Substance Use Disorder

DETAILED METHODOLOGY Phase I: * Research Design: Qualitative * Research Setting: Selected public schools of Pokhara, Nepal * Population: Teachers, Parents, and Students of Pokhara, Nepal * Samples: Selected Teachers, Parents \& students * Sample Size: 38 (The sample will be collected till data Saturation) * Data collection Technique: Focus group discussion * Data collection Tool: Focus group lead questions * Data Analysis: Thematic analysis (Atlas.ti) Phase II Research design: Cluster Randomized Trial Randomization method: Cluster Randomization Research Setting: Selected public schools of Pokhara, Nepal Population: Adolescent students of Pokhara, Nepal Sample: Selected Adolescents, who are in the age group 13-15 years old and studying in 8th \& 9th grades Variables * Independent variables: School-based Substance abuse Prevention Programme (SSPP) * Dependent variables: awareness, attitudes, peer pressure, and life skills related to prevention of substance abuse. * Demographic variables: age in years, gender, religion, education/grade, family type, residence, number of siblings, education of parents, occupation of parents, sources of information, history of substance abuse in the family. Sample size: 210 The expected outcomes of the study is to enhance awareness towards prevention of substance abuse,develop a positive attitude towards the prevention of substance abuse,develop drug refusal skills among adolescents,improve life skills and helps in th reduction of drug abuse behaviour adolescents

The proposed study will be a non-pharmacological, two arm parallel, Prospective, single blind clinical trial to evaluate if there is a difference in retentive characteristics of dentition in two group of post orthodontic treatment patients with vertical growth pattern patients in one group and horizontal growth pattern patients in other group of patients. The present study will be conducted in the Department of Orthodontic and Dentofacial Orthopedics, P.G.I.D.S, Pt. B.D Sharma University of health sciences, Rohtak. The study will be carried out after the institutional approval obtained from ethical committee. Patient will be allocated to two different study group by the investigator. the data analyst will be blinded regarding the intervention group. The sample size for the proposed study was calculated by using the formula. Total sample size = N = 2σ 2 (Zβ + Zα/2) 2 / (difference of mean )2. sample size of 20 patients was calculated by using the above formula at confidence interval 95% with power 99%. GROUP 1: patient with vertical growth pattern have who had undergone, fixed orthodontic cases having FMA of 26 0 or more for hyperdivergent cases. GROUP 2 patient with horizontal growth pattern who had undergone , Fixed orthodontic cases having FMA of 24 o or less for hypodivergent cases. Changes in levels of bone turnover markers CTX-bone resorption and BALP-bone formation using ELISA. These parameters will be charted at T0, T1, T2, T3,T4 for each patient. T0 - Records will be obtained at the time of retainer delivery T1 - Records will be obtained after 1month of retainer delivery T2 - Records will be obtained after 3 month of retainer delivery T3- Records will be obtained after 6 months of retainer delivery T4- Records will be obtained after 12 months of retainer delivery Assessment of bite force will be done using bite force measuring device at T0 - Records will be obtained at the time of retainer delivery T1 - Records will be obtained after 1month of retainer delivery T2 - Records will be obtained after3month of retainer delivery T3- Records will be obtained after 6 months of retainer delivery T4- Records will be obtained after 12 months of retainer delivery

This is a multi-site, double-blind, randomized clinical trial of the 5-HT2A receptor agonist psilocybin for smoking cessation. The investigators previously conducted an open-label pilot trial (N = 15) of psilocybin paired with cognitive behavior therapy (CBT). Data showed a biologically-verified 7-day point-prevalence abstinence rate of 67% at 12 months and 60% at 2.5 years (continuous abstinence rates: 53% and 47%, respectively). The investigators are now conducting an open-label randomized comparative efficacy trial of psilocybin vs. nicotine patch, both in combination with CBT. Interim results (N = 44; 22 per group) show greater biologically-verified abstinence rates at 12 months for psilocybin: 7-day point-prevalence: 59% vs. 27%; continuous abstinence: 36% vs. 9%. Despite these promising findings, the investigators have yet to conduct a double-blind study of psilocybin for smoking cessation. Furthermore, previous psilocybin study samples have been largely White with higher socioeconomic status (SES). The current trial will address these issues across four sites with experience in conducting psilocybin research: Johns Hopkins, the University of Alabama at Birmingham (UAB), and New York University (NYU). A diverse sample with regard to ethno-racial identity and SES will be recruited at each site. The proposed double-blind study will treat 66 participants (22 at each site), randomized to receive either: 1) psilocybin; 30 mg in session 1 and either 30 or 40 mg in session 2, with sessions 1 week apart; or 2) niacin; 150 mg in session 1 and either 150 mg or 200 mg in session 2, with sessions 1 week apart. Niacin was selected because it has been used as an active placebo in two previous randomized therapeutic trials of psilocybin, and the FDA has informed the investigators that niacin is the FDA's preferred active placebo for psilocybin. CBT will be administered to both groups and will allow the investigators to test psilocybin's efficacy above and beyond an established treatment approach. Biochemically-confirmed 7-day point-prevalence abstinence will be assessed throughout for up to 12 months. The investigators hypothesize that psilocybin (compared to niacin) will cause increased biologically-confirmed 7-day point-prevalence abstinence at 12-month follow-up. Based on pilot data, the investigators will test cognitive/psychological mediators of treatment response. The investigators hypothesize that psilocybin will be associated with improved cognitive control and decreased anticipation of withdrawal relief (from smoking) 1 day after the target quit date, which will be associated with greater 7-day point-prevalence abstinence at 12- month follow-up. This trial will provide a rigorous test of efficacy in a diverse study sample, and test relevant mechanisms, for an innovative smoking cessation treatment showing potential for substantial efficacy.

Cocaine use disorder (CUD) is a chronic disorder associated with numerous relapses and periods of abstinence. Studies in CUD suggest that \~ 60 to 75% of abstinent addicts relapse over twelve months. Documenting specific neurochemical abnormalities that lead to relapse in individuals with CUD has the potential to accelerate the development of medications to prevent relapse. Basic investigations postulate an imbalance between brain stress and anti-stress/resilience systems as the underlying mechanism that drives negative reinforcement, craving, and relapse in addiction.. Nociceptin (N/OFQ), which binds to the nociceptive opioid peptide receptors (NOP) is a critical component of the brain's anti-stress system. N/OFQ exerts its anti-stress effect by counteracting the functional effects of the primary stress-promoting neuropeptide corticotrophin releasing factor (CRF) in the brain. Studies have also shown that acute increases in CRF and stress are countered by increased NOP receptor expression (\~ 10% ) in brain regions that regulate stress such as bed nucleus of the stria terminalis. PET studies with the NOP radiotracer \[11C\]NOP-1A show increased binding to NOP in CUD compared to HC. PET studies also show NOP receptors to upregulate (\~ 15%) in response to an acute intravenous hydrocortisone challenge (1 mg/Kg). NOP upregulation may represent an adaptive mechanism in the brain to counteract stress-induced increases in cortisol and CRF. Here, we postulate a failure in this adaptive mechanism as a reason that leads to relapse in CUD. CUD subjects and HC will be studied with \[11C\]NOP-1A before and after an intravenous hydrocortisone challenge (aim 1). Hydrocortisone is used as a challenge because it increases cortisol and CRF in brain regions that regulate stress. We hypothesize that hydrocortisone-induced increases in \[11C\]NOP-1A binding (DELTA VT) will be smaller in CUD relative to HC, and this will be associated with less time to relapse in a 12-week follow up. Mechanistic studies have also shown N/OFQ to act on ventral tegmental area/midbrain NOP receptors to inhibit the firing of dopamine neurons and limit reward to cocaine. Imaging amphetamine-induced dopamine release in a subset of CUD subjects who participate in aim 1 will allow us to link midbrain NOP receptor expression with ventral striatum (VST) dopamine release and examine its role in reinforcement (aim 2). The aims proposed in this study have the potential to clarify the role of N/OFQ and NOP in stress, reward, and relapse in CUD.

Cannabis is the most widely used federally illicit substance among emerging adults (age 18-25) in the U.S., and frequent cannabis use is associated with myriad long-term health, social, and academic/occupational consequences. Despite this, rates of perceived risk of daily/regular cannabis use have steadily declined over the past two decades, and this is associated with increased frequency of use, a risk for for Cannabis Use Disorder (CUD). Brief interventions (BIs) are among the most frequently used approaches for addressing problematic or potentially problematic substance use in non-treatment-seeking adolescents and young adults. Although several cannabis brief interventions have been developed and tested to date, meta-analyses indicate that the efficacy of these interventions for emerging adults is mixed and the quality of studies is low, suggesting that novel approaches and rigorous methodology are necessary to improve efficacy. The current study will evaluate the feasibility, acceptability, and preliminary efficacy of a novel cannabis BI for emerging adults who frequently use cannabis.

The current project will develop and pilot a brief, manualized intervention for improving Veterans' interpersonal functioning, community reintegration, and quality of life during early medication treatment for OUD. The research outlined in the current proposal will yield the necessary information to determine whether a fully powered randomized controlled trial of the intervention is warranted through completion of work outlined in Stages 1a (Phases 1 \& 2) and 1b (Phase 3) of the NIH Stage Model for Behavioral Intervention Development. Phase 1: Initial Development (13 months): In Phase 1, the initial treatment manual will be developed and revised using feedback from key stakeholders. After semi-structured stakeholder interview guides are developed in parallel with the initial manual, qualitative data from interviews with Veterans (n = 18) and VA providers (n = 16) will guide manual adaptations. Phase 2: Open Pilot (14 months): The manual development process will continue via an open pilot trial with n = 10 Veterans in early buprenorphine treatment, with recruitment to begin in the second month of the first quarter of Year 2. This initial field test will allow for the further refinement of the treatment manual and study protocol based on Veteran feedback and the experience of conducting the trial and delivering the intervention. Phase 2 will also involve the development of treatment adherence measures and training procedures for study therapists and adherence raters. Phase 3: Pilot RCT (33 months): The final phase of the proposed research will involve a Stage 1b pilot randomized controlled trial. A sample of n = 40 Veterans will be randomized to the intervention or treatment as usual. This pilot RCT will provide an opportunity to evaluate the refined intervention and assessment procedures and to assess feasibility and acceptability of the intervention. As an exploratory aim, this phase will also provide preliminary data for intervention effects on primary outcomes of interpersonal functioning, community reintegration, and quality of life, as well as secondary outcomes of interest (e.g., substance use) and candidate process measures. Results of this phase will be critical for informing the feasibility of a subsequent, fully powered RCT of the resulting intervention. PHASE 1: INITIAL DEVELOPMENT Phase 1 will focus on the development of a brief, 4-session values intervention to improve interpersonal functioning and community reintegration during early medication treatment for OUD. This phase will begin with the development of the treatment manual and stakeholder interviews by the PI and the mentorship team. Next, semi-structured interviews will be conducted with stakeholders, including n = 16 VA providers (evenly divided between prescribers and therapists) and n = 18 Veterans, evenly divided between those in early buprenorphine treatment (n = 6), sustained treatment (n = 6), and Veterans who opted to leave buprenorphine treatment within the first month (n = 6). Finally, stakeholder interview data will be analyzed and used to guide adaptations to the initial manual. Initial manual content, development \& revision. The initial intervention structure consists of four weekly 50 minute sessions focused on values clarification, committed action, and planning a life in recovery. Manual revisions will occur in an iterative manner during the proposed research, incorporating stakeholder feedback from Phase 1 and Phase 2. Changes may include adaptations to the language, the order of session content, and supplementary content for the intervention. De-identified examples from Veteran stakeholders may be used to enhance the relevance of the intervention for the Veteran population. Rationale for and focus of stakeholder interviews. Semi-structured interview protocols for stakeholders will be developed with mentorship support. These interviews will assess providers' and Veterans' experiences with and impressions of the role of personal values in recovery from OUD and initial impressions of the planned intervention. Through this process of collecting and incorporating feedback early in the development timeline, this project will yield a novel intervention that has been designed with input from key stakeholders within VA. Recruitment and Screening. Stakeholder recruitment will take place over the course of 8-9 months (\~4 interviews per month). Providers (n = 16) will be evenly split between prescribers (MD, NP, PAs) and therapists (PhD, LICSW, LMHC). With permission of clinic directors, the PI will join local addiction treatment program meetings to announce the study and provide contact information for interested providers. Veterans (n = 18) will also be recruited for individual stakeholder interviews, and will be split between those in early buprenorphine treatment (\<1 month), sustained buprenorphine treatment (\>1 year), and those who have discontinued treatment in the first month at some point over the past year. Interested participants will be instructed to contact the Principal Investigator or the study research coordinator directly. During the scheduling process, age, buprenorphine treatment status, duration of treatment episode, and safety with respect to suicide risk or need for detoxification treatment will be confirmed using simple scripted screener questions. Consultant Dr. Dongchan Park, who provides the largest proportion MOUD treatment at VA Bedford HCS, and will assist the PI with recruitment efforts across all phases. Interview Procedures. Provider and Veteran stakeholders will first provide informed consent. Veteran stakeholder interviews will include an abbreviated clinical interview to confirm eligibility. Semi-structured stakeholder interviews will consist of broad, open-ended questions with specific probes to allow the interviewer to follow up on areas of particular interest. The use of initial, broad, questions will help provide an overall view of provider and Veteran perspectives on the role of values-oriented recovery goals in OUD treatment. In the final portion of the interviews, provider and Veteran impressions of the format and focus of the intervention will be assessed by sharing an overview of the planned intervention similar to Table 3 (with expanded explanations of session content). It is anticipated that interviews will last no more than 60 minutes. All interviews will be recorded and transcribed verbatim with the assistance of a VA-approved transcription service. Data Management. All data including audio recorded interviews, transcripts, and qualitative analysis notes will be stored on VA servers behind VA firewall. Files will be password protected, and only active study staff will have access. To the extent possible given their focus area, recorded interviews will not include participant names or other identifying information, though additional procedures as outlined in section 4.b.2 of the Human Subjects section will provide additional protection for these files. Files will be linked to participants using ID numbers that are not connected to participant information. Analytic Plan. The 34 (16 Provider, 18 Veteran) audio-recorded stakeholder interviews will be transcribed verbatim, yielding qualitative data for Aim 1. The sample size for each group was chosen based on previous work which examined the number of interviews required to reach "saturation," or the point at which additional, new insights are unlikely to emerge from additional data. A coding team consisting of the PI and a research assistant will conduct a directed content analysis, using rapid analysis methods to inform the adaptation of the manual. Rapid analysis is conducive to the timeline of the current project, and has recently been shown to yield similar themes when compared to more in depth analytic methods. Matrix analysis methods will also facilitate comparisons among themes and between the stakeholder groups. PHASE 2: PILOT OPEN TRIAL Treatment development activities will continue through Phase 2 of the proposed project, an open trial with a sample of n = 10 Veterans who recently started medication treatment. Specifically, this open trial will provide an opportunity to field test and refine the initial intervention in pursuit of the following sub-aims: (a) further revise the manual and study procedures based on study metrics and Veteran feedback, and (b) develop therapist training, adherence and competency measures, and training for application of adherence and competency measures for the intervention. Recruitment \& Screening. Veterans will be recruited during the initial, intensive stage of outpatient treatment to participate in the study. Similar to the process for Veteran recruitment in Aim 1, basic screening questions for inclusion and safety will be completed as part of the scheduling process for the baseline visit. Procedures. Following brief screening and scheduling, study participation will include three assessment and four intervention sessions. Every effort will be made to complete sessions and assessments in-person, if VA infection control policy permits. Priority will be placed on completing all visits and assessments in the same format both within and across participants. A copy of the consent form, treatment workbook, and visual scales for assessment measures will be mailed immediately following screening and scheduling for any Veterans who complete study sessions remotely. Assessment Procedures. The three study assessments will occur separately from intervention sessions, and will take place at baseline, post-treatment (after session 4), and 3-month and 6-month follow up. An independent evaluator who is not involved in the study intervention will conduct all study assessments and will be supervised by the Principal Investigator, a licensed clinician. At the baseline visit, informed consent will include a brief set of comprehension questions to confirm understanding and ability to provide consent. Measures are estimated to require approximately 90-120 minutes for baseline and 60 minutes for each of the follow up assessment sessions. Every effort will be made to conduct all assessment sessions with Veterans regardless of whether they complete all intervention sessions. Assessment Protocol \& Measures. Opportunities to refine the assessment protocol in this pilot work will be explored in Phases 1 and 2 using (1) individual measure completion rates, (2) assessment session duration, and (3) Veteran feedback in qualitative interviews. In addition to further refining the manual and study procedures, the main focus of Phase 2 will be establishing the initial feasibility and acceptability of the intervention. Measures for Phase 2 and Phase 3 will include diagnostic and demographic measures to confirm eligibility, measures capturing acceptability of and satisfaction with the intervention, interpersonal and community functioning, quality of life, and substance use treatment adherence. Intervention sessions. Intervention sessions will be delivered by the candidate in Phase 2, as is typical for this phase of the intervention development process. Each session is designed to last approximately 50 minutes and occur on a weekly basis. In order to allow scheduling flexibility for Veterans, sessions will be completed within a six-week window. The initial intervention content for each of the four sessions is outlined in Table 2, though adjustments may be made during the initial manual development process and based on feedback from stakeholders in Phase 1. Data Management. Session recordings will password protected and stored securely on a VA server in the same manner as stakeholder interviews in Phase 1. All physical data will be securely stored under lock and key in file cabinets in Building 5 at the main campus of VA Bedford HCS. Local data files will be stored directly to a secure VA drive. The study contact log, used to monitor consented, enrolled participants, will also be password protected, will not include study data, and will be maintained in accordance with VA policy. Intervention \& Study Protocol Revisions (Aim 2a). In coordination with mentors, further revisions to the manual will be made using qualitative interview feedback from Veterans who complete the intervention (sub-aim 2b), together with any necessary changes identified through the process of delivering the intervention in this open pilot phase. A priori benchmarks for feasibility and acceptability to be used in Phase 3 will serve as guides for adaptations the intervention and study procedures in preparation for Phase 3. Refinement of the assessment protocol will be guided by (1) individual measure completion rates, (2) total time spent in each assessment session, and (3) Veteran feedback in qualitative interviews. Development of adherence measures and therapist training procedures (Aim 2b). Therapist adherence and competence scales will be developed by adapting existing rating forms that Dr. Kelly has used across multiple ACT studies. This rating system is designed to assess use of broadly defined ACT-consistent therapeutic strategies, appropriate use of specific ACT techniques from a given manual, and the absence of techniques that are inconsistent with ACT-based interventions. All therapy sessions will be digitally recorded and reviewed to identify the necessary adherence and competence measure components for this brief, simplified intervention. Phase 2 will also include the development of a program for training study therapists to deliver this simplified ACT intervention. Finally, therapists will be evaluated for adherence and competence throughout the trial. This training program will be implemented in Phase 3. PHASE 3: PILOT RANDOMIZED CONTROLLED TRIAL Phase 3 will provide an opportunity to examine (a) the feasibility and acceptability of the finalized intervention and randomized study protocol, and (b) the preliminary effects of the intervention on primary outcomes of interpersonal functioning, community reintegration, and quality of life, and secondary outcomes of substance use and treatment adherence. Procedures. Recruitment and screening will follow the same procedures and timeline as Phase 2. Interested participants will be randomized to the active (n = 20) or treatment as usual control condition (n = 20). Randomization will be stratified by gender and age (specifically above or below age 30) to ensure balance between the two groups, given evidence of these demographic characteristics in predicting treatment response and retention. The randomization list will be generated and maintained by the study coordinator. Assessment Procedures. The three study assessment sessions will follow the same timeline as Phase 2 for both study groups, using the same measures as Phase 2. Post-treatment qualitative interviews will be conducted with each group. The independent assessor for this phase will be blinded to participant study condition. Every effort will be made to conduct all assessment sessions with Veterans regardless of whether they complete all intervention sessions. The therapist adherence and competence scales that were developed and refined in Phase 2 will be piloted in Phase 3. Therapists who fall below the adherence threshold will receive further training and supervision. As part of this process, the rater training procedure for the adherence and competence scales to be used in the subsequent fully powered randomized controlled trial will also be developed. Intervention Procedures Active Condition: All intervention sessions will be delivered by a team of at least two Clinical Psychology postdoctoral fellows. Initial training and supervision will be provided weekly by Dr. Ameral, with as needed support and guidance from Dr. Kelly and Dr. Weisberg, who both have experience in the training and supervision of study interventionists. The intervention will otherwise be delivered following the same procedures as Phase 2 unless adaptations are indicated based on feedback from that phase. Treatment as Usual Control Condition: All Veterans receive intensive case management and regular group therapy in addition to appointments with their prescriber. After the first two weeks, they have the option to continue with a less intensive group schedule and case management support through the Aftercare program. Treatment focuses primarily on relapse prevention (rather than functioning) and is thus both an appropriate complement (for the active condition) and ideal comparison condition for the current study. Data Management \& Analytic Plan. Data management will follow the same procedures as Phase 2. Presentation and publication of results from this final phase will focus on evaluating the feasibility and acceptability of the intervention and randomized trial design for a subsequent fully-powered RCT (Aim 3a). Effect size estimates for the subsequent proposal will not rely solely on the current study, given the limitations of effect size estimates from pilot studies. Examinations and group comparisons on outcome and process measures for the active and TAU conditions will be exploratory in nature (Aim 3b). Final revisions to manual. In coordination with mentors, final revisions to the manual will be made based on qualitative interview feedback from Veterans who complete the intervention, together with any changes identified based on the experience of conducting the intervention. Any adjustments will be selected with careful consideration of the relative benefits versus the costs of changing the intervention between pilot and fully-powered RCT phases.

This study is supported by the HEAL Initiative (https://heal.nih.gov). Opioid overdose deaths have reached historically high records in the U.S. and are particularly concentrated among patients after emergency department (ED) discharge. Medications for opioid use disorder (MOUDs), including buprenorphine, are the most effective treatments for opioid use disorder (OUD) as MOUD reduce opioid-related overdoses and deaths. Despite this, less than 30% patients with OUD are treated with MOUDs. Furthermore, adequate treatment with MOUD can be more difficult in certain patient population, i.e., patients with nonfatal opioid overdoses after ED discharge. This patient population also accounts for substantial health care utilization, frequent ED visits, and the largest at-risk group for repeat overdoses and even deaths. Many barriers, including patients' stigma on MOUDs, lack of appropriate monitoring and support, difficulty in navigating community-based treatment programs and being connected with buprenorphine clinics for continuity of care, have been identified as contributors to poor treatment uptake post-ED discharge. These barriers present a pressing need to develop novel treatment modules. Peer support models and telehealth have been successful in improving service provision and increasing treatment uptake in substance use disorders. However, it remains untested if a bundled intervention of telehealth, peers, buprenorphine, and linkage to definitive addiction programs can increase treatment uptake in this particular population. Thus, the purpose of this proposal is to test this bundled intervention specifically focusing on patients with OUD and nonfatal opioid overdoses post-ED discharge. In the R61 phase, 30 patients with OUD and opioid overdoses in the past 12 months will be enrolled from the University of Alabama at Birmingham Hospital when participants are discharged from the ED. Following ED discharge, peers will contact patients daily in Week 1 post-ED discharge, twice in Week 2, and weekly thereafter for 12 weeks using telehealth. Physicians will continue prescribing buprenorphine. Peers will also motivate and assist participants to engage in community-based treatment programs for continuity of care after intervention is completed. Primary outcomes will be the feasibility and acceptability of this bundled intervention. In the R33 phase, participants will be enrolled and randomized to either the intervention group (N=80) or the usual care group (UC, N=80). Patients will be enrolled from the same ED and same eligibility criteria as in the R61 phase will be applied. In the intervention group, peers and physicians will provide the same intervention to patients as in the R61 phase. Patients in the UC group will receive the usual care that has been established at the ED, including ED-initiated buprenorphine, and a list of community-based substance treatment programs and buprenorphine clinics at ED discharge. However, no further intervention will be provided in the UC group. Primary outcomes will be increased treatment uptake and retention after ED discharge, and reduced opioid overdoses and ED revisits, compared to the UC group. If successful, this project will lay the groundwork for a multi-site trial to validate the treatment and to identify actual implementation and sustainability barriers and best practices.

The goal of this clinical trial is to learn if/how an AI chatbot can support patients who in recovery for substance use, specifically those who are receiving medication for opioid use disorder. Can the chatbot help lower drug use? Can the chatbot help improve clinical appointment adherence? Can the chatbot help patients build self-efficacy in leading their own recovery journey? Will the chatbot help reduce workload burden for primary care teams? Can the chatbot serve as a safe, useful and engaging tool to support patients? Researchers will investigate the effects of using a chatbot to support follow-up care for patients in opioid use recovery. Participants will: * Receive access to a chatbot for 12 weeks that they can use to prepare for upcoming clinical appointments, find community resources, learn about urge-surfing and wellness techniques, and query for assistance with other recovery-related information and tasks * Complete surveys and provide user feedback

The GENESIS study is a multicenter, prospective, non-interventional, clinical study with a target of 12,000 subjects and an anticipated total duration of 36 months. The aim of study GENESIS is to provide a pilot map of HLA genetic variation in the Greek population in order to be used in medical research and for possible clinical applications (evaluation of possible correlations with selected underlying diseases). During the study, each subject will conduct one visit to the participating cite, in which they will provide: 1. Demographic information \[i.e. date of birth, gender, race, ancestry (including information about the subject's grandparents' birthplace), height, weight\], 2. Other information about smoking/vaping, alcohol consumption, arterial blood pressure, diagnosed diseases (if any), current treatments (if any), and 3. Recent (up to 12 months prior to sample collection) results if/when are available from clinical lab tests such as blood count (Hct, Hb, RBC, WBC, PLT count), including a metabolic panel, liver enzymes and biochemical parameters (Glu, HbA1c, TC, TG, LDL-C, HDL-C, ALT, AST, ALP, γGT, bilirubin, LDH, insulin, C-peptide). Upon completion of the data registry, two buccal swabs will be collected per subject and they will be stored at ALTP premises until their shipment to Galatea.Bio. All buccal swab samples will be subjected to genetic material (DNA) extraction. The DNA samples will be further proceeded for HLA genotyping analysis. A follow up analysis will be performed in selected DNA samples via full low-pass whole genome sequencing (LP-WGS), which aims to further investigate the association between the HLA region and autoimmune diseases. Upon completion of the analysis, an individualized ancestry report will be securely made available to all study subjects which they can access, as and if they elect to.

The goal of this clinical trial is to compare buprenorphine formulations (sublingual buprenorphine versus long-acting injectable buprenorphine) for treating opioid use disorder among individuals who use fentanyl and/or other high potency synthetic opioids. Individuals aged 18-65 will be eligible for enrollment. The main questions it aims to answer are: Are there differences in frequency of drug use after individuals start treatment with sublingual buprenorphine compared to injectable buprenorphine? Are there differences in rates of sustained relapse after individuals start treatment with sublingual buprenorphine compared to injectable buprenorphine? Investigators also seek to understand and explore: How factors like body fat, body weight, and quantity of fentanyl use before treatment influence treatment outcomes. How blood levels of buprenorphine and its metabolite norbuprenorphine early on in treatment may influence treatment outcomes. How factors like craving and opioid withdrawal symptoms influence treatment outcomes. Participants will: Complete a brief overnight hospital stay in an inpatient research unit. This hospital stay will enable participants to start treatment with either sublingual buprenorphine or injectable buprenorphine. Provide blood and urine samples while on the inpatient unit and at follow up. Complete in-person follow up visits at 1-, 2-, 3- and 4-weeks after leaving the hospital to measure drug use, craving, withdrawal, quality of life, and physical health.