Effect of D-amphetamine on Reward Functioning

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.

Study Overview

• Status: Completed
• Conditions: Anhedonia
• Intervention / Treatment: Drug: 10 mg d-amphetamine; Drug: 20mg d-amphetamine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Emory University
• Investigators: Principal Investigator: Scott D Lane, PhD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2018
• Primary Completion (Actual): May 23, 2019
• Study Completion (Actual): May 23, 2019

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Decision Making; Reward Learning
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Anhedonia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Amphetamine; Dextroamphetamine
• Other Study ID Numbers: HSC-MS-17-0604

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No