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 pharmacok inetics and pharmacodynamics of d-amphetamine in healthy, normal volun teers. Six men, aged 22 to 31, attended two experimental sessions duri ng which they received single oral doses of 20 mg of d-amphetamine. Pl asma levels of drug and measures of drug effect were collected predrug and at regular intervals for 24 hours after drug administration. Plas ma drug levels peaked at 4 hours and remained at detectable levels for 24 hours after drug administration. Subjective ratings, including ''f eel drug'' and ''feel high'' peaked at 1 1/2 to 2 hours and returned t o baseline levels by 3 to 4 hours. Evaluation of phase plots (i.e., dr ug effect vs. drug concentration) indicated that acute tolerance devel oped to the subjective but not to the cardiopressor effects of d-amphe tamine. This finding implies that individuals who repeatedly administe r the drug to maintain certain levels of subjective effects may increa se plasma drug levels and physiologic effects to toxic levels.