Skip to main content
The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
Download PDF

The effect of bilateral tDCS over dorsolateral prefrontal cortex on the cognitive abilities of men with opioid use disorder under methadone therapy: A sham-controlled clinical trial

The Egyptian Journal of Neurology, Psychiatry and Neurosurgery volume 57, Article number: 146 (2021) Cite this article

Abstract

Background/aim

Opioid use disorder (OUD) can have negative impact on cognitive functions. This study aims to evaluate the effect of bilateral transcranial direct-current stimulation (tDCS) over the right/left dorsolateral prefrontal cortex (DLPFC) on the cognitive abilities of OUD men.

Methods

This study is a double-blind sham-controlled randomized clinical trial with a pretest/posttest design. Participants were 31 men with OUD living in Zanjan, Iran, assigned to three groups of left anode/right cathode tDCS, right anode/left cathode tDCS, and sham tDCS. The two active groups received tDCS (2 mA) at 10 sessions each for 10–20 min. The Cognitive Abilities Questionnaire (CAQ) in Persian was used to measure their cognitive abilities before and after intervention. Collected data were analyzed in SPSS v.22 software.

Results

Bilateral DLPFC stimulation resulted in a significant improvement in cognitive flexibility, planning, decision making, inhibitory control/selective attention, and memory of patients in the two active tDCS groups, while the sham tDCS had no significant effect on their cognitive abilities.

Conclusion

Bilateral tDCS over DLPFC, as an effective and complementary treatment, can improve the cognitive abilities of men with OUD.

Trial registration: This study is a double-blind sham-controlled clinical trial (Parallel, IRCT20170513033946N5. Registered 19 Jan 2019, https://en.irct.ir/trial/36081).

Introduction

Opioid Use Disorder (OUD) is a chronic and relapsing disease that imposes heavy costs on patients and society [1]. It includes an overpowering desire to obtain and take opioids, such as heroin, morphine, and opium despite social and professional consequences. OUD causes various medical complications, opioid craving, increased opioid use, and withdrawal symptoms [2]. Nearly, 3 million people in the US and nearly 16 million people worldwide have current or past OUD [3, 4], and the total OUD-related costs are estimated at 55.7 billion dollars annually [5]. In Iran, a study reported that the 12-month prevalence of OUD among 15–64-year-old people in 2011 was 2.4%, where the most widely used drug was opium. Moreover, its rate was higher in men than in women [6]. The etiology of OUD is multifaceted. It is influenced by biologic, environmental, genetic, and psychosocial factors. A notable side effect of OUD is its negative impact on cognitive functioning which refers to multiple mental abilities, including inhibitory control, remembering, decision making, planning, cognitive flexibility, and attention [7]. Substance abuse can cause impairments in these abilities [8,9,10,11,12]. Cognitive flexibility is described as the ability of the mind to switch between two different subjects and the ability to think about multiple concepts simultaneously [13]. This ability allows the individual to adapt to different situations quickly and efficiently. Chronic opioid use is associated with deficits in cognitive flexibility [14]. Planning ability is an important cognitive skill that forms our executive functions. It is defined as ability to "think about the future" or mentally anticipate the right way to carry-out a task or reach a specific goal [15]. Another cognitive ability that is impaired by substance abuse is the decision-making ability. It is a process, where a decision maker selects at least one option from among a set of possible options. This process seems to be easy, but it is complicated and somehow difficult, because the decision sometimes is a choice between conflicting values. Studies show that opioid users prefer short-term benefits of their decisions instead of long-term benefits [16]. Another study component is attention which has different types (focused, sustained, selective, and divided attention). It is the ability to choose and concentrate on relevant stimuli. Attention may be impaired by a variety of disorders [17]. Various studies have reported a bias in attention in people with substance abuse, such as alcohol [18] and nicotine users [19]. Memory is another cognitive component that can temporarily hold information, and is important for reasoning, learning, and the guidance of decision-making and behavior [20, 21]. Studies have shown the destructive effect of drug addiction on memory. Memory bias has been reported in opioid users [22]. Cortico-striatal circuits, amygdala, hippocampus, nucleus accumbens, and prefrontal cortex that are negatively affected by exposure to drugs, are involved in memory and cognition [23,24,25,26]. The final cognitive component is inhibitory control (response inhibition) which is defined as the ability to control one’s attention, behavior, thoughts, and/or emotions to override a strong internal predisposition, and do what is more needed [20, 27]. Inhibitory control has an important role at different stages of the addiction cycle, i.e., 1) initial use of substance; 2) transition from recreational use to heavier use and abuse; 3) continuation of use for those who get addicted; 4) relapse after abstinence [28]. Multiple studies have focused on the relationship between chronic substance use and inhibitory control, but findings are equivocal [27, 29].

There are a variety of approaches for rehabilitation of OUD patients including: cognitive–behavioral approaches, education, reward cooperation, and medications (e.g., methadone, buprenorphine and naltrexone), and non-pharmacological methods [30]. Despite significant advances in treatments for OUD, these methods have some limitations that emphasize the need for new approaches [31]. For example, despite the effective clinical use of methadone, some neuropsychological studies have shown that methadone has negative effects on cognitive function including attention, memory and information processing [32]. Recently, new therapies, such as non-invasive brain stimulation have emerged for treatment of addiction, one of which is Transcranial Direct-Current Stimulation (tDCS) [33]. It is a non-invasive technique that involves the application of low voltage (usually 0.5–2 mA) electrical current over the scalp through two electrode surfaces (one anode and one cathode). Anodal tDCS causes a depolarization of neurons and thus increases cortical excitability, while cathodal tDCS causes neuronal hyperpolarization and reduces cortical excitability [34]. The current penetrates the skull, reaching the cerebral cortex, and thus regulating neural activity. Due to the ease of implementation of this method, its low side effects and costs, it has been used in many studies [35,36,37]. tDCS-induced modulations of cortical excitability have been proposed as being able not only to affect human cognitive functions but also to modify addictive behaviors [38]. In most of tDCS-related studies, the dorsolateral prefrontal cortex (DLPFC) is selected for stimulation [38,39,40], because the DLPFC is involved in decision making, cognitive control, and attention [41, 42]. Due to the lack of access to traditional therapies, or the failure of gold standard treatment regimens (on methadone or buprenorphine), drug addicts can be benefited from alternative non-invasive methods, such as tDCS. No study was found on the effect of bilateral tDCS on cognitive abilities of patients with OUD. In this regard, this study aimed to evaluate the effect of bilateral tDCS over the DLFC on the cognitive functions of men with OUD. It is hypothesized that anodal stimulation of left DLPFC lead to facilitation and cathodal stimulation of left DLPFC lead to inhibition and vice versa in the right DLPFC.

Methods

Study design and samples

This study is a randomized sham-controlled double-blind clinical trial (Parallel) with a pretest/posttest design. The study population consisted of all men with OUD living in Zanjan, Iran in 2018. Their addiction was diagnosed using Structured Clinical Interview for DSM, axis I and II (SCID-I and SCID-II). The GPower software was used to determine the sample size by setting alpha error probability as P = 0.05 and the effect size as 6%, which was obtained 36. Study samples were selected using a convenience sampling technique based on the inclusion criteria (age 18–50 years, at least a middle school education, history of opium use and its derivatives, being under methadone therapy for at least 2 weeks, and not receiving any psychological or technological treatment in the past 1 month). Having suicidal thoughts, severe mental disorders, such as schizophrenia, history of head trauma, epileptic seizures, existence of any implanted pacemaker, and absent for more than two sessions in the intervention program were the criteria for exclusion from the study. Participants were randomly divided into three groups of A = Left anode/right cathode tDCS (n = 12), B = Right anode/left cathode tDCS (n = 12), and C = Sham tDCS (n = 12) in the Sealed Envelope website (https://www.sealedenvelope.com/). Figure 1 plots the flowchart of the study process.

Fig. 1
figure 1

Flowchart of the study process

Full size image

Assessment tools

After obtaining ethical approval from the Research Ethics Committee and an informed written consent from the participants, their information (Age, marital status, education, disease duration) were recorded using a demographic form. Then, they completed the Cognitive Abilities Questionnaire (CAQ) developed by Nejati et al. [43] in Persian. It has 30 items and 7 subscales (memory, inhibitory control/selective attention, planning, decision making, sustained attention, social cognition, and cognitive flexibility). The items are scored on a 5-point Likert scale from 1 = almost never to 5 = almost always. The total score of CAQ ranges from 36 to 180. With a Cronbach's alpha of 0.83, the CAQ have proper reliability for evaluation of cognitive abilities [43]. It should be mentioned that assessments before and after treatment were performed by another expert (MS in Clinical Psychology) who was unaware of the results.

Intervention

Patients in A and B groups received active tDCS over DLPFC (anode left/cathode right and anode right/cathode left stimulation) for 20 min, once a day, for 10 consecutive days (2-mA intensity) using a FDA-approved device (ActivaDose ll, ActivaTeK Inc., Taiwan), while the C group received sham tDCS. The number of sessions was determined according to De Almeida et al. [44] In the active groups, two electrodes (positive anode and negative cathode) were positioned in the subjects’ head over DLPFC (anode position over F3 and cathode over F4 in one group, and anode position over F4 and cathode over F3 in other group, according to the EEG 10–20 International System) covered by a sponge soaked in saline.

Data analysis

Immediately after the end of intervention, cognitive abilities of subjects were measured again. Out of 36 subjects, 6 were withdrawn from the study (2 in group A due to the death of close relatives, one in group B due to travel, and 2 in group C due to relapse). At the end, the data of 31 subjects were analyzed in SPSS software using descriptive statistics (mean, standard deviation) and statistical tests including Chi-square test (for examining the difference between groups in terms of demographic factors at baseline), one-way ANCOVA (for examining the difference between groups in terms of cognitive abilities after intervention) and Bonferroni test (for pairwise comparison of groups). Before conducting parametric tests, the normality assumption was examined by Kolmogorov–Smirnov (KS) test and the equality of variances was assessed by Levene’s test. The KS test results reported the normal distribution of demographic factors (p > 0.05), and the Levene’s test results showed the equal variances for these factors (P < 0.05).

Results

Table 1 presents the demographic characteristics of participants in three groups. The mean age of participants and their disease duration in group A were 34.40 ± 7.66 and 11.90 ± 4.93 years, respectively; in group B, the values were 32.27 ± 9.99 and 12.36 ± 5.76 years; and in the sham group, as 32.70 ± 9.34 and 12.50 ± 6.58 years. As shown in Table 1, at baseline, there was no significant difference between the groups in terms of marital status and education according to Chi-square test results (P > 0.05), and no significant difference in terms of age and disease duration according to ANOVA results (P > 0.05). Table 2 presents the mean scores of CAQ dimensions before and after intervention. As can be seen, the score of cognitive flexibility, planning, decision making, inhibitory control/selective attention, and memory increased after brain stimulation in the two active groups, while their level were decreased or remained unchanged in the sham group. One-way ANCOVA results showed that these changes in the active groups were statistically significant (p < 0.05), but the changes in sustained attention and social cognition were not significant (Table 3). The partial eta squared value showed that 43, 38, 36, 34 and 37% of variances in cognitive flexibility, planning, decision making, inhibitory control/selective attention and memory are explained by the tDCS. Bonferroni post hoc test was used to discover which specific means differed. The results are presented in Table 4. There was no significant differences between active groups A and B in any dimensions of cognitive functioning after intervention (p > 0.05), but the difference in the post-intervention level of cognitive abilities was significant between groups A and C and between B and C (p < 0.05).

Table 1 Demographic statistics of participants in the three study groups
Full size table
Table 2 Mean and standard deviation (SD) of COQ scores before and after intervention
Full size table
Table 3 Test of between-subjects effects after intervention
Full size table
Table 4 Pairwise comparison results using the Bonferroni test
Full size table

Discussion

To our knowledge, this study is the first sham-controlled clinical trial that investigates the effect of tDCS over the right and left DLPFC on different cognitive abilities of opioid users. Our findings showed that both left and right DLPFC stimulation resulted in improvement of cognitive flexibility, planning, decision-making, inhibitory control, and memory in men with OUD. There are some similar studies that have used tDCS over the DLPFC in different patients. In most of the studies on addicts, the tDCS has been applied over the DLPFC [39, 44,45,46] which indicates the role and importance of this brain region in cognitive functions and its impairment by drug addiction. The prefrontal cortex plays an important role in cognitive control, which determines goals and how to achieve it. It regulates cognitive functions, such as inhibitory control, attention, planning, and risk-taking. Low activity of the prefrontal cortex may lead to defects in these functions and more cognitive and motor impulsivity [44]. DLPFC, as one of the most important areas of the prefrontal cortex, is responsible for diagnosing and determining actions, and evaluating the future consequences of current behavior. Stimulation of this area can improve the mentioned abilities [45]. Dadashi et al. [46] in their study also showed that anodal tDCS over the left DLPFC reduced attentional bias in opium addicts. In Gorini et al.’s study [38] on cocaine users, tDCS over the right and left DLPFC resulted in a reduction of risk-taking behaviors. Teti Mayer et al. [42] applied tDCS over the DLPFC for 5 consecutive days in 50 patients with borderline personality disorder, and reported its effect on the reduction of their impulsivity as a risky behavior. In the study by Cheng and Lee [40], tDCS also significantly reduced risky decision-making in impulsive individuals. These findings are consistent with our results; however, Boggio et al. [47] showed that both right anodal and left anodal DLPFC stimulation increased the propensity for risk-taking in marijuana users which is against the results of present study. This discrepancy may be due to the difference in substance and study area.

Metzuyanim-Gorlick and Mashal [48] suggested that tDCS can improve response inhibition for the long term in healthy adults, which is in agreement with our findings. Inhibitory control ability prevents automatic responses and stops inappropriate cognitive processes that may disrupt the proper performance of a purposeful action. Therefore, it can be said that inhibitory control acts as a filter and is associated with social competence and behavioral and emotional control, and its impairment may cause impulsivity [49]. Andrews et al. [50] found out that anodal tDCS to the left DLPFC combined with cognitive activity can result in greater improvement in working memory performance in healthy subjects, while Keshvari et al. [51] reported that bilateral stimulation of DLFC is not a useful procedure to improve working memory.

Our results showed no significant effect of bilateral tDCS on sustained attention and social cognition of addicts. This may be because addicts in our study were under methadone therapy. Despite the effective clinical use of methadone, some neuropsychological studies have shown that methadone has negative effects on cognitive function including attention, memory and information processing [32]. Henry et al. [52] reported significant impairment in psychomotor performance/attention and episodic memory of patients under methadone maintenance. Stonsaovapak et al. [53] in a sham-controlled trial, examined the effect of anodal tDCS over the right DLPFC on cognitive function in patients with mild cognitive impairment. Their results revealed a significant improvement in visual sustained attention, spatial working memory and visual memory. In terms of sustained attention, their results are against our findings which may be due to the difference in samples and the duration of stimulation. In our study, it was performed for 10 sessions (once a day) on opioid addicts, while participants in their study had mild cognitive impairment treated 3 times per week for 4 weeks (12 sessions).

The results obtained from the current study can be valuable for establishing new concepts for the treatment of opioid addicts. In addition, providing new information regarding the possible effects of tDCS on their cognitive abilities can be useful in the study of mechanisms underlying cognitive behavior. Our study had some disadvantages including: low number of participants, existence of comorbid diseases (e.g., depression, anxiety, and infectious diseases) and not assessing their effect on the study outcome, studying only males with OUD (since women face significant stigmatization regarding their substance use in Iran and are reluctant to receive treatment), lack of a follow-up for relapse (due to the aggressive behavior of addicts), and use of a subjective scale. In this regard, further studies are recommended using a higher sample size, an objective scale (e.g., Wisconsin Card Sorting Test or Trail Making Test), females with OUD, and a follow-up period. The use of advanced MR imaging techniques such as functional MRI (fMRI) and MR spectroscopy are also suggested to identify brain changes caused by tDCS or performing QEEG guided-based neurofeedback treatment.

Conclusion

The bilateral tDCS over the DLPFC can improve cognitive functioning in opioid users. As a non-invasive and complementary treatment, it can be used in improving and enhancing the cognitive abilities of opioid addicts.

Availability of data and materials

The data sets used and/or analysed during the current study available from the corresponding author on reasonable request.

Abbreviations

OUD:

Opioid use disorder

DLPFC:

Dorsolateral prefrontal cortex

KS:

Kolmogorov–Smirnov

SCID-I:

Structured Clinical Interview for DSM, axis I

SCID-II:

Structured Clinical Interview for DSM, axis II

CAQ:

Cognitive Abilities Questionnaire

tDCS:

Transcranial Direct-Current Stimulation

References

  1. Amercian Psychiatric Association. Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5). US: American Psychiatric Pubishing; 2013.

    Book  Google Scholar 

  2. John WS, Zhu H, Mannelli P, Schwartz RP, Subramaniam GA, Wu LT. Prevalence, patterns, and correlates of multiple substance use disorders among adult primary care patients. Drug Alcohol Depend. 2018;187:79–87.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Schuckit MA. Treatment of opioid-use disorders. N Engl J Med. 2016;375(4):357–68.

    Article  PubMed  Google Scholar 

  4. Volkow ND, Jones EB, Einstein EB, Wargo EM. Prevention and treatment of opioid misuse and addiction: a review. JAMA Psychiat. 2019;76(2):208–16.

    Article  Google Scholar 

  5. Meyer R, Patel AM, Rattana SK, Quock TP, Mody SH. Prescription opioid abuse: a literature review of the clinical and economic burden in the United States. Popul Health Manag. 2014;17(6):372–87.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Amin-Esmaeili M, Rahimi-Movaghar A, Sharifi V, Hajebi A, Radgoodarzi R, Mojtabai R, et al. Epidemiology of illicit drug use disorders in Iran: prevalence, correlates, comorbidity and service utilization results from the Iranian Mental Health Survey. Addiction. 2016;111(10):1836–47.

    Article  PubMed  Google Scholar 

  7. Fisher GG, Chacon M, Chaffee DS. Chapter 2—theories of cognitive aging and work. In: Baltes BB, Rudolph CW, Zacher H, editors. Work across the lifespan. London: Academic Press; 2019. p. 17–45.

    Chapter  Google Scholar 

  8. Brand M, Roth-Bauer M, Driessen M, Markowitsch HJ. Executive functions and risky decision-making in patients with opiate dependence. Drug Alcohol Depend. 2008;97(1):64–72.

    Article  PubMed  Google Scholar 

  9. Yan W-S, Li Y-H, Xiao L, Zhu N, Bechara A, Sui N. Working memory and affective decision-making in addiction: a neurocognitive comparison between heroin addicts, pathological gamblers and healthy controls. Drug Alcohol Depend. 2014;134:194–200.

    Article  PubMed  Google Scholar 

  10. Henry PK, Umbricht A, Kleykamp BA, Vandrey R, Strain EC, Bigelow GE, et al. Comparison of cognitive performance in methadone maintenance patients with and without current cocaine dependence. Drug Alcohol Depend. 2012;124(1):167–71.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Karimian BB, Alipor A, Zare H, Nahravanian P. Cognitive abilities (concentration, problem solving and explicit/implicit memory) among healthy and addicted individuals. Social Welfare. 2011;11(42):469–89.

    Google Scholar 

  12. Yam A, Clark L, Verdejo-Román J, Albein-Urios N, Martínez-González J, Gutiérrez B, et al. Neural substrates of cognitive flexibility in cocaine and gambling addictions. Br J Psychiatry. 2015;207(2):158–64.

    Article  Google Scholar 

  13. Dong G, Lin X, Zhou H, Lu Q. Cognitive flexibility in internet addicts: fMRI evidence from difficult-to-easy and easy-to-difficult switching situations. Addict Behav. 2014;39(3):677–83.

    Article  PubMed  Google Scholar 

  14. Gaspari M, and Donnici M. Weekend in Rome: a cognitive training exercise based on planning. First Workshop on Socio-Affective Technologies: An Interdisciplinary Approach, October 7, 2019, Bari, Italy

  15. Baldacchino A, Balfour DJ, Passetti F, Humphris G, Matthews K. Neuropsychological consequences of chronic opioid use: a quantitative review and meta-analysis. Neurosci Biobehav Rev. 2012;36(9):2056–68.

    Article  CAS  PubMed  Google Scholar 

  16. Lemenager T, Richter A, Reinhard I, Gelbke J, Beckmann B, Heinrich M, et al. Impaired decision making in opiate addiction correlates with anxiety and self-directedness but not substance use parameters. J Addict Med. 2011;5(3):203–13.

    Article  PubMed  Google Scholar 

  17. Ordikhani-Seyedlar M, Lebedev MA, Sorensen HB, Puthusserypady S. Neurofeedback therapy for enhancing visual attention: state-of-the-art and challenges. Front Neurosci. 2016;10:352.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Li P, Wu P, Xin X, Fan YL, Wang GB, Wang F, et al. Incubation of alcohol craving during abstinence in patients with alcohol dependence. Addict Biol. 2015;20(3):513–22.

    Article  PubMed  Google Scholar 

  19. Xue YX, Deng JH, Chen YY, Zhang LB, Wu P, Huang GD, et al. Effect of selective inhibition of reactivated nicotine-associated memories with propranolol on nicotine craving. JAMA Psychiat. 2017;74(3):224–32.

    Article  Google Scholar 

  20. Diamond A. Executive functions. Annu Rev Psychol. 2013;64:135–68.

    Article  PubMed  Google Scholar 

  21. Kasaeian K, Kiamanesh A, Bahrami H. A comparison of active memory performance and sustained attention among students with and without learning disabilities. J Learn Disabil. 2014;3(4):112–23.

    Google Scholar 

  22. Hasani J, Ghaedniay JA. Implicit and explicit memory bias in opiate dependent, abstinent and normal individuals. Res Addict. 2013;7(26):127–44.

    Google Scholar 

  23. Milton AL, Everitt BJ. The persistence of maladaptive memory: addiction, drug memories and anti-relapse treatments. Neurosci Biobehav Rev. 2012;36(4):1119–39.

    Article  PubMed  Google Scholar 

  24. Luo YX, Xue YX, Shen HW, Lu L. Role of amygdala in drug memory. Neurobiol Learn Mem. 2013;105:159–73.

    Article  CAS  PubMed  Google Scholar 

  25. Li FQ, Xue YX, Wang JS, Fang Q, Li YQ, Zhu WL, et al. Basolateral amygdala cdk5 activity mediates consolidation and reconsolidation of memories for cocaine cues. J Neurosci. 2010;30(31):10351–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016;3(8):760–73.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Liu Y, van den Wildenberg WPM, de Graaf Y, et al. Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders. Neurosci Biobehav Rev. 2019;105:288–304.

    Article  PubMed  Google Scholar 

  28. Garavan H, Potter AS, Brennan KL, Foxe JJ. Chapter 2 - Neural bases of addiction-related impairments in response inhibition. In: Wilson S, editor. The Wiley Handbook on the Cognitive Neuroscience of Addiction. USA: John Wiley & Sons Ltd; 2015. p. 29–54.

    Google Scholar 

  29. Smith JL, Mattick RP, Jamadar SD, Iredale JM. Deficits in behavioural inhibition in substance abuse and addiction: a meta-analysis. Drug Alcohol Depend. 2014;145:1–33.

    Article  PubMed  Google Scholar 

  30. Dydyk AM, Jain NK, Gupta M. Opioid use disorder. Island: StatPearls Publishing; 2020.

    Google Scholar 

  31. Lupi M, Martinotti G, Santacroce R, Cinosi E, Carlucci M, Marini S, et al. Transcranial direct current stimulation in substance use disorders: a systematic review of scientific literature. J ECT. 2017;33(3):203–9.

    Article  PubMed  Google Scholar 

  32. Wang GY, Kydd R, Wouldes TA, Jensen M, Russell BR. Changes in resting EEG following methadone treatment in opiate addicts. Clin Neurophysiol. 2015;126(5):943–50.

    Article  PubMed  Google Scholar 

  33. Sauvaget A, Trojak B, Bulteau S, Jiménez-Murcia S, Fernández-Aranda F, Wolz I, et al. Transcranial direct current stimulation (tDCS) in behavioral and food addiction: a systematic review of efficacy, technical, and methodological issues. Front Neurosci. 2015;9:349.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation. Neuroscientist. 2011;17(1):37–53.

    Article  PubMed  Google Scholar 

  35. Taremian F, Nazari S, Moradveisi L, Moloodi R. transcranial direct current stimulation on opium craving, depression, and anxiety: a preliminary study. J ECT. 2019;35(3):201–6.

    Article  CAS  PubMed  Google Scholar 

  36. Sadeghi Movahed F, Alizadeh Goradel J, Pouresmali A, Mowlaie M. Effectiveness of transcranial direct current stimulation on worry, anxiety, and depression in generalized anxiety disorder: a randomized, single-blind pharmacotherapy and sham-controlled clinical trial. Iran J Psychiatry Behav Sci. 2018;12(2):e11071.

    Article  Google Scholar 

  37. McClintock SM, Martin DM, Lisanby SH, Alonzo A, McDonald WM, Aaronson ST, et al. Neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression: findings from an international randomized controlled trial. Depress Anxiety. 2020;37(3):261–72.

    Article  CAS  PubMed  Google Scholar 

  38. Gorini A, Lucchiari C, Russell-Edu W, Pravettoni G. Modulation of risky choices in recently abstinent dependent cocaine users: a transcranial direct-current stimulation study. Front Hum Neurosci. 2014;8:661.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Moradi Kelardeh S, Yaryari F, Abdollahi MH. Effectiveness of transcranial direct current stimulation on Dorsolateral prefrontal cortex in cigarette craving and Stress. J Res Psychol Health. 2016;10(3):30–7.

    Google Scholar 

  40. Cheng GL, Lee TM. Altering risky decision-making: influence of impulsivity on the neuromodulation of prefrontal cortex. Soc Neurosci. 2016;11(4):353–64.

    Article  PubMed  Google Scholar 

  41. Luigjes J, Segrave R, de Joode N, Figee M, Denys D. Efficacy of invasive and non-invasive brain modulation interventions for addiction. Neuropsychol Rev. 2019;29(1):116–38.

    Article  PubMed  Google Scholar 

  42. Teti Mayer J, Nicolier M, Gabriel D, Masse C, Giustiniani J, Compagne C, et al. Efficacy of transcranial direct current stimulation in reducing impulsivity in borderline personality disorder (TIMBER): study protocol of a randomized controlled clinical trial. Trials. 2019;20(1):347.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Nejati V. Cognitive abilities questionnaire: development and evaluation of psychometric properties. Adv Cogn Sci. 2013;15(2):11–9.

    Google Scholar 

  44. De Almeida RR, Taiar I, Trevizol AP, Shiozawa P, Cordeiro Q. Effect of a ten-day prefrontal transcranial direct current stimulation protocol for crack craving: a proof-of-concept trial. J ECT. 2016;32(3):e8–9.

    Article  Google Scholar 

  45. Khosravian B, Soleimani E. Comparison of the effectiveness of transcranial direct current stimulation of the brain (tdcs) and neurofeedback on craving in substance abusers. J Stud Med Sci. 2018;29(1):20–32.

    Google Scholar 

  46. Dadashi M, Bastami S, Eskandari Z. Effectivness of anodal transcranial direct current stimulation(TDCS) over left dorsolateral prefrontal cortex on drug craving and attentional bias symptoms in opium addictied males. J Adv Med Biomed Res. 2017;25(112):59–71.

    Google Scholar 

  47. Boggio PS, Zaghi S, Villani AB, Fecteau S, Pascual-Leone A, Fregni F. Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Drug Alcohol Depend. 2010;112(3):220–5.

    Article  PubMed  Google Scholar 

  48. Metzuyanim-Gorlick S, Mashal N. The effects of transcranial direct current stimulation over the dorsolateral prefrontal cortex on cognitive inhibition. Exp Brain Res. 2016;234:1537–44.

    Article  PubMed  Google Scholar 

  49. Brevet-Aeby C, Brunelin J, Iceta S, Padovan C, Poulet E. Prefrontal cortex and impulsivity: Interest of noninvasive brain stimulation. Neurosci Biobehav Rev. 2016;71:112–34.

    Article  PubMed  Google Scholar 

  50. Andrews SC, Hoy KE, Enticott PG, Daskalakis ZJ, Fitzgerald PB. Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. Brain stimul. 2011;4(2):84–9.

    Article  PubMed  Google Scholar 

  51. Keshvari F, Pouretemad HR, Ekhtiari H. The polarity-dependent effects of the bilateral brain stimulation on working memory. Basic Clin Neurosci. 2013;4(3):224–31.

    PubMed  PubMed Central  Google Scholar 

  52. Henry PK, Umbricht A, Kleykamp BA, et al. Comparison of cognitive performance in methadone maintenance patients with and without current cocaine dependence. Drug Alcohol Depend. 2012;124(1–2):167–71.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Stonsaovapak C, Hemrungroj S, Terachinda P, Piravej K. Effect of anodal transcranial direct current stimulation at the right dorsolateral prefrontal cortex on the cognitive function in patients with mild cognitive impairment: a randomized double-blind controlled trial. Arch Phys Med Rehabil. 2020;101(8):1279–87.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all participants in this study for their cooperation.

Funding

This study was extracted from the PhD thesis of last author. This study received financial support from Zanjan University of Medical Sciences (Grant Number: 1249).

Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Hossein Mostafavi

  2. Department of Clinical Psychology, Faculty of Medicine, Social Determinants of Health Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

    Mohsen Dadashi

  3. Department of Psychiatry, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Alireza Armani Kia & Reza Pirzeh

  4. Department of Clinical Psychology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Davod Ahmadi

  5. Department of Addiction Studies, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Zakaria Eskandari

Authors
  1. Hossein Mostafavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohsen Dadashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alireza Armani Kia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Davod Ahmadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Reza Pirzeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zakaria Eskandari
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design, revise and final approval: HM; Interpretation and final approval: MD; Analysis: AA, DA, RP; Acquisition, analysis, interpretation, draft preparation, revise and final approval: ZE. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zakaria Eskandari.

Ethics declarations

Ethics approval and consent to participate

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975. A written informed consent was obtained from all patients for being included in the study and ethical approval was then obtained from Zanjan University of Medical Sciences in Iran (code: IR.ZUMS.REC.1397.127).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mostafavi, H., Dadashi, M., Armani Kia, A. et al. The effect of bilateral tDCS over dorsolateral prefrontal cortex on the cognitive abilities of men with opioid use disorder under methadone therapy: A sham-controlled clinical trial. Egypt J Neurol Psychiatry Neurosurg 57, 146 (2021). https://doi.org/10.1186/s41983-021-00401-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s41983-021-00401-5

Keywords