Acute tolerance to subjective but not cardiovascular effects of d-amphetamine in normal, healthy men

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.