An Early Phase 1 interventional study of Methylphenidate Stimulant medication therapy and Placebo Capsule(s) in Healthy Adult Male and Female Volunteers, sponsored by University of Witwatersrand, South Africa. Completed at 1 site in South Africa. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-03.
Sponsored by University of Witwatersrand, South Africa · Early Phase 1, Interventional, and Basic science
This study evaluated the effects of methylphenidate (MPH), a stimulant medication commonly used to treat attention deficit hyperactivity disorder (ADHD), in healthy adults without ADHD. Although MPH is sometimes used by students and athletes to improve concentration or performance, its true benefits and risks in healthy individuals are uncertain.
The purpose of this study was to determine whether short-term use of MPH improves thinking ability, physical performance, cardiovascular function, balance, muscle strength, or heart safety in healthy adults.
In this randomized, double-blind, placebo-controlled crossover study, 28 healthy adult participants received either MPH (20 mg daily) or a placebo for 14 days, followed by a washout period and then the alternate treatment. Participants underwent repeated testing of heart rate, blood pressure, exercise capacity, balance, muscle strength, cognitive function, and heart electrical activity (ECG).
Methylphenidate (MPH) is a central nervous system stimulant widely prescribed for the treatment of attention deficit hyperactivity disorder (ADHD). In addition to its clinical use, there has been increasing interest in the use of MPH by healthy individuals for potential cognitive enhancement, academic performance, and physical performance. Despite this growing use, there is limited high-quality evidence on its effects across multiple physiological and functional domains in healthy adults. This study was designed to address these gaps.
This investigation used a randomized, double-blind, placebo-controlled crossover design to evaluate the effects of short-term MPH administration in healthy, drug-naïve adults. A crossover design was selected to allow each participant to serve as their own control, thereby reducing variability and improving the precision of comparisons between treatment conditions. Participants were randomly assigned to receive either extended-release MPH (20 mg daily) or a placebo for 14 days, followed by a washout period and subsequent crossover to the alternate treatment.
The study was conducted in a controlled laboratory setting to ensure consistency in testing conditions and measurement accuracy. Participants underwent a comprehensive assessment battery at baseline and repeated assessments after each treatment phase. These evaluations were selected to provide a multidimensional understanding of MPH's effects across several key domains:
Physiological and cardiovascular function: Resting heart rate and blood pressure were measured to assess potential stimulant-related cardiovascular effects. In addition, cardiopulmonary exercise testing (CPET) was used to evaluate exercise capacity, aerobic fitness (including maximum oxygen consumption, VO₂ peak), ventilatory efficiency, and overall cardiopulmonary performance.
Neurocognitive function: Cognitive performance was assessed using a validated computerized neurocognitive test battery (CNS Vital Signs®). This evaluated domains such as attention, memory, processing speed, executive function, and reaction time. These measures were included because MPH is known to influence dopaminergic and noradrenergic pathways involved in cognitive processing.
Postural balance: Objective balance testing was conducted using the Biodex® Balance System, which evaluates stability under different sensory conditions. This allowed assessment of visual, vestibular, and somatosensory contributions to balance control.
Muscle strength: Handgrip strength, a reliable indicator of overall muscular strength and physical performance, was measured using a calibrated dynamometer.
Cardiac electrical activity: Electrocardiography (ECG) was recorded at rest and during exercise to monitor cardiac rhythm and electrical conduction, ensuring detection of any potential stimulant-related cardiac effects.
Participants were instructed to maintain their usual diet and physical activity throughout the study to minimize confounding factors. All assessments were performed at similar times of day across testing sessions to reduce the effects of diurnal variation.
The study also incorporated rigorous safety and screening procedures. Participants underwent pre-participation health screening, including standardized questionnaires and cardiovascular risk assessment, to ensure suitability for exercise testing and stimulant exposure. Continuous monitoring during exercise testing ensured participant safety.
This study specifically targeted healthy adults without ADHD to isolate the effects of MPH independent of its therapeutic role. By integrating physiological, cognitive, neuromuscular, and cardiovascular measures within a single study design, the research provides a comprehensive evaluation of MPH's potential for performance enhancement or health risk in this population.
University of Witwatersrand, South Africa is the lead sponsor of 47 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received extended-release methylphenidate 20 mg once daily for 14 days, followed by a washout period, then matching placebo capsules once daily for 14 days.
Drug: Methylphenidate Stimulant medication therapy · Other: Placebo Capsule(s)
Matching placebo capsules administered orally once daily for 14 days. Capsules were identical in appearance to methylphenidate capsules to maintain blinding.
Drug: Methylphenidate Stimulant medication therapy · Other: Placebo Capsule(s)
Extended-release methylphenidate 20 mg administered orally once daily for 14 days.
Also known as: Methylphenidate
Matching placebo capsules containing inert sucrose, identical in appearance to the active medication capsules.
Also known as: Inactive comparator
Peak Oxygen Consumption (VO₂peak)
Maximal oxygen uptake (VO₂peak) measured during cardiopulmonary exercise testing (CPET)
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate (post-intervention, following crossover design)
Attention (CNS Vital Signs)
Neurocognitive attention performance assessed using the CNS Vital Signs® computerized test battery.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate
Postural Balance Performance (Biodex Balance System)
Postural balance assessed using the Biodex Balance System® under four conditions (eyes open/closed and firm/unstable surfaces), measuring sway and stability indices.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate
Ventilatory Threshold (VT1)
Ventilatory threshold measured during CPET as an indicator of aerobic capacity
Time frame: Baseline, after 14 days placebo, after 14 days methylphenidate
Handgrip Strength
Muscle strength measured using a handgrip dynamometer, assessing maximal grip force of the dominant hand as an indicator of neuromuscular performance.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate
Resting Heart Rate
Resting heart rate (beats per minute) measured using standardised procedures following a 5-minute rest period.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate
Electrocardiogram (ECG) Rhythm Parameters
Cardiac electrical activity assessed using electrocardiography, including measurements of heart rhythm.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate
Oxygen Pulse
Oxygen pulse (mL/beat) measured during cardiopulmonary exercise testing (CPET) as the ratio of oxygen consumption (VO₂) to heart rate, serving as a surrogate marker of stroke volume and cardiovascular efficiency during exercise.
Time frame: Baseline, after 14 days placebo, after 14 days methylphenidate
Ventilatory Efficiency (VE/VCO₂ Slope)
Ventilatory efficiency assessed by the VE/VCO₂ slope during CPET, representing the relationship between minute ventilation (VE) and carbon dioxide production (VCO₂). This parameter reflects ventilatory efficiency and pulmonary gas exchange.
Time frame: Baseline, after 14 days placebo, after 14 days methylphenidate
Oxygen Uptake Efficiency Slope (OUES)
Oxygen uptake efficiency slope (OUES) measured during CPET as the relationship between oxygen consumption (VO₂) and ventilation (VE), reflecting the efficiency of oxygen uptake during exercise, including at submaximal effort levels.
Time frame: Baseline, after 14 days placebo, after 14 days methylphenidate
Oxygen Consumption to Work Rate Ratio (VO₂/Work Rate)
Ratio of oxygen consumption (VO₂) to work rate (mL/min/watt) measured during CPET, indicating the efficiency of oxygen utilisation relative to external workload and overall cardiopulmonary performance.
Time frame: Baseline, after 14 days placebo, after 14 days methylphenidate
Reaction Time (CNS Vital Signs)
Neurocognitive reaction time assessed using the CNS Vital Signs® computerized test battery.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.
Executive Function (CS Vital Signs)
Executive function performance assessed using the CNS Vital Signs® computerized test battery.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.
Complex Attention (CS Vital Signs)
Complex attention performance assessed using the CNS Vital Signs® computerized test battery.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.
Processing Speed
Processing speed assessed using the CNS Vital Signs® computerized test battery.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.
Memory Domains (CNS Vital Signs)
Memory performance (including composite memory domains as defined by CNS Vital Signs®) assessed using the computerized test battery.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.
Electrocardiogram Tracing PR intervals
Electrocardiogram PR intervals
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.
Electrocardiogram tracing QRS intervals
Measurement of QRS intervals on electrocardiogram tracings
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.
Electrocardiogram QT/QTc measurement
Measurement of QT/QTc intervals on electrocardiogram
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.
Blood Pressure
Brachial arterial blood pressure (mmHg) measured using standardised procedures following a 5-minute rest period.
Time frame: Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate
Incidence of Treatment-Emergent Adverse Symptoms [Safety and Tolerability]).
Adverse events and tolerability assessed through participant self-report, clinical monitoring during each intervention period. Participants were monitored for side effects associated with methylphenidate or placebo, including but not limited to cardiovascular symptoms (e.g., changes in heart rate or blood pressure), sleep disturbances, appetite changes, and nervousness. All adverse events were documented, including severity, duration, and assessed relationship to the intervention.
Time frame: Through study completion, an average of 30 days
Incidence of Treatment-Emergent Adverse Electrocardiograph events [Safety and Tolerability]).
Adverse electrical cardiovascular events and tolerability assessed through electrocardiograph tracings recorded through all stages. Events were documented, including severity, duration, and assessed relationship to the intervention.
Time frame: Through study completion, an average of 30 days
Incidence of Treatment-Emergent Adverse Events - Resting Heart Rate [Safety and Tolerability]).
Adverse events and tolerability assessed through participant self-report and clinical monitoring during each intervention period. Participants' resting heart rate was monitored for associated changes or effects with methylphenidate or placebo. All adverse events were documented, including severity, duration, and assessed relationship to the intervention.
Time frame: Through study completion, an average of 30 days
Incidence of Treatment-Emergent Adverse Events - Blood Pressure [Safety and Tolerability]).
Adverse events and tolerability assessed through participant self-report and clinical monitoring during each intervention period. Participants' resting blood pressure was monitored for associated changes with methylphenidate or placebo. All adverse events were documented, including severity, duration, and assessed relationship to the intervention.
Time frame: Through study completion, an average of 30 days
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — The study dataset (de-identified) is securely archived at the University of the Witwatersrand. Ethical restrictions prevent public release of participant data; however, access may be granted to qualified researchers upon reasonable request to the corresponding author and with appropriate institutional approvals.
Ran from Feb 2023 to primary completion in Apr 2024, 14 months.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Methylphenidate
University of Witwatersrand, South Africa