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

Mieke H.J. Schulte; Anna E. Goudriaan; Wouter J. Boendermaker; Wim van den Brink; Reinout W. Wiers

doi:10.1016/j.neulet.2021.136146

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

Mieke H.J. Schulte^*, Anna E. Goudriaan, Wouter J. Boendermaker, Wim van den Brink, Reinout W. Wiers

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	136146
Pages (from-to)	1-5
Number of pages	5
Journal	Neuroscience Letters
Volume	762
Early online date	29 Jul 2021
DOIs	https://doi.org/10.1016/j.neulet.2021.136146
Publication status	Published - 25 Sept 2021

Bibliographical note

Funding Information:
This work was funded by grant 022.003.038 from NWO (Dutch Research Council), awarded to the Dutch-Flemish Research School Experimental Psychopathology.

Funding Information:
The authors would like to thank Dr. Denise S. van Deursen of the Psychology department of the University of Amsterdam and Prof. dr. Malte Friese of the psychology department of the Saarland University for designing the visuo-spatial working memory task that was used in the working memory training of the current study. MHJS, RWW, AEG, and WvdB designed the study and wrote the protocol. MHJS and WJB designed the working memory tasks, and WJB programmed the working memory training. MHJS acquired the data, performed statistical analyses, and wrote the first version of the manuscript. All authors contributed to and have approved the final manuscript. This work was funded by grant 022.003.038 from NWO (Dutch Research Council), awarded to the Dutch-Flemish Research School Experimental Psychopathology.

Publisher Copyright:
© 2021 The Authors

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

Glutamate
Impulsivity
N-acetylcysteine
Proton magnetic resonance spectroscopy
Substance use disorders
Working memory training

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Schulte, M. H. J., Goudriaan, A. E., Boendermaker, W. J., van den Brink, W., & Wiers, R. W. (2021). 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. Neuroscience Letters, 762, 1-5. Article 136146. Advance online publication. https://doi.org/10.1016/j.neulet.2021.136146

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abstract = "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.",

keywords = "Glutamate, Impulsivity, N-acetylcysteine, Proton magnetic resonance spectroscopy, Substance use disorders, Working memory training",

author = "Schulte, {Mieke H.J.} and Goudriaan, {Anna E.} and Boendermaker, {Wouter J.} and {van den Brink}, Wim and Wiers, {Reinout W.}",

note = "Funding Information: This work was funded by grant 022.003.038 from NWO (Dutch Research Council), awarded to the Dutch-Flemish Research School Experimental Psychopathology. Funding Information: The authors would like to thank Dr. Denise S. van Deursen of the Psychology department of the University of Amsterdam and Prof. dr. Malte Friese of the psychology department of the Saarland University for designing the visuo-spatial working memory task that was used in the working memory training of the current study. MHJS, RWW, AEG, and WvdB designed the study and wrote the protocol. MHJS and WJB designed the working memory tasks, and WJB programmed the working memory training. MHJS acquired the data, performed statistical analyses, and wrote the first version of the manuscript. All authors contributed to and have approved the final manuscript. This work was funded by grant 022.003.038 from NWO (Dutch Research Council), awarded to the Dutch-Flemish Research School Experimental Psychopathology. Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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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. / Schulte, Mieke H.J.; Goudriaan, Anna E.; Boendermaker, Wouter J. et al.
In: Neuroscience Letters, Vol. 762, 136146, 25.09.2021, p. 1-5.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - 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

AU - Schulte, Mieke H.J.

AU - Goudriaan, Anna E.

AU - Boendermaker, Wouter J.

AU - van den Brink, Wim

AU - Wiers, Reinout W.

N1 - Funding Information: This work was funded by grant 022.003.038 from NWO (Dutch Research Council), awarded to the Dutch-Flemish Research School Experimental Psychopathology. Funding Information: The authors would like to thank Dr. Denise S. van Deursen of the Psychology department of the University of Amsterdam and Prof. dr. Malte Friese of the psychology department of the Saarland University for designing the visuo-spatial working memory task that was used in the working memory training of the current study. MHJS, RWW, AEG, and WvdB designed the study and wrote the protocol. MHJS and WJB designed the working memory tasks, and WJB programmed the working memory training. MHJS acquired the data, performed statistical analyses, and wrote the first version of the manuscript. All authors contributed to and have approved the final manuscript. This work was funded by grant 022.003.038 from NWO (Dutch Research Council), awarded to the Dutch-Flemish Research School Experimental Psychopathology. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9/25

Y1 - 2021/9/25

N2 - 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.

AB - 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.

KW - Glutamate

KW - Impulsivity

KW - N-acetylcysteine

KW - Proton magnetic resonance spectroscopy

KW - Substance use disorders

KW - Working memory training

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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

Abstract

Bibliographical note

Keywords

UN SDGs

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