Individual differences in responses to ethanol and D-amphetamine: A within-subject study

Background: In some individuals, ethanol (EtOH) produces marked stimulant-l ike subjective effects resembling those of stimulant drugs, like D-amphetam ine (AMP). In this study, we examined the neurochemical basis of these indi vidual differences by examining the same subjects' responses to both EtOH a nd AMP. A positive correlation between subjects' responses to the two drugs may suggest that AMP and EtOH produce their stimulant-like subjective effe cts by a shared mechanism. Methods: Twenty-seven volunteers (17 male, 10 female), aged 21-35, received beverages or capsules containing EtOH 0.8 g/kg, AMP 10 or 20 mg, or placeb o on four separate sessions in random order and under double-blind conditio ns. Various self-reported and objective drug effects were measured, includi ng measures sensitive to subjective and cognitive stimulant-like effects. Results: EtOH and AMP produced their prototypical subjective and behavioral effects, including increased ratings of stimulant-like subjective effects, increased heart rate and blood pressure, and improved vigilance performanc e after AMP and increased ratings of sedative-like subjective effects, incr eased heart rate and blood pressure, and impaired vigilance performance aft er EtOH. Consistent with previous reports, there was substantial intersubje ct variability in subjective responses to EtOH: some subjects reported prim arily stimulant-like effects, whereas others reported primarily sedative-li ke effects. To examine the relationship between these responses to EtOH and subjects' responses to AMP, correlations were examined between effects of EtOH and AMP. For all subjects together, there was a significant positive c orrelation between responses to EtOH and 20 mg AMP on the ARCI A scale (a m easure of stimulant-like subjective effects; r = 0.41, p < 0.05). Among onl y these subjects who reported primarily stimulant-like effects from EtOH, t he correlation between EtOH and AMP was 0.64 (p < 0.05). Conclusions: Subjects who experience pronounced stimulant-like effects from EtOH also report greater stimulant effects from AMP, suggesting that these effects may be mediated through similar mechanisms. These correlations bet ween the drugs' effects were not observed on other measures, such as DSST o r vigilance task performance or heart rate. This may indicate that these ot her effects are mediated by separate mechanisms. The study illustrates a no vel approach to studying the neurochemical basis of drug effects.