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 ۲-month follow-up with a control group. The statistical population of the present study is all the boys and girls (۱۴ to ۱۸ years old) dependent on tramadol in Shahrekord in Iran who contacted the researcher in ۲۰۲۲ through calls published in schools and social media. From this population, ۳۰ people (۱۲ girls and ۱۸ boys) were selected from the people who met the criteria for entering the research. The subjects were randomly divided into two groups of ۱۵ 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 ۱۴ to ۱۸ 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 ۲ 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 ۲۰۰۲ and it measures the desire to drug at the moment. This questionnaire consists of ۱۴ questions, which are ۳ factors of desire and intention towards drug use (questions ۱, ۲, ۱۲ and ۱۴), desire to use and negative reinforcement and pleasure (questions ۴, ۵, ۷, ۹ and ۱۱) and severity of lack of control (questions ۳, ۶, ۸, ۱۰, and ۱۳) on a ۶-point Likert scale from zero (not at all true) to five (completely true). The maximum score of a person on this questionnaire is ۷۰ and the minimum score is zero [۲۶]. In Poursaeid et al.'s study, Cronbach's alpha for the entire scale was ۰.۹۶ for opium users, ۰.۹۵ for crack, ۰.۹۰ for methamphetamine and ۰.۹۴ for heroin [۲۷]. In the present study, Cronbach's alpha coefficient for the whole scale was equal to ۰.۹۱. Go/ No Go Test: This test was used in ۱۹۸۴ 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, ۱۲۸ P stimuli and ۳۲ 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, ۱۲۸ times the R stimulus and ۳۲ 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 [۲۸]. 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 ۰.۸ [۲۹]. In the current study, Cronbach's alpha coefficient for this test (no-go error score) was ۰.۹۲. 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 ۲ 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 ۱۰ sessions of ۲۰ minutes and ۳ 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. F۳ and F۴ regions, respectively, based on the system ۱۰-۲۰ international electroencephalography was placed. In this research, direct electric current was applied with an intensity of ۱.۵ milliamperes and a duration of ۲۰ minutes. A summary of treatment sessions is given in Table ۱. Ethical Permissions: This research has been approved by the research ethics committee of the Shahid Chamran University of Ahvaz in Iran with ethics code ۱۴۰۱.۲.۲۴.۱۸۳۱۷۷/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 ۲۰ software. FINDINGS: Out of the ۳۰ statistical samples selected, ۳ people (۲ people from the control group and ۱ 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 ۱۳ people (۴ girls and ۹ boys) and the size of the experimental group was reduced to ۱۴ people (۴ girls and ۱۰ boys). The demographic information of the statistical sample of the present study showed that the average age of the subjects in the study was ۱۶.۷۰±۱.۳۵ years. The average of the research variables in the pre-test, post-test and follow-up levels can be seen in Table ۲. 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 -۳.۲۹ to +۳.۲۹ (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 ۰.۰۵ 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 ۰.۰۵ 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 ۰.۰۵. 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 ۳. 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<۰.۰۵; F=۲۱.۰۵۳; Eta=۰.۶۵). Also, the results of Wilks's lambda test in the follow-up stage showed that there was a significant difference between the averages of the two experimental and control groups, by controlling the effect of the pre-test, at least in terms of one of the dependent variables, And this meant that transcranial direct current stimulation was successful in affecting at least one of the dependent variables (p<۰.۰۵; F=۱۷.۲۲۱; Eta=۰.۶۱). To examine the difference patterns, univariate covariance analysis was used in the context of multivariate covariance analysis. The F statistic with a value of (۳۹.۳۹۶) was significant for craving at the post-test level (Table ۴). This result showed that there was a significant difference between the research groups in the mean craving scores at the post-test level. Considering the lower average scores of the experimental group compared to the control group, it can be said that the intended treatment was significantly effective in reducing the cravings of tramadol-dependent teenagers at the post-test level. Also, the F statistic with a value of (۲۴.۴۰۴) was significant for cravings at the follow-up level (Table ۴). This result showed that there was a significant difference between the study groups in craving for consumption at the follow-up level. Considering the lower average scores of the experimental group compared to the control group, it can be said that the intended treatment was significantly effective in reducing the cravings of adolescents dependent on tramadol at the follow-up level. Also, the F statistic with a value of (۱۵.۶۷۷) was significant for inhibitory control (number of no-go errors) at the post-test level. This result showed that there was a significant difference between the research groups in the mean scores of inhibitory control at the post-test level. Considering the lower average scores of the experimental group compared to the control group, it can be said that the intended treatment was significantly effective in improving the inhibitory control of adolescents dependent on tramadol at the post-test level. Also, the F statistic with a value of (۱۳.۸۴۰) was significant for inhibitory control in the follow-up level (Table ۴). This result showed that there was a significant difference between the research groups in inhibitory control at the follow-up level. Considering the lower average scores of the experimental group compared to the control group, it can be said that the intended treatment was significantly effective in improving the inhibitory control of adolescents dependent on tramadol at the follow-up level. Conclusion: Transcranial Direct Current Stimulation treatment combined with cognitive rehabilitation is effective in reducing cravings and improving inhibitory control in adolescents addicted to tramadol and can be used by relevant experts as an effective treatment in this field. Clinical & Practical Tips in POLICE MEDICINE: According to the results of the current research on the effectiveness of direct transcranial current stimulation treatment combined with cognitive rehabilitation on reducing cravings and improving the inhibitory control of tramadol-dependent teenagers, such interventions can be implemented in counselling and treatment centers of police c, addiction treatment centers affiliated to this organization. Also, the police can provide free interventions for this purpose in educational environments in cooperation with education to prevent drug abuse among teenagers. Acknowledgements: We thank all the participants who accompanied us in this research. Conflict of interest: The authors of the article stated that there is no conflict of interest regarding the present study. Authors' Contribution: First author, idea design, data collection; Second author, idea design; third author, data analysis; All the authors participated in the initial writing of the article and its revision, and all accept the responsibility for the accuracy and correctness of the contents of the present article by finalizing the present article. Financial Sources: The present study had no financial support.   Table ۱) Summary of treatment sessions meeting content time ۱ Transcranial direct current stimulation treatment (anode on the F۳ area and cathode on the F۴ area) with a current intensity of ۱.۵ mA, introducing the Captain Log software and how to work with it, performing racing point exercises, playing cats and target training ۲۰ minutes ۲ Transcranial direct current stimulation therapy (anode on F۳ area and cathode on F۴ area) with a current intensity of ۱.۵ mA, perform mouse hunt exercises, choose quickly and darts ۲۰ minutes ۳ Transcranial direct current stimulation treatment (anode on the F۳ area and cathode on the F۴ area) with a current intensity of ۱.۵ mA, performing exercises on the road, red light-green light and racing point ۲۰ minutes ۴ Transcranial direct current stimulation treatment (anode on the F۳ area and cathode on the F۴ area) with a current intensity of ۱.۵ mA, performing racing point exercises, playing cats and target training ۲۰ minutes ۵ Transcranial direct current stimulation treatment (anode on the F۳ area and cathode on the F۴ area) with a current intensity of ۱.۵ mA, performing mouse hunt exercises, ۲۰ minutes ۶ Transcranial direct current stimulation treatment (anode on the F۳ area and cathode on the F۴ area) with a current intensity of ۱.۵ mA, performing exercises on the road, red light-green light and racing point ۲۰ minutes ۷ Transcranial direct current stimulation treatment (anode on the F۳ area and cathode on the F۴ area) with a current intensity of ۱.۵ mA, performing racing point exercises, playing cats and target training ۲۰ minutes ۸ Transcranial direct current stimulation treatment (anode on the F۳ area and cathode on the F۴ area) with a current intensity of ۱.۵ milliamperes, performing mouse hunt exercises, ۲۰ minutes ۹ Transcranial direct current stimulation treatment (anode on the F۳ area and cathode on the F۴ area) with a current intensity of ۱.۵ mA, performing exercises on the road, red light-green light and racing point ۲۰ minutes ۱۰ Transcranial direct current stimulation treatment (anode on the F۳ area and cathode on the F۴ area) with a current intensity of ۱.۵ mA, performing racing point exercises, playing cats and target training ۲۰ minutes Table ۲) Average research variables in pre-test, post-test and follow-up of two control and experimental groups Group Index Experimental group (M±SD) Control group (M±SD) pre-exam post-test Follow up pre-exam post-test Follow up Craving ۳۷.۷۱±۳.۸۹ ۳۱.۱۴±۴.۷۳ ۳۲.۴۲±۵.۰۴ ۳۵.۷۶±۳.۴۹ ۳۴.۶۹±۳.۴۴ ۳۵.۱۵±۳.۹۱ Inhibitory control (number of errors) ۱۰.۵۷±۱.۹۴ ۷.۳۵±۲.۷۳ ۸.۲۸±۲.۷۸ ۱۰.۳۸±۱.۸۵ ۱۰/۰۷±۱/۸۴ ۱۰.۴۶±۱.۸۰ Table ۳) Multivariate covariance table to check the indicators  before and after the intervention in the post-test and follow-up level. level Index amount F default DF DF Error Effect size p Post-test Wilks Lambda ۰.۳۴۳ ۲۱.۰۵۳ ۲ ۲۲ ۰.۶۵ ۰.۰۰۰۲ Follow up Wilks Lambda ۰.۳۹۰ ۱۷.۲۲۱ ۲ ۲۲ ۰.۶۱ ۰.۰۰۰۲ Table ۴) ANOVA test results in the MANKOVA text on the average scores of the post-test and the follow-up of cravings and inhibitory control with the pre-test control. level Variable Source Total Square Degrees of freedom mean square F p Eta Square power Post-test Craving group ۱۷۴.۹۳۲ ۱ ۱۷۴.۹۳۲ ۳۹.۳۹۶ ۰.۰۰۱ ۰.۶۳ ۱ Inhibitory control group ۱۸.۸۱۵ ۱ ۱۸.۸۱۵ ۱۵.۶۷۷ ۰.۰۰۱ ۰.۴۰ ۰.۹۶۶ Follow up Craving group ۱۲۱.۱۳۴ ۱ ۱۲۱.۱۳۴ ۲۴.۴۰۴ ۰.۰۰۰۱ ۰.۵۱ ۰.۹۹۷ Inhibitory control group ۲۲.۰۹۵ ۱ ۲۲.۰۹۵ ۱۳.۸۴۰ ۰.۰۰۱ ۰.۳۷ ۰.۹۴۵

کلیدواژه ها:

Substance-Related Disorders ، Tramadol ، Transcranial Direct Current Stimulation ، Cognitive Training ، Craving ، Inhibition ، اختلالات مرتبط با سوء مصرف مواد ، ترامادول ، تحریک الکتریکی مستقیم فراجمجمه ای ، توان بخشی شناختی ، ولع مصرف ، مهار (روان شناختی)