Control of Cognition (Naltrexone, Methylphenidate, and ADHD Study (NMAS))

Study Overview
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Brief Summary
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The goal of this research is to understand the functioning of 'regulatory circuits' in the brain. We are also interested in how the medications methylphenidate and naltrexone affect these regulatory circuits. This research study will use a scanning technique known as functional magnetic resonance imaging (fMRI) which takes a special kind of picture of the brain that enables us to see the brain at work. Adult participants will be given a one-time dose of either methylphenidate, naltrexone,or placebo before each fMRI scan session. The main purpose for this research is to better understand the functioning of regulatory circuits in healthy individuals and individuals with psychiatric disorders. This research may one day help us develop better treatments for these disorders.

Detailed Description
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The goal of this research is to understand the functioning of 'regulatory circuits' in the brain. These are brain circuits which allow a person to regulate their attention, regulate their behavioral responses, and regulate their decision-making. We are also interested in how the medications methylphenidate and naltrexone affect these regulatory circuits. Methylphenidate is a widely-used, FDA approved medication used to treat Attention Deficit Hyperactivity Disorder (ADHD) and is also known as Ritalin. Naltrexone is an FDA approved medication used to help treat alcohol and substance abuse. This research study will use a scanning technique known as functional magnetic resonance imaging (fMRI)which takes a special kind of picture of the brain that enables us to see the brain at work. Adult participants will be given a one-time dose of either methylphenidate, naltrexone,or placebo before each fMRI scan session. There are three total fMRI scan sessions. Therefore, each participant will receive each possible medication/placebo only once. Using the fMRI technique, the main purpose of this research is to better understand the functioning of regulatory circuits in healthy individuals and individuals with psychiatric disorders. This research may one day help us develop better treatments for these disorders.

Official Title
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Control of Cognition: Naltrexone, Methylphenidate, and ADHD Study

Conditions
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Healthy, Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Methylphenidate
* Drug: Naltrexone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for all study participants: Right-Handedness Exclusion Criteria for all study participants: Any clinically significant history of cardiac problems Any current Axis I psychiatric diagnosis as verified by the Structured Clinical Interview for DSM-IV (other than participants with ADHD or history of alcohol dependence) A previous adequate trial with methylphenidate (Ritalin) or naltrexone (ReVia) Currently taking any psychoactive medications Any clinically significant medical condition Any clinically significant neurological problem (seizures, tics, serious head injury) Contraindications to MRI (metal objects in body or claustrophobia) Currently pregnant or lactating Alcohol or substance abuse (current or in the past 2 years) Left-handedness or ambidextrous Liver or kidney disease Inclusion Criteria for the participants with ADHD: Currently un-medicated adults with ADHD Has met full DSM-IV-R criteria (at least six of nine symptoms)for inattentive or hyperactive/impulsive subtypes (or both) by age 7 as well within the past month Has described a chronic course of ADHD symptomatology from childhood to adulthood Has endorsed a moderate or severe level of impairment attributed to the ADHD symptoms

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Controls<br>Healthy individuals will receive a one-time, randomized dose of 40mgs of Methylphenidate, 40mgs of Naltrexone, and a placebo one hour before the fMRI scanning session. | Drug: Methylphenidate<br>* One dose 40mgs of methylphenidate one hour before fMRI scanning.<br>* Other names: Ritalin;Drug: Naltrexone<br>* One dose 40mgs of naltrexone one hour before fMRI scanning.<br>* Other names: ReVia;Drug: Placebo<br>* One dose of placebo one hour before fMRI scanning.<br>* Other names: sugar pill;|
| Experimental: Adult Attention-Deficit/Hyperactivity Disorder<br>ADHD individuals will receive a one-time, randomized dose of 40mgs of Methylphenidate, 40mgs of Naltrexone, and a placebo one hour before the fMRI scanning session. | Drug: Methylphenidate<br>* One dose 40mgs of methylphenidate one hour before fMRI scanning.<br>* Other names: Ritalin;Drug: Naltrexone<br>* One dose 40mgs of naltrexone one hour before fMRI scanning.<br>* Other names: ReVia;Drug: Placebo<br>* One dose of placebo one hour before fMRI scanning.<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reaction Time Variability on the Multi-Source Interference Task | Multi-Source Interference Task is a psychological task that measures the psychological construct of cognitive control, the ability to suppress automatic response tendencies. Reaction time variability is the standard deviation of the trial to trial reaction time measured in seconds. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reaction Time on the Multi-Source Interference Task | Reaction time of the Multi-Source Interference Task is measured in seconds. | Two hours | 
| Accuracy on the Multi-Source Interference Task | Accuracy is the calculated percentage of correct responses over total trials in the Multi-Source Interference Task. | Two hours | 
| Characterize the Effects of Methylphenidate and Naltrexone on Neural Circuits in Prefrontal Cortex Associated With Top-down Control. | The effects of methylphenidate, naltrexone, and placebo on the change in BOLD (Blood Oxygen Level Dependent) signal will be characterized in the incongruent condition (cognitive regulation condition) of the MSIT (multi-source interference task) relative to the congruent condition (no regulation condition). Specifically, the summed BOLD signal in three regions--dorsal lateral prefrontal cortex, anterior insula, anterior cingulate--are measured. | Two hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methylphenidate, Naltrexone, Placebo, Neuroimaging, Prefrontal Control Circuits, Attention Control, Motor Control, Appetitive Control