Hosein Rafiemanesh, 1 Afarin Rahimi-Movaghar, 2 Ali Akbar Haghdoost, 3 , 4 Alireza Noroozi, 2 Jaleh Gholami, 2 Bita Vahdani, 5 Amin Afshar, 6 , 2 Mohammad Salehi, 6 and Koorosh Etemad 1 ,*
1Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran
3Modeling in Health Research Center, Institute for Futures Studies in Health, University of Medical Sciences, Kerman, Iran
4HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
5Assistant Professor of Psychiatry, Clinical Research Development Unit, 22 Bahman Hospital, Qazvin University of Medical Sciences, Qazvin, Iran
6Department of Neurosciences and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Background: The most common drug, illegally used in Iran is opium. The treatment of people with substance use disorder is one of the most important strategies in reducing its burden. The aim of this study was to investigate the effect of different increasing and decreasing opium treatment coverage on the patterns of abstinence, transition to heroin dependence and mortality, over 30 years.
Methods: This study was a dynamic compartmental modeling conducted in three stages: 1) presenting a conceptual model of opium dependence treatment in Iran, 2) estimating model’s parameters value, and 3) modeling of opium dependence treatment and examining the outcomes for different treatment coverage scenarios. The input parameters of the model were extracted from the literature, and secondary data analysis, which were finalized in expert panels.
Results: The number of opium dependence will increase from 1180550 to 1522063 [28.93% (95% CI: 28.6 to 29.2)] over 30 years. With a 25% decrease in coverage compared to the status quo, the number of deaths will increase by 459 cases [3.28% (95% CI: 0.91 to 5.7)] in the first year, and this trend will continue to be 2989 cases [15.63% (95% CI: 13.4 to 17.9)] in the 30th year. A 25% increase in treatment coverage causes a cumulative decrease of heroin dependence by 14451 cases [10.1% (95% CI: 9.5 to 10.8)] in the first decade.
Conclusion: The modeling showed that the treatment coverage level reduction has a greater impact than the coverage level increase in the country and any amount of reduction in the coverage level, even to a small extent, may have a large negative impact in the long run.
Keywords: Opium, Opium dependence, Heroin dependence, Iran
Amirhossein Dakhili1, 2, Arshiya Sangchooli3, Sara Jafakesh4, Mehran Zare Bidoki5, Ghazaleh Soleimani, Seyed Amir Hossein Batouli1,7, Kamran Kazemi4, Ashkan Faghiri8, Mohammad Ali Oghabian1,7, Hamed Ekhtiari9#
1. Neuroimaging and Analysis Group. (NIAG), Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran Iran
2. Medical Physics Department, Iran University of Medical Sciences, Tehran, Iran
3. Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Science, Tehran, Iran
4. Department of Electrical and Electronics Engineering, Shiraz University of Technology, Shiraz, Iran
5. School of Medicine, Shahid-Sadoughi University of Medical Sciences, Yazd, Iran
6. Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
7. Medical Physics and Biomedical Engineering Department, Tehran University of Medical Sciences, Tehran Iran
8. Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University,
Georgia Institute of Technology, and Emory University, Atlanta, GA 30303, USA
9. Laureate Institute for Brain Research (LIBR), Tulsa, OK, USA
Abstract
Background: Drug-related cue-reactivity, dysfunctional negative emotion processing, and response-disinhibition constitute three core aspects of methamphetamine use disorder (MUD). These phenomena have been studied independently, but the neuroscientific literature on their interaction in addictive disorders remains scant. Methods: 62 individuals with MUD were scanned when responding to the geometric Go or No-Go cues superimposed over blank, neutral, negative-emotional and drug-related background images. Neural correlates of drug and negative-emotional cue-reactivity, response-inhibition and their interactions were estimated, and methamphetamine cue-reactivity was compared between individuals with MUD and 23 healthy controls. Relationships between behavioral characteristics and observed activations were investigated. Results: Individuals with MUD had longer reaction times and more errors in drug and negative-emotional compared to blank blocks, and more omission errors in drug compared to neutral blocks. They showed higher drug cue-reactivity than controls across prefrontal, fusiform, and visual regions (Z > 3.1, p-corrected<0.05). Response-inhibition was associated with precuneal, inferior parietal, anterior cingulate, temporal, and inferior frontal activations (Z > 3.1, p-corrected<0.05). Response-inhibition in drug cue blocks coincided with higher activations in the visual cortex and lower activations in the paracentral lobule and superior and inferior frontal gyri, while inhibition during negative-emotional blocks led to higher superior parietal, fusiform, and lateral occipital activations (Z > 3.1, p-corrected<0.05). Conclusion: Drug cue-reactivity may impair response inhibition partly through activating dis-inhibitory regions, while temporal and parietal activations associated with response-inhibition in negative blocks suggest compensatory activity. Results suggest that drug and negative-emotional cue-reactivity influence response-inhibition, and the study of these interactions may aid mechanistic understanding of methamphetamine use disorder.
Hamid Ahmadian-Moghadam 1, Mitra Sadat Sadat-Shirazi 2, Somaiyeh Azmoun 3, Reza Vafadoost 4, Solmaz Khalifeh 2, Mohammad Reza Zarrindast 5
Abstract
Background: Tramadol induces its unique effects through opioid pathways, but the exact mechanism is not known. The study aims to evaluate changes in the level of mu-opioid receptor (µOR), delta-opioid receptor (δOR), and phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB) in the hippocampus (HPC) and amygdala (AL) areas of tramadol-treated rats. Methods: For this purpose, a total of 36 male rats were divided into two main groups for chronic or acute tramadol exposure. The animals were then exposed to 5 mg.kg-1 of tramadol, 10 mg.kg-1 of tramadol, and normal saline. The HPC and AL areas of the animals were dissected upon completion of the period. The levels of p-CREB and µOR were quantified using the western blotting technique. The data were subjected to analysis of variance (ANOVA) followed by Tukey's post-hoc analysis. The differences with the P-value lower than 0.05 were considered as significant. Findings: In the HPC and AL areas of the brain, the level of µOR was decreased by acute tramadol exposure, while no significant difference was observed by chronic tramadol exposure. Moreover, results showed that the level of p-CREB dose-dependently increased by acute and chronic tramadol exposure. Conclusion: HPC and AL are essential in the control of tramadol abuse. Tramadol abuse affects gene expression and transcription factors such as CREB. With acute drug tramadol treatments, the level of cAMP response element-binding protein (CREB) rapidly increases, while by chronic tramadol treatment, "peak and trough pattern is observing". The activation of the rewarding mechanism is a precise instance of addictive behavior in tramadol-treated individuals.
Keywords: Amygdala; Cyclic adenosine monophosphate response element-binding protein A; Hippocampus; Opioid receptor; Tramadol.
Sakineh Alijanpoura, *, Samira Jafaripourb, Zahra Ghasemzadehc, Fatemeh Khakpai,
Mohammad-Reza Zarrindaste, f, g
Department of Biology, Faculty of Science, Gonbad Kavous University, Gonbad Kavous, Iran
Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran
Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Morphine is one of the most effective medications for treatment of pain, but its side effects limit its use. Therefore, identification of new strategies that can enhance morphine-induced antinociception and/or reduce its side effects will help to develop therapeutic approaches for pain relief. Considering antinociceptive efficacy of harmaline and also highlighted the important role of GABA-A receptors in the pain perception, this research aimed to determine whether the ventral hippocampal (vHip) GABA-A receptors are involved in the possible harmaline-induced enhancement of morphine antinociception. To achieve this, vHip regions of adult male mice were bilaterally cannulated and pain sensitivity was measured in a tail-flick apparatus. Intraperitoneally administration of morphine (0, 2, 4 and 6 mg/kg) or harmaline (0, 1.25, 5 and 10 mg/kg) increased the percentage of maximal possible effect (%MPE) and induced antinociception. Interestingly, co-administration of sub-effective doses of harmaline (5 mg/kg) and morphine (2 mg/kg) induced antinociception. Intra-vHip microinjection of muscimol (0, 200 and 300 ng/mice), a GABA-A receptor agonist, enhanced the anti-nociceptive effects of harmaline (2.5 mg/kg)+morphine (2 mg/kg) combination. Microinjection of the same doses of muscimol into the vHip by itself did not alter tail-flick latency. Intra-vHip microinjection of bicuculline (100 ng/mouse), a GABA-A receptor antagonist, did not cause a significant change in MPE%. Bicuculline (60 and 100 ng/mouse, intra-vHip) was administered with the harmaline (5 mg/kg)+morphine (2 mg/kg), and inhibited the potentiating effect of harmaline on morphine response. These findings favor the notion that GABAergic mechanisms in the vHip facilitate harmaline-induced potentiation of morphine response in the tail-flick test in part through GABA-A receptors. These findings shall provide insights and strategies into the development of pain suppressing drugs.
Keywords: GABA-A receptors; Harmaline; Mice; Morphine; Pain; Ventral hippocampus.
hahsanam Abbasi11,2, Mohammad Nasehi3*, Mohaddeseh Ebrahimi‑Ghiri and Mohammad‑Reza Zarrindast
Institute for Cognitive Science Studies (ICSS), Tehran, Iran,
Department of Stem Cells and Regenerative Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran,
Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran,
Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran,
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran,
Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran,
Department of Neuroendocrinology, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran,
Abstract
Evidence suggests that transcranial direct current stimulation (tDCS) modulates conditioned fear memories and has effects on cognitive flexibility via the dopaminergic system. This study examines whether modulation of scopolamine‑induced fear memory deficit by anodal tDCS could be mediated by the dopaminergic system. The male NMRI mice received scopolamine, 30 min before fear conditioning, and showed impaired contextual memory retention. Mice subjected to left frontal anodal stimulation for 20 or 30 min, before fear conditioning, impaired fear memory retrieval. Anodal application for 20 min significantly decreased scopolamine response on fear retention, while the one applied for 30 min did not alter. Moreover, anodal stimulation for 30 min abolished scopolamine‑induced fear memory deficit. Dopaminergic antagonists SCH23390 and sulpiride, alone or in combination, prevented the abolishment effect of anodal stimulation on scopolamine‑induced fear memory deficit, whereas they did not alter the impairing effect of scopolamine at the dose of 2 mg/kg. Our data suggest that anodal stimulation for 30 min abrogates the impairing effect of scopolamine on fear memory retention. This influence could be prevented by dopaminergic antagonists, indicating the involvement of the dopaminergic system in the effect of anodal stimulation on scopolamine‑induced fear memory deficit.
Buprenorphine abuse and health risks in Iran: A systematic review
Mina Ansaria, Yasna Rostam-Abadia, Shahab Baheshmata, b, Marziyeh HamzehzadehJaleh Gholamia, Ramin Mojtabaic, d, Afarin Rahimi-Movaghara,
Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran
Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences, Tehran, Iran
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Johns Hopkins University Bloomberg School of Public Health, Baltimore, USA
Abstract
Introduction: Buprenorphine maintenance treatment (BMT) is widely used in Iran, and its use is growing continuously. We reviewed studies on buprenorphine use, non-prescribed use, use disorder and treatment-seeking for it, buprenorphine-associated poisoning, and mortality in Iran in the current systematic review. Methods: An Iranian database (Scientific Information Database; SID) and three International electronic databases (PubMed, Scopus, and Web of Science) were searched for publications up to August 2020 for the relevant data. Opportunistic methods (Contact with experts and backward citation tracking) were also used for this purpose. Identified records were screened for eligibility criteria, and data of included studies were extracted. For context, the trend of BMT in the country was also examined. Results: Ten studies were found on the prevalence of non-prescribed buprenorphine use, seven were on the regular use and use disorder, and two studies on buprenorphine poisoning. The last 12-month prevalence of non-prescribed use was lower than 0.5 % in the general population, university, and high school students. The indicator was 2.5 % among persons who use drugs in a 2018 national study. The proportion of buprenorphine poisoning was 4.9 % among all illicit substance poisoning cases admitted to a hospital. The proportion of buprenorphine poisoning cases among all acute pediatric drug poisoning cases increased from 1.2 % to 2.5 % in a 3-year study. Conclusion: Despite the expansion of BMT in Iran in the last decade, the adverse health consequences associated with buprenorphine are infrequent, when compared to other opioids used in Iran, suggesting the safety of BMT for future expansion.
Keywords: Buprenorphine; Epidemiology; Mortality; Opioid agonists; Overdose; Systematic review.
Antidepressant efficacy of MLC901 in the 6-hydroxydopamine mice model of Parkinson’s disease
Mohaddeseh Ebrahimi-Ghiri , Sakineh Alijanpour , Fatemeh Khakpai , Mohammad-Reza Zarrindast
Abstract
Introduction: Depression is a common mood disorder in patients with Parkinson’s disease (PD), which negatively influences the quality of life and enhances caregiver burden. MLC901, a traditional medicine, has been demonstrated to be useful in preclinical and clinical studies. The aim was to study the effect of MLC901 on depression behavior in a mouse model of PD, comprising in the unilateral striatal delivery of the neurotoxin 6-hydroxydopamine (6-OHDA). Methods: Female NMRI mice were divided into the following groups: sham/saline group, 6-OHDA/saline group, sham/MLC901 (40μg/kg) group and 6-OHDA/MLC901 group. Intraperitoneal treatments of MLC901 were started one week after the stereotaxic surgery that continued for 4 weeks (5 days/week). Locomotion was monitored using an openfield test and depressive-like responses were measured by forced swim test (FST) and tail suspension test (TST). Results: We found that MLC901 prevented the increased immobility time in the PD mice in both FST and TST, suggesting an antidepressant efficacy for the MLC901. None of the treatments alter locomotion compared to the sham group. Conclusion: In conclusion, we propose that MLC901 is a potential candidate to be used in studies for the treatment of depression in PD.
Keywords: Parkinson’s disease, MLC901, Forced swim test, Tail suspension test
Prevalence of latent tuberculosis infection and HIV among people who inject drugs in Iran
Seyed Ramin Radfar MD, MPH, NIDA/IAS Fellowship, Researcher, Pardis Nematollahi MD, Assistant Professor, Katayoun Tayeri MD, Researcher, Hamidreza Dehghan MD, Assistant Professor, Majid Janani MS, Researcher, Peter Higgs PhD, Associate Professor, Setareh Mohsenifar MD, Psychiatrist, Alireza Noroozi MD, PhD, Researcher.
Introduction: Iran has an human immunodeficiency viruses (HIV) epidemic that is concentrated among people who inject drugs (PWID), who have higher risks of progression from latent tuberculosis infection (LTBI) to active disease. The aim of this study is to measure prevalence of LTBI, HIV infection and any risk behaviors among PWID in Iran. Methods: The cross-sectional study was conducted from August to December 2013 in six cities across Iran. A total of 420 PWID were recruited from drop-in centers using convenience sampling. Trained interviewers collected data on socio-demographic characteristics, drug use history and drug-related risk behaviors across the study sites. A tuberculin skin test (TST) was performed, and HIV infection was assessed by a rapid test. Multivariable modified Poisson regression and logistic regression were used for data analysis. Results: Prevalence of positive TST and HIV positivity was 35.7% and 8.6%, respectively. The prevalence of LTBI and HIV was significantly different across the cities of this study. Positive TST was independently associated with older age (APR 1.03, 95% CI 1.01, 1.05) and being HIV positive (APR 1.89, 95% CI 1.45, 2.47). HIV infection was associated with lifetime history of sharing syringes (AOR 3.28, 95% CI 1.44, 10.71) and lifetime number of imprisonment (AOR 1.09, 95% CI 1.03–1.14). Discussion and Conclusions: Prevalence of LTBI infections among PWID is high and independently associated with HIV infection. Given that there are currently no TB services available within drop-in centers, programs which integrate TB case finding, TB preventive therapy, referral and care services for PWID are urgently needed.
Qualitative analysis of attitudes, behaviors, and demands of vulnerable men in Tehran, Iran
Minoo Mohraz1, SeyedAhmad SeyedAlinaghi1, Ali Asadollahi-Amin1, Rahele Golrokhi, Effat Merghati Khoei2, Habib Yousefi2, Salar Pashangzadeh1, Omid Dadras31
Introduction: Men who have sex with men (MSM) are a vulnerable group, and their psychological, physical, and social well-being could be affected by various factors. They are also at higher risk of HIV and other sexually transmitted infections (STIs). This study was conducted to identify socio-demographic characteristics and HIV-related risk behaviors among MSM in Iran. Material and methods: A qualitative study was conducted among MSM attending a sexual health clinic in a referral hospital, in Tehran in 2018. Data was collected through four focus group discussions. Content analysis approach was used in data analysis. Results: One hundred MSM were enrolled in this study. Majority of them were 18-25 years old. Participants had numerous comments about their sexual identity and orientation; some were confused about it and mentioned stigma, discrimination, and lack of social and legal support as the most important contributing factors. Social media and parties were the most common places to find a partner. Moreover, majority had a negative attitude toward emotional attachment and marriage in sexual minorities; this was attributed to partner’s infidelity, low commitment, and lack of family support by some participants. Conclusions: MSM is a vulnerable to psychosocial problems group due to low sexual knowledge and lack of community and legal supports. Data also indicated high probability of HIV transmission among this group because of risky sexual behaviors.
Letter to the Editor
Discrimination in COVID-19 vaccination programs – A possible risk for mental health
Yasaman Rezaie
Oncopathology Research Center, Iran University of Medical Sciences,
Tehran, Iran
E-mail address:rezaieyasaman35@gmail.com.
Yasna Rostam-Abadi*
Iranian National Center for Addiction Studies (INCAS), Tehran University
of Medical Sciences
Mina Ansari
Iranian National Center for Addiction Studies (INCAS), Tehran University
of Medical Sciences, Tehran, Iran
The World Health Organization (WHO) issued the first Emergency Use Listing (EUL) for the first vaccine in December 2020; nearly a year after the outbreak of Coronavirus Disease (COVID-19) began and was later declared a pandemic. The WHO has approved or is currently reviewing the efficacy and safety of more than 100 vaccines using various platforms (World Health Organization, 2021). Since then, numerous countries have implemented mass vaccination programs. Though the long-term duration of COVID-19 vaccine protection has not been determined, vaccination is strongly recommended if available. Unfortunately, there is considerable variation in the rate and efficacy of COVID-19 vaccination programs across countries, resulting in an alarming inequity of "the right to health." According to some estimates, a high percentage of the total population in some developed countries has been fully vaccinated against COVID-19, while many other countries are expanding the program. On the other hand, vaccination rates are extremely low in some other countries, primarily developing countries, despite the disease's high prevalence.