Biomedical subjects

Craig R Rush

Publications and source records attributed to Craig R Rush.

At least 19 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 low dose of aripiprazole attenuates the subject-rated effects of d-amphetamine.

Despite increased reports of amphetamine abuse and dependence, a putative pharmacotherapy has yet to be identified. In a previous study from our laboratory, 20 mg aripiprazole, an atypical antipsychotic that has partial agonist activity at D(2) receptors, attenuated many of the behavioral effects of d-amphetamine. Aripiprazole (20 mg) also impaired performance on a computerized version of the DSST when administered alone, indicating that the attenuation observed may have been functional as opposed to receptor mediated. The present experiment was conducted to determine whether a lower dose of aripiprazole (10 mg) could acutely attenuate the discriminative-stimulus, subject-rated, and physiological effects of d-amphetamine (2.5-15 mg) without impairing performance as measured with a computerized version of the DSST. The results of the present experiment indicate that 10 mg aripiprazole attenuated some abuse-related behavioral effects of d-amphetamine and was generally devoid of effects, including significant performance impairment, when administered alone. These findings suggest that 10 mg aripiprazole would be a reasonable starting dose for the treatment of stimulant abuse and dependence. Future research should examine the effects of chronic aripiprazole administration in combination with methamphetamine or cocaine.

Adult↗

PubMed2006

Discriminative-stimulus, self-reported, performance, and cardiovascular effects of atomoxetine in methylphenidate-trained humans.

Atomoxetine is marketed as a nonstimulant medication indicated for the treatment of attention-deficit/hyperactivity disorder in adults. Previous laboratory research suggests that atomoxetine has limited abuse potential but that some of its behavioral effects might overlap with traditional psychomotor stimulants like methylphenidate and d-amphetamine. A drug with this profile might be useful for the treatment of stimulant dependence. The aim of this experiment was to compare the discriminative-stimulus and self-reported effects of atomoxetine with methylphenidate, damphetamine, and triazolam in humans who had acquired a methylphenidate (30 mg) discrimination. Six healthy subjects with a recent history of nontherapeutic stimulant use were enrolled in this outpatient study. After subjects acquired the methylphenidate discrimination, a range of doses of methylphenidate (5-30 mg), atomoxetine (15-90 mg), d-amphetamine (2.5-15 mg), triazolam (0.06-0.375 mg), and placebo were tested. To more fully characterize the behavioral effects of atomoxetine, a battery of self-reported drug-effect questionnaires, a performance task, and cardiovascular assessments were also included. Methylphenidate and d-amphetamine increased drug-appropriate responding and produced typical stimulant-like effects (e.g., increased ratings of "Active, Alert, Energetic"). Atomoxetine partially substituted for methylphenidate (i.e., 33%-50%) and produced some dose-dependent, stimulant-like, subject-rated drug effects, although the magnitude of these effects was less than d-amphetamine and methylphenidate and generally did not attain statistical significance. These data suggest that the behavioral effects of atomoxetine overlap to a small degree with psychomotor stimulants and that it has low abuse potential.

Adolescent↗

PubMed2006

Discriminative-stimulus effects of triazolam in women and men.

Benzodiazepines are among the most commonly prescribed therapeutics. Women seem to be more likely than men to be prescribed a benzodiazepine and to use benzodiazepines for nonmedical reasons; they also appear to be at higher risk for benzodiazepine dependence. The aim of the present investigation was to assess the acute behavioral effects of a benzodiazepine in women and men. To accomplish this, 13 volunteers (6 women, 7 men) first learned to discriminate 0.375-mg triazolam, a triazolobenzodiazepine hypnotic. After acquiring the discrimination, (i.e., >80% correct responding on 4 consecutive sessions) a range of doses of triazolam (0, 0.0625, 0.125, 0.25, and 0.375 mg) were tested in each participant. Triazolam dose dependently increased drug-appropriate responding and subject ratings of sedation and impaired performance (i.e., significant effect of dose). The women and men did not differ significantly on any measure. The results of the present experiment suggest that women and men are not differentially sensitive to the behavioral effects of triazolam.

Anti-Anxiety Agents↗

PubMed2006

Acute effects of cocaine in two models of inhibitory control: implications of non-linear dose effects.

AIMS: This study examined dose-response effects of oral cocaine on the inhibitory control of behavior in adult cocaine users using two different behavioral models of inhibitory control. DESIGN: Adults (n = 12) with a history of cocaine use performed the stop-signal and cue-dependent go-no-go task to measure inhibitory control of behavior in response to a range of oral cocaine HCl doses (0, 100, 200 and 300 mg). FINDINGS: Although both tasks showed cocaine-induced facilitation of inhibitory control, dose-response functions differed depending on the measures. The stop-signal measure revealed a quadratic dose-response function and the cued go-no-go measure showed a more orderly, linear improvement as a function of dose. CONCLUSIONS: The evidence suggests a two-phasic dose-response in which facilitating effects of stimulant drugs on inhibitory control might be limited to a range of intermediate doses, above which improvement is no longer evident and impairing effects could possibly emerge.

Adult↗

PubMed2005

Methylphenidate increases cigarette smoking.

RATIONALE: Methylphenidate (Ritalin) and d-amphetamine (Dexedrine), stimulants commonly prescribed for behavioral problems associated with attention deficit hyperactivity disorder (ADHD), produce a similar constellation of behavioral effects. The results of previous studies suggest that d-amphetamine increases rates of smoking and the reinforcing effects of smoking. The effects of methylphenidate on smoking have not been assessed although it is the most commonly prescribed pharmacotherapy for ADHD and individuals with ADHD are at increased risk for smoking. OBJECTIVE: In this experiment the acute effects of a range of doses of methylphenidate (5, 10, 20, and 40 mg) and placebo were assessed in ten cigarette smokers who were not attempting to quit and were without ADHD or other Axis I psychiatric disorders. METHODS: Each dose of methylphenidate was tested once, whereas placebo was tested twice. One hour after ingesting drug, participants were allowed to smoke ad libitum for 4 h. Measures of smoking included total cigarettes smoked, total puffs, latency to the first cigarette, and carbon monoxide levels. Snacks and decaffeinated drinks were available ad libitum, and caloric intake during the 4-h smoking session was calculated. RESULTS: Methylphenidate dose dependently increased the total number of cigarettes smoked, number of puffs, and carbon monoxide levels. As expected, methylphenidate dose dependently decreased the number of food items consumed and caloric intake. CONCLUSIONS: The results of this experiment suggest that methylphenidate, like d-amphetamine, increases rates of cigarette smoking.

Adolescent↗

PubMed2005

Reinforcing effects of modafinil: influence of dose and behavioral demands following drug administration.

RATIONALE: The reinforcing effects of stimulant drugs are modulated by behavioral demands following drug administration. OBJECTIVE: The objective of this study was to assess the reinforcing effects of modafinil, a drug with purportedly low abuse potential, under different behavioral demands using a modified progressive-ratio procedure. METHODS: The reinforcing effects of oral modafinil (0, 100, 200, and 400 mg) were assessed in six healthy adult volunteers under both performance and relaxation conditions. Performance sessions required volunteers to complete simple arithmetic problems for three 50-min blocks. Relaxation sessions required volunteers to sit quietly in a semi-reclined position in a darkened room for three 50-min blocks. Two sampling sessions (one performance and one relaxation session) always preceded two self-administration sessions (one performance and one relaxation session), and the order of performance and relaxation sessions was constant within a dose condition. RESULTS: Modafinil significantly increased break point and number of capsules earned on the modified progressive-ratio procedure as an increasing function of dose under the performance, but not the relaxation, condition. Modafinil produced comparable stimulant-like subjective ratings under both the performance and relaxation conditions. CONCLUSION: The findings of the present experiment demonstrate that modafinil can function as a reinforcer and that the reinforcing effects of modafinil are influenced by behavioral demands following drug administration, similar to those of other stimulant drugs.

Adult↗

PubMed2005

Oxazepam does not modulate the behavioral effects of d-amphetamine in humans.

Benzodiazepines, which are gamma-aminobutyric acid-A (GABA(A)) receptor positive modulators, can block the behavioral effects of psychomotor stimulants. In the present study, the ability of oxazepam, which may have less abuse potential compared to some other benzodiazepines, to attenuate the discriminative-stimulus, subject-rated and psychomotor performance effects of d-amphetamine in humans was determined. Six healthy participants (2 female, 4 male) learned to discriminate 15 mg oral d-amphetamine. After acquiring the discrimination (i.e., > or = 80% correct responding on 4 consecutive days), the effects of d-amphetamine (0, 2.5, 5, 10 and 15 mg), alone and in combination with acutely administered oxazepam (0 and 20 mg) were assessed. d-Amphetamine alone functioned as a discriminative stimulus, produced stimulant-like subject-rated effects (e.g., increased ratings of Stimulated on a Drug-Effect Questionnaire) and enhanced psychomotor performance. Oxazepam alone increased subject ratings of sedation (e.g., increased ratings of Sluggish, Fatigued and Lazy on a Drug-Effect Questionnaire) and impaired psychomotor performance. Oxazepam alone did not occasion d-amphetamine-like discriminative-stimulus effects, and had no effect on the discriminative-stimulus or subject-rated effects of d-amphetamine when given in combination. The results of this experiment are discordant with previous research and suggest that benzodiazepines differ in their ability to modulate the behavioral effects of d-amphetamine.

Adult↗

PubMed2005

Polydrug abusers display impaired discrimination-reversal learning in a model of behavioural control.

Long-term cocaine and alcohol use is associated with neuropsychological impairments that implicate poor inhibitory mechanisms of behavioural control. This study tested acquisition and discrimination-reversal learning in a group of polydrug users (n 20) with a history of cocaine and heavy alcohol use and a group of age-matched controls (n 20). A cued go/nogo task measured subjects' ability to learn stimulus-response associations that involved the quick activation and sudden inhibition of responses. Compared with controls, drug users displayed similar acquisition, but impaired discrimination-reversal learning of both inhibitory and activational responses. The results suggest that some drug-related neuropsychological deficits might reflect specific impairments of the ability to inhibit interference from prior learning. The findings contribute to growing evidence that suggests cocaine and alcohol use could produce broad inhibitory impairments that increase the risk for learning deficits and poor impulse control.

Adolescent↗

PubMed2005

Discriminative stimulus and self-reported effects of methylphenidate, d-amphetamine, and triazolam in methylphenidate-trained humans.

Asymmetrical generalization between drugs on drug-discrimination procedures has been demonstrated for sedative and stimulant drugs in animals and to some extent with sedative drugs in humans. The aim of this experiment was to examine the discriminative-stimulus effects of d-amphetamine in methylphenidate-trained humans. A previous study demonstrated that methylphenidate substitutes for d-amphetamine in d-amphetamine-trained humans. Six healthy human participants first learned to discriminate 30 mg oral methylphenidate. Doses of oral methylphenidate, d-amphetamine, triazolam, and placebo were then tested to determine whether they share discriminative-stimulus and self-reported effects with 30 mg methylphenidate. Methylphenidate and d-amphetamine dose-dependently increased methylphenidate-appropriate responding and produced prototypical stimulant-like effects. Triazolam produced low levels of methylphenidate-appropriate responding and prototypical sedative-like effects. The results of this experiment are concordant with previous studies and suggest that the behavioral effects of oral methylphenidate and d-amphetamine overlap extensively and that the discriminative-stimulus effects of methylphenidate and d-amphetamine are symmetrical.

Adult↗

PubMed2005

d-Amphetamine-induced enhancement of inhibitory mechanisms involved in visual search.

The authors examined the effects of d-amphetamine on the ability to perform a cued target-detection task that measured inhibition of return (IOR). IOR is a reflexive inhibitory mechanism that delays attention from returning to a previously attended location and has been shown to increase the efficiency of a visual search. Adults (N=14) with a history of cocaine use performed the task under 4 doses of d-amphetamine (0, 10, 20, and 30 mg). The results showed active d-amphetamine doses increased the duration of IOR. By increasing the delay in returning attention to a previously attended location, d-amphetamine might reduce time spent searching previously attended locations, increasing the efficiency of visual searches.

Adult↗

PubMed2005

Cocaine improves inhibitory control in a human model of response conflict.

The present study was designed to test the acute effects of cocaine on behavioral control in the presence and absence of motivational conflict. Adults (N = 14) with a history of stimulant use received oral cocaine hydrogen chloride (0, 100, 200, and 300 mg) and performed a cue-dependent go/no-go task to measure inhibitory and activational mechanisms of behavioral control either with or without motivated conflict between the inhibition and the activation of responses. Cocaine improved response inhibition in both conflict conditions, as evident by a decrease in inhibitory failures following active doses. The current study provides a useful model to investigate the effects of other drugs reported to have performance-enhancing effects.

Administration, Oral↗

PubMed2005

Aripiprazole attenuates the discriminative-stimulus and subject-rated effects of D-amphetamine in humans.

The results of animal research suggest that the use of partial agonists at dopamine (DA) D2 receptors may be an effective strategy for the treatment of stimulant dependence. Aripiprazole is an atypical antipsychotic that has partial agonist activity at D2 receptors. In this experiment, seven human participants with a history of nontherapeutic stimulant use learned to discriminate 15 mg oral D-amphetamine. After acquiring the discrimination (ie > or =80% correct responding on four consecutive sessions), the effects of a range of doses of D-amphetamine (0, 2.5, 5, 10, and 15 mg), alone and in combination with aripiprazole (0 and 20 mg), were assessed. D-Amphetamine alone functioned as a discriminative stimulus, produced prototypical subject-rated drug effects (eg increased ratings of Active, Alert, Energetic) and elevated cardiovascular indices. These effects were generally a function of dose. Aripiprazole alone did not occasion D-amphetamine-appropriate responding or produce subject-rated effects, but modestly impaired performance. Administration of aripiprazole significantly attenuated the discriminative-stimulus and cardiovascular effects of D-amphetamine, as well as some of the subject-rated drug effects. These data are consistent with previous preclinical findings and suggest that DA partial agonists deserve further evaluation as potential pharmacotherapies in the management of stimulant dependence. Future studies should investigate the ability of aripiprazole or related compounds to attenuate the behavioral effects of stimulants associated with a greater degree of dependence, such as methamphetamine or cocaine, in dependent individuals.

Adult↗

PubMed2004

Acute administration of the GABA reuptake inhibitor tiagabine does not alter the effects of oral cocaine in humans.

Drugs affecting central gamma-aminobutyric acid (GABA) systems may have promise as treatments for cocaine addiction. In the present study, tiagabine (Gabatril), a GABA reuptake inhibitor, was investigated for its ability to modify the discriminative-stimulus, reinforcing, subject-rated, performance and cardiovascular effects of oral cocaine in non-treatment seeking cocaine users. Initially, acute doses of 4 mg tiagabine were tested alone and in combination with oral cocaine in four participants to establish the safety of cocaine-tiagabine combinations. A higher dose of tiagabine (8 mg) was then tested in a larger group (n = 6). Participants learned to discriminate 150 mg of oral cocaine. The effects of cocaine (0-150 mg, p.o.) administered alone and in combination with tiagabine were then determined. Subject-rated, performance and cardiovascular measures were obtained at regular intervals. The reinforcing effects of cocaine, tiagabine and cocaine-tiagabine combinations were assessed using the Multiple-Choice Procedure. Cocaine alone produced prototypical behavioral and physiological effects (i.e., functioned as a discriminative and reinforcing stimulus, produced stimulant-like subject-rated effects, improved performance and increased heart rate). In general, acute administration of tiagabine did not alter the effects of oral cocaine. These findings suggest that tiagabine would not be effective at preventing continued cocaine use by blocking its acute, abuse-related effects.

Administration, Oral↗

PubMed2004

Reinforcing effects of methylphenidate: influence of dose and behavioral demands following drug administration.

RATIONALE: The reinforcing effects of stimulant drugs such as D-amphetamine, caffeine, and cocaine are modulated by behavioral demands following drug administration. OBJECTIVE: The objective of this study was to assess the reinforcing effects of methylphenidate under different behavioral demands using a modified progressive-ratio procedure. METHODS: The reinforcing effects of oral methylphenidate (0, 10, 20, and 40 mg) were assessed in seven healthy adult volunteers under both performance and relaxation conditions. Performance sessions required volunteers to complete simple arithmetic problems for three 50-min blocks. Relaxation sessions required volunteers to sit quietly in a semi-reclined position in a darkened room for three 50-min blocks. Two sampling sessions (one performance and one relaxation session) always preceded two self-administration sessions (one performance and one relaxation session) and the order of relaxation and performance sessions was constant within a dose condition. RESULTS: Methylphenidate significantly increased break point and number of capsules earned on the modified progressive-ratio procedure as an increasing function of dose under the performance, but not the relaxation, condition. Methylphenidate produced comparable stimulant-like subject ratings under both the performance and relaxation conditions. CONCLUSION: The findings of the present experiment suggest that the reinforcing effects of methylphenidate, like D-amphetamine and cocaine, are influenced by behavioral demands following drug administration.

Administration, Oral↗

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

Alprazolam attenuates the behavioral effects of d-amphetamine in humans.

The results of preclinical behavioral pharmacology studies suggest that gamma-aminobutyric acidA (GABAA) receptor modulators attenuate the behavioral effects of commonly abused stimulants such as amphetamines and cocaine under a variety of behavioral arrangements including drug discrimination and self-administration. In the present experiment, 6 healthy humans learned to discriminate 15-mg oral D-amphetamine. After acquiring the discrimination (ie, . > or = 80% correct responding on 4 consecutive days), the effects of a range of doses of D-amphetamine (0, 2.5, 5, 10, and 15 mg), alone and following pretreatment with alprazolam (0 and 0.5 mg), a GABAA receptor modulator, were assessed. D-Amphetamine alone functioned as a discriminative stimulus and produced stimulant-like self-reported drug effects (eg, increased scores on a Stimulant-Sensitive Adjective-Rating Scale). These effects were generally a function of dose. Alprazolam alone did not occasion D-amphetamine-like discriminative stimulus effects, nor did it increase ratings of sedation or impair performance. Alprazolam pretreatment significantly attenuated the discriminative stimulus effects of D-amphetamine, and some of the self-reported drug effects. Future human laboratory experiments should compare the behavioral effects of D-amphetamine alone and following pretreatment with alprazolam using other behavioral arrangements such as drug self-administration. Future laboratory experiments with humans should also determine if benzodiazepines with lower abuse potential (eg, oxazepam) might also attenuate the behavioral effects of D-amphetamine.

Adolescent↗