Targeting GABA and Opioid Systems for a Pharmacotherapy for Methamphetamine Abuse

Study Overview
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Brief Summary
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The research proposed in this application will determine the initial efficacy, safety and tolerability of a novel drug combination, oxazepam (Serax®) and naltrexone (Revia®), as a pharmacotherapy for methamphetamine (Desoxyn®) dependence. A rigorous, inpatient human laboratory study will be conducted. The proposed study is innovative and important because it will provide the impetus for the conduct of double blind, placebo-controlled trials to further demonstrate the efficacy of combined oxazepam and naltrexone for managing methamphetamine dependence.

Official Title
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Targeting GABA and Opioid Systems for a Pharmacotherapy for Methamphetamine Abuse

Conditions
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Methamphetamine Abuse, Methamphetamine Dependence

Intervention / Treatment
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* Drug: Methamphetamine (Desoxyn®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lifetime methamphetamine use Exclusion Criteria: Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation Females not currently using effective birth control Contraindications to methamphetamine (Desoxyn®), oxazepam (Serax®) or naltrexone (Revia®)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1<br>Subjects will be maintained on oral placebo. | Drug: Methamphetamine (Desoxyn®)<br>* The pharmacodynamic effects of methamphetamine (Desoxyn®) will be determined during placebo, oxazepam (Serax®), naltrexone (Revia®) and combined oxazepam and naltrexone maintenance.<br>|
| Experimental: Arm 2<br>Subjects will be maintained on oral oxazepam (Serax®). | Drug: Methamphetamine (Desoxyn®)<br>* The pharmacodynamic effects of methamphetamine (Desoxyn®) will be determined during placebo, oxazepam (Serax®), naltrexone (Revia®) and combined oxazepam and naltrexone maintenance.<br>|
| Experimental: Arm 3<br>Subjects will be maintained on oral naltrexone (Revia®). | Drug: Methamphetamine (Desoxyn®)<br>* The pharmacodynamic effects of methamphetamine (Desoxyn®) will be determined during placebo, oxazepam (Serax®), naltrexone (Revia®) and combined oxazepam and naltrexone maintenance.<br>|
| Experimental: Arm 4<br>Subjects will be maintained on oral naltrexone (Revia®) and oral oxazepam (Serax®). | Drug: Methamphetamine (Desoxyn®)<br>* The pharmacodynamic effects of methamphetamine (Desoxyn®) will be determined during placebo, oxazepam (Serax®), naltrexone (Revia®) and combined oxazepam and naltrexone maintenance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reinforcing Effects | The reinforcing effects of methamphetamine will be determined using a self-administration procedure in which subjects choose to take previously sampled doses. Reinforcing effects are measured during maintenance on placebo, oxazepam (Serax®), naltrexone (Revia®), and oxazepam and naltrexone combined. | After at least four days of placebo, oxazepam (Serax®), naltrexone (Revia®) or oxazepam and naltrexone maintenance | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Effects | Subjects will complete subjective effects measures during six sessions while they are admitted to our inpatient unit. These items will ask about drug effects and general mood. | 12 sessions over approximately 4 week inpatient admissions | 
| Physiological and Side Effects | Physiological and side effects measures will be completed daily while subjects are admitted to our inpatient unit. Physiological measures include heart rate and blood pressure. Side Effects questions will query subjects about common effects of centrally active medications. | Daily over approximately 4 week inpatient admissions |