Exercise can restore behavioural and molecular changes of intergenerational morphine effects.

In our previous studies, the offspring of morphine-exposed parents (MEO) showed pharmacological tolerance to the morphine's reinforcing effect. According to the role of exercise in treatment of morphine addiction, the current study was designed to utilize exercise to improve the effect of parental morphine exposure on the morphine's reinforcing effect. Male and female rats received morphine for 10 days and were drug-free for another 10 days. Each morphine-exposed animal was allowed to mate either with a drug-naïve or a morphine-exposed rat. The offspring were divided into two groups: (1) offspring that were subjected to treadmill exercise and (2) offspring that were not subjected to exercise. The reinforcing effect of morphine was evaluated using conditioned place preference (CPP) and two-bottle choice (TBC) tests. Levels of dopamine receptors (D1DR and D2DR), µ-opioid receptor (MOR), and ΔFosB were evaluated in the nucleus accumbens. The MEO obtained lower preference scores in CPP and consumed morphine more than the control group in TBC. After 3 weeks of exercise, the reinforcing effect of morphine in the MEO was similar to the control. D1DR, D2DR, and MOR were increased in MEO compared with the controls before exercise. Levels of D1DR and MOR were decreased after exercise in the MEO; however, D1DR was increased in control. D2DR level did not change after exercise in MEO, but it increased in control group. Moreover, the level of ΔFosB was decreased among MEO while it was increased after exercise. In conclusion, exercise might modulate the reinforcing effect of morphine via alteration in levels of D1DR, MOR, and ΔFosB.

Effect of tramadol on apoptosis and synaptogenesis in hippocampal neurons: The possible role of µ-opioid receptor.

Tramadol is a synthetic opioid with centrally acting analgesic activity that alleviates moderate to severe pain and treats withdrawal symptoms of the other opioids. Like other opioid drugs, tramadol abuse has adverse effects on central nervous system components. Chronic administration of tramadol induces maladaptive plasticity in brain structures responsible for cognitive function, such as the hippocampus. However, the mechanisms by which tramadol induces these alternations are not entirely understood. Here, we examine the effect of tramadol on apoptosis and synaptogenesis of hippocampal neuronal in vitro. First, the primary culture of hippocampal neurons from neonatal rats was established, and the purity of the neuronal cells was verified by immunofluorescent staining. To evaluate the effect of tramadol on neuronal cell viability MTT assay was carried out. The western blot analysis technique was performed for the assessment of apoptosis and synaptogenesis markers. Results show that chronic exposure to tramadol reduces cell viability of neuronal cells and naloxone reverses this effect. Also, the level of caspase-3 significantly increased in tramadol-exposed hippocampal neurons. Moreover, tramadol downregulates protein levels of synaptophysin and stathmin as synaptogenesis markers. Interestingly, the effects of tramadol were abrogated by naloxone treatment. These findings suggest that tramadol can induce neurotoxicity in hippocampal neuronal cells, and this effect was partly mediated through opioid receptors.

Cabergoline in Treatment of Methamphetamine-Dependent Patients and Its Effect on Serum Level of Glial Cell-Derived Neurotrophic Factor: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Methamphetamine use disorder is an important public health problem, especially in the younger generation, and associated with various psychiatric, cognitive, social, economic, and legal issues. Cabergoline, a drug with dopaminergic properties and long half-life, has been considered for the treatment of stimulant dependence. The systemic use of cabergoline has been shown to increase glial cell-derived neurotrophic factor (GDNF) expression. OBJECTIVE: In this study, we investigated the effects of cabergoline on the serum level of GDNF and its effect on abstaining from methamphetamine in individuals treated for methamphetamine use disorder. METHOD: Sixty male subjects with methamphetamine use disorder were randomly assigned to 2 groups receiving cabergoline and placebo, respectively. During a 12-week follow-up, we compared the serum level of GDNF, urine test results for methamphetamine use, and depression scale between the 2 groups. RESULTS: We found that serum GDNF was lower in subjects who used methamphetamine than healthy subjects (p < 0.0001). However, the serum level of GDNF was not associated with cabergoline use. The rising number of cases testing positive in the placebo group showed a trend resulting in no significant difference between cases testing positive and negative (p = 0.585) at the end of week 12. In the verum group, however, the significantly high number of cases who tested negative - sober - for substances observed in early stages (weeks 7-8) continued to remain significantly higher till the end of the study (p = 0.043), resembling an association between treatment with cabergoline and remaining sober. Although reduced during treatment, recovery from depression was not associated with cabergoline treatment. CONCLUSION: The findings of this study confirmed the effect of cabergoline in reducing methamphetamine use. However, a serum level of the GDNF increase, as seen in animal studies, was not associated with cabergoline treatment of human subjects. This study was registered at the Iranian Registry of Clinical Trials (TRN:IRCT2015050422077N1, October 06, 2015, https://en.irct.ir/trial/19134).

Drop-out from a drug treatment clinic and associated reasons.

The aim of this study was to assess drop-out rates and associated reasons among patients at the Iranian National Center for Addiction Studies (INCAS) clinic. In a one-year period (April 2014 to March 2015), all patients with drug dependence who had been referred for treatment and attended for a first assessment were included in this study (N=242). Those who received treatment were followed until March 2016. Survival analysis showed that 70.2% had dropped out from treatment. Log rank test showed that treatment drop-out rates differed between the different approaches used (P < 0.001), with the lowest slope inbuprenorphine maintenance treatment and the highest in the detoxification programme. Drop-out rates within the first three months was 62% (SE= 0.05) and 82.4% (SE=0.03) for opioids and stimulants dependence, respectively. Analyses were performed using SPSS (Version 21.0) and STATA software, (version 13.0). From the patients' perspective, motivational inconsistencies were considered as the main reason for not starting or leaving treatment. The findings of this study could give service providers a better grasp of drop-out rates and the associated reasons.

Inter/Transgenerational Effects of Drugs of Abuse: A Scoping Review.

Drug addiction is a chronic relapsing disorder that makes it a global problem. Genetics and environmental factors are the two most important factors that make someone vulnerable to drug addiction. Investigations in the past decade highlighted the role of epigenetics in the inter/transgenerational inheritance of drug addiction. A growing body of evidence showed that parental (paternal, maternal, and biparental) drug exposure before conception changes the phenotype of the offspring, which is correlated with neurochemical and neurostructural changes in the brain. The current paper reviews the effects of parental (maternal, paternal, and biparental) exposure to drugs of abuse (opioids, cocaine, nicotine, alcohol, and cannabis) before gestation in animal models.

Barriers and Facilitators to Substance Use Disorder Treatment: An Overview of Systematic Reviews.

objective: This investigation explored the barriers and facilitators to substance use disorder (SUD) treatment in the integrated paradigm. methods: A search technique for barriers and facilitators of SUD treatment was applied to the PubMed and Web of Science databases to identify relevant systematic reviews. The eligibility criteria included systematic review (SR) or SR plus meta-analysis (MA) articles published before the end of 2021, human research, and the English language. Each of the 12 relevant review articles met the inclusion criteria. AMSTAR was utilised to evaluate the methodological quality of the systematic reviews. results: Two authors analysed 12 SR/SR-MA articles to identify barriers or facilitators of SUD treatment. The cumulative summary results of these 12 evaluations revealed that barriers and facilitators may be classified into 3 levels: individual, social and structural. By analysing these review papers, 37 structural barriers, 21 individual barriers and 19 social barriers were uncovered, along with 15 structural facilitators, 9 social facilitators and 3 individual facilitators. conclusions: The majority of barriers indicated in the review articles included in this analysis are structural, as are the majority of facilitators. Consequently, the design of macro models for the treatment of substance use disorders may yield various outcomes and potentially affect society and individual levels.

Comparing Sexual Function between Opioid Dependents Consuming Methadone or Opium Tincture.

Objective: Sexual dysfunction is a side effect of methadone maintenance therapy (MMT). Opium Tincture (OT) has been used as a maintenance treatment. This study aimed to determine and compare the trend of sexual function and its related factors during treatment with both drugs. Method : An observational study was designed to measure the blood tests including free and total testosterone, prolactin, and sex hormone-binding globulin and a battery of questionnaires, including demographics and drug use history, in 42 and 53 patients entering MMT and OT treatment before and 1 and 3 months after the treatment. Results: Significant changes in testosterone levels were observed in the MMT but not the OT group. The difference between the two groups was not significant. Neither between nor within changes in the sexual function and premature ejaculation scores were significant (P =0.370& 0.698). Anxiety levels were significantly different (P= 0.001) within and between groups. There was a considerable difference in the trend of depression changes in the OT group, but not different in MMT group and between the two groups. Conclusion: No difference was found between MMT and OT effects on sexual function variables. The decrease in Testosterone during the three months of MMT, was not associated with diminished sexual function. In the MMT group, anxiety levels diminished during treatment. It seems that decreased testosterone in the MMT group was compensated by improved anxiety. Gonadotropin levels may not be the sole determinant in sexual activity, and complex interaction of mood and anxiety, agonist levels, and gonadotropins are involved.

Individual differences in nucleus accumbens dopamine receptors predict development of addiction-like behavior: a computational approach.

Clinical and experimental observations show individual differences in the development of addiction. Increasing evidence supports the hypothesis that dopamine receptor availability in the nucleus accumbens (NAc) predisposes drug reinforcement. Here, modeling striatal-midbrain dopaminergic circuit, we propose a reinforcement learning model for addiction based on the actor-critic model of striatum. Modeling dopamine receptors in the NAc as modulators of learning rate for appetitive--but not aversive--stimuli in the critic--but not the actor--we define vulnerability to addiction as a relatively lower learning rate for the appetitive stimuli, compared to aversive stimuli, in the critic. We hypothesize that an imbalance in this learning parameter used by appetitive and aversive learning systems can result in addiction. We elucidate that the interaction between the degree of individual vulnerability and the duration of exposure to drug has two progressive consequences: deterioration of the imbalance and establishment of an abnormal habitual response in the actor. Using computational language, the proposed model describes how development of compulsive behavior can be a function of both degree of drug exposure and individual vulnerability. Moreover, the model describes how involvement of the dorsal striatum in addiction can be augmented progressively. The model also interprets other forms of addiction, such as obesity and pathological gambling, in a common mechanism with drug addiction. Finally, the model provides an answer for the question of why behavioral addictions are triggered in Parkinson's disease patients by D2 dopamine agonist treatments.

Hab-o Shefa, a Persian Medicine Compound for Maintenance Treatment of Opioid Dependence: Randomized Placebo-Controlled Clinical Trial.

Objectives: The major problem in maintenance treatment of opioid use disorder is craving and relapse. The utilization of herbal compounds and complementary therapy for treatment of disease and addiction has been widely expanding. Considering the significant effect of Hab-o Shefa in detoxification phase, this clinical trial has explored the influence of this compound on maintenance treatment of opioid-dependent patients. This product is made of four herbs, including Datura stramonium L., Rheum palmatum L., Zingiber officinale Roscoe, and Acacia senegal L. Design: The authors conducted a two-group parallel randomized double-blind clinical trial on 81 opioid-dependent patients within 12 weeks. After medically assisted detoxification, participants were assigned randomly to Hab-o Shefa (n = 41) and placebo (n = 40). Outcome measures included craving assessed by craving beliefs questionnaire, self-reported opioid use, and lapse (any opioid-positive urine test) according to urinalysis and addiction severity index-lite questionnaire, retention in treatment, and depression and anxiety scores on the Hamilton's anxiety and depression scales. Results: Forty-one participants completed the study for 12 weeks, 21 subjects in the drug group and 20 subjects in the placebo group. The rates of opioid-positive urine tests and self-reported opioid use were significantly lower in Hab-o Shefa group (f = 8.41, p = 0.001). Hab-o Shefa also indicated a significant superiority over placebo in the effect of treatment by time interaction for craving (f = 5.91, p = 0.001), depression (f = 3.40, p = 0.01), and anxiety (f = 2.58, p = 0.035). The retention time was 66.6 days for drug group and 59.6 days for placebo one. Although the causes for dropping out in two groups were different, there was no significant difference (p = 0.623). The side effects of the two groups were not significantly different. Conclusion: Results indicated that Hab-o Shefa could be useful for opioid maintenance treatment, and it can also be considered as a new promising drug for prevention of craving and relapse.

Alteration of orexin-A and PKCα in the postmortem brain of pure-opioid and multi-drug abusers.

Finding changes induced by the drug of abuse is one of the most important approaches to design new drugs for the treatment of substance use disorders (SUD). Postmortem study is the most reliable method for detecting alteration in the brain of SUD patients. Recently, the role of orexinergic system in SUD is in consideration. In the current study, we evaluated the level of orexin-A in the CSF and protein kinase Cα (PKCα) in the brain of pure-opioid (POA) and multi-drug abusers (MDA). A total of 56 POA, 45 MDA, and 13 matched control brains were collected from the legal medicine center, Tehran, Iran. The CSF was gathered from the third ventricle immediately after opening the skull and kept at -80 °C. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), orbitofrontal cortex (OFC), nucleus accumbens (NAc), and amygdala were dissected from fresh brain, frozen with liquid nitrogen and kept at -80 °C. The level of orexin-A evaluated in the CSF. Using western blotting, the level of PKCα assessed in the brain. Obtained data revealed that the level of orexin-A increased in POA and MDA compared with the control group (p < 0.05). In addition, the level of PKCα increased in the prefrontal cortex and amygdala of the abusers compared with the control group, although we did not detect changes in the level of PKCα in the NAc. Along with animal studies, the current results showed that the level of orexin increased in the CSF of drug abusers, which might be related to increases in the activation of lateral hypothalamic orexinergic neurons faced with the drug of abuse. Enhancement in the level of PKCα in the drug reward circuits might be adaptational changes induced by orexin and drugs of abuse.

Beneficial effects of physical activity on depressive and OCD-like behaviors in the male offspring of morphine-abstinent rats.

The role of parental morphine exposure before gestation on mood disorder in the offspring was well described. Besides, physical activity can improve the symptoms of mood disorders. So, the current study aimed to investigate the role of physical activity on depressive and OCD-like behaviors induced by parental morphine exposure. 40 male and 40 female Wistar rats (60-days old) received morphine for consecutive 10 days and were drug-free for 10 days. They were prepared for mating either with a morphine-abstinent or with a drug-naïve rat. The adult male offspring were divided into two groups as follows: (1) those that were subjected to treadmill exercise for three weeks (3-days each week), and (2) those without exercise. Also, the offspring were subjected to forced swimming and marble-burying tests. The levels of 5-HT3 receptor (R), D1, and D2 dopamine receptor (DR) were evaluated as well as the level of monoamine oxidase-B (MAO-B) in the prefrontal cortex (PFC). Results showed that exercise improved depressive and OCD-like behaviors in the offspring of morphine-abstinent rats. Western blotting data revealed that the levels of 5-HT3R, D1DR, D2DR, and MAO-B in the PFC increased in the offspring of morphine-abstinent rats compared to the control. However, it was shown that treadmill exercise decreases the levels of 5-HT3R, MAO-B, and D2DR. Morphine exposure, even before conception, could affect the behaviors in the offspring. Besides, the molecular changes were also detected in the brain. We found that mild physical activity might modulate OCD and depressive-like behavior in the offspring of morphine-abstinent rats by decreasing the levels of 5-HT3R, D2DR, and MAO-B located in the PFC.

The evolution of addiction treatment and harm reduction programs in Iran: a chaotic response or a synergistic diversity?

BACKGROUNDS AND AIMS: Iran has 2.1 and 1.8% of its 15-64-year-old population living with illicit substance and opioid use disorders, respectively. To address these problems, Iran has been developing a large and multi-modality addiction treatment system, spanning the time before and after the Islamic Revolution. METHODS: Iran's current drug treatment scene is a combination of services, ranging from medical/harm reduction services to punitive/criminal justice programs. Included in this array of services are drop-in centers providing low-threshold harm reduction services, such as distribution of sterile needles and syringes; opioid maintenance treatment clinics providing methadone, buprenorphine and opium tincture; and abstinence-based residential centers. We will review the evolution of this system in four phases. RESULTS: In 1980, Iran's revolutionary government shut down all voluntary treatment programs and replaced them with residential correctional programs. The first shift in the addiction treatment policies came 15 years later after facing the negative consequences. Addiction is viewed as a disease, and new voluntary treatment centers offering non-agonist medications and psychosocial services were established. With an increased number of people who inject drugs and HIV/AIDS epidemics, in the second shift an extensive move towards harm reduction strategies and opioid-maintenance programs has been implemented to reduce HIV-related high-risk behavior. The emergence of a methamphetamine use crisis creating an increased number of socially marginalized addicted people resulted in public and political demands for stricter policies and ended in the third shift starting in 2010, with extended compulsory court-based residential programs. Currently, there is a new shift towards reducing the severity of criminal penalties for drug use/sales and promoting proposals for opium legalization. CONCLUSION: Iran's evolutionary experience in developing a large addiction treatment program in a complex combination of medical/harm reduction and punitive/criminal justice addiction treatment can be examined in its political, clinical and pragmatic context.

COVID-19 and Substance Use Disorders: Recommendations to a Comprehensive Healthcare Response. An International Society of Addiction Medicine Practice and Policy Interest Group Position Paper.

Coronavirus Disease 2019 (COVID-19) is escalating all over the world and has higher morbidities and mortalities in certain vulnerable populations. People Who Use Drugs (PWUD) are a marginalized and stigmatized group with weaker immunity responses, vulnerability to stress, poor health conditions, high-risk behaviors, and lower access to health care services. These conditions put them at a higher risk of COVID-19 infection and its complications. In this paper, an international group of experts on addiction medicine, infectious diseases, and disaster psychiatry explore the possible raised concerns in this issue and provide recommendations to manage the comorbidity of COVID-19 and Substance Use Disorder (SUD).

A Randomized Controlled Trial of Brief Cognitive Behavioral Therapy for Regular Methamphetamine Use in Methadone Treatment.

This study evaluated the efficacy of brief cognitive behavioral therapy (BCBT) for regular methamphetamine use among methadone-maintained women. A randomized controlled trial was conducted in four methadone treatment services. Eligible women were assigned to receive either BCBT or drug education. Five questionnaires were used to assess the research hypotheses at weeks 0, 4, and 12. Urinalysis was used to verify self-reported methamphetamine use at week 0. Urinalyses were used for those participants who reported abstinence from methamphetamine at weeks 4 and 12. Overall, 120 women were enrolled. Sixteen participants were lost to follow-up. Compared with the control group, the treatment group showed significant reductions in frequency of methamphetamine use (p < 0.001), severity of methamphetamine dependence (p < 0.001), and number of days of methamphetamine use (p < 0.001) at weeks 4 and 12. Significant improvements in readiness to change (p < 0.001), psychological well-being (p < 0.001), and social functioning (p = 0.001) were found in the treatment group at weeks 4 and 12. Nineteen urine specimens (31.66%) in the treatment group were negative for methamphetamine use at post-treatment and follow-up, while no change was found in the control group (0.00%). The study supported the efficacy of BCBT for methamphetamine use and associated harms.

Key findings from the WHO collaborative study on substitution therapy for opioid dependence and HIV/AIDS.

AIMS: Opioid substitution treatment has been studied extensively in industrialized countries, but there are relatively few studies in developing/transitional countries. The aim of this study was to examine the effectiveness of opioid substitution treatment (OST) in less resourced countries. DESIGN: Longitudinal cohort study. SETTING: Purposively selected OST sites in Asia (China, Indonesia, Thailand), Eastern Europe (Lithuania, Poland, Ukraine), the Middle East (Iran) and Australia. PARTICIPANTS: Seven hundred and twenty-six OST entrants. MEASUREMENTS: Participants were interviewed at treatment entry, 3 and 6 months. Standardized instruments assessed drug use, treatment history, physical and psychological health, quality of life, criminal involvement, blood-borne virus (BBV) risk behaviours and prevalence of human immunodeficiency virus (HIV) and hepatitis C. FINDINGS: Participants were predominantly male, aged in their early 30s and had attained similar levels of education. Seroprevalence rates for HIV were highest in Thailand (52%), followed by Indonesia (28%) and Iran (26%), and lowest in Australia (2.6%). Treatment retention at 6 months was uniformly high, averaging approximately 70%. All countries demonstrated significant and marked reductions in reported heroin and other illicit opioid use; HIV (and other BBV) exposure risk behaviours associated with injection drug users (IDU) and criminal activity, and demonstrated substantial improvement in their physical and mental health and general wellbeing over the course of the study. CONCLUSIONS: OST can achieve similar outcomes consistently in a culturally diverse range of settings in low- and middle-income countries to those reported widely in high-income countries. It is associated with a substantial reduction in HIV exposure risk associated with IDU across nearly all the countries. Results support the expansion of opioid substitution treatment.

The medieval Persian manuscript of Afyunieh: the first individual treatise on the opium and addiction in history.

According to historical evidence, the abuse of opium has been reported all over the globe-specifically throughout Eastern nations-since the sixteenth century. Before that, opium had mostly been applied as medication. Reference has been made in traditional Persian medical literature to the method of cultivation, properties, side effects and toxicity. In sixteenth century Iran, during the reign of the Safavids, opium abuse began. It was from then that prominent Persian scholars started to think of solutions to this societal problem. One of the most famous scholars was Imad al-Din Mahmud ibn Mas'ud Shirazi, who composed a book concerning addiction-Afyunieh, a comprehensive book on the topic of opium and all issues of opium. Furthermore, he recommended methods for reducing opium dose as well as substitution with other medications that had a narrower range of side effects, in order to eradicate dependency upon opium and opium-derived materials. This is most likely the first book that comprehensively addressed opium and discussed drug rehabilitation methodology, in traditional Persian medical literature. In this historical review, the authors have introduced the book Afyunieh, which presents methods for treating addiction to and giving up opium; the text comprises a synthesis of the author's opinions, professional experience and references to the work of other famous physicians.

Setting research priorities to achieve long-term health targets in Iran.

BACKGROUND: In 2015, it was estimated that the burden of disease in Iran comprised of 19 million disability-adjusted life years (DALYs), 74% of which were due to non-communicable diseases (NCDs). The observed leading causes of death were cardiovascular diseases (41.9%), neoplasms (14.9%), and road traffic injuries (7.4%). Even so, the health research investment in Iran continues to remain limited. This study aims to identify national health research priorities in Iran for the next five years to assist the efficient use of resources towards achieving the long-term health targets. METHODS: Adapting the Child Health and Nutrition Research Initiative (CHNRI) method, this study engaged 48 prominent Iranian academic leaders in the areas related to Iran's long-term health targets, a group of research funders and policy makers, and 68 stakeholders from the wider society. 128 proposed research questions were scored independently using a set of five criteria: feasibility, impact on health, impact on economy, capacity building, and equity. FINDINGS: The top-10 priorities were focused on the research questions relating to: health insurance system reforms to improve equity; integration of NCDs prevention strategy into primary health care; cost-effective population-level interventions for NCDs and road traffic injury prevention; tailoring medical qualifications; epidemiological assessment of NCDs by geographic areas; equality in the distribution of health resources and services; current and future common health problems in Iran's elderly and strategies to reduce their economic burden; the status of antibiotic resistance in Iran and strategies to promote rational use of antibiotics; the health impacts of water crisis; and research to replace the physician-centered health system with a team-based one. CONCLUSIONS: These findings highlight consensus amongst various prominent Iranian researchers and stakeholders over the research priorities that require investment to generate information and knowledge relevant to the national health targets and policies. The exercise should assist in addressing the knowledge gaps to support both the National General Health Policies by 2025 and the health targets of the United Nations' Sustainable Development Goals by 2030.

HIV risk behavior among injection drug users in Tehran, Iran.

AIMS: Iran faces parallel human immunodeficiency virus (HIV) and injection drug use epidemics; more than 62% of known HIV cases occur among injection drug users (IDU). We conducted a formative study of IDU in Tehran to explore risk behavior in the wake of the recent harm reduction efforts. PARTICIPANTS AND DESIGN: Key informant interviews (n = 40), focus group discussions (nine groups of IDU, n = 66) and a review of existing published and unpublished literature were conducted. Participants included IDU, physicians, policy makers, police, IDU advocates and their families. IDU were diverse in gender, education, income and neighborhood of residence. Interviews were transcribed and analyzed using grounded theory. A typology of IDUs in Tehran, categorized according to self-defined networks as well as HIV risks, is presented. This categorization is based on the groups identified by IDUs, compared to those identified by other key informants, and on a secondary data review. FINDINGS: Homeless, female, young IDU and users of a more potent form of heroin were identified as having increased risks for HIV. Participants described shortening transitions from smoked opium to injected opiates. Whereas a majority of participants considered needle sharing less common than previously, sharing continues in locations of group injection, and in states of withdrawal or severe addiction. System-wise barriers to harm reduction were discussed, and include the cost or stigma of purchasing needles from pharmacies, over-burdened clinics, irregular enforcement of laws protecting IDU and lack of efforts to address the sexual risks of IDU. CONCLUSIONS: This research is one of the first to describe a diversity of IDU, including women and higher socio-economic class individuals, in Tehran. While efforts in harm reduction in Iran to date have been notable, ongoing risks point to an urgent need for targeted, culturally acceptable interventions.

Validation for Persian Versions of "Desire for Drug Questionnaire" and "Obsessive Compulsive Drug Use Scale" in Heroin Dependents.

OBJECTIVE: Drug Craving could be defined as a subjective motivational state associated with a strong desire to consume drugs. Craving is a subjective phenomenon; therefore, self-report (subjective) craving measures are usually referenced. Two well-known questionnaires for measurement of drug craving severity are Desire for Drug Questionnaire or DDQ (for instant craving) and Obsessive Compulsive Drug Use Scale or OCDUS [for craving in a period of time (periodic craving), usually one week]. In this study, we evaluated the content-related validity of these questionnaires for Persian-language speaking crystalline-heroin abusers. METHODS: After translation by two different groups, back translation and retranslation process of the DDQ and OCDUS questionnaires were achieved by an expert team in English language; we used them for evaluation of instant and periodic craving among 131 male crystalline-heroin abusers. Then, both DDQ and OCDUS questionnaire's scores were subjected to an exploratory principal components factor analysis (PCA). The criterion for factor extraction was an eigenvalue equal to or more than 1. RESULTS: The factor analysis of DDQ and OCDUS led to three factors for DDQ and four factors for OCDUS; each group of factors together explained 62% and 65% of the common factor variance, respectively. There was no significant correlation between different DDQ and OCDUS components and demographic factors. Nevertheless, approximately all of the seven OCDUS and DDQ components were significantly correlated to each other. CONCLUSION: The Persian version of DDQ and OCDUS questionnaires could be considered as valid and reliable instruments for evaluation of drug craving in male crystalline-heroin Persian-language speaking abusers.

Medical treatments for opioid use disorder in Iran: a randomized, double-blind placebo-controlled comparison of buprenorphine/naloxone and naltrexone maintenance treatment.

AIMS: With the broad goals of developing a clinical research and training program and disseminating effective opioid use disorder treatments in Iran, this pilot clinical trial compared the effectiveness of oral naltrexone (NTX) and sublingual buprenorphine/naloxone (BNX). DESIGN: Twelve-week single-site, two-group parallel randomized double-blind clinical trial. SETTING: An out-patient clinical research program in Tehran, Iran. PARTICIPANTS: Following medically assisted withdrawal, participants with opioid use disorder were assigned randomly to NTX (n = 51) or BNX (n = 51). INTERVENTION: Medications were administered three times per week, double-blind, double-dummy for 12 weeks. All participants received weekly group drug counseling. MEASUREMENTS: The primary outcome was initial duration of opioid abstinence verified by urine toxicology tests. Secondary outcomes included the number of opioid-negative urine tests, treatment retention and proportions with sustained, verified opioid-abstinence for 12 weeks. FINDINGS: Mean [95% confidence interval (CI)] number of days of initial duration of verified abstinence was 28.8 (20.0-37.5) with BNX and 21.6 (14.4-28.7) with NTX (P = 0.205). The mean (95% CI) number of opioid-negative urine tests was 19.7 (17.7-21.6) with BNX and 15.4 (13.1-17.8) with NTX (P = 0.049). The mean (95% CI) number of days in treatment was 70.6 (63.6-77.7) with BNX versus 56.5 (47.8-65.3) with NTX (P = 0.013). The rate of sustained, 12-week opioid abstinence was 16% (8/51) in the BNX group and 8% (4/51) in the NTX group (P = 0.219). CONCLUSIONS: Among patients with opioid use disorder in Iran, sublingual buprenorphine/naloxone was associated with a greater number of opioid-negative urine tests and treatment retention than oral naltrexone, but not significantly greater initial abstinence duration or proportions with sustained abstinence.