Context: Non-alcoholic substance abuse is a major public health concern worldwide, with methamphetamine being the second most widely used non-alcoholic substance globally, and Iran ranks fifth in methamphetamine addiction. To date, no approved pharmacological or non-pharmacological treatment by the Food and Drug Administration has been introduced for methamphetamine use disorder (MUD). Therefore, various treatment methods are currently utilized. One non-pharmacological approach that has gained attention is transcranial-direct current stimulation (tDCS), with various clinical evaluations focused on it. Objectives: The aim of this review is to assess the effectiveness of this method in improving symptoms in individuals with MUD. Materials and Methods: Databases were reviewed up to October 10, 2023, in both Persian and English languages, using PubMed, Scopus, Web of Science, Google Scholar, Science Direct, Scientific Information Database (SID), and Noormags. Keywords were MUD, tDCS, Addiction, Craving, and Cognitive Function. Studies were included based on Population, Intervention, Comparison (sham or active control), Outcomes (craving or cognition), and Study Design (randomized controlled trial). Studies were excluded if they involved brain mapping or neuroimaging. Meta-analysis was conducted based on Standardized Mean Difference (SMD) to compare tDCS to sham intervention (P ≤ 0.05, two-tailed). Random effects models were used for individual MUD data from studies that reported end-of-treatment craving data. The risk of bias was calculated using the Cochrane Risk-of-Bias Tool (RoB-2), and meta-analysis was conducted using Comprehensive Meta-Analysis Software. Results: A total of 870 studies were initially identified; twenty-three studies (mean age 30.13 ± 6.67) were identified that examined the effects of tDCS on MUD outcomes (e.g., craving, cognition). After removing heterogeneous studies, meta-analyses were performed for tDCS vs. sham control studies in the craving domain. We found that tDCS reduced craving, indicated by medium to large effect sizes (Hedges' g: -0.64; SMD -0.58, 95% CI -0.85 to -0.30; I² = 10.71%, Q value: 8.96). Results showed that complementary treatment with tDCS can be useful. The DLPFC (F3, F4) was the most commonly targeted brain region for stimulation or inhibition. However, the number of sessions and their duration varied significantly across studies. Conclusions: This systematic review and meta-analysis found that tDCS can reduce momentary and cue-induced cravings. However, the studies varied in quality and sample size and used different scales for assessing cravings and cognitive functions, leading to inconsistencies. The review highlighted the importance of targeting the DLPFC due to its role in executive functions and self-control, with right-sided stimulation showing greater effectiveness. Emotional dysregulation in MUD, such as anxiety and depression, was also noted, with tDCS showing limited support for emotion regulation. The review identified the need for larger RCTs, standardized measurement tools, and detailed participant information to improve the understanding and effectiveness of tDCS in treating MUD.
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