Blended smartphone intervention for patients in opioid maintenance treatment in Iran: protocol for a randomized controlled trial.

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 .

Prevalence of alcohol consumption among clients of opioid agonist treatment (OAT) centers in Golestan province, Iran.

Introduction: Opioid agonist treatments (OATs) with methadone and buprenorphine are known to be effective treatments for people with opioid use disorder (OUD). However, concomitant use of other substances such as alcohol can negatively affect OAT outcomes. This study aimed to determine the prevalence of alcohol use among clients of OAT centers in the Golestan province in the northern part of Iran. Materials and methods: This is a secondary analysis of a sample of 706 clients who were receiving OATs from certified OAT centers in Golestan province in 2015. They had been on OATs for at least 1 month and were randomly selected for the study. Data were collected via interviews with selected OAT clients. The main indicators studied in the present study were lifetime history of alcohol consumption, alcohol consumption during last month, lifetime history of excessive alcohol use on one occasion, and years of regular alcohol consumption. Results: The prevalence of lifetime history of alcohol consumption was estimated at 39.2%. Prevalence of alcohol consumption during last month and lifetime history of excessive alcohol use on one occasion was 6.9 and 18.8%, respectively. Conclusion: Despite a total ban on alcohol consumption in Iran, a sub-sample of participants admitted past-month alcohol use concurrent with their OATs. The estimated past-month prevalence of alcohol use was lower than the reported prevalence in countries where the production, distribution, and consumption of alcohol are legal.

Identification of the socio-cultural barriers of drug addiction treatment in Iran.

Introduction: Socio-cultural norms can either be encouraging or a barrier to addiction treatment. More, rigorous research is needed on nonindigenous models in addiction treatment, to better understand the role of socio-cultural differences. Methods: The present qualitative study is part of the project, "The Inclusive Assessment of the Barriers of Drug Addiction Treatment Services in Iran," which was conducted in Tehran from 2018 to 2021. The participants consisted of eight people who used drugs, seven individual family members of the people who used drugs participants, seven service providers, and four policymakers. A purposeful sampling method was used for the selection of the participants, and the process continued until reaching the theoretical saturation of data. Analysis used the Graneheim and Lundman methods, classifying primary codes, the sub-themes, and themes were classified according to the similarities and differences between primary codes. Finding: The most important socio-cultural barriers to addiction treatment in Iran are: unrealistic expectations of the family and society from the people who use drugs, addiction stigma, mistrust between various components of the treatment system, perceptions that professional substance use disorder treatment is inefficient and low uptake of that treatment, the disturbed relational boundaries between the people who use drugs and their relatives, the interweaving of treatment and ethical and religious principles, low acceptance of maintenance treatments, treatment focusing on short-term outcomes, and presence of facilitating backgrounds of using drugs. Conclusions: The Iranian socio-cultural characteristics play an important role in the addiction treatment of the people who use drugs, so it is necessary for treatment interventions to be sensitive to these characteristics.

Post-Exposure Prophylaxis for COVID-19: A Systematic Review.

INTRODUCTION: SARS-CoV-2 cause pneumonia can spread across the lung and lead to acute respiratory distress syndrome (ARDS) in severe cases. Post-exposure prophylaxis has shown great potential to prevent the transmission of some viral infections; however, such results for COVID-19 are still inconclusive. METHODS: Therefore, the aim of this study was to systematically review the resources that utilized postexposure prophylaxis (PEP) for COVID-19 and the possible clinical benefits of such drugs. An organized search of relevant literature was done using the keywords and search queries on public databases of Cochrane, PubMed, Web of Science and Scopus from December 2019 to August 23, 2021. Original resources that had the inclusion criteria were included after two-phase title/abstract and full-text screenings. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta- Analysis (PRISMA) statement. RESULTS: Out of 841 retrieved records 17 resources were appropriate to include in the systematic review. Hydroxychloroquine with a daily dose of 400-800 mg and a duration of 5-14 days was the most frequently used agent for PEP. Chloroquine was recommended to use to control treatment in patients with mild to severe COVID-19 pneumonia. Other agents like Lopinavir-ritonavir (LPV/r), angiotensinconverting enzyme inhibitors (ACEIs), Angiotensin receptor blockers (ARBs), Vitamin D, arbidol, thymosin drugs, and Xin guan no.1 (XG.1, a Chinese formula medicine) have also been applied in some studies. CONCLUSION: Current evidence demonstrated no established clinical benefits of any drug as PEP in individuals with COVID-19. However, scarce indication occurs for the beneficial effects of some agents, but more studies are needed to explore such effects.

Cryoablation for the Palliation of Painful Bone Metastasis: A Systematic Review.

BACKGROUND: Cryoablation is a minimally invasive procedure to treat painful bone metastases in patients with cancer. We designed a systematic review to understand the safety and effects of cryoablation on the pain and quality of life (QoL) of cancer patients. METHOD: We searched PubMed, ISI, Cochrane library, and Scopus databases using the keywords "Cryoablation," "Pain," and "Bone metastasis." Inclusion criteria were: (1) Original studies published until September 8, 2022; (2) studies on patients over 18 years and affected by bone metastasis; (3) bone metastasis treated with stand-alone cryoablation; (4) studies reporting patients' pain before and at least one time-point following cryoablation; and (5) English-language studies. RESULTS: We screened 696 articles. Fifteen studies on 376 patients were included. Time points for pain assessment ranged from 1 day to 6 months. Spine was the most frequent treated location. All studies reported a significant pain reduction between 1 day and 6 months after the cryoablation procedure. The highest mean difference between pre- and post-procedure scores was 5.8 (VAS scale) after 4 weeks. The overall rate of minor and major complications was 12.74%. Cryoablation improved the QoL of cancer patients and decreased the need for analgesics. CONCLUSION: Cryoablation is a safe and useful procedure for palliating painful bone metastasis and increasing the QoL of cancer patients. Future studies should adopt a standardized pain reporting scale to allow for meta-analysis.

Management of gabapentin misuse in a patient with previous history of opioid use disorder: Case report.

We present a 37-year-old male who misuses 12 g of gabapentin per day associated with dependence and withdrawal. He had a previous history of opioid use disorder (OUD) which has been in remission. An outpatient gradual dose reduction regimen was tried and failed and the patient decided to discontinue gabapentin abruptly. Symptomatic medication to relieve gabapentin withdrawal was also unsuccessful and resulted in the reinstatement of OUD. Finally, the patient was stabilized using buprenorphine maintenance treatment and discontinued opioids and gabapentin misuse. The clinical implications and significance of taking regulatory actions to control gabapentin misuse have been discussed.

Population Size Estimation of People Who Use Illicit Drugs and Alcohol in Iran (2015-2016).

BACKGROUND: Estimating the number of people using illicit drugs and alcohol is necessary for informing health policy and programming. However, it is often challenging to reliably estimate the size of these marginalized populations through direct methods. In this study, we estimated the population size of these groups using the indirect Network Scale-Up (NSU) method in Iran from 2015 to 2016. METHODS: Using a self-administered questionnaire, we asked 15 124 individuals (54% men) about the number of people they know who used different types of drugs at least once in the past 12 months. Prevalence estimates were reported per 100 000 population. The uncertainty level (UL) was calculated using the bootstrap method. RESULTS: The average age of the respondents was 33 years old, and 35.1% of them were unmarried. The most common drugs and their prevalence were as follows: opium (2534 [95% UL: 2467-2598]), hashish (849 [95% UL: 811-886]), stimulants (methamphetamine, ecstasy pills, cocaine, and Ritalin) (842 [95% UL: 802-879]), heroin/crack (578 [95% UL: 550-607]), and drug injection (459 [95% UL: 438-484]). Additionally, we estimated the prevalence of alcohol use as 2797 (95% UL: 2731-2861). On average, substance use was 5.23 times more prevalent among men than women. Opium use was more prevalent among individuals aged >50 years old. Moreover, alcohol use was more prevalent among participants between 18 and 30 years old (5164 per 100 000 population). CONCLUSION: Although opium continues to be the most prevalent illicit drug in Iran, the patterns of illicit drug use are heterogeneous among different age groups, genders, and provinces. Age-gender specific and culturally appropriate interventions are warranted to meet the needs of people in different subgroups.

The relationship between C-reactive protein and levels of various cytokines in patients with COVID-19: A systematic review and correlation analysis.

Introduction: C-reactive protein (CRP) and cytokines levels could alter in patients with coronavirus disease (COVID-19) due to the inflammatory response caused by the virus. This analysis aimed to assess the relationship between the CRP levels and the levels of various cytokines in COVID-19 patients. Materials and Methods: We searched the databases of PubMed, Cochrane, and Web of Science for relevant articles on May 29th, 2021. Applying the inclusion/exclusion criteria, the retrieved records underwent two-phase screenings; first, a title/abstract screening process, and then, a full-text screening to find the eligible studies. Data for study variables were extracted, including the CRP levels and the levels of all reported cytokines. A strong and significant relationship between Interleukins and CRP was defined as: p ≤ 0.05, 0.7 ≤ r ≤ 1. Results: In this study, 103 studies were included for systematic review and correlation analysis. The aggregate mean and SD of study variables were calculated and reported. The correlation between Interleukins and CRP was measured using correlation coefficient (r). It appeared that interleukin (IL)-10 has a moderate and significant relationship with CRP (p ≤ 0.05, r = 0.472). IL-10 predicted almost 10% of CRP changes. Conclusion: This correlation analysis suggests IL-10 is moderately correlated with CRP levels in patients with COVID-19 infection. A better understanding of the pro-inflammatory markers could contribute to the implementation of therapeutic and preventive approaches. More prospective studies are suggested to explore the relationship between CRP and cytokines as potential markers for the early identification of COVID-19 progression and severity.

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.

Effects of Transcranial Direct Current Stimulation on Attentional Bias to Methamphetamine Cues and Its Association With EEG-Derived Functional Brain Network Topology.

BACKGROUND: Although transcranial direct current stimulation (tDCS) has shown to potentially mitigate drug craving and attentional bias to drug-related stimuli, individual differences in such modulatory effects of tDCS are less understood. In this study, we aimed to investigate a source of the inter-subject variability in the tDCS effects that can be useful for tDCS-based treatments of individuals with methamphetamine (MA) use disorder (IMUD). METHODS: Forty-two IMUD (all male) were randomly assigned to receive a single-session of either sham or real bilateral tDCS (anodal right/cathodal left) over the dorsolateral prefrontal cortex. The tDCS effect on MA craving and biased attention to drug stimuli were investigated by quantifying EEG-derived P3 (a measure of initial attentional bias) and late positive potential (LPP; a measure of sustained motivated attention) elicited by these stimuli. To assess the association of changes in P3 and LPP with brain connectivity network (BCN) topology, the correlation between topology metrics, specifically those related to the efficiency of information processing, and the tDCS effect was investigated. RESULTS: The P3 amplitude significantly decreased following the tDCS session, whereas the amplitudes increased in the sham group. The changes in P3 amplitudes were significantly correlated with communication efficiency measured by BCN topology metrics (r = -0.47, P = .03; r = -0.49, P = .02). There was no significant change in LPP amplitude due to the tDCS application. CONCLUSIONS: These findings validate that tDCS mitigates initial attentional bias, but not the sustained motivated attention, to MA stimuli. Importantly, however, results also show that the individual differences in the effects of tDCS may be underpinned by communication efficiency of the BCN topology, and therefore, these BCN topology metrics may have the potential to robustly predict the effectiveness of tDCS-based interventions on MA craving and attentional bias to MA stimuli among IMUD.

Psychometric properties of the shortened Farsi version of the Food Cravings Questionnaire-Trait.

BACKGROUND: Food craving contributes to the incidence of weight and food-related disorders. Thus, an accurate measurement of food craving is important for clinical and research purposes. AIMS: We aimed to evaluate the psychometric properties of the shortened Farsi version of the Food Craving Questionnaire- Trait (FCQ-T-r), an internationally validated tool. METHODS: For this cross-sectional study, data was collected from 153 students of the University of Tehran between February and March 2019 using the Farsi version of FCQ-T-r; Depression, Anxiety and Stress Scale (DASS-21); and the Quality of Life questionnaire (WHOQOL-BREF). Confirmatory factor analysis using SPSS AMOS (version 21) failed to support the one-factor structure of FCQ-T-r in Farsi, so we conducted an exploratory factor analysis to investigate the factor structure of the questionnaire. RESULTS: Exploratory factor analysis reflected a 3-factor structure responsible 73.3% of the variance factor 1 "preoccupation with food", factor 2 "lack of control over eating" and factor 3 "emotional eating". Internal consistency of the FCQ-T-r was excellent (McDonald's ω = 0.950). The FCQ-T-r scores were correlated with body mass index, DASS-21, and WHOQOL-BREF values, which supports concurrent validity of the tool. CONCLUSION: The Farsi version of FCQ-T-r is a reliable and valid self-administrated tool to measure food craving traits among Iranian university students. Given the unstable factor structure of the questionnaire in different studies, further research should be conducted explore the factor structure of the tool.

Factors influencing engagement and utilisation of opium tincture-assisted treatment for opioid use disorder: A qualitative study in Tehran, Iran.

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.

Public health risks associated with methadone in Iran: A systematic review and meta-analysis.

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.

Baseline executive functions and receiving cognitive rehabilitation can predict treatment response in people with opioid use disorder.

BACKGROUND: Impaired cognitive functions, particularly executive function, predicts poor treatment success in people with substance use disorders. The current study investigated the effect of receiving adjunct cognitive rehabilitation and baseline executive function (EF) measures on treatment response among people with opioid use disorder (OUD). METHOD: The analysis sample consisted of 113 participants with OUD who were discharged from a compulsory court-mandated methadone maintenance treatment (MMT) and followed for 3 months. We used the Backward digit span/Auditory verbal learning, Stroop, and Trail making tests to assess the three measures of EF, including working memory, inhibition, and shifting, respectively. Treatment response was operationalized as (1) treatment retention and (2) the number of positive urine tests for morphine during 3-month follow-up periods. The study used Cox's proportional hazards model and linear mixed model to identify predictive factors. RESULTS: Lower Stroop interference scores predicted increased length of stay in treatment (χ2 = 33.15, P < 0.001). The linear mixed model showed that scores on auditory verbal learning test and group intervention predicted the number of positive urine tests during a 3-month follow-up. CONCLUSION: Working memory and inhibitory control, as well as receiving cognitive rehabilitation, could be potentially considered as predictors of treatment response for newly MMT admitted patients with OUD. Assessment of EF before treatment initiation may inform treatment providers about patient's cognitive deficits that may interfere with therapeutic interventions.

Opium dependence and the potential impact of changes in treatment coverage level: A dynamic modeling study.

Background : The most common drug, illegally used in Iran is opium. The treatment of people with substance use disorder is one of the most important strategies in reducing its burden. The aim of this study was to investigate the effect of different increasing and decreasing opium treatment coverage on the patterns of abstinence, transition to heroin dependence and mortality, over 30 years. Methods: This study was a dynamic compartmental modeling conducted in three stages: 1) presenting a conceptual model of opium dependence treatment in Iran, 2) estimating model's parameters value, and 3) modeling of opium dependence treatment and examining the outcomes for different treatment coverage scenarios. The input parameters of the model were extracted from the literature, and secondary data analysis, which were finalized in expert panels. Results: The number of opium dependence will increase from 1180550 to 1522063 [28.93% (95% CI: 28.6 to 29.2)] over 30 years. With a 25% decrease in coverage compared to the status quo, the number of deaths will increase by 459 cases [3.28% (95% CI: 0.91 to 5.7)] in the first year, and this trend will continue to be 2989 cases [15.63% (95% CI: 13.4 to 17.9)] in the 30th year. A 25% increase in treatment coverage causes a cumulative decrease of heroin dependence by 14451 cases [10.1% (95% CI: 9.5 to 10.8)] in the first decade. Conclusion: The modeling showed that the treatment coverage level reduction has a greater impact than the coverage level increase in the country and any amount of reduction in the coverage level, even to a small extent, may have a large negative impact in the long run.

Willingness to utilize supervised injection facilities among people who inject drugs in Iran: Findings from 2020 national HIV bio-behavioral surveillance survey.

BACKGROUND: Supervised injection facilities (SIFs) have not yet been integrated into Iran's harm reduction programs. This study aimed to report the extent to which people who inject drugs (PWID) in Iran are willing to use SIFs. METHODS: Participants were recruited from 11 major cities using respondent-driven sampling. Willingness to use SIFs was defined as a three-level categorical variable: low, moderate, or high. RESULTS: Of 2,490 PWID, 52.8% and 23.8% reported high and moderate willingness to use SIFs, respectively. PWID with a history of homelessness (relative-risk ratio (RRR): 2.22, 95% CI: 1.76-2.80), incarceration (1.86 [1.48-2.35]), hepatitis C infection (1.49 [1.13-1.97]), and non-fatal overdose (2.30 [1.69-3.13]) were more likely to be willing to utilize SIFs. Willingness to use SIFs was also higher among PWID who reported recent public injecting (2.24 [1.70-2.97]), daily injection (1.82 [1.35-2.45]), stimulants injection (2.39 [1.41-4.07]), syringe sharing (3.09 [1.23-7.74]), harm reduction services utilization (2.80 [2.13-3.68]), and food insecurity (8.28 [5.43-12.63]). CONCLUSION: The majority of PWID in Iran expressed willingness to use SIFs, in particular, those who were involved in higher-risk injection practices, dealing with structural risks, and had experienced drug-related harms. SIFs represent critical opportunities to deliver comprehensive harm reduction services to improve the health and well-being of PWID in Iran.

Opium tincture-assisted treatment for opioid use disorder: A systematic review.

BACKGROUND: Some countries have used opioid agonist medications other than methadone and buprenorphine as a strategy to increase treatment diversity. In Iran and other countries where opium use is common and culturally tolerated, opium tincture (OT) has gained growing popularity and been approved to treat opioid use disorder (OUD). Given the increasing interest in this intervention, we conducted a systematic review of the literature to evaluate the safety and efficacy of OT-assisted treatment for OUD. METHODS: We systematically searched international (MEDLINE, Embase, CINAHL, PsychInfo, Google Scholar, and clinicaltrials.gov) and Iranian (Scientific Information Database (SID), Iranmedex, IranDoc, digital library of Iran's Drug Control Headquarters and the Iranian Registry for Clinical Trials) databases on November 04, 2020 without any language or publication date limitations. Two reviewers screened the titles, abstracts, and full-text of the retrieved records to find clinical trials or observational studies that assessed the safety and efficacy of OT-assisted treatment for OUD. RESULTS: We screened 1301 records and included 21 unique studies on assisted withdrawal (n = 5), maintenance (n = 9), and gradual dose reduction (n = 7) treatment regimens. Most studies included men and people with opium use disorder. We found only six randomized controlled trials (RCT). Our results showed that OT-assisted treatment is associated with comparable outcomes with methadone treatment in both assisted withdrawal and maintenance treatment regimens. We also found promising results for using gradual dose reduction regimen of OT-assisted treatment from observational studies. The overall quality of scientific evidence was low due to the limited number RCT and high risk of bias in the included studies. CONCLUSIONS: The body of evidence supporting the safety and efficacy of OT-assisted treatment in assisted withdrawal, maintenance, and gradual dose reduction regimens is limited but somewhat promising, in particular among people with opium use disorder. Our review calls for higher-quality studies to investigate the comparative efficacy of these treatment methods with standard pharmacotherapies for OUD.