Despite the fact that the database documenting amphetamine-related effects in humans has increased over the past decade, there remain important gaps in our knowledge of the effects of these drugs in humans. The current investigations, which examined the acute, repeated-dose and residual effects of amphetamine derivatives on various psychological measures in humans, addressed two of these gaps. The first was the lack of empirical evidence directly comparing d-amphetamine and methamphetamine. Study 1 was the first direct comparison of the regulatory focus effects of intranasal d-amphetamine and methamphetamine (12, 50 mg/70kg). Results indicate that the drugs produced overlapping effects on most measures (e.g. increased "prevention" focus state and task engagement). Under the low dose condition, only methamphetamine increased "prevention" focus. Study 2 was a within-participant investigation on the impact of three 3,4-methylenedioxymethamphetamine (MDMA) administrations (12 and 24 hours intervals) on physiological, subjective, and behavioral measures in experienced MDMA users. Heart rate, blood pressure, oral temperature, subjective effects, psychomotor performance, and sleep were assessed repeatedly throughout the study. Acute administration of MDMA produced systematic increases in heart rate, blood pressure, and subjective effects, but oral temperature was unaltered. Following repeated drug administration, heart rate elevations were no longer statistically significant; blood pressure and subjective-effect ratings remained significantly increased, but such increases were diminished relative to acute drug effects. Measures of sleep were decreased only on the evening following two active MDMA administrations. Performance alterations were not observed nor were MDMA-related toxic effects. Overall, the data from both studies do not support either: 1) the conventional notion that d-amphetamine and methamphetamine produce markedly different effects in humans; or 2) the general perception that MDMA produces dangerous cardiovascular and subjective effects in humans following repeated administration.