Introduction
Cannabis is the most commonly used illicit substance worldwide, with up to 200 million users. In recent years, cannabis use has increased in Iran, making it the second most commonly used substance after opioids. Prolonged cannabis use is associated with various social, psychiatric, and cognitive consequences. The cannabis use, by stimulating cannabinoid receptors, particularly CB1 receptors, can cause dopaminergic nerve stimulation and dopamine release. Studies have indicated that cannabis use can have long-term negative impact on the brain, causing differences in brain activity between cannabis users and non-users. Addiction to cannabis is characterized by compulsive drug-seeking behavior and craving. The neurobiological mechanism of cannabis craving is still under investigation. Understanding the brain processes involved in cannabis craving can contribute to the development of effective intervention strategies and improve treatment outcomes. There is a need to focus on exploring the neural correlates of cannabis craving using quantitative electroencephalography (QEEG). This study aims to use QEEG to examine the relationship between brain activity and cannabis craving.

Methods
This is a descriptive-analytical study. The study population comprised individuals with cannabis use disorder based on the diagnostic criteria outlined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), referred to the Iran Psychiatric Hospital, of whom 20 were selected  based on the entry and exit criteria, using a convenience sampling method. The inclusion criteria were: having cannabis use disorder based on DSM-5 criteria, and age 18-40 years. Exclusion criteria were a history of active brain injury, epilepsy, seizures, trauma, underlying medical conditions, or severe psychiatric disorders (such as schizophrenia, bipolar disorder, and major depressive disorders), concurrent use of psychiatric medications, and concurrent use of substances other than cigarettes. The EEG recordings were obtained from all participants, and the marijuana craving questionnaire-short form was used to assess cravings. The EEG data were recorded using 19 silver cup electrodes referenced to attached ears according to the 10-20 international system, at a rate of 250 Hz. Each recording lasted about 15-20 minutes and was done at a resting state once with closed eyes and once with eyes open. Quantitative analysis of EEG raw data was done using the EEGLAB module of MATLAB software, version 22. The collected data were analyzed using the fast Fourier transform algorithm, and the relative power values were calculated. The assumption of normality for the data distribution was confirmed using the Kolmogorov-Smirnov test, and Pearson correlation test was used to examine the relationship between craving and brain activity.

Results
Participants included 19 men and one woman. Table 1 presents the results of correlation test between craving and activity of brain regions at different frequency bands under eyes-open and eyes-closed conditions. A significant negative correlation was observed between craving and relative power at theta frequency band in the frontal (F7) and temporal (T3) regions under eyes-open condition, while there was a significant positive correlation between craving and relative power in the beta frequency band in the temporal (T4) and occipital (O2) regions and in the gamma frequency band in the temporal (T3), frontal (F3), and central (C3) regions. Under eyes-closed condition, a significant positive correlation was found between craving and relative power in the beta and gamma frequency bands in the temporal regions (T3, T5) and parietal region (P3). The results of the linear regression analysis demonstrated that the activity of brain regions was able to predict cravings.



Conclusion
Our findings revealed significant associations between cannabis craving and brain activity in several frequency bands. Consistent with previous studies, we observed that individuals with higher cannabis craving level had lower relative power in the theta band within the frontal and temporal regions. This finding suggests that alterations in power of theta band may be related to the experience of cannabis craving. Moreover, our results indicated that individuals with craving had higher relative power in the beta band within the temporal, occipital, and parietal regions. This increase in beta band power may indicate the impact of cannabis use on working memory and cognitive performance, as well as potential differences in the activity of temporal region. These findings are consistent with existing evidence. For example, fMRI studies reported increased brain activity among cannabis users and a correlation between cannabis craving and the activity of specific brain regions such as the amygdala, striatum, and orbitofrontal cortex.
Furthermore, our study revealed a positive and significant correlation between cannabis craving and relative power in the gamma band within the temporal, frontal, and central regions. This suggests that higher cannabis craving is associated with elevated gamma band power. Interestingly, we did not find any significant correlation between cannabis craving and relative power in the alpha and delta bands. It is important to note that discrepancies in findings may be due to individual differences in factors such as age of onset, dosage and duration of cannabis use, genetics, methodologies, data recording and analysis techniques, EEG devices.
This study provides evidence of a significant relationship between brain activity and craving among individuals with cannabis use disorder. However, further research is needed to enhance our understanding of this relationship and to address the limitations of this study. Continued investigation in this area field can lead to the development of more effective treatment strategies.

Ethical Considerations

Compliance with ethical guidelines
This study has ethical approval from Iran University of Medical Sciences (Code: IR.IUMS.REC.1401.622). 

Funding
This article was extracted from the PhD thesis of Neda Vahad, approved by the School of Behavioral Sciences and Mental Health, Tehran Psychiatric Institute. The study was funded by Iran University of Medical Sciences (Grant number: 24915).

Authors contributions
Conceptualization, methodology, data interpretation, writing original draft: Neda Vahad; Supervision, design, review & editing, and funding acquisition: Mohammad Baqer Saberi Zafarkandi and Reza Arzumendan; Counseling: Mohammadreza Pirmoradi; Reading and final approval: All authors.

Conflicts of interest
The authors declared no conflict of interest.

Acknowledgments
The authors would like to thank all participants, the Vice-Chancellor for Research of Iran University of Medical Sciences, Iran Psychiatric Hospital, and Dr. Hamidreza Ahmadkhaniha and Dr. Ahmad Hajebi from the Addiction and Risky Behaviors Research Center for cooperation and support in this study.