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

J Clin Psychopharmacol. 1996 Feb;16(1):72-6. doi: 10.1097/00004714-199602000-00012.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Affect / drug effects*
  • Blood Pressure / drug effects
  • Central Nervous System Stimulants / pharmacokinetics
  • Central Nervous System Stimulants / pharmacology*
  • Dextroamphetamine / pharmacokinetics
  • Dextroamphetamine / pharmacology*
  • Drug Tolerance
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Humans
  • Male


  • Central Nervous System Stimulants
  • Dextroamphetamine