Opioid Modulation and Neural Reward Activation in Healthy Adults

Study Overview
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Brief Summary
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This is a double blind study of the effects of opioid antagonism on the brain's reward response. The investigators will recruit participants to undergo two scans, one on active medication and one on placebo. During the scan, the investigators will assess reward.

Detailed Description
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The study will employ a crossover design. The study will use the monetary incentive delay task during functional MRI to assess reward. This task presents participants with cues indicating whether they are playing to win $5, win $0, or to avoid losing $5. This task has been well-validated to elicit activation in a key reward response area of the brain called the ventral striatum.

Official Title
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Opioid Modulation and Neural Reward Activation in Healthy Adults

Conditions
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Alcohol Drinking, Opioid Use, Unspecified

Intervention / Treatment
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* Drug: Naltrexone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 18 and 35 years of age, Is a moderate drinker (i.e. consumes 1-14 drinks/week for males, or 1-7 drinks/week for females). Exclusion Criteria: Non-drinker Positive result on urine drug screen or breathalyzer at the start of any study visit Inability to complete MRI (e.g. presence of ferromagnetic objects in body) Current use of medications that alter the hemodynamic response such as insulin History of trauma resulting in loss of consciousness longer than 15 minutes Currently taking opioid medications Pregnancy

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: Crossover Assignment
Interventional Model Description: Participants will be counterbalanced for the order they undergo placebo and medication.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo, Then Naltrexone<br>Participants first received placebo capsules each day in a blister pack for 5 days. After a washout period of at least 3 days, they then received naltrexone capsules (matching placebo capsules) at 25mg/day for days 1 and 2 and then 50mg/day for days 3-5 for 5 days. | Drug: Naltrexone<br>* Naltrexone is an opioid antagonist with primary action at the mu opioid receptor.<br>Other: Placebo<br>* Placebo will be used to control for expectancy effects<br>|
| Experimental: Naltrexone, Then Placebo<br>Participants first received naltrexone capsules each day in a blister pack for 5 days. Days 1 and 2 were at 25mg/day, and days 3-5 were at 50mg/day. After a washout period of at least 3 days, they then received placebo capsules (matching naltrexone capsules) for 5 days. | Drug: Naltrexone<br>* Naltrexone is an opioid antagonist with primary action at the mu opioid receptor.<br>Other: Placebo<br>* Placebo will be used to control for expectancy effects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brain Activation to Reward Between Placebo and Active Medication | Percent signal change relative to baseline in the nucleus accumbens during cue to win $5 as assessed during functional MRI. Higher values of percent signal change indicate greater activation to reward. We will compare the active medication condition to the placebo, establishing whether there is a difference between the conditions. | one week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Value | Maximum alcohol expenditure, or Omax, is the maximum amount of money that a person will pay for alcohol in a hypothetical alcohol consumption task called the Alcohol Purchase Task. Higher values of Omax indicate that a person values consuming alcohol at a greater level. | one week | 
| Brain Activation to Emotion Regulation | Percent signal change from baseline in the amygdala during trials to regulate emotion relative to trials to passively experience emotion during a functional MRI scan. Cues will be negative images, and instructions will be either decrease or look. | one week |