Alcohol Use Disorder (AUD)

Using a randomized controlled trial (RCT), the goal of this study is to evaluate the ability of evidence based behavioral treatment (contingency management: CM) to significantly decrease alcohol use and cigarette smoking among treatment-seeking smokers with an alcohol use disorder (AUD) who have initiated pharmacotherapy (varenicline; VC) for smoking cessation.

The goal of this study is to develop a machine-learning guided recovery messaging system. The main question it aims to answer is can messages be used to: * help people to improve their health * make changes in people's lives to address alcohol and substance use Participants will: * complete surveys * use a recovery-support digital therapeutic system

This study is to determine if suvorexant (SUV) will reduce insomnia in 76 men and women veteran and non-veterans between the ages 21-65 with posttraumatic stress disorder (PTSD) symptoms and alcohol use disorder (AUD). All participants will have a 7-day placebo run-in period, followed by a random assignment to receive placebo or suvorexant for an additonal 14 days. Post-randomization, participants will attempt to stop drinking for two weeks and will complete daily virtual diaries and study outcome assessments via in-person clinic visits on days 7 and 14.

The goal of this clinical trial is to learn if a short, Zoom-based intervention, Cognitive Behavioral Therapy for Treatment-Seeking for Deaf Individuals (Deaf CBT-TS) can change beliefs about mental health treatment and increase treatment-seeking behaviors in Deaf adults with untreated mental health or alcohol use problems. It will also see if Deaf CBT-TS may reduce suicide risk and explore factors that may increase the effectiveness of Deaf CBT-TS. The main questions it aims to answer are: * Does Deaf CBT-TS increase positive beliefs about treatment and increase treatment-seeking behaviors? * Does Deaf CBT-TS increase hope and reduce mental health symptoms, suicide ideation, and alcohol use? * Is Deaf CBT-TS more effective for individuals with less cultural stress compared to those with high levels of cultural stress? * Is Deaf CBT-TS more effective for Deaf individuals in residential areas with more Deaf resources than those with less Deaf resources? Researchers will compare individuals who complete Deaf CBT-TS to those on a waitlist to see if Deaf CBT-TS works to increase positive beliefs about treatment and treatment-seeking behaviors. Participants will: * Complete a baseline assessment including demographic information, measures of hope, general mental health and functioning, alcohol use, suicide ideation, cultural stress, and beliefs about treatment. * Receive Deaf CBT-TS (2 sessions) or be placed on a waitlist with the option of receiving Deaf CBT-Ts after 4 months * Complete two follow-up assessments in 2 and 4 months.

Background: Glucagon-like peptide 1 (GLP-1) agonist drugs are used to treat diabetes and aid weight loss. They may also help reduce cravings for drugs and alcohol. Researchers want to know if a GLP-1 drug (tirzepatide) can lessen the urge to drink in people with alcohol use disorder (AUD). Objective: To learn how the brains of people with AUD respond to a GLP-1 drug. Eligibility: People aged 21 to 65 years with AUD who are non-treatment seeking. They must be enrolled in protocol 14-AA-0181. Healthy volunteers are also needed. Design: This study consists of Part 1 and Part 2. Part 1 (Imaging Procedures): Five healthy volunteers will undergo 2 to 3 combined positron emission tomography/magnetic resonance imaging (PET/MRI) scans, with an interval of 2 to 3 weeks between scans. For each scan, a radioactive substance (tracer) will be administered intravenously. Participants will undergo PET/MRI scanning to assess brain activity during resting state. Methylphenidate (Ritalin) will be administered during each scan. Each imaging session will last approximately 2 hours. Tirzepatide and placebo will not be administered in Part 1. Participants with alcohol use disorder (AUD) are not included in Part 1. The purpose of this part of the study is to assess test/retest reproducibility of the PET/MRI combined scan measures. Part 2 (Randomization to Tirzepatide \& Placebo): Participants will be randomized to receive either Tirzepatide or Placebo first. Healthy Volunteers and AUD participants will receive both treatments in a crossover design. Tirzepatide and placebo will be administered via subcutaneous injection (under the skin) once weekly for 2 to 3 weeks. This treatment period will be followed by 2 to 3 PET/MRI combined imaging scans described in the next paragraph. After a washout interval of approximately 2 to 3 weeks, participants will cross over to the alternate treatment (tirzepatide or placebo), administered once weekly for 2 to 3 weeks. This second treatment period will be followed by an additional 2 to 3 PET/MRI scans. Participants may receive up to 3 doses of tirzepatide and 3 doses of placebo. Part 2 (Imaging Procedures): Healthy Volunteers and participants with an AUD will undergo PET/MRI scans at two time points: following tirzepatide administration and following placebo administration. For each scan a radioactive substance (tracer) will be administered intravenously. Brain activity will be measured during PET/MRI acquisition during resting state. Methylphenidate will be administered during 1 of the scans at each time point. Each imaging session will last approximately 2 hours. Participants will wear a device to track their activity for at least 1 week before each set of scans. They will have tests of their thinking, memory, and attention.

Background: Alcohol use disorder (AUD) is a leading cause of disease and death worldwide. New treatments for AUD are needed. Dopamine, a chemical that carries signals between brain cells, is thought to play a role in alcohol addiction. Researchers want to learn how Suvorexant, a drug used to treat sleep disorders, affects dopamine receptors in the brain. Objective: To see how Suvorexant affects dopamine receptors in people with AUD and in healthy people. Eligibility: People aged 18 to 75 years seeking treatment for AUD. Healthy volunteers are also needed. Design: Participants with AUD will stay in the clinic for at least 10-28 days for alcohol detoxification. They will receive normal treatment for AUD. Suvorexant is a medicine used to treat sleep problem that is taken taken by mouth, once a day. Some participants will take the study drug. Others will take a placebo. The placebo looks like the study drug but does not contain any medicine. Participants will not know which they are taking. Participants will wear a device that looks like a wristwatch to track their movements during their clinic stay. Participants will have blood tests and 3 brain imaging scans before starting on the study drug: 2 positron emission tomography (PET) and 1 magnetic resonance imaging (MRI) scan. They will be injected with a radioactive tracer during each PET scan. Participants will have tests to assess their thinking, memory, and attention. They will have sleep studies. Imaging scans and other tests will be repeated at the end of the study. Healthy volunteers will have 1 MRI and 2 PET scans. They will have tests to assess of their thinking, memory, and attention. They will wear a wristwatch like movement monitor for 1 week. ...

The goal of this clinical trial is to evaluate the effects of oleoylethanolamide (OEA) supplementation on inflammation, the oral microbiome, neurocognitive function, and alcohol use in young adults ages 18 to 25 with alcohol use disorder (AUD). The main questions it aims to answer are: * Does OEA reduce peripheral markers of immune activation (IL-6, TNF-α, IL-1β, and LPS)? * Does OEA alter oral microbiome composition? * Does OEA improve neurocognitive measures of reward sensitivity and impulsivity? Researchers will compare OEA to a placebo (a look-alike substance with no active ingredient) to determine whether OEA improves biological and behavioral outcomes associated with AUD. Participants (N = 42) will: * Be randomly assigned to receive 300mg TRIPTI (providing 250 mg/day of OEA) or placebo for 6 weeks. * Provide blood, saliva, and urine samples * Complete cognitive testing and questionnaires * Report alcohol use during the study * Attend in-person study visits for monitoring and assessments This randomized, double-blind, placebo-controlled pilot trial will provide preliminary data on the potential efficacy of OEA as a multi-system intervention for young adults with AUD.

Imaging PDE4B in people with psychiatric disorders with PET and the radiotracer \[18F\]PF974

The purpose of this research study is to find out about the effects of a drug called mavoglurant on alcohol consumption.

The study is aimed to find out that combining Nurse-Conducted Brief Intervention (NCBI) with a Smart Mobile is better than Nurse-Conducted Brief Intervention (NCBI) only in preventing relapse among Alcohol Use Disorder patients. The high relapse rates among alcohol disorder patients may be benefitted by new technology using application for improved outcomes in managing and preventing alcohol addiction relapse.

This study aims to understand the health and social care needs and experiences of adults who frequently use urgent and emergency care services in Dorset. Using a mixed-methods design, the study combines analysis of non-patient-identifiable business intelligence data with qualitative interviews and co-production activities. The business intelligence data contextualises patterns of high intensity service use and informs participant identification. Qualitative interviews will explore the personal, social and system-level factors that contribute to frequent attendance. Co-production activities with an advisory group, supported by The Lantern Trust in Weymouth, will use these findings to develop a preventative intervention model grounded in lived experience. The study will recruit up to 50 patients, up to 10 carers and up to 20 health and social care professionals. The findings will contribute to the development of more effective, person-centred approaches to supporting people who frequently use urgent and emergency care services and will inform national and local policy in this area.

Mental disorders have become a major contributor to the global burden of non-communicable diseases, with disability-adjusted life years (DALYs) attributable to these conditions continuing to rise. Although evidence suggests that environmental factors may account for up to 40% of the attributable risk for mental disorders such as major depressive disorder, anxiety disorders, and alcohol use disorder, the underlying mechanisms remain unclear, particularly regarding how dynamic environmental stress influences disease onset, progression, and relapse. Traditional research has primarily focused on individual-level psychosocial factors, including socioeconomic status and life events, while lacking real-time, multidimensional assessments of objective urban environmental stressors such as air pollution, noise exposure, and reduced green space. This study proposes a prospective longitudinal cohort design based in real-world environments, enrolling both patients with mental disorders and healthy controls. Using wearable devices integrated with the "'StreetMind'" mobile application and wear the visible watch, we will continuously and dynamically collect multimodal data on environmental exposures and physiological responses in urban settings. These include photoplethysmography (PPG)-derived heart rate, oxygen saturation, physical activity, and gait parameters, as well as objective environmental indicators such as temperature, humidity, light intensity, and noise levels. At baseline, all participants will undergo standardized psychiatric assessments to characterize depressive, anxiety, and addictive conditions. Peripheral blood and urine samples will also be collected for subsequent molecular and multi-omics analyses. The study aims to systematically evaluate the associations between urban environmental factors-including air pollution, noise exposure, and green space availability-and the risk of mental disorder relapse. Furthermore, it seeks to elucidate the potential mechanisms by which environmental stress affects mental health through neuroinflammation and alterations in brain circuitry. The findings are expected to provide novel insights for risk prediction, early intervention, and precision management of mental disorders.

The goal of this study is to validate the virtual version of the Multiple Errands Test (V-MET) as a tool for assessing executive functions in patients with alcohol use disorder (AUD). More specifically, the project aims to: 1. evaluate if the performance in the virtual version of the test is related to the performance in the original test in patients with AUD. 2. establish whether the virtual version of the test is sensitive enough to detect patients with or without an executive function deficit. All participants will perform the original version (in a real-life supermarket) and the virtual version of the test (in a virtual reality environment). Performance in the two versions of the test will be compared. Participants will also complete a battery of neuropsychological tests and questionnaires.

Theoretical Framework: Cigarette smoking is the leading preventable cause of death worldwide, with nicotine dependence notably common among individuals with Substance Use Disorders (SUD). Smoking exacerbates both physical and mental health issues, further complicating the treatment of SUD. Current therapeutic approaches for SUD often prove inadequate, indicating a need for new strategies. Recent advancements in metabolomics and gut microbiome research have provided valuable insights into the biological mechanisms underlying addiction. Objectives: This study aims to investigate the therapeutic potential of smoking cessation for individuals with SUD, using a six-week intervention within a therapeutic community. The research specifically explores the psychobehavioral, metabolic, and gut microbiome domains. It is hypothesized that smoking cessation will improve emotional regulation, self-efficacy, and reduce substance craving, mediated by changes in metabolic and microbiome profiles linked to brain reward systems. Methods: A randomized controlled trial (N=150) will be conducted, examining outcomes such as clinical relapse rates, microbial and metabolic markers, particularly in choline and folate metabolism. Participants with SUD (n=100) will undergo a six-week smoking cessation intervention, with pre- and post-assessments, compared to a control group receiving treatment as usual. Metabolomic and microbiome analyses will be conducted using blood and stool samples, alongside psychological assessments via questionnaires. Assessments on a behavioural level will take place at a 3-months follow-up. A cross-sectional, non-interventional healthy control group (n=50) will be examined at a single timepoint with an anologous panel of psychological variables, blood and stool to ascertain differences between smokers with SUD and healthy controls.

The purpose of this study is to evaluate the efficacy of deep transcranial magnetic stimulation as a treatment for Veterans with Alcohol Use Disorder (AUD) to decrease the exceedingly high rate of relapse associated with this condition.

Cannabidiol (CBD), one of the most prevalent cannabinoids in cannabis (marijuana) has been shown to reduce alcohol withdrawal symptoms in laboratory animals. In people without alcohol use disorder (AUD), CBD has been show to be effective in reducing anxiety, sleep problems, and seizures; all of these are common symptoms of alcohol withdrawal. This randomized placebo-controlled clinical trial will evaluate the potential of CBD to improve alcohol withdrawal symptoms and reduce craving during acute abstinence among individuals with moderate-to-severe AUD. Adult participants with moderate-to-severe AUD will be admitted to an inpatient research unit at the Johns Hopkins Hospital for a 5-day, 4-night stay that includes alcohol abstinence with management of their alcohol withdrawal. In addition to standard care, participants will receive CBD or placebo (no CBD), complete assessments of withdrawal, sleep quality and provide breath and blood samples.

The overarching goal of this study is to develop and examine the feasibility of a music-listening intervention that can be deployed in "real time" to regulate emotions and reduce momentary stress among young adults within the first 12 months of recovery from alcohol use disorder. The investigators design the study with two phases to address three aims: Phase I includes the first two aims. For Aim 1, the investigators will conduct formative research with a sample of young adults who have are within 12 months of recovery (N = 30) to identify features of music selections that are most effective in reducing momentary stress in real-world, ambulatory settings. For Aim 2, the investigtors will focus on developing mobile health technology that uses passive sensing and machine learning to automatically predict moments of heightened stress in real-time and suggest specific musical selections when stress is detected. During Phase II (Aim 3), the investigators will test the feasibility of a novel music-listening intervention among a second unique sample of young adults who are within 12 months of recovery from AUD (N = 30). This protocol refers only to Phase II of the larger study.

This is an observational study which does NOT directly administer a psychedelic substance but rather recruits participants who are already participating in another clinical trial in which they may receive a serotonergic psychedelic. The goal of this observational study is to learn how the brain's information processing changes during and following administration of serotonergic psychedelics (psilocybin, N,N-Dimethyltryptamine/DMT, Lystergic Acid Diethylamide/LSD, etc.) for people with and without mental illness receiving serotonergic psychedelics through any clinical trial at Yale University. The main questions it aims to answer are: 1. Do serotonergic psychedelics cause the brain to rely on new information more than previously learned information while under the influence? What about 1 day, 5-14 days, and 4-6 weeks after use? 2. Do serotonergic psychedelics cause long-lasting side-effects in how people perceive (see, hear, feel, etc.) the world and how easily people change their beliefs? 3. How does the brain's electrical activity change after using serotonergic psychedelics? How does the balance between excitation and inhibition change while under their effect? 4. Can changes in how the brain uses information predict who will benefit from a psychedelic and who will have side effects from psychedelics? Researchers will compare with people given placebos to see what changes in brain processing are unique to serotonergic psychedelics. Participants will have the opportunity to do some combination of the following: 1. Online computer assessments consisting of games and questionnaires that probe how participants think. 2. Magnetoencephalography (MEG) or electroencephalography (EEG) with eyes closed and with repeated clicks, images, or sensations delivered. 3. A magnetic resonance imaging (MRI) scan. 4. Semi-structured qualitative interviews about their experience after taking a serotonergic psychedelic recorded via Zoom.

This proposed study is a double-blind, randomized, placebo-controlled, parallel-group, laboratory study to determine the effects of DMT, plus psychotherapy, on Alcohol Use Disorder.

Alcohol use causes more overall harm than any other drug and is the seventh leading risk factor for both deaths and disability-adjusted life years. Alcohol use disorders (AUD) are among the most common and undertreated mental disorders in developed countries. Pharmacological and psychotherapeutic treatments only show limited efficacy, and around 60% of the patients relapse in the short term after withdrawal. Lysergic acid diethylamide (LSD) was investigated in numerous clinical trials during the 1950s and 1960s. Specifically, the use of LSD in the treatment of AUD was investigated extensively. A pooled analysis of six historical clinical trials demonstrated that a single dose of LSD significantly reduced alcohol use at three and six months after LSD administration. However, these trials are limited by several factors, including the use of diagnostic standards that are no longer up to date, single, high-dose treatment regimes, missing biological assessment for alcohol use, and no consequent assessment of blinding. This trial will assess the efficacy and safety of two moderate to high doses of LSD to decrease alcohol consumption in patients with AUD. The trial has a double-blind, active placebo-controlled, randomized, parallel design and will be conducted in specialized treatment centers for addictive disorders in Switzerland. The study will include 128 patients who have undergone detoxification. Participants will be allocated to one of the two intervention arms (1:1 allocation). Each arm comprises nine study visits (no drug administration) and two study days (involving LSD administration) within 30 weeks. Patients allocated to the control intervention (active placebo group) will receive 10 µg LSD on the first study day and either 10 or 20 µg LSD on the second study day. Patients allocated to the treatment intervention will receive 150 µg LSD on the first study day and either 150 µg or 250 µg LSD on the second study day. The dose will be retained or increased depending on the patient's individual response on the first study day. Participants in the control intervention will be offered to attend an open-label LSD session (150 µg) at week 31. The open-label phase will comprise three additional visits. This trial will further compare the effectiveness of LSD-assisted therapy in both group and individual therapeutic settings. To this end, participants in both drug conditions will be randomly assigned to group or individual settings. The primary outcome is the mean of percent heavy drinking days after administration of two doses of LSD during the 12 weeks following the second administration. Secondary objectives: The second aim of this study is to explore long-term changes in the cortical thickness, white matter microstructure, resting state functional connectivity (rs-FC) and cerebral blood flow (CBF) of regions associated with addiction pathophysiology. Furthermore, we will assess alterations in depressive symptoms, anxiety, and persisting effects of LSD. We will also assess biological markers of alcohol use and several predictors for treatment-response (genetics, personality traits, blinding, expectancy, and quality of acute drug effects). Lastly, we will compare LSD treatment within a group setting with treatment within an individual setting.

This observational study investigates differences in psychological processes and emotional symptoms between individuals with Alcohol Use Disorder (AUD) and a non-clinical control group. PBAT, PHQ-9, and GAD-7 will be used. MANCOVA will test group differences controlling for demographics.

The purpose of this study is to develop transcranial magnetic stimulation (TMS), specifically TMS at a frequency known as theta burst stimulation (TBS), to see how it affects the brain and changes the brain's response to alcohol-related pictures. TMS and TBS are stimulation techniques that use magnetic pulses to temporarily excite specific brain areas in awake people (without the need for surgery, anesthetic, or other invasive procedures). TBS, which is a form of TMS, will be applied over the medial prefrontal cortex, (MPFC), which has been shown to be involved with drinking patterns and alcohol consumption. This study will test whether TBS can be used as an alternative tool to reduce the desire to use alcohol and reducing the brain's response to alcohol-related pictures.

This study seeks to determine the feasibility, acceptability, and preliminary efficacy of an intervention consisting of off-label use of a medication with strong efficacy data for alcohol use disorder (AUD) with medical management and a clinical pharmacist-delivered behavioral intervention in reducing alcohol use among individuals with HIV and AUD.

The goal of this research is to replicate findings previously conducted in a pilot trial and to understand, mechanistically, the role of stress in the development of AUD pharmacotherapies that target noradrenergic blockade.

This study proposes a 16-week, between-subject, double-blind, randomized controlled trial (RCT) with probenecid (2g /day) compared to placebo in individuals with AUD to test if reduces craving and alcohol consumption.