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Farahnaz Mohammad_Ghezelayagh1 
, Mohsen Roshanpajouh2 , Reza Arezoomandan3 , Mohammadreza Pirmoradi1
, Mohsen Roshanpajouh2 , Reza Arezoomandan3 , Mohammadreza Pirmoradi1
1- Addiction Studies Department, School of Behavioral Sciences and Mental Health, Tehran Institute of Psychiatry, Iran University of Medical Sciences, Tehran, Iran
2- Addiction Studies Department, School of Behavioral Sciences and Mental Health, Tehran Institute of Psychiatry, Iran University of Medical Sciences, Tehran, Iran ,roshanpajouh@gmail.com
3- Addiction Studies Department, School of Behavioral Sciences and Mental Health, Tehran Institute of Psychiatry, Iran University of Medical Sciences, Tehran, Iran & School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, USA
2- Addiction Studies Department, School of Behavioral Sciences and Mental Health, Tehran Institute of Psychiatry, Iran University of Medical Sciences, Tehran, Iran ,
3- Addiction Studies Department, School of Behavioral Sciences and Mental Health, Tehran Institute of Psychiatry, Iran University of Medical Sciences, Tehran, Iran & School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, USA
Abstract: (87 Views)
Objectives: Cannabis use disorder is characterized by intense craving and impairments in executive functions, including inhibitory control and cognitive flexibility. These two factors may interact in a reciprocal cycle that sustains substance use and increases the risk of relapse. The present study aimed to compare the efficacy of repetitive transcranial magnetic stimulation (rTMS), computerized cognitive rehabilitation (CR), and their combined intervention on executive functions, craving, and neurophysiological indices in individuals with cannabis use disorder.
Materials and Methods: This study was conducted as a randomized controlled trial with a 2×2 factorial design. Forty individuals with cannabis use disorder, with a mean age of 32.4±5.6 years, were randomly assigned to four groups: combined rTMS+CR, rTMS only, CR only, and control. The interventions were delivered over four weeks in 20 sessions. Executive functions, craving, and quantitative electroencephalographic indices were assessed at baseline, at the end of Week 4, and at the Week 8 follow-up. Data were analyzed using mixed-design analysis of variance and two-way factorial analysis of variance.
Results: The combined intervention group showed the greatest improvement in inhibitory control, as measured by the Stroop test (F(6,72)=6.45, p<0.001, ηp²=0.30), and in cognitive flexibility, as measured by the Trail Making Test-Part B (F(6,72)=7.12, p<0.001, ηp²=0.37). Craving decreased by approximately 20% in the combined group, compared with 12.9% in the CR-only group, 4.7% in the rTMS-only group, and 3.5% in the control group. QEEG findings showed significant increases in theta, beta, and gamma power in prefrontal and frontal regions, together with a sustained increase in parietal alpha power. Delta-band functional connectivity between frontal and parietal regions was also strengthened in the combined group, and some of these changes persisted at the four-week follow-up. However, in the factorial analysis, the rTMS×CR interaction was statistically significant only for parietal alpha power (F(1,36)=4.63, p=0.038, ηp²=0.11) and did not reach statistical significance for craving, Stroop performance, or TMT-B performance.
Conclusion: The combined rTMS and cognitive rehabilitation intervention was associated with greater improvements in neurophysiological indices, executive functions, and craving than either intervention alone. Nevertheless, statistical evidence of synergy was limited to parietal alpha power, and the observed superiority in behavioral outcomes cannot be interpreted as definitive evidence of a synergistic effect. Given the small sample size and the absence of objective measures of actual cannabis consumption, these findings should be confirmed in larger studies with longer follow-up periods and biological verification of substance use.
Materials and Methods: This study was conducted as a randomized controlled trial with a 2×2 factorial design. Forty individuals with cannabis use disorder, with a mean age of 32.4±5.6 years, were randomly assigned to four groups: combined rTMS+CR, rTMS only, CR only, and control. The interventions were delivered over four weeks in 20 sessions. Executive functions, craving, and quantitative electroencephalographic indices were assessed at baseline, at the end of Week 4, and at the Week 8 follow-up. Data were analyzed using mixed-design analysis of variance and two-way factorial analysis of variance.
Results: The combined intervention group showed the greatest improvement in inhibitory control, as measured by the Stroop test (F(6,72)=6.45, p<0.001, ηp²=0.30), and in cognitive flexibility, as measured by the Trail Making Test-Part B (F(6,72)=7.12, p<0.001, ηp²=0.37). Craving decreased by approximately 20% in the combined group, compared with 12.9% in the CR-only group, 4.7% in the rTMS-only group, and 3.5% in the control group. QEEG findings showed significant increases in theta, beta, and gamma power in prefrontal and frontal regions, together with a sustained increase in parietal alpha power. Delta-band functional connectivity between frontal and parietal regions was also strengthened in the combined group, and some of these changes persisted at the four-week follow-up. However, in the factorial analysis, the rTMS×CR interaction was statistically significant only for parietal alpha power (F(1,36)=4.63, p=0.038, ηp²=0.11) and did not reach statistical significance for craving, Stroop performance, or TMT-B performance.
Conclusion: The combined rTMS and cognitive rehabilitation intervention was associated with greater improvements in neurophysiological indices, executive functions, and craving than either intervention alone. Nevertheless, statistical evidence of synergy was limited to parietal alpha power, and the observed superiority in behavioral outcomes cannot be interpreted as definitive evidence of a synergistic effect. Given the small sample size and the absence of objective measures of actual cannabis consumption, these findings should be confirmed in larger studies with longer follow-up periods and biological verification of substance use.
Keywords: Cannabis use disorder, repetitive transcranial magnetic stimulation, cognitive rehabilitation, executive functions, craving, quantitative electroencephalography
Type of Study: Original Research |
Subject:
Psychiatry and Psychology
Received: 2025/11/5 | Accepted: 2026/07/19
Received: 2025/11/5 | Accepted: 2026/07/19
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