421
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Potential subjects will be screened to determine their eligibility for the study within 28 days of the first dose in the Qualification Phase (i.e., Days -28 to -2). Eligible subjects will be admitted to the clinical site on Day -1 of the Qualification Phase (Part 1) and randomized on Day 1 to receive placebo and MPH (60 mg) in 1 of 2 sequences with a 48-hour washout between dose administrations (i.e., dose administration on Days 1 and 3).; Potential subjects will be screened to determine their eligibility for the study within 28 days of the first dose in the Qualification Phase (i.e., Days -28 to -2). Eligible subjects will be admitted to the clinical site on Day -1 of the Qualification Phase (Part 1) and randomized on Day 1 to receive placebo and MPH (60 mg) in 1 of 2 sequences with a 48-hour washout between dose administrations (i.e., dose administration on Days 1 and 3).; Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.; Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.; Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.; Subjects will be administered single doses on Days 1, 4, 7, and 10 of the Treatment Phase.
Other intervention name(s): Qualification Phase (Part A); Qualification Phase (Part A); Treatment 1; Treatment 2; Treatment 3; Treatment 4
Intervention MeSH terms: Methylphenidate
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The study will consist of a 2-period crossover Qualification Phase (Part 1) to ensure subject eligibility for the treatment phase of the study, and a 4-period crossover Treatment Phase (Part 2) to determine the effect of concomitant administration of MPH and NTX on subjective pharmacodynamic (PD) measures of abuse, relative to MPH and placebo.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: ADHD; attention deficit hyperactivity disorder; stimulant