Does Caffeine Facilitate Human Reward Learning Behaviors? (ADoRe)

Caffeine and Reward Learning: Characterizing Behavioral Expression of Adenosine-Dopamine Interaction

"Learning from the rewards" is underlying the formulation of knowledge and habits in daily life. Caffeine is the most commonly used "psychoactive" substance that could change one's mind state by affecting the brain and nervous system. By such effects, caffeine enhances reward signals - dopamine - in human brains. In this research study, we will find out whether taking caffeine acutely or daily can enhance reward learning processes.

Study Overview

• Status: Active, not recruiting
• Conditions: Caffeine
• Intervention / Treatment: Dietary supplement: mannitol; Dietary supplement: caffeine

Detailed Description

Reward learning is associated with the formulation of habits, memories, and beliefs. Positive (receiving an unexpected reward) and negative reinforcement (eliminating an unwanted state) learning are primarily modulated by striatal dopamine D1 and D2 receptors. While caffeine, a psychostimulant regularly consumed by 80% worldwide population, is known to facilitate striatal dopamine signaling, the potential of caffeine on enhancing reward learning in humans remains unknown.

In this double-blind, randomized, crossover study, 36 young healthy non-smoking habitual caffeine consumers (daily dose 100 - 450 mg) who are aged between 18 and 40 will be examined. Each of the 36 participants (18 F, 18 M) will undergo an acute caffeine condition, a daily caffeine condition, and a daily placebo condition. Each condition consists of 7 days - 6 ambulatory days followed by 1 laboratory visit.

In the ambulatory part, participants will abstain from caffeine, nicotine, medications, and recreational drugs. Compliance to the interventions and abstinence of caffeine will be monitored by salivary caffeine concentration every day. Bedtime and sleep quality will be recorded in sleep diary. On the laboratory visit, participants will perform cognitive tasks on a 2.5h task battery, which includes a probabilistic selection task, a motor inhibition task, and a salience attribution test. We also measure their arousal and anxiety levels 1h after the second intake on the laboratory visit.

We will use Bayes factor analyses to test our confirmatory hypotheses (on the primary outcomes): 1) Caffeine enhances the accuracy of reward learning; 2) Daily intake of caffeine facilitates the negative reinforcement compared to acute its intake. On the secondary outcomes, we examine the exploratory hypotheses that caffeine enhances motor inhibition and motivational salience. Arousal and anxiety levels will be examined as a covariate which potentially contribute to the caffeine-induced changes in reward learning performance.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, CH-4002
      • Centre for Chronobiology, University Psychiatric Clinics Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≥ 18 and ≤ 40
• Clinically healthy
• Non-smokers

Exclusion Criteria:

• Habitual caffeine intake < 100 mg or > 450 mg
• Pregnant or lactating women
• Women using hormonal contraceptives
• BMI < 18.5 or > 29.9
• Sleep disturbance or extreme chronotypes
• Nicotine or recreational drug users
• Depression, anxiety, psychosis, or neurologic disorders
• Severe heart or cardiovascular diseases
• Diabetes or metabolic diseases
• Under chronic medications
• Incapable to operate the tasks or comprehend the study information in German or English
• Users of the Bopomo alphates utilized as stimuli in the reward learning tasks
• Current enrolment in other clinical trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 7 days placebo intake.	Dietary supplement: mannitol; two doses per day: 200 mg in the morning & 100 mg in the afternoon
Active Comparator: Acute caffeine; 6 days placebo followed by 1 day caffeine intake.	Dietary supplement: mannitol; two doses per day: 200 mg in the morning & 100 mg in the afternoon; Dietary supplement: caffeine; two doses per day: 200 mg caffeine in the morning; 100 mg caffeine in the afternoon
Experimental: Daily caffeine; 7 days caffeine intake	Dietary supplement: caffeine; two doses per day: 200 mg caffeine in the morning; 100 mg caffeine in the afternoon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The accuracy (% of correct answers) in implicit learning through different probabilities of monetary reward feedback	Through a probabilistic selection task, participant will go through a training phase to learn the rules which options may be more likely to return monetary feedback, and the knowledge learned will be tested in a second phase where the task difficulty is increased, and no feedback is provided. The overall accuracy in the testing phases will be examined, as well as the accuracies in choosing or avoiding the highest and lowest reward-probability stimuli.	1-hour after the second intake on the 7th day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The errors in motor inhibition (rates of false alarm) in a motor inhibition task	Through a reaction-inhibition task (Go/NoGo), participants will go through two phases of the task: 1) Only respond to a specific stimulus when it shows; 2) Respond to all stimuli except for the specific stimulus. The accuracy in motor inhibition will be indicated by the errors made in the no-go signals (i.e. false alarm).	1.5-hour after the second intake on the 7th day
Salience attribution behaviors	subjective perception towards the probabilities (0 -100%) of reward feedback from each choice in the probabilistic selection task.	1.5-hour after the second intake on the 7th day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-report anxiety levels	State-Trait Anxiety Inventory for Adults (STAI-A) is used to examine the subjective anxiety levels in general as a trait (20 questions) and as a current state (20 questions). Participants will rate the levels using a Likert's scale (For trait - 0: Almost never, 1: Sometimes, 2: Often, 3: Almost always; For current state - 0: not at all, 1: Somewhat, 2: Moderately so, 3: Very much so).	1-hour after the second intake on the 7th day
Subjective sleepiness and alertness	Self-report one-question Karolinska Sleepiness Scale is used to rate the subjective sleepiness/alertness from 1 (very awake), 3 (awake), 5 (neither awake or tired), 7 (tired but no problem to stay awake), to 9 (very tired, big problem to stay awake, struggling with sleep), and 2, 4, 6, 8 for intermediate levels.	1-hour after the second intake on the 7th day
heart rate measurement	heart rates (per min)	1-hour after the second intake on the 7th day
blood pressure measurement	systolic and diastolic blood pressure	1-hour after the second intake on the 7th day

Collaborators and Investigators

• Sponsor: Yu-Shiuan Lin
• Investigators: Principal Investigator: Yu-Shiuan Lin, PhD, Centre for Chronobiology, University Psychiatric Clinics Basel

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2022
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 28, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carbohydrates; Alkaloids; Purinones; Purines; Alcohols; Sugar Alcohols; Xanthines; Caffeine; Mannitol
• Other Study ID Numbers: CChronobiology

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD data, including SAP, CSR, and analytic codes, will be made available on OSF or provided upon requests after the data requested are published.
• IPD Sharing Time Frame: Data will be made available after publishing (estimated to be July 2023).
• IPD Sharing Access Criteria: Researchers who are interested in using IPD data from ADoRe can either contact the Sponsor-Investigator (ys.lin@unibas.ch, Yu-Shiuan Lin, PhD) or access from ADoRe project on OSF (https://osf.io/wzf2y/). Please note that the data folder of this project will be only accessible after publishing.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No