Effect of D-amphetamine on Reward Functioning

Phase 1

Completed

• Conditions: Anhedonia
• Interventions: Drug: 10 mg d-amphetamine; Drug: 20mg d-amphetamine; Drug: Placebo

• Registration Number: NCT03369015
• Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-20
• Study First Submitted QC: 2017-12-04
• Study First Posted: 2017-12-11
• Study Start: 2018-01-24
• Primary Completion: 2019-05-23
• Study Completion: 2019-05-23
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
20 mg d-amphetamine, then 10mg d-amphetamine, then placebo	20mg d-amphetamine	-
20 mg d-amphetamine, then placebo, then 10mg d-amphetamine	10 mg d-amphetamine	-
20 mg d-amphetamine, then placebo, then 10mg d-amphetamine	20mg d-amphetamine	-
20 mg d-amphetamine, then 10mg d-amphetamine, then placebo	10 mg d-amphetamine	-
Placebo, then 20 mg d-amphetamine, then 10mg d-amphetamine	20mg d-amphetamine	-
Placebo, then 10 mg d-amphetamine, then 20mg d-amphetamine	10 mg d-amphetamine	-
Placebo, then 20 mg d-amphetamine, then 10mg d-amphetamine	Placebo	-
10 mg d-amphetamine, then placebo, then 20mg d-amphetamine	20mg d-amphetamine	-
10 mg d-amphetamine, then 20mg d-amphetamine, then placebo	Placebo	-
20 mg d-amphetamine, then placebo, then 10mg d-amphetamine	Placebo	-
Placebo, then 10 mg d-amphetamine, then 20mg d-amphetamine	20mg d-amphetamine	-
10 mg d-amphetamine, then placebo, then 20mg d-amphetamine	Placebo	-
10 mg d-amphetamine, then 20mg d-amphetamine, then placebo	10 mg d-amphetamine	-
10 mg d-amphetamine, then 20mg d-amphetamine, then placebo	20mg d-amphetamine	-
20 mg d-amphetamine, then 10mg d-amphetamine, then placebo	Placebo	-
Placebo, then 10 mg d-amphetamine, then 20mg d-amphetamine	Placebo	-
10 mg d-amphetamine, then placebo, then 20mg d-amphetamine	10 mg d-amphetamine	-
Placebo, then 20 mg d-amphetamine, then 10mg d-amphetamine	10 mg d-amphetamine	-

Primary Outcome Measures

Name	Time	Method
Reward motivation as assessed by the Effort Expenditure for Reward Task (EEfRT)	about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study session	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.
Reward learning as assessed by the Probabilistic Reward Task (PRT)	about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study session	The Probabilistic Reward Task (PRT), which uses a signal detection paradigm, will be used to measure response bias towards rewarded stimuli.

Secondary Outcome Measures

Name	Time	Method
Level of influence of counterfactual information on later decision-making, as measured by the Counterfactual Gambling Task (CGT)	about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study session	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.
Subjective effects of drug as assessed by the Drug Effects Questionnaire (DEQ)	15 minutes before receiving drug and 30, 90, 180, and 210 minutes after receiving drug at 1st, 2nd, and 3rd study sessions	The pharmacodynamics of d-amphetamine will be assessed throughout the study and will be used as a manipulation check.
Reward learning as assessed by the Effort Learning Task (ELT)	about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study sessions	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.
Mood state as assessed by the Profile of Mood States (POMS)	15 minutes before receiving drug and 30, 90, 180, and 210 minutes after receiving drug at 1st, 2nd, and 3rd study sessions	The effect of d-amphetamine on mood state will be assessed throughout sessions and will be used as a manipulation check.

Trial Locations

Locations (1)

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States