Individual differences in responses to ethanol and d-amphetamine: a within-subject study.
BACKGROUND
In some individuals, ethanol (EtOH) produces marked stimulant-like subjective effects resembling those of stimulant drugs, like d-amphetamine (AMP). In this study, we examined the neurochemical basis of these individual differences by examining the same subjects' responses to both EtOH and AMP. A positive correlation between subjects' responses to the two drugs may suggest that AMP and EtOH produce their stimulant-like subjective effects 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 placebo on four separate sessions in random order and under double-blind conditions. Various self-reported and objective drug effects were measured, including 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 performance after AMP and increased ratings of sedative-like subjective effects, increased heart rate and blood pressure, and impaired vigilance performance after EtOH. Consistent with previous reports, there was substantial intersubject variability in subjective responses to EtOH: some subjects reported primarily stimulant-like effects, whereas others reported primarily sedative-like 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 correlation between responses to EtOH and 20 mg AMP on the ARCI A scale (a measure of stimulant-like subjective effects; r = 0.41, p < 0.05). Among only those subjects who reported primarily stimulant-like effects from EtOH, the 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 between the drugs' effects were not observed on other measures, such as DSST or vigilance task performance or heart rate. This may indicate that these other effects are mediated by separate mechanisms. The study illustrates a novel approach to studying the neurochemical basis of drug effects.
Holdstock
L
L
Department of Psychiatry, The University of Chicago, Chicago, Illinois 60637, USA.
de Wit
H
H
D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology
D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D000431:Ethanol; D000661:Amphetamine