Addiction, Development, and Psychopathology (ADAPT) Lab, Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Meibergdreef 5, Amsterdam, Netherlands; Faculty of Movement and Behavioral Science, Department of Clinical, Neuro- and Developmental Psychology, Section of Clinical Psychology, VU University, Amsterdam, the Netherlands.
Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Meibergdreef 5, Amsterdam, Netherlands; Arkin, Department of Research and Quality of Care, Amsterdam, the Netherlands.
Neurosci Lett. 2021 Sep 25;762:136146. doi: 10.1016/j.neulet.2021.136146. Epub 2021 Jul 29.
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.
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.
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.
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.
目前治疗可卡因使用障碍（CUD）的效果并不理想，需要更好的治疗方法。本研究旨在探究一种联合干预措施对可卡因使用者假设的谷氨酸病理的有效性。为此，我们采用随机、双盲、安慰剂对照设计，研究了 N-乙酰半胱氨酸（NAC）和工作记忆（WM）训练对背侧和额极前皮质（ACC）谷氨酸浓度的综合影响。
本研究纳入 38 名经常使用可卡因的男性，随机分为 NAC 联合 WM 训练组（每天 2400mg，共 25 天）和安慰剂联合 WM 训练组（共 25 天）。在基线和治疗后，采用质子磁共振波谱技术评估 dACC 和 rACC 中的可卡因使用情况、冲动性和谷氨酸浓度。
24 名参与者完成了研究，其中 9 名接受 NAC 治疗，15 名接受安慰剂治疗。dACC 或 rACC 中的谷氨酸浓度与可卡因使用量或冲动性均无基线相关性。此外，NAC、WM 训练或两者联合均未对 dACC 或 rACC 中的谷氨酸浓度（变化）产生影响。
这项随机概念验证研究未能证实我们的假设。可能的解释是研究的效力不足，以及纳入的参与者中谷氨酸浓度可能没有出现异常。未来的研究应考虑更大的样本量和非使用者对照组，以确认可卡因使用者的谷氨酸基线偏差。
