Search

Abnormal cue reactivity is a central characteristic of addiction, associated with increased activity in motivation, attention and memory related brain circuits. In this neuroimaging study, cue reactivity in problem gamblers (PRG) was compared with cue reactivity in heavy smokers (HSM) and healthy controls (HC). A functional magnetic resonance imaging event-related cue reactivity paradigm, consisting of gambling, smoking-related and neutral pictures, was employed in 17 treatment-seeking non-smoking PRG, 18 non-gambling HSM, and 17 non-gambling and non-smoking HC. Watching gambling pictures (relative to neutral pictures) was associated with higher brain activation in occipitotemporal areas, posterior cingulate cortex, parahippocampal gyrus and amygdala in PRG compared with HC and HSM. Subjective craving in PRG correlated positively with brain activation in left ventrolateral prefrontal cortex and left insula. When comparing the HSM group with the two other groups, no significant differences in brain activity induced by smoking cues were found. In a stratified analysis, the HSM subgroup with higher Fagerström Test for Nicotine Dependence scores (FTND M = 5.4) showed higher brain activation in ventromedial prefrontal cortex, rostral anterior cingulate cortex, insula and middle/superior temporal gyrus while watching smoking-related pictures (relative to neutral pictures) than the HSM subgroup with lower FTND scores (FTND M = 2.9) and than non-smoking HC. Nicotine craving correlated with activation in left prefrontal and left amygdala when viewing smoking-related pictures in HSM. Increased regional responsiveness to gambling pictures in brain regions linked to motivation and visual processing is present in PRG, similar to neural mechanisms underlying cue reactivity in substance dependence. Increased brain activation in related fronto-limbic brain areas was present in HSM with higher FTND scores compared with HSM with lower FTND scores. [ABSTRACT FROM AUTHOR]

Aims: To test the effectiveness of a digital intervention to reduce cannabis use (ICan) with adherence-focused guidance compared with educational cannabis information., Design: This was a single-blind randomized controlled trial. Follow-up clinical outcome measurements took place 3 and 6 months after randomization., Setting: The trial was conducted in the Netherlands. The intervention and guidance took place on-line, with recruitment via Facebook/Instagram advertisement campaigns., Participants: Inclusion criteria were ≥ 18 years, cannabis use on ≥ 3 days/week, the desire to reduce/quit cannabis and using a smartphone. Participants were allocated to either ICan (n = 188) or control (n = 190) (69% male, mean age = 27.5 years)., Intervention and Comparator: ICan is a mobile (web-)application based on motivational interviewing and cognitive behavioural therapy and includes three main components: screening, brief intervention (six modules) and referral to treatment. The control condition consisted of non-interactive educational cannabis information., Measurements: Primary outcome was the number of cannabis use days in the 7 days prior to the 6-month follow-up measurement. Secondary outcome measures at 3- and 6-month follow-up were the number of grams of cannabis used and attitudes towards seeking professional help for cannabis use related problems., Findings: Intention-to-treat analysis showed that 6 months after randomization the mean number of cannabis use days in the past 7 days was reduced in both conditions (time P < 0.001), with no significant group × time interaction effect [ICan = 4.17 days, control = 4.31 days, Cohen's d between  = 0.06, 95% confidence interval (CI) = -0.15, 0.26, P = 0.93]. Three months after randomization the mean number of grams used in the past 7 days was reduced in both conditions, with a significantly larger reduction in the ICan condition (P = 0.009, Cohen's d between  = 0.15). At 6-month follow-up the significant group × time interaction effect was no longer present (P = 0.30). In both conditions, attitudes towards seeking professional help remained virtually unchanged over time., Conclusions: A digital intervention to reduce cannabis use (ICan) was more effective than non-interactive educational cannabis information in reducing grams of cannabis used over 3 months, but not more effective at reducing cannabis use days at 6-month follow-up. Cannabis use reductions were maintained in both conditions between 3 and 6 months' follow-up., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background and Aims: Alcohol use disorder (AUD) is a chronic disorder with high relapse rates. There are currently few clinical trials of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) to reduce alcohol use among AUD patients, and results are mixed. The current study tested the effect of 10 add-on sessions of HF-rTMS over the right dorsolateral pre-frontal cortex (DLPFC) on alcohol use and craving., Design: Single-center, single blind sham-controlled parallel-group RCT (n = 80), with 3 and 6 months follow-up., Setting: Clinical treatment center in Amsterdam, the Netherlands., Participants: Eighty detoxified and abstinent AUD inpatients in clinical treatment (20 females, average age = 44.35 years)., Intervention: Ten sessions of active or sham HF-rTMS (60 10 Hz trains of 5 sec at 110% motor threshold) over the right DLPFC on 10 consecutive work-days., Measurements: The primary outcome measure is the number of abstinent days over 6-month follow-up (FU). Secondary outcome measures are craving over 6-month FU (alcohol urge questionnaire and obsessive-compulsive drinking scale), time to first relapse over 6-month FU and grams of alcohol consumed over 6-month FU. Additional outcome measures: full abstinence over 6-month FU and treatment success over 12-month FU., Findings: HF-rTMS did not affect the number of abstinent days over 6 months FU [sham = 124 ± 65.9 days, active = 115 ± 69.8 days, difference: 9 days, 95% confidence interval (CI) = Poisson model: 0.578-3.547]. Moreover, HF-rTMS did not affect craving (AUQ/OCDS) (sham = 15.38/5.28, active = 17.48/4.75, differences = 2.1/-0.53, 95% CI mixed-effects model = -9.14 to 2.07/-1.44 to 2.40)., Conclusions: There was no clear evidence that high-frequency repetitive transcranial magnetic stimulation over the right dorsolateral pre-frontal cortex treatment has a long-term positive effect on alcohol use or craving as add-on treatment for alcohol use disorder. High treatment response at 6-month follow-up could have limited the possibility to find an effect., (© 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

While it has been suggested that cocaine use and relapse in women is more strongly related to stress-relief craving, whereas cocaine use in men is more strongly related to reward craving, the neural mechanisms that underlie these differences are poorly understood. The aim of this study was to investigate sex-dependent differences in insular morphometry and associations with craving, in a sample of regular cocaine users (CUs) and non-drug using controls (non-CUs). It was hypothesized that insular volume, thickness and surface area would be lower in CU women, compared with CU men and non-CUs. It was furthermore hypothesized that insular morphometry, particularly insular thickness, would be negatively associated to reward craving in CU men, while being negatively associated with stress-relief craving in CU women. In contrast to the hypothesis, we did not find evidence of sex-specific differences in insular morphometry in CUs. However, sex-specific association between stress-relief craving and insular morphometry were found: Right insular volume was negatively associated with stress-relief craving in CU women, whereas this association was positive in CU men. Additionally, right insular surface area was negatively associated with stress-relief craving in cocaine-using men, whereas this association was positive in cocaine-using women. In conclusion, the current study provides first evidence of sex-specific differences in the association between craving and insular morphometry in a sample of regular cocaine users. Although speculative, these sex-specific alterations in insular morphometry may underlie higher stress-induced craving and relapse in CU women compared with CU men., (© 2022 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence., (© 2021 Society for the Study of Addiction.)

Background: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD., Methods: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis., Results: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months)., Conclusions: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD., (© 2021 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.)

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures., (© 2019 Society for the Study of Addiction.)

Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study, we therefore investigated neural cue-reactivity in a sample of male (n = 28) and female (n = 27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural cue-reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p < 0.05. While the cue-reactivity paradigm induced similar levels of self-reported craving in men and women, visual alcohol cues induced significantly stronger striatal activation in men compared to drinkers. While sex differences in ventral striatal cue-reactivity were partly explained by sex differences in alcohol intake, cannabis use, negative affect and anxiety, this was not the case for sex differences in dorsal striatal cue-reactivity. These results suggest that alcohol cues are differentially processed by men and women and that the neurobiological mechanisms behind cue-reactivity differ between the sexes. Consequently, paradigms using alcohol-related pictures may not be optimal to induce cue-reactivity in female drinkers and may not be optimal to measure neurobiological markers of alcohol use severity and relapse. Future alcohol cue-reactivity studies should, in addition to including both men and women, include different types of cues (e.g., stressors and imagery in addition to pictures) to assess sex differences in alcohol cue-reactivity., (© 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Cannabis use is highly prevalent and often considered to be relatively harmless. Nonetheless, a subset of regular cannabis users may develop dependence, experiencing poorer quality of life and greater mental health problems relative to non-dependent users. The neuroanatomy characterizing cannabis use versus dependence is poorly understood. We aimed to delineate the contributing role of cannabis use and dependence on morphology of the hippocampus, one of the most consistently altered brain regions in cannabis users, in a large multi-site dataset aggregated across four research sites. We compared hippocampal volume and vertex-level hippocampal shape differences (1) between 121 non-using controls and 140 cannabis users; (2) between 106 controls, 50 non-dependent users and 70 dependent users; and (3) between a subset of 41 controls, 41 non-dependent users and 41 dependent users, matched on sample characteristics and cannabis use pattern (onset age and dosage). Cannabis users did not differ from controls in hippocampal volume or shape. However, cannabis-dependent users had significantly smaller right and left hippocampi relative to controls and non-dependent users, irrespective of cannabis dosage. Shape analysis indicated localized deflations in the superior-medial body of the hippocampus. Our findings support neuroscientific theories postulating dependence-specific neuroadaptations in cannabis users. Future efforts should uncover the neurobiological risk and liabilities separating dependent and non-dependent use of cannabis., (© 2018 Society for the Study of Addiction.)

Background: The US National Institutes of Mental Health Research Domain Criteria (RDoC) seek to stimulate research into biologically validated neuropsychological dimensions across mental illness symptoms and diagnoses. The RDoC framework comprises 39 functional constructs designed to be revised and refined, with the overall goal of improving diagnostic validity and treatments. This study aimed to reach a consensus among experts in the addiction field on the 'primary' RDoC constructs most relevant to substance and behavioural addictions., Methods: Forty-four addiction experts were recruited from Australia, Asia, Europe and the Americas. The Delphi technique was used to determine a consensus as to the degree of importance of each construct in understanding the essential dimensions underpinning addictive behaviours. Expert opinions were canvassed online over three rounds (97% completion rate), with each consecutive round offering feedback for experts to review their opinions., Results: Seven constructs were endorsed by ≥ 80% of experts as 'primary' to the understanding of addictive behaviour: five from the Positive Valence System (reward valuation, expectancy, action selection, reward learning, habit); one from the Cognitive Control System (response selection/inhibition); and one expert-initiated construct (compulsivity). These constructs were rated to be related differentially to stages of the addiction cycle, with some linked more closely to addiction onset and others more to chronicity. Experts agreed that these neuropsychological dimensions apply across a range of addictions., Conclusions: The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment., (© 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background and Aims: Patients with co-occurring substance use and other mental disorders are vulnerable to crime victimization, yet no evidence-based preventive interventions exist. Our aim was to test the efficacy of a new intervention, Self-wise, Other-wise, Streetwise training (SOS training), to prevent victimization in these dual-diagnosis patients as an add-on to care as usual., Design: Multi-site single-blind parallel randomized controlled trial., Setting: Three sites within one psychiatric service in Amsterdam, the Netherlands., Participants: Adult in-patients and out-patients with dual diagnosis (n = 250), who were predominantly male (70.4%), aged on average 42.1 years, and diagnosed with 3.7 DSM-IV disorders., Intervention and Comparator: Care as usual, consisting of pharmacotherapy combined with individual psychotherapy, group psychotherapy and/or supportive counselling (n = 125) was compared with care as usual plus SOS training: a 6-week, 12-session manualized group training focused on enhancing emotion regulation skills, conflict resolution skills and street skills (n = 125)., Measurements: Victimization was assessed with the Safety Monitor, the Dutch equivalent of the International Crime Victims Survey, in a face-to-face assessment. The primary outcome measure was treatment response (yes/no), with 'yes' defined as reporting at least a 50% reduction in the number of past-year victimization incidents at the 14-month follow-up compared with baseline. Analyses were performed according to the intention-to-treat principle., Findings: The proportion of participants achieving treatment response for total victimization was 54.0% in the control group and 67.6% in the experimental group, a significant difference [odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.02-3.11, P = 0.042]. Treatment response for violent victimization was achieved by 68.7% of the control group and 79.3% of the experimental group (OR = 1.75, 95% CI = 0.91-3.34, P = 0.092). With a Bayes factor of 2.26, this result was inconclusive., Conclusions: Among dual-diagnosis patients, care as usual plus Self-wise, Other-wise, Streetwise training was more effective in preventing victimization than care as usual alone., (© 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Pathological gambling (PG) is a behavioral addiction characterized by an inability to stop gambling despite the negative consequences, which may be mediated by cognitive flexibility deficits. Indeed, impaired cognitive flexibility has previously been linked to PG and also to reduced integrity of white matter connections between the basal ganglia and the prefrontal cortex. It remains unclear, however, how white matter integrity problems relate to cognitive inflexibility seen in PG. We used a cognitive switch paradigm during functional magnetic resonance imaging in pathological gamblers (PGs; n = 26) and healthy controls (HCs; n = 26). Cognitive flexibility performance was measured behaviorally by accuracy and reaction time on the switch task, while brain activity was measured in terms of blood oxygen level-dependent responses. We also used diffusion tensor imaging on a subset of data (PGs = 21; HCs = 21) in combination with tract-based spatial statistics and probabilistic fiber tracking to assess white matter integrity between the basal ganglia and the dorsolateral prefrontal cortex. Although there were no significant group differences in either task performance, related neural activity or tract-based spatial statistics, PGs did show decreased white matter integrity between the left basal ganglia and prefrontal cortex. Our results complement and expand similar findings from a previous study in alcohol-dependent patients. Although we found no association between white matter integrity and task performance here, decreased white matter connections may contribute to a diminished ability to recruit prefrontal networks needed for regulating behavior in PG. Hence, our findings could resonate an underlying risk factor for PG, and we speculate that these findings may extend to addiction in general., (© 2016 Society for the Study of Addiction.)

Cognitive flexibility has been associated with prefrontal white matter (WM) integrity in healthy controls (HCs), showing that lower WM integrity is associated with worse performance. Although both cognitive flexibility and WM integrity have been found to be aberrant in alcohol-dependent (AD) patients, the relationship between the two has never been tested. In this study, we investigated the association between WM tract density and cognitive flexibility in patients with AD (n = 26) and HCs (n = 22). In order to assess the influence of AD severity, we also included a group of problematic drinkers (PrDs; n = 23) who did not meet the AD criteria. Behavioral responses and brain activity during a cognitive flexibility task were measured during functional magnetic resonance imaging. Probabilistic fiber tracking was performed between the dorsolateral prefrontal cortex and the basal ganglia; two crucial regions for task switching. Finally, the task-related functional connectivity between these areas was assessed. There were no significant group differences in the task performance. However, compared with HCs, AD patients and PrDs showed decreased WM integrity and increased prefrontal brain activation during task switching. Evidence is presented for a compensatory mechanism, involving recruitment of additional prefrontal resources in order to compensate for WM and neural function impairments in AD patients and PrDs. Although present in both alcohol groups, the PrDs were more successful in invoking this compensatory mechanism when compared to the AD patients. We propose that this may therefore serve as a protective factor, precluding transition from problematic drinking into alcohol dependence., (© 2014 Society for the Study of Addiction.)

Aims: To provide an overview of gambling in the Netherlands, focusing on historical background, policy, legislation, prevalence of problem gambling, availability of treatment options and research base., Methods: Literature review., Results: Contradictions between gambling policy and practice have been present in the past 15-20 years, and have led to an increasingly stricter gambling regulation to retain the government policy to restrict gambling within a national monopoly. Conversely, political efforts have been made to legalize internet gambling, but have not yet been approved. Compared to other European countries, slot machine gambling and casino gambling are relatively popular, whereas betting is relatively unpopular. Last-year problem gambling prevalence (South Oaks Gambling Screen score > 5) is estimated at 0.22-0.15% (2005, 2011). Treatment for problem gambling is covered by health insurance under the same conditions as substance dependence, but only a small proportion of Dutch problem gamblers seeks help at addiction treatment centres., Conclusions: Gambling policy in the Netherlands has become stricter during recent last years in order to maintain the Dutch gambling monopoly. Problem gambling in the Netherlands is relatively stable. Dutch research on problem gambling has a lack of longitudinal studies. Most of the epidemiological gambling studies are reported in non-peer-reviewed research reports, which diminishes control by independent peers on the methodology and interpretation of results. Recent efforts to enhance consistency in research methods between gambling studies over time could enhance knowledge on changes in (problem) gambling in the Netherlands., (© 2013 Society for the Study of Addiction.)

Background: Patients with alcohol dependence (AD) and pathological gambling (PG) are characterized by dysfunctional reward processing and their ability to adapt to alterations of reward contingencies is impaired. However, most neurocognitive tasks investigating reward processing involve a complex mix of elements, such as working memory, immediate and delayed rewards, and risk-taking. As a consequence, it is not clear whether contingency learning is altered in AD or PG. Therefore, the current study aimed to examine performance in a deterministic contingency learning task, investigating discrimination, reversal, and extinction learning., Methods: Thirty-three alcohol-dependent patients (ADs), 28 pathological gamblers (PGs), and 18 healthy controls (HCs) performed a contingency learning task in which they learned stimulus-reward associations that were first reversed and later extinguished while receiving deterministic feedback throughout. Accumulated points, number of perseverative errors and trials required to reach a criterion in each learning phase were compared between groups using nonparametric Kruskal-Wallis rank-sum tests. Regression analyses were performed to compare learning curves., Results: PGs and ADs did not differ from HCs in discrimination learning, reversal learning, or extinction learning, on the nonparametric tests. Regression analyses, however, showed differences in the initial speed of learning: PGs were significantly faster in discrimination learning compared to ADs, and both PGs and ADs learned slower than HCs in the reversal learning and extinction phases of the task., Conclusions: Learning rates for reversal and extinction were slower for the alcohol-dependent group and PG group compared to HCs, suggesting that reversing and extinguishing learned contingencies require more effort in ADs and PGs. This implicates a diminished flexibility to overcome previously learned contingencies., (© 2014 The Authors Alcoholism: Clinical and Experimental Research published by Wiley Periodicals, Inc. on behalf of Research Society on Alcoholism.)

Deficient executive functions play an important role in the development of addiction. Working-memory may therefore be a powerful predictor of the course of drug use, but chronic substance use may also impair working-memory. The aim of this 3-year longitudinal neuro-imaging study was to investigate the relationship between substance use (e.g. alcohol, cannabis, nicotine, illegal psychotropic drugs) and working-memory network function over time in heavy cannabis users and controls. Forty-nine participants performed an n-back working-memory task at baseline and at 3-year follow-up. At follow-up, there were 22 current heavy cannabis users, 4 abstinent heavy cannabis users and 23 non-cannabis-using controls. Tensor-independent component analysis (Tensor-ICA) was used to investigate individual differences in working-memory network functionality over time. Within the group of cannabis users, cannabis-related problems remained stable, whereas alcohol-related problems, nicotine dependence and illegal psychotropic substance use increased over time. At both measurements, behavioral performance and network functionality during the n-back task did not differ between heavy cannabis users and controls. Although n-back accuracy improved, working-memory network function remained stable over time. Within the group of cannabis users, working-memory network functionality was not associated with substance use. These results suggest that sustained moderate to heavy levels of cannabis, nicotine, alcohol and illegal psychotropic substance use do not change working-memory network functionality. Moreover, baseline network functionality did not predict cannabis use and related problems three years later, warranting longitudinal studies in more chronic or dependent cannabis users., (© 2013 Society for the Study of Addiction.)

Decision-making deficits are thought to play an important role in the development and persistence of substance use disorders. Individual differences in decision-making abilities and their underlying neurocircuitry may, therefore, constitute an important predictor for the course of substance use and the development of substance use disorders. Here, we investigate the predictive value of decision making and neural mechanisms underlying decision making for future cannabis use and problem severity in a sample of heavy cannabis users. Brain activity during a monetary decision-making task (Iowa gambling task) was compared between 32 heavy cannabis users and 41 matched non-using controls using functional magnetic resonance imaging. In addition, within the group of heavy cannabis users, associations were examined between task-related brain activations, cannabis use and cannabis use-related problems at baseline, and change in cannabis use and problem severity after a 6-month follow-up. Despite normal task performance, heavy cannabis users compared with controls showed higher activation during wins in core areas associated with decision making. Moreover, within the group of heavy cannabis users, win-related activity and activity anticipating loss outcomes in areas generally involved in executive functions predicted change in cannabis use after 6 months. These findings are consistent with previous studies and point to abnormal processing of motivational information in heavy cannabis users. A new finding is that individuals who are biased toward immediate rewards have a higher probability of increasing drug use, highlighting the importance of the relative balance between motivational processes and regulatory executive processes in the development of substance use disorders., (© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.)

Background: Recent research findings suggest that heavy alcohol use is associated with alterations of the hypothalamic-pituitary-adrenal axis and autonomic nervous system function and that early abstinence is associated with blunted stress responsiveness., Methods: This study investigated abstinent alcohol-dependent participants (AADs; n = 31), who had a drinking history of levels about 97 drinks per week (abstinence range: 2 weeks to 24 months), actively drinking problem drinkers (PRDs; n = 23), who reported drinking levels about 47 drinks per week and who were abstinent for at least 24 hours, and healthy control (HC) participants (n = 20). It was investigated how participants responded to a psychosocial stress task. All of them were exposed to a modified Trier Social Stress Test. Salivary cortisol, heart rate, skin conductance levels, and negative affect were assessed as stress indicators., Results: AADs showed stress reactions comparable to HC participants, whereas active PRDs showed increased heart rate and cortisol stress responses. In the AAD group, duration of abstinence was positively related to cortisol stress responses., Conclusions: Active PRDs showed increased responses to psychosocial stress. Results indicate that duration of abstinence is a key factor when analyzing and interpreting stress responses in alcohol abuse and dependence., (Copyright © 2013 by the Research Society on Alcoholism.)

Cue-reactivity reflects enhanced motivational processing underlying continued substance use and relapse in substance use disorders. Substance use disorders are associated with greater cue-reactivity in orbitofrontal cortex, anterior cingulate cortex, striatum, ventral tegmental area and amygdala. Here we examine whether this also holds for frequent cannabis users. Using functional magnetic resonance imaging (fMRI), neural responses to neutral and cannabis-related cues were compared between frequent cannabis users (n = 31), sporadic cannabis users (n = 20) and cannabis-naive controls (n = 21). In addition, fMRI findings were correlated with the level of cannabis use, problem severity and craving. In frequent users compared with sporadic users and controls, cannabis images engendered higher activation than control images in the ventral tegmental area. Activation of the orbitofrontal cortex, anterior cingulate cortex and striatum was only higher in a subgroup of frequent users with high compared with low-problem severity. Activity in the right putamen and right dorsolateral prefrontal cortex correlated negatively with subjective craving in frequent users. Activity was not correlated with level of cannabis use. These findings indicate that cannabis cues activate areas associated with addiction pathology in frequent cannabis users compared with sporadic users and controls. However, among frequent users, cue-reactivity seems to be primarily associated with problem severity, not with amount of cannabis use. These findings imply neural cue-reactivity as a tool in assessing problem severity of cannabis use., (© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.)

Background: Differences in clinical characteristics between early and late onset alcohol dependent patients have been examined intensively, but little is known about the differences in neuropsychological functioning between these patient groups. Clinical characteristics and neuropsychological functions of inpatients with early onset and late onset alcohol dependence are therefore investigated in this study., Methods: Ninety-three abstinent alcohol dependent inpatients meeting a current diagnosis of DSM-IV alcohol dependence were divided into early onset alcohol dependent patients (EOA; ≤25 years; n = 36) and late onset alcohol dependent patients (LOA; >25 years; n = 57). Patients using psychoactive medication and patients dependent on other substances than alcohol (and nicotine) were excluded. A comprehensive neuropsychological test battery was administered., Results: EOA reported higher trait impulsivity, antisocial traits, and attention deficit hyperactivity disorder-related traits and exhibited an impulsive reflection style, especially in a high-risk context, compared with LOA. Against expectations, EOA performed significantly better on measures of planning, cognitive control, visual memory, and delayed recognition memory than LOA, whereas no significant group differences occurred on measures of delay discounting, digit span, and attention. Better Stroop interference, better visual memory, and a more impulsive reflection style was predictive of an early age of onset, and explained a significant and additional amount of variance (18.8%) on top of the clinical characteristics, together explaining 53.4% of the variance., Conclusions: Both clinical characteristics and neuropsychological variables contributed independently to the age of onset of problematic alcohol use. Results indicate that especially an impulsive reflection style, besides higher trait impulsivity, may be the core feature of early onset alcohol dependence. However, the contribution of the neuropsychological variables is complex and more research is needed to clarify the role of psychiatric comorbidity and poly-substance abuse in an unselected sample of alcohol dependent patients., (Copyright © 2012 by the Research Society on Alcoholism.)

Aims: Repeated drug exposure can lead to an approach-bias, i.e. the relatively automatically triggered tendencies to approach rather that avoid drug-related stimuli. Our main aim was to study this approach-bias in heavy cannabis users with the newly developed cannabis Approach Avoidance Task (cannabis-AAT) and to investigate the predictive relationship between an approach-bias for cannabis-related materials and levels of cannabis use, craving, and the course of cannabis use., Design, Settings and Participants: Cross-sectional assessment and six-month follow-up in 32 heavy cannabis users and 39 non-using controls., Measurements: Approach and avoidance action-tendencies towards cannabis and neutral images were assessed with the cannabis AAT. During the AAT, participants pulled or pushed a joystick in response to image orientation. To generate additional sense of approach or avoidance, pulling the joystick increased picture size while pushing decreased it. Craving was measured pre- and post-test with the multi-factorial Marijuana Craving Questionnaire (MCQ). Cannabis use frequencies and levels of dependence were measured at baseline and after a six-month follow-up., Findings: Heavy cannabis users demonstrated an approach-bias for cannabis images, as compared to controls. The approach-bias predicted changes in cannabis use at six-month follow-up. The pre-test MCQ emotionality and expectancy factor were associated negatively with the approach-bias. No effects were found on levels of cannabis dependence., Conclusions: Heavy cannabis users with a strong approach-bias for cannabis are more likely to increase their cannabis use. This approach-bias could be used as a predictor of the course of cannabis use to identify individuals at risk from increasing cannabis use., (© 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.)

Background: Very few studies have investigated the "real world" prospective, predictive value of behavioral instruments used in laboratory studies to test decision-making abilities or impulse control. The current study examines the degree to which 2 commonly used decision-making/impulse control measures prospectively predict (heavy) alcohol use in a sample of college students., Methods: Two hundred healthy young adults (50% women) performed the Iowa Gambling Task (IGT) and a StopSignal inhibition task in the second college year. At testing and at the end of the fourth college year, heavy alcohol use was assessed., Results: Disadvantageous performance on the IGT was associated with higher scores on a heavy drinking measure and higher quantity/frequency of alcohol use 2 years past neurocognitive testing in male students even after controlling for prior drinking. These results were corrected for heavy drinking and alcohol use in the period before neurocognitive testing. Interactions with gender indicated that this general pattern held for male but not for female students. Level of response inhibition was not associated with either of the alcohol use measures prospectively., Conclusion: These findings indicate that a neurocognitive decision-making task is predictive of maladaptive alcohol use. Advantageous decision makers appear to show adaptive real-life decision making, changing their drinking habits to the changing challenges of early adulthood (e.g., finishing college), whereas disadvantageous decision makers do not, and continue to drink heavily. These findings extend earlier findings of neurocognitive predictors of relapse in clinical substance-dependent groups, to subclinical alcohol use and abuse., (Copyright © 2011 by the Research Society on Alcoholism.)

Aims: To investigate which clusters of gambling activities exist within a longitudinal study of college health, how membership in gambling clusters change over time and whether particular clusters of gambling are associated with unhealthy risk behaviour., Design: Four-year longitudinal study (2002-2006)., Setting: Large, public university., Participants: Undergraduate college students., Measurements: Ten common gambling activities were measured during 4 consecutive college years (years 1-4). Clusters of gambling activities were examined using latent class analyses. Relations between gambling clusters and gender, Greek membership, alcohol use, drug use, personality indicators of behavioural undercontrol and psychological distress were examined., Findings: Four latent gambling classes were identified: (1) a low-gambling class, (2) a card gambling class, (3) a casino/slots gambling class and (4) an extensive gambling class. Over the first college years a high probability of transitioning from the low-gambling class and the card gambling class into the casino/slots gambling class was present. Membership in the card, casino/slots and extensive gambling classes were associated with higher scores on alcohol/drug use, novelty seeking and self-identified gambling problems compared to the low-gambling class. The extensive gambling class scored higher than the other gambling classes on risk factors., Conclusions: Extensive gamblers and card gamblers are at higher risk for problem gambling and other risky health behaviours. Prospective examinations of class membership suggested that being in the extensive and the low gambling classes was highly stable across the 4 years of college.

Background: Behavioral decision making, as measured by the Iowa Gambling Task (IGT) is found to be diminished in individuals with substance dependence and other types of disinhibitory psychopathology. However, little is known regarding the relation between heavy alcohol use and decision-making skills in young adults. This study therefore investigated whether binge drinking is related to disadvantageous decision making, as measured by the IGT. We also examined the relation between decision making and impulsivity., Methods: Latent class growth analysis was used to classify college students into 4 groups (each group n=50, 50% male), based on their binge drinking trajectories over a 2-year time period (precollege through second year of college). Participants were 200 college students, divided in 4 subgroups: (1) low binge drinkers, (2) stable moderate binge drinkers, (3) increasing binge drinkers, and (4) stable high binge drinkers. A measure of decision making, the IGT, impulsivity questionnaires, and multiple indicators of heavy alcohol use were included., Results: The stable high binge-drinking group made less advantageous choices on the IGT than the low binge-drinking group. Impulsivity was not related to decision-making performance. Decision-making performance did not differ by gender, but deck preferences and decision time patterns did differ; women preferred low frequency, high amount punishments to a greater extent than men., Conclusions: Although disadvantageous decision making is related to binge-drinking patterns in emerging adulthood, this relation is independent of impulsivity. Additionally, the association appears attributable to those who engage in heavy (binge) drinking at an early age, but not to age of onset of drinking in general.

Aims: Neurocognitive functions in pathological gambling have relevance for the aetiology and treatment of this disorder, yet are poorly understood. This study therefore investigated neurocognitive impairments of executive functions in a group of carefully screened Diagnostic and Statistical Manual version IV (DSM-IV-TR) pathological gamblers. Performance was compared to a group of normal control participants. To study the specificity of these neurocognitive deficits, a substance dependence group (alcohol dependence) and an impulse control disorder group (Tourette syndrome) were included., Design: Cross-sectional study., Setting: Addiction and general mental health treatment centres., Participants: Forty-nine pathological gamblers, 48 abstinent alcohol-dependent patients, 46 participants with Tourette syndrome and 49 normal control participants., Measurements: A comprehensive neuropsychological battery measuring executive functions as well as basic cognitive functions., Findings: Both the pathological gambling and the alcohol dependent groups were characterized by diminished performance on inhibition, time estimation, cognitive flexibility and planning tasks. The Tourette syndrome group showed deficits only on inhibition tasks. Basic cognitive functions were intact in all clinical groups. Comorbid attention deficit hyperactivity disorder, antisocial personality disorder and nicotine dependence influenced the impaired functions of the clinical groups only minimally., Conclusions: Carefully screened groups of pathological gamblers and alcohol dependents were characterized by diminished executive functioning, suggesting a dysfunction of frontal lobe circuitry in these disorders. The resemblance between the pathological gambling group and the alcohol dependence group suggests a common neurocognitive aetiology for these disorders. Psychosocial treatment of these disorders could benefit from assessing and targeting deficits in executive functions, as they probably influence the course of these disorders negatively.