Janna Cousijn

Grey matter alterations associated with cannabis use: results of a VBM study in heavy cannabis users and healthy controls

Cannabis abuse is related to impairments in a broad range of cognitive functions. However, studies on cannabis abuse in relation to brain structure are sparse and results are inconsistent, probably due to differences in imaging methodology, severity of cannabis abuse, and use of other substances. The goal of the current MRI study was to investigate brain morphology related to current and lifetime severity of cannabis use and dependence in heavy cannabis users without intensive use of other illicit drugs. Voxel-based morphometry was used to assess differences in regional grey and white matter volume between 33 heavy cannabis users and 42 matched controls. Within heavy cannabis users, grey and white matter volume was correlated with measures of cannabis use and dependence. Analyses were focused a priori on the orbitofrontal cortex, anterior cingulate cortex, striatum, amygdala, hippocampus, and cerebellum, regions implicated in substance dependence and/or with high cannabinoid receptor-1 concentrations. Regional grey matter volume in the anterior cerebellum was larger in heavy cannabis users. Within the group of heavy cannabis users, grey matter volume in the amygdala and hippocampus correlated negatively with the amount of cannabis use or dependence. No associations were found between white matter volume and measures of cannabis use or dependence. These findings indicate that associations between heavy cannabis use and altered brain structure are complex. Differential patterns of structural changes for various cannabis use levels imply that alterations in brain structure are associated with specific characteristics of cannabis use and dependence.

Reaching out towards cannabis: approach-bias in heavy cannabis users predicts changes in cannabis use

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.

Neural responses associated with cue-reactivity in frequent cannabis users

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.

Efficacy of N-acetylcysteine in the treatment of nicotine dependence: a double-blind placebo-controlled pilot study.

Relapse is the rule rather than the exception in smokers aiming to quit smoking. Recently, evidence has emerged that glutamate transmission plays an important role in relapse. N-acetylcysteine (NAC), a cysteine prodrug, restores glutamate homeostasis and appears to be a potential new treatment for substance dependence. In the current pilot study, the effects of NAC on short-term abstinence of smoking were investigated. Subjects were heavy smokers randomized to receive placebo (n = 12) or NAC 3,600 mg/day (n = 10) in a double-blind fashion during 3.5 days. Subjects were asked to stop smoking and report on nicotine craving, nicotine withdrawal symptoms, and cigarette smoking during treatment. At the end of the treatment, subjects were invited to smoke a cigarette and to rate the rewarding effect of this cigarette. There was no significant effect of NAC on craving (p = 0.23, d = 0.52) and only a statistical trend towards fewer withdrawal symptoms in the NAC condition (p = 0.07, d = 0.80). Interestingly, subjects receiving NAC rated the first cigarette after the abstinence period of 3.5 days as significantly less rewarding than subjects on placebo (p = 0.04, d = 0.85). It is concluded that the results of this pilot study are encouraging and suggest that NAC might be a promising new treatment option for relapse prevention in nicotine dependence.

Approach-Bias Predicts Development of Cannabis Problem Severity in Heavy Cannabis Users: Results from a Prospective FMRI Study

A potentially powerful predictor for the course of drug (ab)use is the approach-bias, that is, the pre-reflective tendency to approach rather than avoid drug-related stimuli. Here we investigated the neural underpinnings of cannabis approach and avoidance tendencies. By elucidating the predictive power of neural approach-bias activations for future cannabis use and problem severity, we aimed at identifying new intervention targets. Using functional Magnetic Resonance Imaging (fMRI), neural approach-bias activations were measured with a Stimulus Response Compatibility task (SRC) and compared between 33 heavy cannabis users and 36 matched controls. In addition, associations were examined between approach-bias activations and cannabis use and problem severity at baseline and at six-month follow-up. Approach-bias activations did not differ between heavy cannabis users and controls. However, within the group of heavy cannabis users, a positive relation was observed between total lifetime cannabis use and approach-bias activations in various fronto-limbic areas. Moreover, approach-bias activations in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) independently predicted cannabis problem severity after six months over and beyond session-induced subjective measures of craving. Higher DLPFC/ACC activity during cannabis approach trials, but lower activity during cannabis avoidance trials were associated with decreases in cannabis problem severity. These findings suggest that cannabis users with deficient control over cannabis action tendencies are more likely to develop cannabis related problems. Moreover, the balance between cannabis approach and avoidance responses in the DLPFC and ACC may help identify individuals at-risk for cannabis use disorders and may be new targets for prevention and treatment.

Individual differences in decision making and reward processing predict changes in cannabis use: a prospective functional magnetic resonance imaging study

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.

Recovery of neurocognitive functions following sustained abstinence after substance dependence and implications for treatment

BACKGROUND Substance Use Disorders (SUDs) have been associated with impaired neurocognitive functioning, which may (partly) improve with sustained abstinence. New treatments are emerging, aimed at improving cognitive functions, and being tested. However, no integrated review is available regarding neurocognitive recovery following sustained abstinence. OBJECTIVES In this review, results from prospective studies on neurocognitive recovery using neuropsychological assessments before and after sustained abstinence from SUDs are summarized and discussed. RESULTS Thirty-five prospective studies were selected for this review, including twenty-two alcohol, three cannabis, four cocaine, three (meth)amphetamine, and three opioid studies. Results suggest that some cognitive functions (partially) recover after sustained abstinence, and that there are predictors of an unfavorable course such as poly-substance use and number of previous detoxifications. CONCLUSIONS Prospective studies indicate that sustained abstinence after SUDs generally results in (partial) neurocognitive recovery. However, a final answer regarding full recovery awaits prospective studies with neurocognitive assessments before, during, and after sustained abstinence from SUDs. New interventions that might enhance neurocognitive recovery after abstinence are discussed, including neurocognitive training, medication and neuromodulation.

Cannabis dependence, cognitive control and attentional bias for cannabis words

One of the characteristics of people suffering from addictive behaviors is the tendency to be distracted by drug cues. This attentional bias for drug cues is thought to lead to increased craving and drug use, and may draw individuals into a vicious cycle of drug addiction. In the current study we developed a Dutch version of the cannabis Stroop task and measured attentional bias for cannabis words in a group of heavy cannabis users and matched controls. The classical Stroop task was used as a global measure of cognitive control and we examined the relationship between cognitive control, cannabis-related problems, cannabis craving and cannabis attentional bias. Using our version of the cannabis Stroop task, a group of heavy cannabis users showed attentional bias to cannabis words, whereas a control group of non-users did not. Furthermore, within the group of cannabis users, those who were clinically recognized as dependent showed a stronger attentional bias than the heavy, non-dependent users. Cannabis users who displayed reduced cognitive control (as measured with the classical Stroop task) showed increased session-induced craving. Contrary to expectations, however, cognitive control did not appear to modulate the relationship between attentional bias to cannabis words (cannabis Stroop task) and cannabis dependence. This study confirmed the relationship between cannabis dependence and attentional bias and extends this by highlighting a moderating role for cognitive control, which may make some more vulnerable to craving.

Effect of baseline cannabis use and working-memory network function on changes in cannabis use in heavy cannabis users: a prospective fMRI study

Theoretical models of addiction suggest that a substance use disorder represents an imbalance between hypersensitive motivational processes and deficient regulatory executive functions. Working‐memory (a central executive function) may be a powerful predictor of the course of drug use and drug‐related problems. Goal of the current functional magnetic resonance imaging study was to assess the predictive power of working‐memory network function for future cannabis use and cannabis‐related problem severity in heavy cannabis users. Tensor independent component analysis was used to investigate differences in working‐memory network function between 32 heavy cannabis users and 41 nonusing controls during an N‐back working‐memory task. In addition, associations were examined between working‐memory network function and cannabis use and problem severity at baseline and at 6‐month follow‐up. Behavioral performance and working‐memory network function did not significantly differ between heavy cannabis users and controls. However, among heavy cannabis users, individual differences in working‐memory network response had an independent effect on change in weekly cannabis use 6 months later (ΔR2 = 0.11, P = 0.006, f2 = 0.37) beyond baseline cannabis use (ΔR2 = 0.41) and a behavioral measure of approach bias (ΔR2 = 0.18): a stronger network response during the N‐back task was related to an increase in weekly cannabis use. These findings imply that heavy cannabis users requiring greater effort to accurately complete an N‐back working‐memory task have a higher probability of escalating cannabis use. Working‐memory network function may be a biomarker for the prediction of course and treatment outcome in cannabis users. Hum Brain Mapp 35:2470–2482, 2014.

Attempted training of alcohol approach and drinking identity associations in US undergraduate drinkers: null results from two studies

There is preliminary evidence that approach avoid training can shift implicit alcohol associations and improve treatment outcomes. We sought to replicate and extend those findings in US undergraduate social drinkers (Study 1) and at-risk drinkers (Study 2). Three adaptations of the approach avoid task (AAT) were tested. The first adaptation – the approach avoid training – was a replication and targeted implicit alcohol approach associations. The remaining two adaptations – the general identity and personalized identity trainings – targeted implicit drinking identity associations, which are robust predictors of hazardous drinking in US undergraduates. Study 1 included 300 undergraduate social drinkers. They were randomly assigned to real or sham training conditions for one of the three training adaptations, and completed two training sessions, spaced one week apart. Study 2 included 288 undergraduates at risk for alcohol use disorders. The same training procedures were used, but the two training sessions occurred within a single week. Results were not as expected. Across both studies, the approach avoid training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. The general identity training also yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes with one exception; individuals who completed real training demonstrated no changes in drinking refusal self-efficacy whereas individuals who completed sham training had reductions in self-efficacy. Finally, across both studies, the personalized identity training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. Despite having relatively large samples and using a well-validated training task, study results indicated all three training adaptations were ineffective at this dose in US undergraduates. These findings are important because training studies are costly and labor-intensive. Future research may benefit from focusing on more severe populations, pairing training with other interventions, increasing training dose, and increasing gamification of training tasks.