Acute Tolerance to Subjective but not Cardiovascular Effects of d-Amphetamine in Normal, Healthy Men

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Abstract
This is a descriptive report on the relationship between the pharmacokinetics and pharmacodynamics of d-amphetamine in healthy, normal volunteers. Six men, aged 22 to 31, attended two experimental sessions during which they received single oral doses of 20 mg of d-amphetamine. Plasma levels of drug and measures of drug effect were collected predrug and at regular intervals for 24 hours after drug administration. Plasma drug levels peaked at 4 hours and remained at detectable levels for 24 hours after drug administration. Subjective ratings, including "feel drug" and "feel high" peaked at 1 1/2 to 2 hours and returned to baseline levels by 3 to 4 hours. Evaluation of phase plots (i.e., drug effect vs. drug concentration) indicated that acute tolerance developed to the subjective but not to the cardiopressor effects of d-amphetamine. This finding implies that individuals who repeatedly administer the drug to maintain certain levels of subjective effects may increase plasma drug levels and physiologic effects to toxic levels. (J Clin Psychopharmacol 1996;16:72-76).