Erika Pike

Drug-related stimuli impair inhibitory control in cocaine abusers

BACKGROUND Cocaine users show impaired inhibitory control on cued go/no-go tasks and attention bias to drug-related stimuli in the emotional Stroop task. The results of a previous study suggested that there is a relationship between inhibitory control and attention bias in alcohol drinkers such that the presentation of alcohol-related images as a go cue in a cued go/no-go task significantly impaired inhibitory control compared to neutral images as a go cue. The present study determined the generality of these previous findings by assessing inhibitory control in cocaine users utilizing a modified cued go/no-go task with cocaine or neutral images as the cues. METHODS Non-treatment seeking cocaine users (N=30) completed the modified task after completing detailed measures of demographics and drug use. Participants were matched on basic demographic factors and were assigned to groups in which they saw either a cocaine or neutral image as the go cue. RESULTS Participants assigned to the cocaine image go cue condition had a significantly higher proportion of inhibitory failures to the no-go target than their counterparts assigned to the neutral cue condition, but there were no group differences on reaction time (i.e., accuracy was not traded for speed). CONCLUSIONS Cocaine users were less able to inhibit pre-potent responses when a cocaine-related image served as the go cue than when a neutral image served as the go cue, consistent with previous research in alcohol users. The outcomes suggest that cocaine-related cues produce disinhibition, perhaps contributing to the high incidence of relapse or continued cocaine use.

Fixation time is a sensitive measure of cocaine cue attentional bias

BACKGROUND AND AIMS Attentional bias has been demonstrated to a variety of substances. Evidence suggests that fixation time is a more direct measure of attentional bias than response time. The aims of this experiment were to demonstrate that fixation time during the visual probe task is a sensitive and stable measure of cocaine cue attentional bias in cocaine-using adults compared to controls. DESIGN A between-subject, repeated-measures experiment. SETTING An out-patient research unit. PARTICIPANTS Fifteen cocaine using and 15 non-cocaine-using adults recruited from the community. MEASUREMENTS Participants completed a visual probe task with eye tracking and a modified Stroop during two experimental sessions. FINDINGS A significant interaction between cue type and group (F = 13.5; P < 0.05) indicated that cocaine users, but not controls, displayed an attentional bias to cocaine-related images as measured by fixation time. There were no changes in the magnitude of attentional bias across sessions (F = 3.4; P > 0.05) and attentional bias correlated with self-reported life-time cocaine use (r = 0.64, P < 0.05). Response time on the visual probe (F = 1.1; P > 0.05) as well as on the modified Stroop (F = 0.1; P > 0.05) failed to detect an attentional bias. CONCLUSIONS Fixation time on cocaine-related stimuli (propensity to remain focused on the stimulus) is a sensitive and stable measure of cocaine cue attentional bias in cocaine-using adults.

Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine.

Naltrexone and bupropion, when administered alone in clinical trials, modestly reduce amphetamine use. Whether combining these drugs would result in greater reductions in methamphetamine taking relative to either drug alone is undetermined. This study examined the influence of naltrexone, bupropion and a naltrexone-bupropion combination on methamphetamine self-administration in humans. Seven subjects reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind study in which the reinforcing, subject-rated and physiological effects of intranasal methamphetamine (0, 10 and 30 mg) were assessed during maintenance on placebo, naltrexone (50 mg), bupropion (300 mg/day), and naltrexone combined with bupropion. Methamphetamine maintained responding and produced prototypic subjective and physiological effects (e.g., increased ratings of good effects, elevated systolic blood pressure). Maintenance doses were well tolerated and generally devoid of effects. No maintenance condition reduced methamphetamine self-administration or systematically altered the subject-rated effects of methamphetamine. These outcomes demonstrate the robust behavioral effects of methamphetamine that could make it resistant to pharmacological manipulation. Although these outcomes indicate that this combination may be ineffective for managing methamphetamine use disorder, future work should evaluate longer maintenance dosing, individuals with different levels of amphetamine use, adding this combination to a behavioral platform and other pharmacotherapy combinations for reducing methamphetamine use.

Test-retest reliability of eye tracking during the visual probe task in cocaine-using adults.

BACKGROUND Stimuli associated with cocaine use capture attention. Evidence suggests that fixation time measured on the visual probe task is a valid measure of cocaine cue attentional bias. The aim of this experiment was to demonstrate the test-retest reliability of cocaine cue attentional bias as measured by fixation time during the visual probe task. METHODS In a within-subject, repeated-measures design, thirty-six non-treatment seeking cocaine-using adults completed a visual probe task with eye tracking. RESULTS Participants displayed an attentional bias to cocaine-related images as measured by fixation time across two occasions (F (1, 35) = 56.5, p < 0.0001). A Pearson correlation indicated significant test-retest reliability for this effect (r = 0.51, p = 0.001). Response time failed to detect an attentional bias and test-retest reliability was low (r = 0.24, p = 0.16). CONCLUSION Fixation time during the visual probe task is a reliable measure of cocaine cue attentional bias in cocaine-using adults across time.

The Magnitude of Drug Attentional Bias Is Specific to Substance Use Disorder

The visual probe task with eye tracking is a sensitive measure of cocaine and alcohol cue attentional bias. Despite the high comorbidity between cocaine and alcohol dependence, attentional bias studies have examined the influence of cocaine- and alcohol-related cues separately. The aim of this experiment was to directly compare the magnitude of cocaine and alcohol cue attentional bias in individuals dependent on cocaine or cocaine and alcohol. Individuals who met criteria for cocaine dependence (n = 20) or both cocaine and alcohol dependence (n = 20) completed a visual probe task with eye tracking. Cocaine-dependent participants displayed an attentional bias toward cocaine, but not alcohol. In contrast, cocaine-alcohol dependent participants displayed an attentional bias to both cocaine and alcohol, and the magnitude of these biases did not differ. The magnitude of cocaine cue attentional bias, however, was significantly smaller in the cocaine-alcohol dependent group compared to the cocaine-dependent group. These results suggest that fixation time during the visual probe task is sensitive to clinically relevant differences in substance use disorders. The incentive value of cocaine-related cues, however, may differ for individuals who are also dependent on alcohol.

Methamphetamine self-administration in humans during D-amphetamine maintenance.

Abstract Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of d-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted that d-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested 2 d-amphetamine maintenance conditions in counterbalanced order (0 and 40 mg/d). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled 1 of 4 doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive-ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 12 items of the drug-effects questionnaires, 8 of which were attenuated by d-amphetamine maintenance (eg, increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by d-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during d-amphetamine maintenance and no adverse events occurred. Although d-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that d-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders.

Cocaine-related stimuli impair inhibitory control in cocaine users following short stimulus onset asynchronies

BACKGROUND AND AIMS Cocaine users display a significant increase in inhibitory failures following cocaine-related images compared with neutral images in a modified cued Go/No-Go task, the Attentional Bias-Behavioral Activation (ABBA) task. The aim of this study was to demonstrate that stimulus onset asynchrony (SOA) impacts inhibitory failures on the ABBA task. DESIGN A between-subjects experiment. SETTING An out-patient research unit in the United States. PARTICIPANTS Ninety-one cocaine users recruited from the community. MEASUREMENTS Participants were assigned to groups in which they saw either cocaine (n=46) or neutral (n=45) images as the go condition. Cues were presented for one of five SOAs (i.e. 100, 200, 300, 400 or 500 ms) before a go or no-go target was displayed. FINDINGS Participants in the cocaine go condition had a significantly higher proportion of inhibitory failures to no-go targets (F4,356=2.50, P=0.04) with significantly more inhibitory failures following all SOAs (P<0.05) than those in the neutral go condition. Within the cocaine go condition, significantly more inhibitory failures were observed following the 100 and 200 ms SOAs than after the 300, 400 or 500 ms SOAs (P<0.05). CONCLUSIONS Cocaine-related stimuli appear to decrease inhibitory control in cocaine users at short (100 and 200 ms) stimulus onset asynchronies (SOAs: the amount of time between the start of one stimulus and the start of another stimulus), but not at longer (300, 400 and 500 ms) SOAs.

Alcohol Administration Increases Cocaine Craving But Not Cocaine Cue Attentional Bias.

BACKGROUND Alcohol consumption is a known antecedent to cocaine relapse. Through associative conditioning, it is hypothesized that alcohol increases incentive motivation for cocaine and thus the salience of cocaine-related cues, which are important in maintaining drug-taking behavior. Cocaine-using individuals display a robust cocaine cue attentional bias as measured by fixation time during the visual probe task. The purpose of this study was to evaluate the influence of alcohol administration on cocaine cue attentional bias using eye-tracking technology to directly measure attentional allocation. METHODS Twenty current cocaine users completed a double-blind, placebo-controlled, within-subjects study that tested the effect of 3 doses of alcohol (0.00, 0.325, and 0.65 g/kg) on cocaine cue attentional bias using the visual probe task with eye-tracking technology. The participant-rated and physiological effects of alcohol were also assessed. RESULTS Participants displayed a robust cocaine cue attentional bias following both placebo and alcohol administration as measured by fixation time, but not response time. Alcohol administration did not influence cocaine cue attentional bias, but increased craving for cocaine in a dose-dependent manner. Alcohol produced prototypic psychomotor and participant-rated effects. CONCLUSIONS Alcohol administration increases cocaine craving but not cocaine cue attentional bias. Alcohol-induced cocaine craving suggests that alcohol increases incentive motivation for cocaine but not the salience of cocaine-related cues.

Acute buspirone dosing enhances abuse-related subjective effects of oral methamphetamine.

There is not an approved pharmacotherapy for treating methamphetamine use disorder. This study sought to determine the effects of acute buspirone treatment on the subjective and cardiovascular effects of oral methamphetamine in order to provide an initial assessment of the utility, safety, and tolerability of buspirone for managing methamphetamine use disorder. We predicted that acute buspirone administration would reduce the subjective effects of methamphetamine. We also predicted that the combination of buspirone and methamphetamine would be safe and well tolerated. Ten subjects completed the protocol, which tested three methamphetamine doses (0, 15, and 30mg) in combination with two buspirone doses (0 and 30mg) across 6 experimental sessions. Subjective effects and physiological measures were collected at regular intervals prior to and after dose administration. Methamphetamine produced prototypical subjective and cardiovascular effects. Acute buspirone administration increased some of the abuse-related subjective effects of methamphetamine and also attenuated some cardiovascular effects. The combination of oral methamphetamine and buspirone was safe and well tolerated. Acute buspirone administration may increase the abuse liability of oral methamphetamine. Chronic buspirone dosing studies remain to be conducted, but given preclinical findings and the outcomes of this work, the utility of buspirone for treating methamphetamine use disorder appears limited.

A pilot investigation of acute inhibitory control training in cocaine users

BACKGROUND Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals. METHODS Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using the stop-signal task and visual-probe task with eye tracking, respectively. RESULTS Training condition groups did not differ on demographics, inhibitory control training performance, response inhibition, or cocaine-cue attentional bias. Response inhibition performance improved as a function of inhibitory control training in both conditions. Cocaine-cue attentional bias was observed, but did not change as a function of inhibitory control training in either condition. CONCLUSIONS Response inhibition in cocaine-using individuals was augmented by acute inhibitory control training, which may improve treatment outcomes through better behavioral inhibition. Future studies should investigate longer-term implementation of inhibitory control training, as well as combining inhibitory control training with other treatment modalities.