title: 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.
authors.affiliation: Department of Psychology, Vanderbilt University, Nashville, TN, USA christopher.t.smith@vanderbilt.edu.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Smith
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Weafer
authors.affiliation: Department of Psychology, Vanderbilt University, Nashville, TN, USA Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Cowan
authors.affiliation: Department of Radiology, UAB School of Medicine, Birmingham, AL, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kessler
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA Department of Human Genetics, University of Chicago, Chicago, IL, USA Department of Psychiatry University of California San Diego, La Jolla, CA, USA.
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Palmer
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors.forename: Harriet
authors.initials: H
authors.lastname: de Wit
authors.affiliation: Department of Psychology, Vanderbilt University, Nashville, TN, USA Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Zald
mesh_terms: D000328:Adult; D016739:Behavior, Addictive / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007206:Individuality; D008297:Male; D019966:Substance-Related Disorders / Q000097:blood / Q000209:etiology / Q000378:metabolism; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine
keywords: addiction; d-amphetamine; individual differences; pharmacokinetics; subjective effects