Effect of D-amphetamine on Reward Functioning

Study Overview
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Brief Summary
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The purpose of this study is to establish the dose-response curve for therapeutic doses of d-amphetamine on tasks of motivation and reward learning in the same participants and to use d-amphetamine as a dopaminergic probe to test newer theories about the role of dopamine in reward-related decision-making.

Official Title
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Effect of D-amphetamine on Reward Functioning

Conditions
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Anhedonia

Intervention / Treatment
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* Drug: 10 mg d-amphetamine
* Drug: 20mg d-amphetamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Healthy individuals Exclusion Criteria: Individuals with a body mass index (BMI) <19 or >26, as this alters dosing requirements Individuals with high blood pressure, abnormal Electrocardiography (EKG), any medical condition requiring regular medication (except birth control), any other regular use of a drug or supplement with potentially hazardous interactions with d-amphetamine (e.g. St. John's wort), or any other medical contraindication to amphetamine administration as determined by our study physician Individuals who report no prior experience with recreational drugs of any kind (including alcohol), or who report a previous adverse reaction to amphetamine Individuals with a current Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) Axis I diagnosis, excluding mild Substance Use Disorders (≤ 3 symptoms) Individuals with a lifetime history of moderate to severe Substance Use Disorder (≥ 4 symptoms), mania or psychosis. Women who are pregnant. individuals smoking more than 10 cigarettes per week will also be excluded, to avoid confounding the effects of nicotine withdrawal with the effects of the study drugs/procedures, as participants will not be allowed to smoke during the sessions. individuals with less than a high-school level of education or fluency in English will be excluded as our questionnaires require high-school level fluency in English, and have not been translated and validated in other languages.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo, then 10 mg d-amphetamine, then 20mg d-amphetamine<br> | Drug: 10 mg d-amphetamine<br>* 10 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: 20mg d-amphetamine<br>* 20 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: Placebo<br>* Placebo dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>|
| Experimental: Placebo, then 20 mg d-amphetamine, then 10mg d-amphetamine<br> | Drug: 10 mg d-amphetamine<br>* 10 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: 20mg d-amphetamine<br>* 20 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: Placebo<br>* Placebo dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>|
| Experimental: 10 mg d-amphetamine, then placebo, then 20mg d-amphetamine<br> | Drug: 10 mg d-amphetamine<br>* 10 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: 20mg d-amphetamine<br>* 20 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: Placebo<br>* Placebo dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>|
| Experimental: 10 mg d-amphetamine, then 20mg d-amphetamine, then placebo<br> | Drug: 10 mg d-amphetamine<br>* 10 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: 20mg d-amphetamine<br>* 20 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: Placebo<br>* Placebo dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>|
| Experimental: 20 mg d-amphetamine, then 10mg d-amphetamine, then placebo<br> | Drug: 10 mg d-amphetamine<br>* 10 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: 20mg d-amphetamine<br>* 20 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: Placebo<br>* Placebo dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>|
| Experimental: 20 mg d-amphetamine, then placebo, then 10mg d-amphetamine<br> | Drug: 10 mg d-amphetamine<br>* 10 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: 20mg d-amphetamine<br>* 20 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>Drug: Placebo<br>* Placebo dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reward motivation as assessed by the Effort Expenditure for Reward Task (EEfRT) | A measure of effort-based decision-making in humans, the Effort Expenditure for Reward Task (EEfRT), will be used. The EEfRT requires participants to choose between a low-effort, low reward task vs a high-effort, high reward task. Willingness to exert effort, or reward motivation, is measured by taking the average number of hard task choices from the first 50 trials. | about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study session | 
| Reward learning as assessed by the Probabilistic Reward Task (PRT) | The Probabilistic Reward Task (PRT), which uses a signal detection paradigm, will be used to measure response bias towards rewarded stimuli. | about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reward learning as assessed by the Effort Learning Task (ELT) | The novel Effort Learning Task (ELT) will be used, in which participants learn to associate abstract shapes with reward, loss, high effort and low effort outcomes, to examine the effect of dopaminergic stimulation on reward learning. Learning rates are determined for each symbol, and trial-wise learning curves are calculated as metrics of reward learning. | about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study sessions | 
| Level of influence of counterfactual information on later decision-making, as measured by the Counterfactual Gambling Task (CGT) | Striatal dopamine is involved in signalling counterfactual information, i.e. encoding differences between the value of actual outcomes and hypothetical outcomes of alternative choices. The CGT is a gambling task used to assess the relationship between choice factors (available options, expected value, and outcomes) on self-reported measures of momentary happiness and regret. Participants complete a gambling task and are informed of their outcome and of the counterfactual outcome (i.e. hypothetical outcome had the participant selected another option). With this task, the degree to which participants make choices to avoid potential regret can be estimated. | about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study session | 
| Mood state as assessed by the Profile of Mood States (POMS) | The effect of d-amphetamine on mood state will be assessed throughout sessions and will be used as a manipulation check. | 15 minutes before receiving drug and 30, 90, 180, and 210 minutes after receiving drug at 1st, 2nd, and 3rd study sessions | 
| Subjective effects of drug as assessed by the Drug Effects Questionnaire (DEQ) | The pharmacodynamics of d-amphetamine will be assessed throughout the study and will be used as a manipulation check. | 15 minutes before receiving drug and 30, 90, 180, and 210 minutes after receiving drug at 1st, 2nd, and 3rd study sessions | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reward Learning, Decision Making