Methylphenidate: Physiological, neurocognitive, balance, and physical performance effects

Abstract

Methylphenidate (MPH), a central nervous system stimulant, is widely used for Attention Deficit Hyperactivity Disorder (ADHD) and increasingly misused for cognitive enhancement and physical performance in healthy individuals. Despite its prevalent use, the effects of MPH on physiological, neurocognitive, and physical performance in healthy adults remain unclear. This study aimed to investigate these effects in a controlled setting. A randomised, double-blind, placebo-controlled crossover design was employed with 28 drug-naïve healthy adults (25 females, 3 males; mean age 30.2 years). Participants received either MPH (extended release 20 mg/day) or placebo for 14 days, followed by a washout period and crossover. Outcome measures included physiological parameters (heart rate, blood pressure, cardiopulmonary exercise testing [CPET] variables), neurocognitive function (CNS Vital Signs® battery), postural balance (Biodex® Balance System), handgrip strength (Takei™ dynamometer), and cardiac electrical activity on electrocardiogram (ECG) tracings (Customed®). Data were analysed using ANOVA for differences and Cohen’s d for effect sizes, and significance was set at p < 0.05. Physiological Parameters: Resting heart rate was significantly higher at baseline compared to placebo (p = 0.03), but no differences were observed between placebo and MPH (p=0.06). Blood pressure and CPET variables (VO₂peak, ventilatory threshold (VT), VT1 at % VO2 peak, oxygen pulse, standard slopes) showed no significant changes. Neurocognitive Function: Significant improvements in reaction time, complex attention, and executive function were noted from baseline to placebo and MPH (p < 0.05), but no statistically significant differences between placebo and MPH, but with large effect sizes (Cohen’s d = -2.13 and -1.89, respectively). Balance: No significant differences were found in postural balance on firm and unstable surfaces with eyes open and eyes closed. Physical Strength Performance: No significant differences were found in handgrip strength across all conditions. Cardiac Electrical Activity: No abnormalities were detected in ECG tracings during rest or with exercise at baseline, with placebo or with MPH. Extended-release methylphenidate did not significantly enhance physiological, balance, or physical performance measures in healthy adults. While cognitive v improvements were observed, these were comparable to placebo effects, suggesting limited pharmacological benefit in this population. The findings additionally highlight the importance of controlling for practice and placebo effects in cognitive research and support the safety of short-term MPH use in healthy individuals. Further long-term studies are needed to assess sustained effects and risks.