Neurocognitive Effects of Extended-Release Methylphenidate in Healthy Adults

NCT07742631 | Completed Early Phase 1

• 2 other identifiers: 180611PACTR202011697726048
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy Adult Male and Female Volunteers

Keywords

methylphenidate; central nervous system stimulants; cognitive function; exercise performance; cardiopulmonary exercise testing; cardiovascular effects; electrocardiography; postural balance; randomized crossover study

Outcome Measures

Primary Outcomes (1)

• Peak Oxygen Consumption (VO₂peak)

  Maximal oxygen uptake (VO₂peak) measured during cardiopulmonary exercise testing (CPET)

  Baseline (pre-intervention), after 14 days of placebo, and after 14 days of methylphenidate (post-intervention, following crossover design)

Secondary Outcomes (19)

• 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

• Ventilatory Threshold (VT1)

  Baseline, after 14 days placebo, after 14 days 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

Other Outcomes (4)

• Incidence of Treatment-Emergent Adverse Symptoms [Safety and Tolerability]).

  Through study completion, an average of 30 days

• Incidence of Treatment-Emergent Adverse Electrocardiograph events [Safety and Tolerability]).

  Through study completion, an average of 30 days

• Incidence of Treatment-Emergent Adverse Events - Resting Heart Rate [Safety and Tolerability]).

  Through study completion, an average of 30 days

Study Arms (2)

Mehylphenidate -> Placebo

ACTIVE COMPARATOR

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)

Placebo -> Methylphenidate

PLACEBO COMPARATOR

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)

Interventions

Methylphenidate Stimulant medication therapy DRUG

Extended-release methylphenidate 20 mg administered orally once daily for 14 days.

Also known as: Methylphenidate

Mehylphenidate -> Placebo; Placebo -> Methylphenidate

Placebo Capsule(s) OTHER

Matching placebo capsules containing inert sucrose, identical in appearance to the active medication capsules.

Also known as: Inactive comparator

Mehylphenidate -> Placebo; Placebo -> Methylphenidate

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Witwatersrand, South Africa: lead

Study Sites (1)

University of the Witwatersrand

Johannesburg, Gauteng, 2193, South Africa

Location

Related Publications (32)

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MeSH Terms

Interventions

Methylphenidate

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomised, double-blind, placebo-controlled cross-over design.

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: August 3, 2026
• Study Start: February 6, 2023
• Primary Completion: April 15, 2024
• Study Completion: April 15, 2024
• Last Updated: August 3, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)