Take control Developing and testing novel treatments of substance dependence by targeting underlying neurocognitive processes

In this PhD project we investigated the effect of N-acetylcysteine (NAC) and working memory (WM) training on substance use, and associated changes in neural correlates of substance dependence. N-acetylcysteine is a glutamatergic agent that reduces craving by restoring the imbalance in the brain glutamate homeostasis, whereas WM-training increases cognitive control and associated brain functioning. In addition, ecological momentary assessment (EMA) was used to acquire fine-grained and contextualized information on treatment effects in order to investigate correspondence of laboratory data with EMA data in regular cocaine using participants. In this thesis, an overview was provided on the recovery of neurocognitive functions and associated brain structures and functions after a substantial period of substance use cessation. More specifically, there was an increase in glutamate, but not GABA, concentrations in the dACC between substance users (smokers and smoking polysubstance users) and non-users, but not between the substance using groups. Although there were differences in impulsivity between groups, impulsivity was not correlated with glutamate or GABA concentrations in the dACC. Little evidence was found for clinical, cognitive or neurobiological effects of NAC and/or WM-training. In addition, the EMA data corresponded with the laboratory data. The main limitations were small sample sizes due to substantial dropout and lack of a non-using control group. Future research should increase sample sizes by increasing motivation, include a control group and focus on the timing of these interventions in treatment.