A randomized placebo controlled trial demonstrates the effect of dl-methylephedrine on brain functions is weaker than that of pseudoephedrine.

Intellectual drug doping in athletics by using stimulants that affect central nervous system functions has been diversified. Stimulants are regulated by the World Anti-Doping Agency according to their levels of urinary concentration. Positron emission tomography could evaluate how stimulants affect central nervous system functions. We aimed to evaluate the effect of stimulants on brain function by examining the difference in brain dopamine transporter occupancy by PET after administration of dl-methylephedrine or pseudoephedrine at the clinical maximum daily dose. Four PET scans without and with drug administration (placebo, dl-methylephedrine 150 mg and pseudoephedrine 240 mg) were performed. The concentrations of dl-methylephedrine and pseudoephedrine in plasma and urine were measured. DAT occupancies in the striatum with placebo, dl-methylephedrine and pseudoephedrine were calculated by PET images. The urinary concentration of dl-methylephedrine (12.7 µg/mL) exceeded the prohibited concentration (10 µg/mL), but the DAT occupancy with dl-methylephedrine (6.1%) did not differ (p = 0.92) from that with placebo (6.2%). By contrast, although the urinary concentration of pseudoephedrine (144.8 µg/mL) was below the prohibited concentration (150 μg/mL), DAT occupancy with pseudoephedrine was 18.4%, which was higher than that with placebo (p = 0.009). At the maximum clinical dose, dl-methylephedrine was shown to have weaker effects on brain function than pseudoephedrine.