Cortical activation deficits during facial emotion processing in youth at high risk for the development of substance use disorders

Background

Recent longitudinal studies demonstrate that addiction risk may be influenced by a cognitive, affective and behavioral phenotype that emerges during childhood. Relatively little research has focused on the affective or emotional risk components of this high-risk phenotype, including the relevant neurobiology.

Methods

Non-substance abusing youth (N = 19; mean age = 12.2) with externalizing psychopathology and paternal history of a substance use disorder and demographically matched healthy comparisons (N = 18; mean age = 11.9) were tested on a facial emotion matching task during functional MRI. This task involved matching faces by emotions (angry, anxious) or matching shape orientation.

Results

High-risk youth exhibited increased medial prefrontal, precuneus and occipital cortex activation compared to the healthy comparison group during the face matching condition, relative to the control shape condition. The occipital activation correlated positively with parent-rated emotion regulation impairments in the high-risk group.

Conclusions

These findings suggest a preexisting abnormality in cortical activation in response to facial emotion matching in youth at high risk for the development of problem drug or alcohol use. These cortical deficits may underlie impaired affective processing and regulation, which in turn may contribute to escalating drug use in adolescence.     

Beliefs and attitudes regarding drug treatment: Application of the Theory of Planned Behavior in African-American cocaine users

Background

The Theory of Planned Behavior (TPB) can provide insights into perceived need for cocaine treatment among African American cocaine users.

Methods

A cross-sectional community sample of 400 (50% rural) not-in-treatment African-American cocaine users was identified through respondent-driven sampling in one urban and two rural counties in Arkansas. Measures included self-reports of attitudes and beliefs about cocaine treatment, perceived need and perceived effectiveness of treatment, and positive and negative cocaine expectancies. Normative beliefs were measured by perceived stigma and consequences of stigma regarding drug use and drug treatment. Perceived control was measured by readiness for treatment, prior drug treatment, and perceived ability to cut down on cocaine use without treatment.

Findings

Multiple regression analysis found that older age (standardized regression coefficient β = 0.15, P < 0.001), rural residence (β = − 0.09, P = 0.025), effectiveness of treatment (β = 0.39, P < 0.001), negative cocaine expectancies (β = 0.138, P = 0.003), experiences of rejection (β = 0.18, P < 0.001), need for secrecy (β = 0.12, P = 0.002), and readiness for treatment (β = 0.15, P < 0.001) were independently associated with perceived need for cocaine treatment.

Conclusions

TPB is a relevant model for understanding perceived need for treatment among African-American cocaine users. Research has shown perceived need to be a major correlate of treatment participation. Study results should be applicable for designing interventions to encourage treatment participation.     

Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys

Background

The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with phendimetrazine on cocaine vs. food choice in rhesus monkeys (N = 4).

Methods

Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0–0.1 mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose–effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-phendimetrazine (0.32–1.0 mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1–0.32 mg/kg/h; N = 5) and d-amphetamine (0.032–0.1 mg/kg/h; N = 6) were also examined for comparison.

Results

During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1 mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects.

Conclusions

These results demonstrate that phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability.     

Differences in self-reported and behavioral measures of impulsivity in recreational and dependent cocaine users

Background

Dependent cocaine users consistently display increased trait impulsivity on self-report questionnaires and less consistently exhibit elevated motor impulsivity in some behavioral tasks. However, trait and behavioral impulsivity measures have rarely been investigated in recreational users. Therefore, we examined self-reported trait and motor impulsivities in recreational and dependent cocaine users to clarify the role of impulse control in cocaine addiction and non-dependent cocaine use.

Methods

We investigated relatively pure recreational (n = 68) and dependent (n = 30) cocaine users, as well as psychostimulant-naïve controls (n = 68), with self-report questionnaires (Barratt Impulsiveness Scale 11; Temperament and Character Inventory) and behavioral tasks (Rapid Visual Information Processing Task; Stop-Signal Task).

Results

Compared with controls, recreational and dependent cocaine users displayed higher trait impulsivity and novelty seeking scores on self-report questionnaires. Trait impulsivity scores were strongly associated with an increased number of symptoms of depression and attention deficit hyperactivity disorder and correlated significantly with long-term cocaine intake parameters. By contrast, none of the behavioral motor impulsivity measures showed significant group effects or correlated with cocaine use parameters. The correlations among the self-report measures were high, but self-reports were scarcely correlated with behavioral task measures.

Conclusions

These findings suggest that relatively pure cocaine users already display increased trait impulsivity at a recreational level of use. However, the results do not indicate any cocaine-related elevation of behavioral impulsivity in terms of motor or response inhibition. In summary, our data imply that elevated trait impulsivity is not a specific feature of dependent cocaine use.     

Atypical neural activity during inhibitory processing in substance-naïve youth who later experience alcohol-induced blackouts

Background

Alcohol-induced blackouts are associated with the development of alcohol abuse and dependence, so it is important to consider potential neurobiological risk factors for experiencing this problem prior to the onset of substance use. This study examines whether neural activity during inhibitory processing might be atypical in substance-naïve youth who later experience alcohol-induced blackouts.

Methods

We examined inhibitory processing during fMRI with a go/no-go task that requires withholding a prepotent response in substance-naïve youth who would later transition into heavy drinking (n = 40) and youth who remain abstinent (n = 20). After approximately 5 years of annual follow-up assessments, youth were classified as nondrinkers (n = 20), and heavy drinking youth were classified as having experienced an alcohol-induced blackout (blackout+; n = 20) or not (blackout−; n = 20). Groups were matched on demographic variables, and youth who experienced blackouts were matched on follow-up substance use.

Results

Prior to initiating substance use, blackout+ youth showed greater activation during inhibitory processing than nondrinkers and blackout− youth in frontal and cerebellar brain regions. Mean activation during correct inhibitory responses relative to go responses in the left and right middle frontal gyri at baseline predicted future blackout experience, after controlling for follow-up externalizing behaviors and lifetime alcohol consumption.

Conclusions

Substance-naïve adolescents who later experience alcohol-induced blackouts show increased neural effort during inhibitory processing, as compared to adolescents who go on to drink at similar levels but do not experience blackouts and healthy, nondrinking controls, suggesting a neurobiological vulnerability to alcohol-induced memory impairments.     

Enhancing brief cognitive-behavioral therapy with motivational enhancement techniques in cocaine users

Background

We investigated the impact of enhancing brief cognitive-behavioral therapy with motivational interviewing techniques for cocaine abuse or dependence, using a focused intervention paradigm.

Methods

Participants (n = 74) who met current criteria for cocaine abuse or dependence were randomized to three-session cognitive-behavioral therapy (CBT) or three-session enhanced CBT (MET + CBT), which included an initial session of motivational enhancement therapy (MET). Outcome measures included treatment retention, process measures (e.g., commitment to abstinence, satisfaction with treatment), and cocaine use.

Results

Participants who received the MET + CBT intervention attended more drug treatment sessions following the study interventions, reported significantly greater desire for abstinence and expectation of success, and they expected greater difficulty in maintaining abstinence compared to the CBT condition. There were no differences across treatment conditions on cocaine use.

Conclusions

These findings offer mixed support for the addition of MET as an adjunctive approach to CBT for cocaine users. In addition, the study provides evidence for the feasibility of using short-term studies to test the effects of specific treatment components or refinements on measures of therapy process and outcome.     

A tale of two stimulants: Mentholated cigarettes may play a role in cocaine,but not methamphetamine,dependence

Background

Research suggests that mentholated cigarettes may play a role in cocaine dependence. The purpose of the present study was to expand upon the research on mentholated cigarettes and cocaine dependence and to evaluate the role of mentholated cigarettes in methamphetamine dependence.

Methods

Secondary analysis of a multisite, randomized trial evaluating the impact of smoking-cessation treatment in stimulant-dependent outpatients (N = 538). Participants’ reasons for concurrent use of cigarettes and illicit stimulants were assessed via self-report. Stimulant-abstinence was measured by self-report and urine drug screens. Smoking cessation was assessed via self-report and carbon monoxide levels.

Results

Of the 301 cocaine-dependent participants, 201 (67%) were menthol and 100 (33%) were non-menthol cigarette smokers. Cocaine-dependent participants who smoked menthol, compared to non-menthol, cigarettes were significantly more likely to report that cigarettes prolong their cocaine high (X²(1) = 16.3, p < .0001, OR = 3.58 [95% CI: 1.88–6.79]) and were less likely to be stimulant abstinent during active treatment (W = 3.6, p < 0.001, d = .39 [95% CI: 0.16–0.62]), at 3-month follow-up (X²(1) = 14.4, p < 0.001, OR = .32 [95% CI: 0.17–0.58]), and at 6-month follow-up (X²(1) = 4.6, p = 0.03, OR = .53 [95% CI: 0.29–0.95]). No parallel differences were found between menthol and non-menthol methamphetamine-dependent smokers. The prevalence of Caucasian menthol smokers was significantly greater in the cocaine-dependent participants (37.2%) than in the methamphetamine-dependent participants (17.61%), (X²(1) = 14.4, p < .001, OR = 2.77 [95% CI:1.62–4.73]). Smoking cessation was not significantly associated with cigarette type for either cocaine- or methamphetamine-dependent participants.

Conclusions

The present results suggest that mentholated cigarettes play a role in cocaine, but not methamphetamine, dependence.     

Adolescents' fMRI activation to a response inhibition task predicts future substance use

Background

Deficient behavioral regulation may be a risk factor for substance use disorders in adolescents. Abnormalities in brain regions critical to cognitive control have been linked to more intense and problematic future substance use (e.g., Durazzo, Gazdzinski, Mon, & Meyerhoff, 2010; Falk, Berkman, Whalen, & Lieberman, 2011; Paulus, Tapert, & Schuckit, 2005). The goal of this study was to examine the degree to which brain response to an inhibition task measured in mid-adolescence can predict substance use 18 months later.

Method

Adolescents aged 16–19 (N = 80) performed a go/no-go response inhibition task during fMRI at project baseline, and were followed 18 months later with a detailed interview on substance use and dependence symptoms. Participants were 39 high frequency users and 41 demographically similar low frequency users (458 versus 2 average lifetime drug use occasions at baseline, respectively).

Results

Across all subjects, no-go trials produced significant increases in neural response in the ventromedial prefrontal cortex and a region including the left angular and supramarginal gyri (p(FWE) < .01, cluster threshold ≥ 30 voxels). Less ventromedial prefrontal activation but more left angular gyrus activation predicted higher levels of substance use and dependence symptoms in the following 18 months, particularly for those who were high frequency users in mid-adolescence (p < .05).

Conclusions

These findings are consistent with studies showing that impairments in cognitive control have strong associations with substance use. We found a predictive relationship between atypical activation patterns at baseline and substance use behavior 18 months later, particularly among adolescents with histories of previous heavy use.     

Differential effects of acute and chronic treatment with the α2-adrenergic agonist,lofexidine, on cocaine self-administration in rhesus monkeys

Background

Lofexidine, an α₂-adrenergic agonist, is being investigated as a treatment for reducing opioid withdrawal symptoms and blocking stress-induced relapse to cocaine taking. Opioid abusers are often polydrug abusers and cocaine is one frequent drug of choice. However, relatively little is known about lofexidine interactions with cocaine. The present study investigated the effects of acute and chronic treatment with lofexidine in a pre-clinical model of cocaine self-administration.

Methods

Male rhesus monkeys were trained to respond for food (1 g) and cocaine (0.01 mg/kg/injection) under a fixed ratio 30 (FR30) or a second order FR2 (VR16:S) schedule of reinforcement. Systematic observations of behavior were conducted during and after chronic treatment with lofexidine.

Results

Acute treatment with lofexidine (0.1 or 0.32 mg/kg, IM) significantly reduced cocaine self-administration but responding for food was less effected. In contrast, chronic treatment (7–10 days) with lofexidine (0.1–0.32 mg/kg/h, IV) produced a leftward shift in the cocaine self-administration dose–effect curve, but had no effect on food-maintained responding. Lofexidine did not produce any observable side effects during or after treatment.

Conclusions

Lofexidine potentiated cocaine's reinforcing effects during chronic treatment. These data suggest that it is unlikely to be effective as a cocaine abuse medication and could enhance risk for cocaine abuse in polydrug abusers.     

Efficacy of buspirone for attenuating cocaine and methamphetamine reinstatement in rats

Background

There are no approved pharmacotherapies for preventing psychomotor stimulant relapse. The operant reinstatement model has been suggested as a screen for identifying candidate medications. The present study examined if the anxiolytic buspirone could attenuate reinstatement of extinguished responding in Long–Evans rats that previously self-administered intravenous cocaine or methamphetamine.

Methods

Rats were trained in 2-h daily sessions to self-administer 0.5 mg/kg cocaine or 0.1 mg/kg methamphetamine infusions followed by 12 days of instrumental extinction. Reinstatement was evoked by 17 mg/kg i.p. cocaine primes or response-contingent cocaine-paired cues in cocaine-reinforced rats, and by 1 mg/kg i.p. methamphetamine primes or response-contingent methamphetamine-paired cues in methamphetamine-reinforced rats.

Results

Buspirone (1 and 3 mg/kg) significantly (p < 0.05) attenuated cocaine cue but not cocaine prime reinstatement. Buspirone (1 and 3 mg/kg) also significantly attenuated methamphetamine cue reinstatement. Buspirone (3 mg/kg) significantly attenuated methamphetamine prime reinstatement. During all reinstatement tests, 3 mg/kg buspirone reduced levels of inactive lever pressing relative to those of vehicle, significantly so during the cocaine cue-induced reinstatement tests.

Conclusions

Given the complexity of buspirone's neuropharmacology consisting of serotonin 5-HT_1A receptor partial agonist activity, and dopamine D2, D3 and D4 receptor antagonist effects, it is uncertain which of these activities or their combination is responsible for the present results. Overall, these results suggest that buspirone may reduce the likelihood of relapse to cocaine and methamphetamine use under some conditions, although this speculation must be interpreted with caution given buspirone's similar potency to attenuate inactive-lever responding.     

The influence of monetary punishment on cognitive control in abstinent cocaine-users

Background

Dependent drug users show a diminished neural response to punishment, in both limbic and cortical regions, though it remains unclear how such changes influence cognitive processes critical to addiction. To assess this relationship, we examined the influence of monetary punishment on inhibitory control and adaptive post-error behavior in abstinent cocaine dependent (CD) participants.

Methods

15 abstinent CD and 15 matched control participants performed a Go/No-go response inhibition task, which administered monetary fines for failed response inhibition, during collection of fMRI data.

Results

CD participants showed reduced inhibitory control and significantly less adaptive post-error slowing in response to punishment, when compared to controls. The diminished behavioral punishment sensitivity shown by CD participants was associated with significant hypoactive error-related BOLD responses in the dorsal anterior cingulate cortex (ACC), right insula and right prefrontal regions. Specifically, CD participants’ error-related response in these regions was not modulated by the presence of punishment, whereas control participants’ response showed a significant BOLD increase during punished errors.

Conclusions

CD participants showed a blunted response to failed control (errors) that was not modulated by punishment. Consistent with previous findings of reduced sensitivity to monetary loss in cocaine users, we further demonstrate that such insensitivity is associated with an inability to increase cognitive control in the face of negative consequences, a core symptom of addiction. The pattern of deficits in the CD group may have implications for interventions that attempt to improve cognitive control in drug dependent groups via positive/negative incentives.     

Effects of bupropion on cognitive performance during initial tobacco abstinence

Background

Bupropion may aid tobacco abstinence by quickly relieving symptoms of nicotine withdrawal, perhaps including impaired cognitive performance. We examined whether bupropion would attenuate abstinence-induced cognitive deficits on the first day of a brief quit attempt, when smokers are most likely to relapse.

Methods

Smokers (N = 24) with high quit interest were recruited for within-subjects cross-over test of bupropion vs placebo on ability to abstain during separate short-term practice quit smoking attempts. After introduction to working memory (N-back) and sustained attention (continuous performance task; CPT) tasks during the pre-quit smoking baseline, performance on these tasks was assessed after abstaining overnight (CO < 10 ppm) on the first day of each quit attempt, while on bupropion and on placebo.

Results

Compared to placebo, bupropion after abstinence improved correct response times for working memory (p = .01 for medication by memory load interaction) and for one measure of sustained attention (numbers, but not letters; p < .05).

Discussion

Bupropion may attenuate some features of impaired cognitive performance due to withdrawal on the first day of a quit attempt. Future studies could examine whether this effect of bupropion contributes to its efficacy for longer-term smoking cessation.     

A randomized trial of intensive outpatient (IOP) vs. standard outpatient (OP) buprenorphine treatment for African Americans

Background

Buprenorphine is increasingly being used in community-based treatment programs, but little is known about the optimal level of psychosocial counseling in these settings. The aim of this study was to compare the effectiveness of OP and IOP level counseling when provided as part of buprenorphine treatment for opioid-dependent African Americans.

Methods

Participants were African American men and women starting buprenorphine treatment at one of two community-based clinics (N = 300). Participants were randomly assigned to OP or IOP. Measures at baseline, 3- and 6-month included the primary outcome of DSM-IV opioid and cocaine dependence criteria, as well as additional outcomes of illicit opioid and cocaine use (urine test and self-report), criminal activity, retention in treatment, Quality of Life, Addiction Severity Index composite scores, and HIV risk behaviors.

Results

Participants assigned to OP received, on average, 3.67 (SD = 1.30) h of counseling per active week in treatment. IOP participants received an average of 5.23 (SD = 1.68) h of counseling per active week (less than the anticipated 9 h per week of counseling). Both groups showed substantial improvement over a 6-month period on nearly all measures considered. There were no significant differences between groups in meeting diagnostic criteria for opioid (p = .67) or cocaine dependence (p = .63). There were no significant between group differences on any of the other outcomes. A secondary analysis restricting the sample to participants meeting DSM-IV criteria for baseline cocaine dependence also revealed no significant between-group differences (all ps > .05).

Conclusions

Buprenorphine patients receiving OP and IOP levels of care both show short-term improvements.     

Effects of tolcapone on working memory and brain activity in abstinent smokers: A proof-of-concept study

Background

Dopamine levels in the prefrontal cortex (PFC) are thought to play an important role in cognitive function and nicotine dependence. The catechol-O-methyltransferase (COMT) inhibitor tolcapone, an FDA-approved treatment for Parkinson's disease, increases prefrontal dopamine levels, with cognitive benefits that may vary by COMT genotype. We tested whether tolcapone alters working memory-related brain activity and performance in abstinent smokers.

Methods

In this double-blind crossover study, 20 smokers completed 8 days of treatment with tolcapone and placebo. In both medication periods, smokers completed blood oxygen level-dependent (BOLD) fMRI scans while performing a working memory N-back task after 24 h of abstinence. Smokers were genotyped prospectively for the COMT val¹⁵⁸met polymorphism for exploratory analysis.

Results

Compared to placebo, tolcapone modestly improved accuracy (p = 0.017) and enhanced suppression of activation in the ventromedial prefrontal cortex (vmPFC) (p = 0.002). There were no effects of medication in other a priori regions of interest (dorsolateral PFC, dorsal cingulate/medial prefrontal cortex, or posterior cingulate cortex). Exploratory analyses suggested that tolcapone led to a decrease in BOLD signal in several regions among smokers with val/val genotypes, but increased or remained unchanged among met allele carriers. Tolcapone did not attenuate craving, mood, or withdrawal symptoms compared to placebo.

Conclusions

Data from this proof-of-concept study do not provide strong support for further evaluation of COMT inhibitors as smoking cessation aids.     

Randomized clinical trial examining duration of voucher-based reinforcement therapy for cocaine abstinence

Background

This is the first study to systematically manipulate duration of voucher-based reinforcement therapy (VBRT) to see if extending the duration increases abstinence during and following VBRT.

Methods

We randomized cocaine-dependent methadone-maintained adults to Standard (12 weeks; n = 62) or Extended (36 weeks; n = 68) VBRT and provided escalating voucher amounts contingent upon urinalysis verification of cocaine abstinence. Urinalysis was scheduled at least every 2 weeks during the 48-week study and more frequently during VBRT (3/week) and 12 weeks of Aftercare (2/week).

Results

Extended VBRT produced longer durations of continuous cocaine abstinence during weeks 1–24 (5.7 vs 2.7 weeks; p = 0.003) and proportionally more abstinence during weeks 24–36 (X² = 4.57, p = .03, OR = 2.18) compared to Standard VBRT. Duration of VBRT did not directly predict after-VBRT abstinence; but longer continuous abstinence during VBRT predicted abstinence during Aftercare (p = 0.001) and during the last 12 weeks of the study (p < 0.001). Extended VBRT averaged higher monthly voucher costs compared to Standard VBRT ($96 vs $43, p < .001); however, the average cost per week of abstinence attained was higher in the Standard group ($8.06 vs $5.88, p < .001). Participants in the Extended group with voucher costs exceeding $25 monthly averaged 20 weeks of continuous abstinence.

Conclusions

Greater abstinence occurred during Extended VBRT, but providing a longer duration was not by itself sufficient to maintain abstinence after VBRT. However, if abstinence can be captured and sustained during VBRT, then providing longer durations may help increase the continuous abstinence that predicts better long-term outcomes.     

A double-blind,placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence

Background

Topiramate increases GABAergic activity and antagonizes the AMPA/kainate subtype of glutamate receptors. Through these mechanisms of action, topiramate may reduce alcohol and cocaine reward and may reduce alcohol and cocaine craving. Topiramate has been shown to reduce drinking in persons with alcohol dependence, and reduce relapse in stimulant-dependent patients. The current trial was intended to test the ability of topiramate to promote cocaine and alcohol abstinence among patients addicted to both drugs.

Methods

The study was a double-blind, placebo-controlled, 13-week trial involving 170 cocaine and alcohol dependent subjects. After achieving a period of cocaine and alcohol abstinence, subjects were randomized to topiramate, 300 mg daily, or identical placebo capsules. In addition, subjects received weekly individual psychotherapy. Primary outcome measures included self-reported alcohol and cocaine use, and thrice weekly urine drug screens. Secondary outcome measures included cocaine and alcohol craving, Addiction Severity Index results, cocaine withdrawal symptoms, and clinical global improvement ratings.

Results

Topiramate was not better than placebo in reducing cocaine use on the a priori primary outcome measure, or in reducing alcohol use. Topiramate was not better than placebo in reducing cocaine craving. Topiramate-treated subjects, compared to placebo-treated subjects, were more likely to be retained in treatment and more likely to be abstinent from cocaine during the last three weeks of the trial. Subjects who entered treatment with more severe cocaine withdrawal symptoms responded better to topiramate.

Discussion

Topiramate plus cognitive behavioral therapy may reduce cocaine use for some patients with comorbid cocaine and alcohol dependence.     

Binge drinking trajectory and neuropsychological functioning among university students: A longitudinal study

Background

Adolescence is a time of considerable neurodevelopment. Binge drinking (BD) during this period increases the vulnerability to its neurotoxic effects. This longitudinal study aimed to investigate the relationship between BD trajectory over university years and neuropsychological functioning.

Methods

Cohort-study. Two-year follow-up. A total of 89 university students were assessed: 40 Non-BD (at Initial and Follow-up), 16 Ex-BD (BD at Initial but not at Follow-up) and 33 BD (at both times). Neuropsychological assessment of working memory, episodic memory and executive abilities was carried out during their first (Initial) and third (Follow-up) academic year at the University of Santiago de Compostela.

Results

BD subjects performed less well on the Wechsler Memory Scale-III (WMS-III) Logical Memory Subtest (immediate theme recall, P = .034; delayed theme recall, P = .037; and percent retention, P = .035) and committed more perseverative errors on the Self-Ordered Pointing Task (SOPT) (P = .021) than Non-BD. There were no differences between Ex-BD and Non-BD.

Conclusions

Binge drinking trajectory during adolescence is associated with neuropsychological performance. Persistent BD, but not Ex-BD, is associated with verbal memory and monitoring difficulties. This is compatible with the hypothesis that heavy alcohol use during adolescence may affect cognitive functions that rely on the temporomesial and dorsolateral prefrontal cortex.     

The effect of rumination on craving across the continuum of drinking behaviour

Background

Rumination is an abstract, persistent, and repetitive thinking style that can be adopted to control negative affect. Recent studies have suggested the role of rumination as direct or indirect cognitive predictor of craving experience in alcohol-related problems.

Aims

The goal of this study was to explore the effect of rumination induction on craving across the continuum of drinking behaviour.

Methods

Participants of three groups of alcohol-dependent drinkers (N = 26), problem drinkers (N = 26) and social drinkers (N = 29) were randomly allocated to two thinking manipulation tasks: distraction versus rumination. Craving was measured before and after manipulation and after a resting phase.

Results

Findings showed that rumination had a significant effect on increasing craving in alcohol-dependent drinkers, relative to distraction, but not in problem and social drinkers. This effect was independent of baseline depression and rumination and was maintained across the resting phase. Conclusions: Rumination showed a direct causal impact on craving that is specific for a population of alcohol-dependent drinkers.     

Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans

Background

Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo.

Methods

Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 h.

Results

Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100–300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10–30 times the therapeutic dose of DXM.

Conclusion

The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100–300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse.     

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.