The effect of N-acetylcysteine and working memory training on glutamate concentrations in the dACC and rACC in regular cocaine users - A randomized proof of concept study.

INTRODUCTION: Current treatments for cocaine use disorder (CUD) are not very effective and better treatments are needed. This study investigates the effectiveness of a combined intervention that targets the assumed underlying glutamate pathology in cocaine users. To this end, the combined effects of N-acetylcysteine (NAC) and working memory (WM) training on glutamate concentrations in the dorsal and rostral ACC were investigated in a randomized, double-blind placebo-controlled design. METHODS: In this study, 38 regular cocaine-using men were randomized to either 25-days with 2400 mg/day NAC and WM-training or 25 days with placebo with WM-training. Cocaine use, impulsivity, and glutamate concentrations in the dACC and rACC using proton Magnetic Resonance Spectroscopy were assessed at baseline and after treatment. RESULTS: Twenty-four participants completed the study, of which 9 received NAC and 15 received placebo. There were no baseline correlations of glutamate concentrations in the dACC or rACC with cocaine use measures or impulsivity. Additionally, there were no effects of NAC, WM-training, or the combination thereof on (changes in) glutamate concentrations in the dACC or rACC. DISCUSSION: This randomized proof of concept study could not confirm our hypotheses. Possible explanations are insufficient power and the possible absence of deviant baseline glutamate concentrations in the included participants. Future studies should consider larger samples and a non-using control group to confirm baseline deviations in glutamate in cocaine users.

The effect of N-acetylcysteine and working memory training on neural mechanisms of working memory and cue reactivity in regular cocaine users.

The current study investigated the combined effects of N-acetylcysteine and working memory (WM) training on behavioral and neural mechanisms of cue reactivity and WM in cocaine users in a randomized, double-blind design. Twenty-four of 38 cocaine-using men completed a 25-day treatment with either 2400 mg/day NAC or placebo. Both groups performed WM-training. During pre- and post-test lab-visits, neural mechanisms of cue reactivity and WM, and cue-induced craving and WM performance were assessed. Additionally, exploratory whole brain analyses were performed. Overall, the hypotheses were not confirmed, possibly due to small sample size, low WM-training adherence and/or ongoing substance use.

The effect of N-acetylcysteine and working memory training on cocaine use, craving and inhibition in regular cocaine users: correspondence of lab assessments and Ecological Momentary Assessment.

INTRODUCTION: Effective treatment for cocaine use disorder should dampen hypersensitive cue-induced motivational processes and/or strengthen executive control. Using a randomized, double-blind, placebo-controlled intervention, the primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC) and working memory (WM)-training to reduce cocaine use and craving and to improve inhibition assessed in the laboratory and during Ecological Momentary Assessment (EMA). The second aim was to examine correspondence between laboratory and EMA data. METHODS: Twenty-four of 38 cocaine-using men completed a 25-day intervention with 2400mg/day NAC or placebo and WM-training as well as two lab-visits assessing cocaine use, craving and inhibition (Stop Signal task). Additionally, cocaine use, craving and cognition (Stroop task) were assessed using EMA during treatment, with 26 participants completing 819 assessments. RESULTS: Cocaine problems according to the Drug Use Disorder Identification Test (DUDIT) decreased more after NAC than after placebo, and the proportion of cocaine-positive urines at lab-visit 2 was lower in the NAC group. No NAC effects were found on craving. For cocaine use and craving, results from the lab data were generally similar to EMA results. NAC also showed some effects on cognitive control: improved inhibition assessed with the Stop Signal task in the lab, and decreased classic Stroop performance during EMA. There were no significant effects of number of completed WM-training sessions. CONCLUSIONS: Overall this study revealed mixed findings regarding the treatment of cocaine use disorders with NAC and WM-training. The effect of NAC on inhibition should be further investigated.

Do online assessed self-report and behavioral measures of impulsivity-related constructs predict onset of substance use in adolescents?

INTRODUCTION: To prospectively predict the onset of use of alcohol, cigarettes and marijuana among Dutch adolescents, using behavioral and self-report measures of impulsivity-related facets. Specifically, we investigated whether behavioral measures of impulsivity predicted the onset of substance use above and beyond self-report measures of impulsivity and sensation seeking in an online sample. METHODS: Self-report and behavioral data from 284 adolescents (195 girls, mean age = 14.8 years, SD = 1.26) were collected at four time points over a period of two years, using an online survey system. Impulsivity-related facets were assessed at time point 1 with the Delay Discounting Task, the Balloon Analogue Risk Task and the Passive Avoidance Learning Task. We conducted logistic regression analysis to examine whether behavioral and self-report measures uniquely predicted onset of alcohol use, heavy episodic drinking, smoking and marijuana use. RESULTS: Onset of cigarette smoking was associated with behavioral assessment of impulsive decision making, but not after controlling for self-reported impulsivity and sensation seeking. Behavioral measures were sometimes associated with, but appeared not to prospectively predict, the onset of substance use in this online sample after controlling for self-report measures. CONCLUSIONS: Based on the present results, the added value of online behavioral assessment of impulsivity-related factors in the prediction of onset of substance use was not confirmed. We suggest that factors specific to each behavioral task underlie their lack of prediction and suggest that future research addresses limitations of current behavioral tasks to increase their validity in online testing.