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Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine's effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects questionnaire at multiple time points post d-amphetamine. Based on the observation of distinct individual differences in time course of drug effects questionnaire "feel", "high", and "like" ratings (DEQH+L+F) in Study 1, subjects in both studies were categorized as early peak responders (peak within 60 minutes), late peak responders (peak > 60 minutes) or nonresponders; 20-25% of participants were categorized as early peak responders, 50-55% as late peak responders and 20-30% as nonresponders. Physiological (both studies) and plasma d-amphetamine (Study 1) were compared among these groups. Early peak responders exhibited an earlier rise in plasma d-amphetamine levels and more sustained elevation in heart rate compared to late peak responders. The present data illustrate the presence of significant individual differences in the temporal pattern of responses to oral d-amphetamine, which may contribute to heightened abuse potential.

Blood pressure, heart rate, and echocardiographic parameters of left ventricular size and shortening were measured both under baseline conditions and during handgrip exercise (50% maximum handgrip effort held to fatigue) in 20 normal women (20 through 29 years of age). As a group, there was a significant increase in heart rate (72 +/- 10 vs 83 +/- 12; P less than .001), systolic blood pressure (111 +/- 8 vs 133 +/- 14 mm Hg; P less than .001), diastolic blood pressure (67 +/- 8 vs 89 +/- 12 mm Hg; P less than .001), and calculated cardiac output (4.3 +/- 1.5 vs 5.2 +/- 1.7 liters/minute; P less than .005). There was no significant change in left ventricular internal dimension in diastole or systole, shortening fraction, or calculated stroke volume. The average group response of an increase in cardiac output secondary to an increase in heart rate is similar to that of male subjects in their second decade. Individual variability in responses was of specific interest since only three of the 20 women demonstrated a totally characteristic response to handgrip exercise. Handgrip exercise in young women may not provide a uniformly characteristic response from which to predict hemodynamic changes in a given individual and may lead to clinical misinterpretation if appropriate caution is not used.