The Effectiveness of Transcranial Direct Current Stimulation Treatment with Cognitive Rehabilitation on Reducing Craving and Improving Inhibitory Control in Tramadol-Dependent Adolescents

Aims: Abuse of substances leads to much damage in different fields. Therefore, necessary measures should be taken to prevent infection, withdrawal and prevent return. The present study was conducted to investigate the effectiveness of transcranial Direct Current Stimulation combined with cognitive rehabilitation in reducing cravings and improving inhibitory control in adolescents dependent on tramadol. MATERIALS & METHODS: The current research is a semi-experimental type using a pre-test-post-test design and a 2-month follow-up with a control group. The statistical population of the present study is all the boys and girls (14 to 18 years old) dependent on tramadol in Shahrekord in Iran who contacted the researcher in 2022 through calls published in schools and social media. From this population, 30 people (12 girls and 18 boys) were selected from the people who met the criteria for entering the research. The subjects were randomly divided into two groups of 15 people, experimental and control, based on gender matching. The criteria for entering the study were the diagnosis of substance abuse disorder (tramadol), not suffering from other psychological disorders, age 14 to 18 years, not having a history of epilepsy and convulsions, not receiving any other psychological or drug treatment at the same time, no history of direct transcranial current stimulation treatment, no intracranial implants or any other metal object near the head that cannot be removed, having a high motivation to participate as determined through the initial interview and agreeing to participate in the research and signing a written consent form. And the exclusion criteria were the inability to perform cognitive rehabilitation tasks, not participating in more than 2 consecutive sessions in therapy sessions, and the participant's lack of motivation in therapy sessions. To collect data, the desire for drug questionnaire and go/ no go test were used. The Desires for drug questionnaire (DDQ): this questionnaire was designed by Franken et al. in 2002 and it measures the desire to drug at the moment. This questionnaire consists of 14 questions, which are 3 factors of desire and intention towards drug use (questions 1, 2, 12 and 14), desire to use and negative reinforcement and pleasure (questions 4, 5, 7, 9 and 11) and severity of lack of control (questions 3, 6, 8, 10, and 13) on a 6-point Likert scale from zero (not at all true) to five (completely true). The maximum score of a person on this questionnaire is 70 and the minimum score is zero [26]. In Poursaeid et al.'s study, Cronbach's alpha for the entire scale was 0.96 for opium users, 0.95 for crack, 0.90 for methamphetamine and 0.94 for heroin [27]. In the present study, Cronbach's alpha coefficient for the whole scale was equal to 0.91. Go/ No Go Test: This test was used in 1984 by Hoffman to measure response inhibition. In the go/no-go test, there are two situations, in the first situation (go) by presenting a stimulus, the person must provide a response that is compatible with the existing stimulus as quickly as possible and in the second situation (no go), after the presentation of the first stimulus, another stimulus is also presented, and the person must refrain from responding when the second stimulus appears. A person's ability to control his response in the second situation, i.e. the no-go level, is an indicator of his inhibitory control. This test has different versions. In the present study, the second version of PEBL software was used. In the go/ no go test of this software, there are two target stimuli, one of which appears on the screen each time. These two stimuli are P and R. The test consists of two levels. In the first stage, 128 P stimuli and 32 R stimuli appear. The subject must click on the screen when he sees the P, and if the R appears, he must refrain from answering. In the second level, 128 times the R stimulus and 32 times the P stimulus appears, where the person has to click on the screen when they see the R stimulus but refrain from responding when they see the P. The number of wrong responses to the no-go stimulus (R in the first stage and P in the second stage) or in other words, the commission error is considered the main indicator of measuring inhibitory control [28]. Since this test is non-verbal, it is not dependent on culture and foreign research can be used to cite validity and reliability. The reliability and retest coefficient of this test has been reported above 0.8 [29]. In the current study, Cronbach's alpha coefficient for this test (no-go error score) was 0.92. To carry out the current research, calls were first published in the schools of Shahrekord city and on the channels and pages of social media to recruit subjects to carry out the research. After checking the conditions for entering the project, to conduct the current research, the subjects who were contacted to participate in the research were interviewed and received sufficient information about the conditions and duration of the intervention and its safety. Also, before participating in the research, all the subjects completed the informed personal consent form to participate in the research and they were assured of confidentiality and non-disclosure of information. Then the subjects or their parents were given explanations about the treatment methods used and also the research procedure. Before starting the interventions, the subjects were evaluated through the desired tools, i.e. the desires for drug questionnaire and the go/no-go test. Then the members of the experimental group were treated with transcranial direct current stimulation combined with cognitive rehabilitation, but the members of the control group did not receive any intervention and were placed in the waiting line. After completing the interventions, the subjects were re-evaluated. Also, after a period of intervention and a second evaluation, the third evaluation or two-month follow-up was done. In the present study, transcranial direct current stimulation was used through the Neurostim 2 electric current generating device, manufactured by Medina Medicine Company, which continuously and mildly passes the electric current through the head. In this research, the subjects of the experimental group also performed cognitive rehabilitation tasks related to inhibitory control with Captain Log software while receiving transcranial direct current stimulation. Transcranial direct current stimulation was applied in 10 sessions of 20 minutes and 3 sessions every week. The intervention was such that the anode (excitatory) electrode in the posterior lateral region of the left prefrontal lip (left DLPFC) and the cathode (inhibitory) electrode on the posterior lateral region of the right prefrontal lip (right DLPFC), i.e. F3 and F4 regions, respectively, based on the system 10-20 international electroencephalography was placed. In this research, direct electric current was applied with an intensity of 1.5 milliamperes and a duration of 20 minutes. A summary of treatment sessions is given in Table 1. Ethical Permissions: This research has been approved by the research ethics committee of the Shahid Chamran University of Ahvaz in Iran with ethics code 1401.2.24.183177/scu.ac.ir. The ethical principles of the current research were fully observed; Subjects could leave the research whenever they wanted and all their confidential information was protected and destroyed without exploitation. Statistical analysis: To check the effectiveness of the intervention, the method of covariance analysis (MANCOVA) was used. Data were analyzed through SPSS 20 software. FINDINGS: Out of the 30 statistical samples selected, 3 people (2 people from the control group and 1 person from the experimental group) were not able to continue cooperating with the researchers and were excluded from the study. The size of the control group was reduced to 13 people (4 girls and 9 boys) and the size of the experimental group was reduced to 14 people (4 girls and 10 boys). The demographic information of the statistical sample of the present study showed that the average age of the subjects in the study was 16.70±1.35 years. The average of the research variables in the pre-test, post-test and follow-up levels can be seen in Table 2. The Kolmogorov-Smirnov one-sample test was used to check the default normality of the distribution of the variables, and the results showed that except for the inhibitory control in the control group of the follow-up level, the rest of the data had a normal distribution. Since the skewness and kurtosis of this case were in the range of -3.29 to +3.29 (in samples with small volumes), we were able to use parametric tests for analysis. Leven's test was used to check the default homogeneity of variances. The results obtained from Leven's test showed that the F value was not significant at the alpha level of 0.05 in both the post-test and follow-up levels, so the default of homogeneity of variances was maintained. Also, the default homogeneity of the regression slope was investigated. The results showed that the F value of the interaction between the independent variable and the covariance variable, both craving and inhibitory control variables was not significant at the alpha level of 0.05 in both the post-test and follow-up levels, so the default of homogeneity of the regression slopes was also maintained in both the post-test and follow-up levels. Also, based on the Box's M test, the equality of the covariance matrix of the dependent variables between the experimental and control groups in both the post-test and follow-up levels was not significant at the alpha level of 0.05. Considering that the presuppositions of multivariate covariance analysis were established, this test was used to answer the research hypotheses. The results are given in Table 3. The results of Wilk's lambda test at the post-test level showed that there was a significant difference between the averages of the two experimental and control groups, controlling for the effect of the pre-test, at least in terms of one of the dependent variables. And this meant that transcranial direct electrical current stimulation was successful in influencing at least one of the dependent variables (p