Healthy Adult Male and Female Volunteers
Conditions
Keywords
methylphenidate, central nervous system stimulants, cognitive function, exercise performance, cardiopulmonary exercise testing, cardiovascular effects, electrocardiography, postural balance, randomized crossover study
Brief summary
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).
Detailed description
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.
Interventions
DRUGMethylphenidate Stimulant medication therapy
Extended-release methylphenidate 20 mg administered orally once daily for 14 days.
OTHERPlacebo Capsule(s)
Matching placebo capsules containing inert sucrose, identical in appearance to the active medication capsules.
Sponsors
University of Witwatersrand, South Africa
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomised, double-blind, placebo-controlled cross-over design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults without a diagnosis of ADHD * Age 18 to 50 years * Willing to participate after being informed about the study * Willing to receive both methylphenidate and placebo during the study period * Willing to undergo non-invasive physiological, cognitive, cardiovascular, balance, and physical performance assessments * Able to comply with all study procedures and visits
Exclusion criteria
* Current use of any medication that may affect cognitive performance, physical performance, electrocardiogram (ECG) findings, cardiovascular function, or balance * Any medical, neurological, musculoskeletal, psychiatric, or other condition that may interfere with the safe or successful completion of study assessments and physical performance testing * Any contraindication to methylphenidate administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Oxygen Consumption (VO₂peak) | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate (post-intervention, following crossover design) | Maximal oxygen uptake (VO₂peak) measured during cardiopulmonary exercise testing (CPET) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Attention (CNS Vital Signs) | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate | Neurocognitive attention performance assessed using the CNS Vital Signs® computerized test battery. |
| Postural Balance Performance (Biodex Balance System) | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate | Postural balance assessed using the Biodex Balance System® under four conditions (eyes open/closed and firm/unstable surfaces), measuring sway and stability indices. |
| Ventilatory Threshold (VT1) | Baseline, after 14 days placebo, after 14 days methylphenidate | Ventilatory threshold measured during CPET as an indicator of aerobic capacity |
| Handgrip Strength | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate | Muscle strength measured using a handgrip dynamometer, assessing maximal grip force of the dominant hand as an indicator of neuromuscular performance. |
| Resting Heart Rate | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate | Resting heart rate (beats per minute) measured using standardised procedures following a 5-minute rest period. |
| Electrocardiogram (ECG) Rhythm Parameters | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate | Cardiac electrical activity assessed using electrocardiography, including measurements of heart rhythm. |
| Oxygen Pulse | Baseline, after 14 days placebo, after 14 days methylphenidate | 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. |
| Ventilatory Efficiency (VE/VCO₂ Slope) | Baseline, after 14 days placebo, after 14 days methylphenidate | 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. |
| Oxygen Uptake Efficiency Slope (OUES) | Baseline, after 14 days placebo, after 14 days methylphenidate | 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. |
| Oxygen Consumption to Work Rate Ratio (VO₂/Work Rate) | Baseline, after 14 days placebo, after 14 days methylphenidate | 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. |
| Reaction Time (CNS Vital Signs) | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate. | Neurocognitive reaction time assessed using the CNS Vital Signs® computerized test battery. |
| Executive Function (CS Vital Signs) | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate. | Executive function performance assessed using the CNS Vital Signs® computerized test battery. |
| Complex Attention (CS Vital Signs) | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate. | Complex attention performance assessed using the CNS Vital Signs® computerized test battery. |
| Processing Speed | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate. | Processing speed assessed using the CNS Vital Signs® computerized test battery. |
| Memory Domains (CNS Vital Signs) | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate. | Memory performance (including composite memory domains as defined by CNS Vital Signs®) assessed using the computerized test battery. |
| Electrocardiogram Tracing PR intervals | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate. | Electrocardiogram PR intervals |
| Electrocardiogram tracing QRS intervals | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate. | Measurement of QRS intervals on electrocardiogram tracings |
| Electrocardiogram QT/QTc measurement | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate. | Measurement of QT/QTc intervals on electrocardiogram |
| Blood Pressure | Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate | Brachial arterial blood pressure (mmHg) measured using standardised procedures following a 5-minute rest period. |
Countries
South Africa
Outcome results
None listed