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Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology.

ABSTRACT: Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine's effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects questionnaire at multiple time points post d-amphetamine. Based on the observation of distinct individual differences in time course of drug effects questionnaire "feel", "high", and "like" ratings (DEQH+L+F) in Study 1, subjects in both studies were categorized as early peak responders (peak within 60 minutes), late peak responders (peak > 60 minutes) or nonresponders; 20-25% of participants were categorized as early peak responders, 50-55% as late peak responders and 20-30% as nonresponders. Physiological (both studies) and plasma d-amphetamine (Study 1) were compared among these groups. Early peak responders exhibited an earlier rise in plasma d-amphetamine levels and more sustained elevation in heart rate compared to late peak responders. The present data illustrate the presence of significant individual differences in the temporal pattern of responses to oral d-amphetamine, which may contribute to heightened abuse potential.

SUBMITTER: Smith CT

PROVIDER: S-EPMC5049703 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology.

Smith Christopher T CT Weafer Jessica J Cowan Ronald L RL Kessler Robert M RM Palmer Abraham A AA de Wit Harriet H Zald David H DH

Journal of psychopharmacology (Oxford, England) 20160215 4

Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine's effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects ...[more]

PMID: 26880226

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Project description:Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC) in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants' drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female), aged 21-31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg), alcohol (0.8 g/kg), or THC (7.5 mg), each paired with a placebo session. Participants rated the drugs' effects on both global measures (e.g. feeling a drug effect at all) and drug-specific measures. In general, participants' responses to the three drugs were unrelated. Unexpectedly, "wanting more" alcohol was inversely correlated with "wanting more" THC. Additionally, in women, but not in men, "disliking" alcohol was negatively correlated with "disliking" THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity) was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a "drug of choice" model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types of drugs.

Dataset Information

Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology.

Publications

Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology.

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