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Background: Comorbid major depressive disorder (MDD) and opium use disorder (OUD) are known to increase the risk of suicide. The purpose of this study was to compare the efficacy and safety of adjunctive therapy with either ketamine or buprenorphine in patients with comorbid MDD and OUD., Methods: This was a randomized double-blind controlled trial in adults admitted to a hospital in Iran. Sixty-six participants were enrolled and received either ketamine or buprenorphine, along with current antidepressant therapy. The primary outcome was change in depressive symptoms assessed using the Beck Depression Inventory (BDI) after 2 hours, 24 hours, and 7 days following initiation of treatment. Secondary outcomes included changes in suicidal ideation, evaluated by the Beck Scale for Suicidal Ideation (BSSI)., Results: Both groups experienced a significant decrease in the severity of depression following the interventions ( p < .05). However, there was no significant difference in the between-group comparison ( p > .05). Both groups also exhibited a significant reduction in suicidal ideation compared to before the study, with the decrease in severity being over 85% in both groups ( p < .05)., Conclusion: Both ketamine and buprenorphine appear to be equally effective in reducing symptoms of depression and suicidal ideation among individuals with MDD and OUD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Precipitated opioid withdrawal syndrome (OWS) is a severe and intolerable situation that may occur by a pharmaceutical agent. Reactivation of inhibited N-methyl-d-aspartate (NMDA) receptor in person with prolonged opioid use can led to severe OWS. We conducted a double-blind, randomized clinical trial to assess the effect of magnesium sulfate (MGSO 4 ) as an NMDA receptor antagonist on OWS., Materials and Methods: The study randomly divided forty patients with precipitated OWS due to partial agonist (buprenorphine) use referred to the emergency unit of Toxicology Department of Mashhad University of Medical Sciences, Iran; into two groups. The control group received conventional therapies, including clonidine 0.1 mg tablet each hour, intravenous infusion of 10 mg diazepam every 30 min, and IV paracetamol (Acetaminophen) 1 g, while the intervention group received 3 g of MGSO 4 in 20 min and then 10 mg/kg/h up to 2 h, in addition to the conventional treatment. The clinical opiate withdrawal scale (COWS) evaluated OWS at the start of the treatment, 30 min, and 2 h later., Results: Both groups had similar demographic, opiate types, and COWS severity at the start of the intervention. COWS was lower in the intervention than the control group at 30 min (11.20 ± 2.86 and 14.65 ± 2.36, respectively, P = 0.002) and at 2 h (3.2 ± 1.61 and 11.25 ± 3.27, respectively, P < 0.001) after treatment. The intervention group received lesser doses of clonidine (0.12 ± 0.51 and 0.17 ± 0.45 mg, P = 0.003) and Diazepam (13.50 ± 5.87, 24.0 ± 6.80 mg, P = 0.001) than the control group. Serum magnesium levels raised from 1.71 ± 0.13 mmol/L to 2.73 ± 0.13 mmol/L in the intervention group., Conclusion: Magnesium can significantly reduce the severity of OWS. Additional studies are required to confirm these results., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier Inc.)

The monitoring of essential and toxic elements in patients with Opioid Use Disorder (OUD) undergoing methadone treatment (MT) is important, and there is limited previous research on the urinary levels of these elements in MT patients. Therefore, the present study aimed to analyze certain elements in the context of methadone treatment compared to a healthy group. In this study, patients with opioid use disorder undergoing MT (n = 67) were compared with a healthy group of companions (n = 62) in terms of urinary concentrations of some essential elements (selenium (Se), zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), calcium (Ca)) and toxic elements (lead (Pb), cadmium (Cd), arsenic (As), and chromium (Cr)). Urine samples were prepared using the acid digestion method with a mixture of nitric acid and perchloric acid and assessed using the ICP-MS method. Our results showed that the two groups had no significant differences in terms of gender, education level, occupation, and smoking status. Urinary concentrations of Se, Cu, and Fe levels were significantly lower in the MT group compared to the healthy subjects. However, the concentrations of Pb, Cd, As, Mn, Cr, and Ca in the MT group were higher than in the healthy group (p < 0.05). No significant difference was established between the levels of Zn in the two groups (p = 0.232). The results of regression analysis revealed that the differences between the concentration levels of all metals (except Zn) between two groups were still remained significant after adjusting for all variables (p < 0.05). The data obtained in the current study showed lower urinary concentrations of some essential elements and higher levels of some toxic elements in the MT group compared to the healthy subjects. These findings should be incorporated into harm-reduction interventions., (© 2024. The Author(s).)

Background: The pattern of substance use in Iran is characterized by a high prevalence of opioid use and opioid use disorder (OUD). Although opioid maintenance therapy (OMT) has been introduced in Iran, approximately 50% of people with opioid use disorder remain unreached. Moreover, psychosocial treatment of OUD and common mental health symptoms during OMT is limited. Digital interventions have been shown to improve psychological distress, depression, anxiety, and post-traumatic stress disorder symptoms. In addition, providing psychoeducation and risk reduction counseling to prevent communicable diseases like HIV and infectious hepatitis is common via the Internet. However, despite these promising advances, no smartphone intervention in OMT has been investigated for the treatment of OUD and common comorbid mental health symptoms., Objective: We examine the effectiveness of adding a blended smartphone intervention based on community reinforcement approach, motivational interviewing- and cognitive behavioral therapy compared to OMT as usual that aims to improve OMT outcomes and addresses common mental health symptoms in OMT patients in Iran., Method: Adults with opioid dependence entering 8 treatment centers in Tehran, Iran will be randomly assigned to receive either OMT plus a smartphone intervention or OMT as usual. The primary outcomes will be the percentage of negative urine tests for illicit, non-prescribed use of opioids (opium, heroin, tramadol) and treatment retention. Secondary outcomes will include the longest period of abstinence from the illicit, non-prescribed use of opioids (opium, heroin, and tramadol) confirmed by urine samples, changes in communicable disease risk-taking behaviors, changes in stress and common mental health symptoms, and client satisfaction. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models., Discussion: This study will provide substantial knowledge for designing effective blended interventions for OUD. Moreover, it will investigate if treatment retention and OMT-related outcomes and common mental health symptoms can be improved by adding a smartphone intervention to OMT., Trial Registration: https://en.irct.ir/trial/53578 ., (© 2023. The Author(s).)

Despite a large body of evidence showing that early-life malnutrition influences adult outcomes, there is no evidence that early-life starvation causes use of opioids. Studying the long-term effects of a food shortage in Iran caused by WWII, we find that the rate of people who use drugs in this cohort increased significantly higher than in surrounding cohorts. Then, we examine a broad spectrum of outcomes for this cohort to shed light on potential causes of opioid use in the survivors of this cohort. Our findings suggest that pain contributes significantly to opioid use., (Copyright © 2023 The Author. Published by Elsevier Ltd.. All rights reserved.)

Background: Considering different factors, such as high withdrawal rates in methadone maintenance treatment (MMT) programs alongside mental health (MH) problems appearing in patients with opioid use disorder and the lack of prior research on the effect of zinc supplementation in this respect, the present study aimed to investigate the effect of zinc supplementation on the probability of relapse (PoR) and MH problems in patients with opioid use disorder undergoing MMT., Methods: For this purpose, a randomized controlled trial with a clinical basis was fulfilled on a total of 68 patients with opioid use disorder receiving MMT, allocated to two groups, viz. intervention, and control (each one consisting of 34 individuals). Then, the participants in the intervention group were given zinc supplements combined with methadone for three months, and the controls only took methadone, according to the treatment plan. The data were collected using the Relapse Prediction Scale (RPS) and the Depression, Anxiety, and Stress Scale 21 (DASS-21) before, one month after, and at the end of the intervention program., Findings: Compared to the control group, the likelihood of drug use (p = 0.01), drug craving (p = 0.002), and the RPS total score (p = 0.002) in the intervention group was significantly lower. Moreover, the results revealed a significant decreasing trend in depression (p = 0.01), anxiety (p < 0.001), stress (p = 0.001), and the DASS-21 total score (p = 0.001) in the intervention. Compared to the control group, the DASS-21 total score (p < 0.001) in the intervention group was significantly lower., Conclusion: Accordingly, it was concluded that zinc supplementation could reduce the PoR and improve MH problems in patients with opioid use disorder experiencing MMT. However, further research is recommended to fill the gaps., Trial Registration: The research protocol has also been listed on the Iranian Registry of Clinical Trials (IRCT) with code no. IRCT2020050904736N1., (© 2023. The Author(s).)

Background and Aims: There is a paucity of data on outcomes of opioid use disorder (OUD) from low- and middle-income countries. We aimed to investigate the mortality as well as negative social and health outcomes in a 6-year follow-up study of a cohort of individuals with opioid use, including those with OUD, in Iran., Design and Setting: Participants with opioid use initially interviewed in late 2011 in the Iranian National Mental Health Survey (IranMHS)-a household survey of 15-64-year-old population-were followed-up in early 2018., Participants: All respondents (n = 236) who had reported use of any opioids at least five times during the 12-month period prior to the index interview were included in the study., Measurements: Composite International Diagnostic Interview (CIDI) version 2.1 was used for assessment of opioid use and OUD at baseline. Vital status in the follow-up was ascertained through contact with participants/informants, primarily via telephone calls and also through the death registration systems. Weighted incidence rates of negative consequences of opioid use (e.g. incarceration, suicide attempts, violent behavior) were estimated for those who were interviewed., Findings: Seven (3.3%) of the 236 participants with opioid use including four (3.1%) of the 136 with OUD had died by the time of the follow-up interview, resulting in death rates of 0.49 [95% confidence interval (CI) = 0.21-1.38] and 0.53 (95% CI = 0.16-2.62) per 100 person-years, respectively. Overall, 35.0% of participants with opioid use and 44.0% of those with OUD among the 145 individuals interviewed at follow-up experienced non-fatal serious adverse outcomes., Conclusions: In Iran, opioid use and opioid use disorder are associated with increased mortality and other adverse outcomes., (© 2022 Society for the Study of Addiction.)

Introduction: In the Middle East and Asia, illicit opioid use exists across a spectrum between heroin and opium. The impact of primary opioid of choice on opioid agonist treatment retention has not been well evaluated previously, especially for opium tincture, an increasingly popular form of opioid agonist treatment in Iran. This study investigates the relationship between primary opioid of choice, namely heroin or opium, and retention in opium tincture and methadone treatment., Methods: Participants with opioid use disorder (n = 204) were randomised to receive opium tincture or methadone. All participants were categorised as mainly using opium or heroin. Bivariate analyses between treatment retention and primary opioid of choice (P < 0.05) and logistic regression were conducted., Results: Among the 191 participants included in this analysis, heroin was the primary substance of choice for 135 participants (70.7%) and opium for 56 (29.3%). Bivariate analysis showed that the opium group was more likely to be satisfied with family situation, employed and retained in treatment than the heroin group while less likely to experience incarceration and use multiple substances. When adjusting for covariates, primary opioid of choice was not significantly associated with retention in either methadone or opium tincture treatment arm., Discussion and Conclusions: Positive factors, such as employment, housing and family support, seem to collectively explain the higher retention in treatment among those who primarily use opium compared to those who use heroin. To optimise retention in opioid agonist treatment, biopsychosocial care models should be further evaluated to improve psychosocial functioning., (© 2022 Australasian Professional Society on Alcohol and other Drugs.)

Introduction: Patients under methadone maintenance treatment programs (MMTPs) are susceptible to numerous complications (e.g., mental and metabolic disorders). This study evaluated the effects of probiotics on clinical symptoms, biomarkers of oxidative stress, inflammation, insulin resistance, and serum lipid content in patients receiving MMTPs., Materials and Methods: A randomized, double-blind, placebo-controlled trial was conducted among 70 patients receiving MMTPs to receive either 1.8 × 10 9  CFU/day probiotics ( n  = 35) or placebo ( n  = 35) for 12 weeks. Clinical symptoms and metabolic profiles were measured before and after the intervention in patients receiving MMTPs., Results: Compared with the placebo group, probiotic supplementation resulted in a significant improvement in the severity of depression ( P < 0.05). In addition, probiotic administration significantly decreased fasting plasma glucose (FPG), total cholesterol, and low-density lipoprotein cholesterol (LDL cholesterol) ( P < 0.05). Furthermore, probiotics resulted in a significant reduction in high-sensitivity C-reactive protein (hs-CRP) and a significant elevation in total antioxidant capacity (TAC) and total glutathione (GSH) levels ( P < 0.05)., Conclusion: Treatment with probiotics for 12 weeks to patients receiving MMTPs had beneficial effects on symptoms of depression, as well as several metabolic profiles. Clinical Trial Registration: this study was registered in the Iranian website (https://www.irct.ir) for clinical trials registration (https://fa.irct.ir/trial/46363/IRCT20170420033551N9). The registration date is March 22, 2020., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Nader Molavi et al.)

Background: There has been a marked growth in methadone maintenance treatment (MMT) in Iran in the past two decades with positive health outcomes. We conducted a systematic review of studies on the prevalence of non-prescribed methadone use, methadone use disorder, and methadone-related poisoning and mortality in Iran., Methods: We searched International and Iranian databases up to May 2020 and contacted relevant experts. The pooled proportions were estimated through random-effects model. Methadone-related adverse outcomes were evaluated over time., Results: Sixty-five studies were included. The pooled estimates of non-prescribed methadone use in the last 12-month were 2.7% (95%CI: 0.9-5.4) and 0.1% (95%CI: 0.03-0.2) in the male and female general population, respectively. Among people who use drugs, 8.4% reported daily non-prescribed use in 2018. Four heterogeneous studies in drug treatment centers reported the existence of treatment-seeking for methadone use disorder. Methadone was responsible for 10.4% (95%CI: 4.5-18.3) of cases of acute poisoning in adults and 16.0% (95%CI: 9.3-24.1) in children. Methadone was reported as a cause of death in 53.5% of substance-related deaths referred to the Legal Medicine Organization while being the only cause in 35.8% of all cases., Conclusion: Non-prescribed use of methadone in the general population is much less than opiates and some other available prescription opioids, like tramadol. However, notwithstanding the large and successful MMT program in Iran, increasing trends in methadone-related poisoning and deaths pose serious public health concerns. There is an urgent need to explore these fatal and non-fatal poisoning cases and implement policies to curb the harms associated with methadone use., Competing Interests: Declarations of Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: In response to a high burden of opioid use disorder (OUD), Iran established a network of opioid agonist treatment (OAT) centres beginning in 2002. To increase treatment diversity, particularly for patients who use opium as their drug of choice, opium tincture (OT)-assisted treatment was introduced to the network. This study aimed to explore factors influencing OT-assisted treatment selection for OUD in Tehran, Iran., Methods: We conducted 54 in-depth interviews with patients with OUD (n = 33), family members of patients (n = 9) and drug treatment providers (n = 12). Participants were recruited from 12 drug treatment centres across Tehran, between September and November 2019. All interviews were audio-recorded, transcribed and coded in OpenCode 4.02 software and analysed using thematic analysis., Results: Study participants more commonly reported individual-level factors as facilitators (e.g. to reduce harms associated with illicit opioid use, achieve recovery through a gradual dose reduction regimen combined with Congress 60 recovery program) and structural level factors (e.g. low adoption by OAT system and lack of familiarity of treatment providers) as barriers for utilisation of OT-assisted treatment regimens. OT was perceived to produce lower levels of physiological dependence than methadone, but the requirement for twice supervised dosing was restrictive. Low familial and community acceptance were also seen as barriers to access., Discussion and Conclusions: This research identified a range of perceived benefits for OT-assisted treatment ranging from harm reduction to an intermediate step to achieve recovery. However, several structural-, individual-, familial- and community-level barriers impede its availability and acceptability., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)

Background: Opioid is the second most prevalent illicit drug worldwide, whose consumption is very high in Iran, due to Iran's geographical proximity to producing countries. Methadone maintenance therapy is one of the most prevalent and accepted methods of substance abuse treatment. Nevertheless, cognitive disorders have been reported as one of its complications., Aim: This study was conducted to evaluate cognitive impairment in methadone maintenance patients (MMPs) and to compare it with abstinent opioid users (AOUs)., Materials and Methods: This cross-sectional analytical study was performed on 25 MMPs and 25 AOUs. Samples were selected through convenience sampling method whereby a self-made questionnaire was distributed among them to assess demographic information, clinical variables such as methadone and opioid use history, underlying disease and medication history, as well as 13-item Beck depression inventory. Then, they were interviewed using the Montreal Cognitive Assessment (MoCA) questionnaire., Results: Significant differences were found in MoCA questionnaire total scores ( p  = 0.018) and orientation to time and place dimension ( p  = 0.008) between the two groups, with the mean scores being higher in AOU group. Duration of opioid use was the only factor influencing cognitive assessment score in both Groups. ( p  = 0.029)., Conclusion: We suggest monitoring and assessing cognition function in patients receiving methadone especially for those with a long history of opioid use.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Investigations proposed that genetic polymorphisms within proteins in methadone pharmacokinetic and pharmacodynamics are critical factors in determination of methadone dose in methadone maintenance therapy (MMT)., Objective: This study aimed to assess the associations between two polymorphisms, CYP3A4 (rs2740574) and OPRM1 (rs1799971), with dose of methadone in Iranian patients undergoing MMT., Methods: A total of 124 Iranian male subjects aged 18-65 years old who were confirmed to be addicted by the addiction diagnostic tests and underwent MMT were assessed. Patients were divided into three groups of low (less than 40 mg/day), moderate (more than 40 mg/day and less than 110 mg/day) and high (more than 110 mg/day) methadone dose consumption. DNAs of included patients were extracted from their blood samples and were assessed for CYP3A4 and OPRM1 polymorphisms., Results: Results showed that there was no significant association between the studied polymorphisms and methadone dose in Iranian addicted patients underwent MMT (P > 0.05)., Conclusions: CYP3A4 and OPRM1 single variations cannot explain variability in methadone dosage in MMT. Studying the interactions of more genetic factors in larger samples may elucidate factors influencing the required dose of methadone and better individualized therapy.

Background: Opioid agonist treatment (OAT) reduces many of the harms associated with opioid dependence. We use mathematical modelling to comprehensively evaluate the overall health benefits of OAT in people who inject drugs in Perry County (KY, USA), Kyiv (Ukraine), and Tehran (Iran)., Methods: We developed a dynamic model of HIV and hepatitis C virus (HCV) transmission, incarceration, and mortality through overdose, injury, suicide, disease-related and other causes. The model was calibrated to site-specific data using Bayesian methods. We evaluated preventable drug-related deaths (deaths due to HIV, HCV, overdose, suicide, or injury) averted over 2020-40 for four scenarios, added incrementally, compared with a scenario without OAT: existing OAT coverage (setting-dependent; community 4-11%; prison 0-40%); scaling up community OAT to 40% coverage; increasing average OAT duration from 4-14 months to 2 years; and scaling up prison-based OAT., Outcomes: Drug-related harms contributed differentially to mortality across settings: overdose contributed 27-47% (range of median projections) of preventable drug-related deaths over 2020-40, suicide 6-17%, injury 3-17%, HIV 0-59%, and HCV 2-18%. Existing OAT coverage in Tehran (31%) could have a substantial effect, averting 13% of preventable drug-related deaths, but will have negligible effect (averting <2% of preventable drug-related deaths) in Kyiv and Perry County due to low OAT coverage (<4%). Scaling up community OAT to 40% could avert 12-24% of preventable drug-related deaths, including 13-22% of overdose deaths, with greater effect in settings with significant HIV mortality (Tehran and Kyiv). Improving OAT retention and providing prison-based OAT would have a significant additional effect, averting 27-51% of preventable drug-related deaths., Interpretation: OAT can substantially reduce drug-related harms, particularly in settings with HIV epidemics in people who inject drugs. Maximising these effects requires research and investment into achieving higher coverage and provision and longer retention of OAT in prisons and the community., Funding: UK National Institute for Health Research, US National Institute on Drug Abuse., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Opioids addiction and misuse are among the major problems in the world today. There have been several preliminary studies examining the effect of methadone on depression among addicts, however, these studies have reported inconsistent and even contradictory results. Therefore, the aim of the present study was to determine the effect of methadone on depression in addicts in Iran and around the world, using a meta-analysis approach., Methods: This study was a systematic review and meta-analysis including articles published in the SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed and Web of Science databases were searched systematically to find articles published from 2006 to March 2019. Heterogeneity index was determined using the Cochran's test (Qc) and I 2 . Considering heterogeneity of studies, the random effects model was used to estimate the standardized difference of mean score for depression. Subsequently, the level of depression reduction in Iran and worldwide in the intervention group before and after the testwas measured., Results: A total of 19 articles met the inclusion criteria, and were therefore selected for this systematic review and meta-analysis. The sample size of the intervention group in the selected studies was 1948. According to the meta-analysis results, the mean depression score in the intervention group was 26.4 ± 5.6 and 18.4 ± 2.6 before and after intervention respectively, indicating the reducing effect of methadone on depression, and this difference was statistically significant (P < 0.01)., Conclusion: The results of the present study show that methadone significantly reduces depression in addicts. Therefore, regular methadone use can be part of a drug treatment plan.

Various types of medications are used as maintenance therapies for substance use disorder; However, the side effects of these drugs are shown to restrict their use and increase the risk of relapse in patients. As a result, alternative maintenance therapies are tested in the hope for optimum therapy. Since opium tincture is a new and innovative maintenance treatment in Iran, we attempted to compare the therapeutic and side effects of opium tincture with two standard therapies, i.e., methadone and buprenorphine. Hence, thyroid function was tested in three methods of maintenance therapies with methadone, buprenorphine, and opium tincture in a cross-sectional study. In this study, 150 patients with the mean age of 51.63 ± 13.56 years and a history of opioid or opioid-derivatives use disorder, underwent the maintenance treatment with methadone, buprenorphine, and opium tincture at Bojnurd Addiction Treatment Centers in northeastern Iran. These patients were selected using convenience sampling. Then, they were placed into three treatment groups of methadone, buprenorphine, and opium tincture. The thyroid functionality was assessed with measuring TSH, fT4, fT3, T3RU, and Anti TPO, carried out in a reference laboratory. Finally, these data were analyzed by ANOVA using SPSS.16 software. The results showed that there was no significant difference in the average levels of TSH, fT3, fT4, and Anti TPO in these treatment groups; except for T3RU concentration, which was increased significantly in the opium tincture group as compared to the methadone treated group. Also, the frequency of fT4, and T3RU disorders demonstrated a significant change in three groups. The findings of the present study demonstrated that opium tincture in comparison with methadone could increase T3RU levels resulting in euthyroidism possibly through TBG.

Background: Opioid agonist therapy (OAT) uptake has been associated with multiple positive health outcomes among people who inject drugs (PWID). This study evaluated the pattern of OAT uptake among PWID in two consecutive national bio-behavioral surveillance surveys (2010 and 2014) in Iran., Methods: Data were obtained from two national bio-behavioral surveillance surveys (N 2010 = 1783 and N 2014 = 2166) implemented using convenience sampling at the harm reduction facilities and street venues in 10 geographically diverse urban centers across Iran. Multivariable logistic regression models were built to determine the correlates of OAT uptake for the 2014 survey, and adjusted odds ratios (AORs) along with 95% confidence intervals (CI) were reported., Results: The prevalence of OAT uptake decreased from 49.2% in 2010 to 45.8% in 2014 (P value = 0.033). OAT uptake varied across the studied cities ranging from 0.0 to 69.3% in the 2010 survey and 3.2 to 75.5% in the 2014 survey. Ever being married (AOR = 1.40; 95% CI 1.12, 1.75), having a history of incarceration (AOR = 1.56; 95% CI 1.16, 2.09), and human immunodeficiency virus (HIV) sero-positivity (AOR = 1.63; 95% CI 1.08, 2.50) were associated with OAT uptake. Conversely, PWID who reported using only non-opioid drugs (AOR = 0.43; 95% CI 0.26, 0.71) and those who reported concurrent use of opioid and non-opioid drugs (AOR = 0.66; 95% CI 0.51, 0.86) were less likely to uptake OAT., Conclusions: Although OAT uptake among PWID in Iran is above the 40% threshold defined by the World Health Organization, there remain significant disparities across urban settings in Iran. Importantly, the OAT services appear to be serving high-risk PWID including those living with HIV and those with a history of incarceration. Evaluating service integration including mental health, HIV and hepatitis C virus care, and other harm reduction services may support the optimization of health outcomes associated with OAT across Iran.

Objective: Social support is a key factor in the treatment and rehabilitation process of persons who use drug (PWUD). This highlights the need for a valid and reliable tool for assessing social support. The cultural and psychometric properties of community assessment inventory (CAI) in PWUDs under methadone therapy were examined in Iran in 2019., Methods: The study was carried out as a validation and methodological study. At first, the original tool was translated into Farsi using forward-backward method. After ensuring face validity and content validity, construct reliability of the tool was supported using explorative and confirmatory factor analysis (EFA & CFA) using a sample group of 392 participants. The participants were selected through convenient-quota sampling from 24 drug clinics. Reliability of the questionnaire was supported using Pearson correlation coefficient and internal consistency based on Cronbach's alpha., Results: To determine content validity of the tool, CVI and CVR of it were obtained, which were on average equal to 0.79 and 0.59 respectively. The EFA supported correlation of the 37itmes of the tool (KMO = 0.975, Chi-square = 15,051.6, P value= 0.0001). The main indices of the model, based on CFA were higher than 0.9, which support goodness of fit of the model (χ2/DF = 2.98, CFI = 0.91, NFI, TLI = 0.905 GF = 0.92, REMSEA = 0.07, R2 = 0.99). Reliability of the tool based on internal consistency (Cronbach's alpha) for the subscales were in 0.8-0.95 interval and equal to 0.85 for the whole tool., Conclusion: As the results showed, CAI had acceptable indices for Iranian PWUDs under methadone therapy. The tool can be used for assessing social support level in the study population. It is a reliable and valid tool for studies in pertinent fields.

The literature review was planned to discuss the extent of opioid, alcohol and methamphetamine use disorder in Pakistan, the neurobiology of opioids, alcohol and methamphetamine, the importance of medication-assisted treatment and recommendations for Pakistan. A PubMed literature search was conducted and newspaper articles were also reviewed. In per capita terms, Pakistan is reported to be the most heroin-addicted country in the world. Pakistan has a significant alcohol abuse issue as well. The newest epidemic is that of crystal methamphetamine or "ice" which is consuming the youth and urban elite. There are long-term structural and functional changes in the opioid-addicted brain and factors that influence the vulnerability to addiction. The genesis of Pakistan's opioid epidemic is critical to understand as the country became victim to the proximity to, and politics of, Iran and Afghanistan. There is poor resource allocation for the treatment of substance use disorder, especially in comparison to what is spent on counter-terrorism. Addiction has had a devastating effect on children and the youth of Pakistan. It is vital to recognise addiction as a chronic disease comparable to diabetes, hypertension and asthma; and not a personal weakness. Medication-assisted treatment includes using buprenorphine-naloxone and naltrexone for opioid use disorder, injectable naltrexone for alcohol use disorder, and mirtazapine and bupropion for amphetamine use disorder. Coordination between the healthcare system, the Anti-Narcotics Force, the pharmaceutical industry and parliament is important. A university-affiliated addiction centre should be developed so it can provide guidance with research and treatment. Buprenorphine-naloxone and injectable naltrexone are urgently needed at an institutional level for the treatment of opioid and alcohol use disorder.

The associations of OPRM1 gene variants with opioid dependence have been demonstrated. This study investigated the association of rs495491, rs1799971 (A118G), rs589046, and rs10457090 variants of OPRM1 gene with opium dependence and their haplotypes among addicted individuals undergoing methadone treatment. Moreover, we investigated whether any of these variants were associated with libido dysfunction or insomnia among addicted people. A total of 404 individuals were genotyped by amplification refractory mutation system (ARMS) PCR. In silico studies were designed through homology modeling of A118G structures (N40 and D40) and docked with 41 FDA-approved drugs of OPRM1 protein by SWISS-MODEL, COACH, MolProbity, ProSA, Errat, Glide XP, and Autodock 4. Results revealed that rs495491, A118G, rs589046, and rs10457090 were significantly associated with opium dependence under recessive (P = 6.66E-10), dominant (P = 0.017), co-dominant (P = 0.001), and recessive (P = 9.28E-6) models of inheritance, respectively. Further analyses indicated three significant haplotypes including A-A-A-C (P-permutation < 1E-9), G-G-A-C (P-permutation = 0.04), and G-A-G-C (P-permutation = 8.69E-4). Genotype-phenotype associations of OPRM1 variants with insomnia and libido dysfunction showed no significant association. Docking showed the higher binding affinity of N40 rather than D40 model; however, methadone and morphine were bonded with D40 structure more powerful. Consequently, rs495491, A118G, rs589046, and rs10457090 were associated with opioid dependence among Iranians; also, A118G might be the most remarkable marker of OPRM1 owing to its vital structural roles.

Background: In 2016, in a lead poisoning outbreak in Iran, physicians reported thousands of opium users who presented to emergency departments (EDs) with intractable severe abdominal pain which did not respond to any narcotic medication. During the same period of time, we investigated the efficacy of intravenous calcium gluconate in alleviating lead-induced abdominal pain., Methods: In a single-center, single blinded, randomized controlled trial, a convenient sample of adult opium-addicted patients who presented to an academic ED with abdominal pain and had an initial diagnosis of lead poisoning were included and randomly subjected to two treatment groups receiving conventional treatment (morphine 0.1 mg/kg + normal saline; group 1) and conventional treatment plus 1 g of intravenous calcium gluconate (group 2) to alleviate their abdominal pain. The visual analogue scale (VAS) was determined by each patient (0 to 100 mm) before treatment, and 15, 30, and 60 min after intervention., Results: A total of 50 patients (25 in each group) were enrolled. Blood lead levels, VAS scores before treatment, and mean administered dose of morphine were similar between the two groups. After treatment, mean VAS score dropped to 64.7± 10.4 vs. 67.1± 10.9 at 15 min (P = 0.437), 64.6± 10.9 vs. 58.0 ± 11.2 at 30 min (P = 0.041), and 63.8± 10.7 vs. 53.6± 10.9 at 60 min (P = 0.002) in groups 1 and 2, respectively., Conclusion: Intravenous calcium gluconate administration along with morphine can improve abdominal pain in lead poisoning due to the ingestion of lead-contaminated opium. Further interventional studies are recommended to see if response to calcium salts in suspected lead-induced abdominal pain can rule in lead toxicity., Trial Registration: IRCT20171009036661N2. Registered 27 May 2018 - Retrospectively registered.

Objectives: Vitamin D deficiency may be linked to several mental complications including cognitive deficits, depression, and anxiety in patients under methadone maintenance treatment (MMT). This study was designed to explore the effect of vitamin D supplementation on cognitive functions and mental health parameters in subjects under MMT., Methods: This randomized, double-blinded, placebo-controlled clinical trial was carried out among 64 patients under MMT. Participants were randomly allocated to receive either 50,000 IU vitamin D supplements (n = 32) or placebo (n = 32) every 2 weeks for 24 weeks. Cognitive functions and mental health parameters were taken at baseline and posttreatment to evaluate relevant variables., Results: After the 24-week intervention, compared with the placebo, serum 25(OH) vitamin D levels significantly increased in participants who received vitamin D supplements (β 14.50; 95% confidence interval [CI], 13.17-15.83; P < 0.001). In addition, compared with the placebo, subjects who received vitamin D had a significant reduction in Iowa Gambling Task (β -6.25; 95% CI, -8.60 to -3.90; P < 0.001), and significant increases in Verbal Fluency Test (β 2.82; 95% CI, 0.78-4.86; P = 0.007), Immediate Logic Memory (β 1. 32; 95% CI, 0.27-2.37; P = 0.01), Reverse Digit Span (β 2.06; 95% CI, 1.18-2.94; P < 0.001) and visual working memory (β 0.75; 95% CI, 0.33-1.16; P = 0.001). Also, vitamin D supplementation significantly improved BDI (β -2.76; 95% CI, -3.97 to -1.55; P < 0.001) compared with the placebo. When we applied Bonferroni correction, LM-Immediate (P = 0.07) became nonsignificant, and other mental health parameters did not alter., Conclusions: Overall, taking 50,000 IU vitamin D supplements every 2 weeks for 24 weeks by patients under MMT had beneficial effects on cognitive functions and some mental health parameters. Further studies are needed to confirm our findings.

As the most populated Persian Gulf country in West Asia, methamphetamine use in methadone maintenance treatment (MMT) is a new health concern in Iran. Methamphetamine use in MMT can originate in methadone misconceptions or the stimulant effects of methamphetamine use. Several research studies have highlighted the prevalence of methamphetamine use in Iran and conducting further studies on this issue is being developed. Opiate use is treated with MMT. But, there is no effective pharmacological treatment for methamphetamine use and cognitive-behavioral interventions have still remained the best practice. As a psychostimulant drug, methamphetamine use can lead to poor treatment outcomes or even treatment failure among patients in MMT. Therefore, the implementation of methamphetamine education and prevention programs in MMT is required. Prescribing adequate methadone dose and the treatment of comorbidities as well as, doing a series of activities outside treatment is underscored. Methamphetamine use has a chronic nature and methamphetamine treatment is a long-term procedure with a high rate of relapse. Therefore, the implementation of long-term motivational interviewing, teaching necessary skills to prevent relapse and case management is highlighted. A long-term collaboration between treatment teams, patients and their families is suggested to manage methamphetamine use in MMT.

Addiction is a chronic and recurring disease that recurrence phenomenon is the most important challenge in treatment of this disease. Recent experiences have shown that synthetic drugs have undesirable side effects. Recent studies on medicinal plants have shown that they might be effective in treatment of different stages of addiction with lower side effects and costs. The aim of this study was to review the effects of medicinal plants in the treatment of morphine addiction in experimental animals. In this review article, by using keywords of morphine, withdrawal, and plants or herbal medicine in databases of indexing cites, desired articles were obtained since 1994. Inclusion criteria for selecting articles were the articles related to application of medicinal plants in decreasing symptoms resulting from morphine withdrawal were selected. Results of this study on experimental studies have shown that medicinal plants such as Trachyspermum copticum L and Melissa officinalis decrease the symptoms of withdrawal syndrome in a dose-dependent. Also, medicinal plants like Avena sativa, Hypericum perforatu, Passiflora incarnate, Valeriana officinalis, Satureja hortensis L, and Mentha piperita can have effects on behavior, emotions, and other problems of addicts, decreasing withdrawal symptoms. Results of this study showed that medicinal plants can be effective in controlling deprivation, decreasing dependency creation, and possibly DETOXIFICATION: of opioid addicts., (© The Author(s) 2015.)

Background: To identify correlates related to retention time of a cohort study of the opioid-dependent patients participating in the Methadone Maintenance Treatment (MMT) program offered by a major addiction treatment clinic in Tehran, Iran between April 2007 and March 2011., Methods: Several parametric Survival models assuming Weibull, Log-normal and Log-logistic distributions were compared to search for association between covariates and risk of relapse and dropping out of treatment among 198 patient participants., Results: According to Akaike Information Criterion (AIC), Log-normal model had the best fitting. Estimates of this model indicated that increase in average methadone dosage was associated with longer retention time. Correlates associated with shorter retention time were suffering from mental disorders, using stimulant drugs, being poly-substance dependents and having prior treatments., Conclusions: Findings of this study provide support for giving more attention to patients who are poly-substance or stimulant-drug dependents, have non-substance psychiatric comorbidity and the ones with addiction treatment history. Independent of patient characteristics, retention improved as the dose of methadone increased.

Study Objective: Naltrexone is a competitive opioid receptor antagonist acting at the µ- and k-opioid receptors that blocks the euphoric effects of exogenous administered opioids. When used in opioid-dependent patients, naltrexone can cause acute and severe withdrawal symptoms., Methods: This was a cross-sectional study conducted from December 2007 to March 2008 and consisted of patients who had used naltrexone accidentally or deliberately and were referred to Loghman-Hakim Poison Hospital, Tehran, Iran. All symptoms and signs were assessed and the relationship between the dose of naltrexone, opioid dependence, and outcome was evaluated., Results: In 132 patients referred to our hospital, the most frequently reported symptoms and signs occurring in more than 10% of patients were agitation (96.2%), altered level of consciousness (38.6%), nausea (28%), vomiting (27.3%), abdominal pain (24.2%), diarrhea (16.7%), bone and muscle pain (15.9%), tachycardia (12.9%), and dilated pupils (11.4%). Being the most prominent symptom, the agitation was the most difficult aspect of withdrawal to manage. Except for agitation, no relationship was found between the presence of these symptoms and the dose of naltrexone used. Outcome of the patients (classified as complete recovery, partial recovery, death, and no follow-up) was related to the substance of addiction (p < 0.05) but not to the naltrexone dose., Conclusion: Emergency physicians should be aware of the potential for severe agitation from naltrexone-precipitated hyperacute withdrawal and its appropriate management. Opioid-dependent patients who wish to continue withdrawal and abstinence must be encouraged to visit trained physicians and be warned about misuse of naltrexone., (© The Author(s) 2014.)

Objective: To examine the 3-month effect of methadone maintenance treatment (MMT) on quality of life (QOL) of substance-dependent outpatients in Iran., Methods: The qausi-experimental study performed at the Oral Maintenance Methadone Treatment Clinic of the Baharan Psychiatric Hospital, a university hospital in Zahedan, southeast of Iran, from 2009 to 2010. One hundred patients with substance-dependence disorder were recruited from the outpatient clinic. Quality of life parametres were measured through the World Health Organization Quality of Life scale (WHO QOL-BREF) prior to the treatment, and 1, 2 and 3 months after starting the treatment in order to assess changes in the Quality of Life across the treatment period. Repeated measurement analysis was used for data analysis., Results: Of the 100 subjects initially recruited, 83 (83%) completed the study period. The total Quality of Life score improved from pre-treatment to the first month into treatment. The improvement was maintained at the 2-month and 3-month points (P < .05). According to the World Health Organization subscales, the treatment was effective in improving physical and social relationship domains over time (P < .05), but there were no significant improvements in psychological and environmental domains., Conclusions: Oral methadone maintenance treatment was effective in improving the overall Quality of Life during the first three months of treatment in substance-dependent outpatients.

Background: In the west, men are twice as likely as women to develop a drug problem, but female users have higher rates of morbidity than male users. Iran has the world highest per capita opiate consumption, but little is known about female drug users. In 2007, we established a free methadone clinic with ancillary services for female drug users in South Tehran. The aim was to explore the characteristics of female drug users seeking treatment for heroin dependence in Iran. Clients were interviewed about demographic characteristics, drug use and treatment history, and drug-related health problems. Urine and blood samples were collected and tested for morphine, HIV, hepatitis C virus (HCV), and sexually transmitted infections (STIs)., Methods: Between August 2007 and October 2008, 78 women completed a baseline interview. The median age was 37 years, the main ethnic background was Persian (65%), and half of the clients were married. Opium and heroin and opium use was reported by 69% (n=54) and 87% (n=68) of clients, respectively. The mean duration of heroin use problems was 10.5 years, and only 20% of women reported ever having received drug treatment. HIV and HCV seroprevalence was 5% and 24%, respectively. Forty percent were sexually active when interviewed, and one third tested positive for an STI. Women had poor social functioning, high levels of depression, and poor general health., Results and Conclusions: Our clients were dependent users with a multitude of problems who had little or no contact with treatment agencies before this study. Many clients had made a transition from using opium to using heroin, and some had commenced injecting, placing them at risk for HIV and HCV infection. More women-only drug treatment services are needed to facilitate women's entry into drug treatment.

Background: Research evidence indicates that prisoners in Iran are at risk of drug-related harm, including acquisition of blood-borne infections. In response, several prevention interventions including methadone maintenance treatment (MMT) have been introduced into prisons in Iran., Methods: This report reviews and presents some important information extracted from published articles, and available documents on HIV sentinel surveillance and provision of MMT inside correctional settings in Iran., Results: Biological surveillance data in 2005 showed that on average about 3% of prisoners in the country tested positive for HIV infection. MTT that constitutes a main component of the Prison Organisation's HIV prevention package is becoming increasingly accessible to opioid-dependent prisoners. Between 2002 and 2008, the number of opioid-dependent prisoners receiving MMT increased steadily from 100 to more than 25000., Conclusion: Experiences in Iran suggest that access to MMT would be helpful for reducing illicit drug injection in a prison setting and can be considered as a major intervention for preventing the transmission of blood-borne infections among prisoners., (Copyright 2010 Elsevier B.V. All rights reserved.)

Introduction: The aim of this retrospective study was to assess ultra-rapid opiate detoxification (UROD) and to estimate the retention rate in naltrexone maintenance treatment., Methods: 45 opiate-addicted male patients (DSM-IV 304.00; opiate per oral or per inhalation n=40, heroin intravenous n=5; concomitant cannabis abuse n=6) were detoxified by 6 h of naloxone infusion under general anesthesia with midazolam, propofol, clonidine and atracurium. Withdrawal signs were evaluated by the objective opiate withdrawal scale (OOWS, range 0-13) up to 24 h after awakening. After UROD, naltrexone 50 mg/day was prescribed for 9 months with assessments in 4-week intervals., Results: Adverse events after UROD were prolonged unconsciousness (n=1), transient confusion (n=8) and depressive mood (n=6). The total sample showed a median OOWS score of 2 (mild withdrawal syndrome). The only two extreme outliers were found only in the subgroups "intravenous" (score 8) and "cannabis" (score 11). 96% (43/45) of the patients could be discharged the day after UROD. Thirty-six patients (80%) continued naltrexone therapy for the entire 9-month observation period., Discussion: UROD and subsequently induction of naltrexone maintenance therapy can be regarded as safe and effective in patients with pure opiate addiction. Owing to cultural and economical factors our Iranian results may not correspond to European and American treatment modalities., (Copyright Georg Thieme Verlag KG Stuttgart New York.)

In the final days of the year 2003, an earthquake in the city of Bam, Iran, led to the death of some 35,000 of its inhabitants. The rate of opium abuse, which had been high among the male population in this city, caused problems after the earthquake. The aim of the following study was to examine the status of substance abusers during the first 2 weeks after the earthquake. The study was carried out in the city of Bam, one of its nearby villages and eight hospitals admitting earthquake victims. One hundred and sixty-three individuals were interviewed, including substance abusers, their family members, people living in Bam, service providers, and the authorities. During the first 2 weeks after the earthquake, about half of drug-dependent interviewees suffered from withdrawal symptoms. About half reported their problems to health care providers and asked for morphine or other analgesics. Around one third had used opium on the first day and two thirds in the course of the second day to the end of the second week after the earthquake. Although smoking had been the most common means of abuse before the earthquake, oral intake has become the most prevalent route after the disaster. Almost all obtained their opium from inhabitants of other cities as gifts. Members of rescue and health delivery systems had a lot of encounters with opium abusers, especially in the first 3 days after the earthquake, and had prescribed morphine and other analgesics. In societies with a considerable prevalence of substance abuse, this issue becomes a matter of utmost health care and social importance at times of disasters, and the necessary arrangements to deal with it should be present beforehand.

The goal of this study was to evaluate the efficacy of 1-, 3-, and 8-mg per day doses of buprenorphine in the maintenance treatment of opium-dependent patients over a 6-month treatment period. Participants were 513 opium-dependent individuals who were seeking treatment in an urban outpatient clinic, offering a 1-hr weekly individual counseling session. Overall, 305 patients (59.5%) completed the 6-month study. Completion rates by dosage group were 33.9% for the 1-mg dose group, 64.3% for the 3-mg dose group, and 80.1% for the 8-mg dose group-each significantly different from the other two groups. The results support the efficacy and safety of buprenorphine for outpatient treatment of opium dependence and seem to indicate that the highest dose (8 mg) of buprenorphine was the best of the three doses for Iranian opium-dependent patients to increase their retention in treatment.

Aims: To evaluate the effect of a 4 mg/day sublingual dose of buprenorphine in the maintenance treatment of opium dependence in comparison with a 1 mg/day dose over an 18-week treatment period. As a secondary objective, the results were determined concurrently for subjects treated with a 2 mg/day dose., Design: Subjects were assigned randomly to three dosage groups., Participants: 330 consecutive (320 men and 10 women) opium addicts who met the DSM-IV criteria for opioid dependence and were seeking treatment., Intervention: Subjects received a 1, 2 or 4 mg/day dose of buprenorphine and were treated in an outpatient clinic where they also received a weekly 1-hour clinical counseling session., Measurements: Addiction Severity Index, retention in treatment, and illegal opioid use as determined by random urine testing., Findings: The mean age was 37.5 years (SD=11.4, range 19-72). Overall, 194 (58.8%) of the patients completed the 18 week study. Completion rates by dosage groups were 47.3% for the 1 mg group, 58.2% for the 2 mg group and 70.9% for the 4 mg group (chi(2)=12.7, df=2, P=0.0017)., Conclusions: The results support the efficacy and safety of buprenorphine for opium addiction and suggest that an adequate dose of buprenorphine would help to increase the success rate.