An interventional study of caffeine and mannitol in Caffeine, sponsored by Yu-Shiuan Lin. Active, not recruiting at 1 site in Switzerland. Open to participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-17.
Sponsored by Yu-Shiuan Lin · Not applicable, Interventional, and Basic science
"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.
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.
This is the only study on the registry with Yu-Shiuan Lin as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
7 days placebo intake.
Dietary Supplement: mannitol
6 days placebo followed by 1 day caffeine intake.
Dietary Supplement: caffeine · Dietary Supplement: mannitol
7 days caffeine intake
Dietary Supplement: caffeine
two doses per day: 200 mg caffeine in the morning; 100 mg caffeine in the afternoon
two doses per day: 200 mg in the morning \& 100 mg in the afternoon
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.
Time frame: 1-hour after the second intake on the 7th day
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).
Time frame: 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.
Time frame: 1.5-hour after the second intake on the 7th day
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).
Time frame: 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.
Time frame: 1-hour after the second intake on the 7th day
heart rate measurement
heart rates (per min)
Time frame: 1-hour after the second intake on the 7th day
blood pressure measurement
systolic and diastolic blood pressure
Time frame: 1-hour after the second intake on the 7th day
Plan to share: Yes — IPD data, including SAP, CSR, and analytic codes, will be made available on OSF or provided upon requests after the data requested are published.
Supporting information: Study protocol, Csr, Analytic code
No publications or documents are linked to this record.
This study is active, not recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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