Biomedical subjects

Thomas H Kelly

Publications and source records attributed to Thomas H Kelly.

13 recordsLinked to original sources

PubMed2006

The reinforcing, subject-rated, performance, and cardiovascular effects of d-amphetamine: influence of sensation-seeking status.

Individual differences that may contribute to vulnerability to abuse drugs have been identified. Sensation-seeking status has been shown to influence both vulnerability to drug use and response to acute drug administration. The purpose of the present experiment was to examine the reinforcing effects of d-amphetamine in high and low sensation-seeking subjects using a modified progressive-ratio procedure. A battery of subject-rated, performance, and cardiovascular measures was also included to better characterize the effects of d-amphetamine in these groups. Ten high sensation seekers and ten low sensation seekers that were matched for education, age, drug use, height, and weight, first sampled doses of d-amphetamine (0, 8, and 16 mg). In subsequent sessions, subjects were offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. d-Amphetamine functioned as a reinforcer and produced prototypical stimulant-like effects (e.g., increased subject-ratings of Like Drug, enhanced performance, and increased heart rate). High sensation seekers were more sensitive than low sensation seekers to the reinforcing and some of the subject-rated effects of d-amphetamine. The results of the present experiment extend those of previous findings by demonstrating that the reinforcing effects of d-amphetamine vary as a function of the biologically based sensation-seeking personality trait. These results suggest that increased stimulant drug use and abuse among high sensation seekers may be related, in part, to increased sensitivity to the reinforcing effects of stimulants among these individuals.

Adult↗

PubMed2006

Individual differences in drug abuse vulnerability: d-amphetamine and sensation-seeking status.

RATIONALE: While the personality dimensions of novelty seeking and sensation seeking are associated with drug abuse vulnerability, the mechanisms associated with this vulnerability remain obscure. OBJECTIVE: This study examined the behavioral effects of d-amphetamine in healthy volunteers scoring in the upper and lower quartiles based on age- and gender-adjusted population norms on the impulsive Sensation-Seeking Scale (SSS) of the Zuckerman-Kuhlman personality questionnaire (ZKPQ). METHOD: Participants completed 7-day outpatient studies examining the subjective, performance, and cardiovascular effects of d-amphetamine (0, 7.5, and 15 mg/70 kg, p.o.) under double-blind conditions according to a randomized block design. Performance tasks included behavioral measures of impulsivity, including attention, inhibition, and risk-taking behavior. RESULTS: No differences in baseline performance or d-amphetamine effects on measures of attention, inhibition, and risk-taking behavior were observed. High impulsive sensation seekers reported greater increases on several subjective report measures associated with drug abuse potential, including visual analog scales feel drug, like drug, and high. CONCLUSIONS: Healthy adults scoring in the top quartile on the population of the impulsive SSS of the ZKPQ may be vulnerable to the abuse potential of d-amphetamine.

Adult↗

PubMed2006

A pilot study: attention deficit hyperactivity disorder, sensation seeking, and pubertal changes.

This study was designed to examine the relationship of pubertal changes and sensation seeking (SS) in adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Patients with current or past histories of uncomplicated stimulant medication use for ADHD between the ages of 11 and 15 (13 +/- 1.5) were recruited from a Child Psychiatry and a General Pediatric Clinic. SS was measured using the SS Scale for Children. Pubertal development was measured using Tanner staging, free testosterone, and DHEAS. Subjects and their parent were interviewed with the Diagnostic Interview Schedule for Children (DISC). SS total score was correlated with Tanner stage, free testosterone, and DHEAS (p < or = 0.01). The combined parent and child reports of symptoms of Oppositional Defiant Disorder from the DISC were inversely related to age (p < or = 0.05). Understanding SS in ADHD adolescents as they move through puberty will aid clinicians in monitoring ADHD adolescents and their trajectory into high-risk behaviors.

Adolescent↗

PubMed2006

Pharmacokinetics and pharmacodynamics of a new intranasal midazolam formulation in healthy volunteers.

We evaluated the pharmacokinetics and pharmacodynamics of single 5-mg doses of midazolam after administration of a novel intranasal (IN) formula, IM, and IV midazolam in an open-label, randomized, 3-way cross-over study in 12 healthy volunteers. IN doses were delivered as 0.1-mL unit-dose sprays of a novel formulation into both naris. Blood samples were taken serially from 0 to 12 h after each dose. Plasma midazolam concentrations were determined by liquid chromatography/mass spectrometry/mass spectrometry. Noncompartmental analysis was used to estimate pharmacokinetic parameters. The mean midazolam bioavailabilities and % coefficient of variation were 72.5 (12) and 93.4 (12) after the IN and IM doses, respectively. Median time to maximum concentration was 10 min for IN doses. Adverse events were minimal with all routes of administration, but nasopharyngeal irritation, eyes watering, and a bad taste were reported after IN doses. Our results support further development of this novel midazolam nasal spray.

Administration, Intranasal↗

PubMed2005

Effects of d-amphetamine in human models of information processing and inhibitory control.

Although stimulants are generally associated with enhanced information processing, reports of stimulant effects on behavioral functions that rely on inhibitory processes have been inconsistent. The present research tested the joint effects of d-amphetamine on information processing and inhibitory control in healthy adults (N = 22) with no reported history of illicit stimulant use or drug dependence. Information processing was measured by a rapid information processing (RIP) task and inhibitory control was measured using a stop-signal task. Performance was measured in response to 15 mg/70 kg, 7.5 mg/70 kg, and 0 mg/70 mg (placebo) doses of d-amphetamine, administered double-blind in a randomized, within-subjects design. Results showed that d-amphetamine improved information processing in a dose-dependent manner. By contrast, no enhancement of response inhibition was observed. Stimulant effects were also observed in physiological and subjective effects measures. The findings indicate that a stimulant drug can enhance aspects of cognitive functioning without producing a concomitant improvement in inhibitory control of behavior. The findings highlight the complex nature of stimulant effects on human behavior and the utility of performance tasks as models of complex behavioral and cognitive functions.

Adolescent↗

PubMed2005

Crewmember performance before, during, and after spaceflight.

The development of technologies for monitoring the welfare of crewmembers is a critical requirement for extended spaceflight. Behavior analytic methodologies provide a framework for studying the performance of individuals and groups, and brief computerized tests have been used successfully to examine the impairing effects of sleep, drug, and nutrition manipulations on human behavior. The purpose of the present study was to evaluate the feasibility and sensitivity of repeated performance testing during spaceflight. Four National Aeronautics and Space Administration crewmembers were trained to complete computerized questionnaires and performance tasks at repeated regular intervals before and after a 10-day shuttle mission and at times that interfered minimally with other mission activities during spaceflight. Two types of performance, Digit-Symbol Substitution trial completion rates and response times during the most complex Number Recognition trials, were altered slightly during spaceflight. All other dimensions of the performance tasks remained essentially unchanged over the course of the study. Verbal ratings of Fatigue increased slightly during spaceflight and decreased during the postflight test sessions. Arousal ratings increased during spaceflight and decreased postflight. No other consistent changes in rating-scale measures were observed over the course of the study. Crewmembers completed all mission requirements in an efficient manner with no indication of clinically significant behavioral impairment during the 10-day spaceflight. These results support the feasibility and utility of computerized task performances and questionnaire rating scales for repeated measurement of behavior during spaceflight.

Adult↗

PubMed2004

Wake-promoting agents with different mechanisms of action: comparison of effects of modafinil and amphetamine on food intake and cardiovascular activity.

Despite efforts to achieve a desirable weight, two-thirds of the population has an elevated body weight. Medications are useful in supporting weight loss, but produce adverse effects. This study compared the effects of amphetamine and modafinil on food intake and cardiovascular activity in healthy men and women. Participants (n = 11) completed 11 sessions. In random order, participants received placebo on five separate sessions and single oral doses of modafinil (1.75, 3.5, or 7.0 mg/kg) and amphetamine (0.035, 0.07, 0.14 mg/kg). Free time between hourly performance testing intervals gave participants the opportunity to eat. Like amphetamine, modafinil reduced the amount of food consumed and decreased energy intake, without altering the proportion of macronutrients consumed. Although both medications significantly increase heart rate and blood pressure at higher doses, the dose of modafinil that was efficacious in decreasing food intake did not significantly increase heart rate. Modafinil may be well suited for the treatment of obesity, although further studies with repeated dosing in overweight populations are warranted. Modafinil may have less adverse health consequences than some anorectic agents and greater treatment efficacy.

Adult↗

PubMed2004

Sensation seeking and symptoms of disruptive disorder: association with nicotine, alcohol, and marijuana use in early and mid-adolescence.

This study examined the association of Sensation Seeking and symptoms of Disruptive Disorders and investigated the associations of each with the risk of nicotine, alcohol, and marijuana use in 11- to 14-yr.-old boys and girls from psychiatric and pediatric clinics (n = 206). Sensation Seeking and symptoms of Disruptive Disorder were significantly related, and both were associated with drug use. In particular, Sensation Seeking was strongly associated with drug use in early and mid-adolescents seen in a clinical setting. Measurement of Sensation Seeking and symptoms of Disruptive Disorder should help identify and characterize youth who are at increased risk for drug use during early and mid-adolescence-a time when onset of use may be a harbinger of long-term habit.

Alcoholism↗

PubMed2003

Discriminative-stimulus effects of triazolam in light and moderate drinkers.

BACKGROUND: The results of previous laboratory experiments with humans suggest that light and moderate drinkers respond differentially to the effects of benzodiazepines. The aim of this study was to further assess the behavioral effects of a benzodiazepine in light and moderate drinkers. METHODS: To accomplish this aim, 12 volunteers (6 light drinkers and 6 moderate drinkers) learned to discriminate 0.375 mg of triazolam, a triazolobenzodiazepine hypnotic. After they learned this discrimination, a test-of-novel-doses phase was conducted in which a range of doses of triazolam (0, 0.06, 0.125, 0.25, and 0.375 mg) was tested in both groups of volunteers. The subject-rated and performance-impairing effects of triazolam were assessed concurrently. RESULTS: There was not a significant difference between the groups in terms of the number of trials needed to learn the discrimination, nor did the proportion of light and moderate drinkers who learned to accurately discriminate 0.375 mg of triazolam differ significantly. The discriminative-stimulus, subject-rated, and performance-impairing effects of triazolam were an orderly function of dose but did not differ across the light and moderate drinkers. CONCLUSIONS: Future studies should examine the discriminative-stimulus effects of a lower dose of triazolam (e.g., 0.25 mg) in light and moderate drinks or use a fading procedure to determine differences in terms of the lowest discriminable dose.

Adult↗

PubMed2003

Clinical neuropharmacology of drugs of abuse: a comparison of drug-discrimination and subject-report measures.

Advances in molecular pharmacology and behavioral science have helped elucidate the structure and function of the central nervous system and its relationship to behavior and has sparked the development of pharmacological agents that have increasingly selective and potent effects with fewer adverse side effects. The sensitivity and predictive validity of the two most commonly used methodologies for assessing the neuropharmacological effects of centrally active drugs, subject report of drug effects and drug discrimination, were examined. The sensitivity of the measures was comparable across stimulant, sedative, and opioid drugs. Results with drug-discrimination methodologies were generally consistent with hypothesized neuropharmacological mechanisms across all drug classes, whereas subject reports conformed under more limited testing conditions. Firm conclusions regarding the relative utility of drug-discrimination and subject-report measures for clinical studies of neuropharmacological mechanisms are limited by the small number of studies in which the two methodologies have been tested using identical pharmacological pretreatment manipulations.

Cues↗

PubMed2002

Discriminative-stimulus effects of modafinil in cocaine-trained humans.

Modafinil is a novel stimulant that is effective in the treatment of narcolepsy and excessive daytime sleepiness. In vitro and in vivo neuropharmacological data suggest that the mechanism of action of modafinil is distinct from that of prototypical abused stimulants like cocaine and d-amphetamine. In the present experiment, six human volunteers with recent histories of cocaine use learned to discriminate 150 mg oral cocaine HCL. After acquiring the discrimination (i.e. > or = 80% correct responding on 4 consecutive days), a range of doses of oral cocaine (50, 100, and 150 mg), modafinil (200, 400, and 600 mg), and placebo were tested to determine if they shared discriminative-stimulus and self-reported effects with 150 mg cocaine. Methylphenidate (60 mg) and triazolam (0.5 mg) were included as positive and negative controls, respectively. Cocaine and methylphenidate, but neither modafinil nor triazolam, produced cocaine-like discriminative-stimulus, subject-rated, and cardiovascular effects. The results of the present experiment suggest that cocaine discrimination in humans is pharmacologically specific within and across drug classes.

Adult↗

PubMed2002

Conditioning history and the reinforcing effects of drugs: comment on Alessi, Roll, Reilly, and Johanson (2002).

Drug reinforcement plays a central role in drug abuse. Drugs of abuse are unconditioned reinforcers whose functional effects are mediated through neuropharmacological mechanisms. The role of conditioning has received attention, but the focus has been on associations between environmental cues and unconditioned drug stimuli. Recent studies by C.-E. Johanson, A. Mattox, and C. R. Schuster (1995) and S. M. Alessi, J. M. Roll, M. P. Reilly, and C.-E. Johanson (2002) have demonstrated that drugs can also acquire functional control over human behavior through conditioning processes. Given the potent effects that conditioned reinforcers (e.g., money) can have on human behavior, studies by Johanson et al. and Alessi et al. should engender further examination of conditioning processes and drug reinforcement.

Anti-Anxiety Agents↗

PubMed2002

Sensation seeking, puberty, and nicotine, alcohol, and marijuana use in adolescence.

OBJECTIVE: To examine the relationship among nicotine, alcohol, and marijuana use; level of sensation seeking (SS); and pubertal development. METHOD: Subjects were early and middle adolescent males and females recruited from a psychiatric clinic (n = 77) and two general pediatric clinics (n = 131). SS was measured by using the Sensation Seeking Scale for Children. Pubertal development was measured with a modified Pubertal Development Scale that was completed by the adolescent and his/her parent about the adolescent. Adolescent self-reports of nicotine, alcohol, and marijuana use were also obtained using questionnaires. RESULTS: SS was higher in males and females who reported nicotine and alcohol use and in males who reported marijuana use. SS was positively associated with pubertal development in males and females, even when controlling for age. Furthermore, SS mediated the relationship of pubertal development and drug use in males and females. CONCLUSIONS: The observation that SS mediates the relationship between pubertal development and drug use in males and females may contribute to understanding changes in drug use that are seen during adolescence. In addition, SS is associated with drug use and is easily measured in a variety of clinical settings.

Adolescent↗