The Neurocognitive Effects of Extended-Release Methylphenidate in Healthy Adults: A Review and Placebo-Controlled Randomized Controlled Trial
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Peak Oxygen Consumption (VO₂peak)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- All
- Accepts 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
Outcomes
Primary Outcomes
Peak Oxygen Consumption (VO₂peak)
Time Frame: 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 Outcomes
- Ventilatory Threshold (VT1)(Baseline, after 14 days placebo, after 14 days methylphenidate)
- Processing Speed(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.)
- Attention (CNS Vital Signs)(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate)
- Postural Balance Performance (Biodex Balance System)(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate)
- Handgrip Strength(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate)
- Resting Heart Rate(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate)
- Electrocardiogram (ECG) Rhythm Parameters(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate)
- Oxygen Pulse(Baseline, after 14 days placebo, after 14 days methylphenidate)
- Ventilatory Efficiency (VE/VCO₂ Slope)(Baseline, after 14 days placebo, after 14 days methylphenidate)
- Oxygen Uptake Efficiency Slope (OUES)(Baseline, after 14 days placebo, after 14 days methylphenidate)
- Oxygen Consumption to Work Rate Ratio (VO₂/Work Rate)(Baseline, after 14 days placebo, after 14 days methylphenidate)
- Reaction Time (CNS Vital Signs)(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.)
- Executive Function (CS Vital Signs)(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.)
- Complex Attention (CS Vital Signs)(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.)
- Memory Domains (CNS Vital Signs)(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.)
- Electrocardiogram Tracing PR intervals(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.)
- Electrocardiogram tracing QRS intervals(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.)
- Electrocardiogram QT/QTc measurement(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate.)
- Blood Pressure(Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate)
Investigators
Demitri Constantinou
Professor
University of Witwatersrand, South Africa