"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.

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

IPD data, including SAP, CSR, and analytic codes, will be made available on OSF or provided upon requests after the data requested are published.

Data will be made available after publishing (estimated to be July 2023).

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.