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

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.

Residual effects of intranasal methamphetamine on sleep, mood, and performance

“…A related point is that 24 hours following methamphetamine administration (primarily the 50-mg dose), physiological measures remained significantly elevated and this might have potential implications for toxicity. For example, de Wit and colleagues showed that tolerance develops more rapidly to oral amphetamine-related subjective effects relative to physiological effects (Brauer et al 1996). Thus, in the natural environment, some users may take repeated methamphetamine doses in order to achieve a certain level of intoxication, which might increase the likelihood of physiological harm (e.g., cardiotoxicity).…”

An fMRI Study of the Effect of Amphetamine on Brain Activity,

“…For example, amphetamine is known to have vasoconstrictive effects, which can result in alterations of blood flow (Simpson 1976;Angrist et al 1987;Brauer et al 1996). Although it seems unlikely, amphetamine may have directly affected blood flow only in the specific brain areas where changes in the activation pattern were observed.…”

Amphetamine Primes Motivation to Gamble and Gambling-Related Semantic Networks in Problem Gamblers

“…S began the Lexical Salience Task 90 min after dosing, at which time the subjective-behavioral effects of oral AMPH are maximal (Brauer et al, 1996). Upon completion of the task (3-5 min), S completed the modified visual analog scales and the MAACL.…”