Relationship of plasma amphetamine levels to physiological, subjective, cognitive and biochemical measures in healthy volunteers.

Acute administration of the stimulant dextro-amphetamine produces multiple physiological, subjective cognitive and biochemical changes. These effects are similar to those seen in mania, and may be a useful model for mania. The aim of the present study was more fully to determine the multiple effects of dextro-amphetamine and to relate these to changes in plasma levels of the drug. In a double-blind, placebo-controlled crossover study in 25 healthy volunteers (ages 18–45), the effects of 25 mg of oral dextro-amphetamine were examined. Physiological, subjective, cognitive changes, concentrations of amino acids and metabolites of biogenic amines period were related to changes in plasma amphetamine concentrations over 500 min. Peak concentrations of dextro-amphetamine occurred at 2.5–3.5 h post-administration and levels decreased to 75% of peak value after 500 min. The results from the present study indicate that the subjective psychological, cognitive and blood pressure changes frequently did not mirror the time course of plasma levels of the drug. Thus, there was no clear-cut relationship between plasma levels and effects. In addition, dextro-amphetamine caused no significant changes in amino acids or amino metabolite concentrations. In conclusion, while dextro-amphetamine administration definitely causes several changes which are seen in mania, there remain some physiological and metabolic differences between these two conditions. Copyright © 2003 John Wiley & Sons, Ltd.