Alcohol Addiction

The study will compare alcohol use in two groups of subjects. One group will be assigned to the Deep TMS treatment and the other group will be assigned to the sham treatment. This is a prospective, 6-month, double blind, randomized, controlled, multi-center trial in outpatients recruited in both academic and private research centers. The study population will consist of subjects diagnosed with moderate to severe AUD. The study is comprised of three phases: 1. Pre-study Screening and Baseline Phase 2. Acute Treatment Phase and 3. Maintenance Treatment and Follow up Phase Subjects of all ethnic and gender categories, ages ranging between 18-86 years will be screened for study eligibility according to the inclusion and exclusion criteria. Subjects who meet the eligibility criteria and are willing to sign an informed consent form will be enrolled in the study. The subjects' demographic and baseline characteristics, as well as their overall medical condition will be assessed prior to treatment administration. Eligible patients will be randomized with a 1:1 ratio to one of two study groups (treatment or sham) and stratified by site. Randomization will be employed to avoid bias in the assignment of subjects to treatment group. All subjects will undergo the same treatment regimen, regardless of the assigned treatment group. The acute treatment phase will include 15 treatment visits over a period of 3-5 weeks. The Maintenance Treatment \& Follow-up phase will include one treatment visit per week from the end of the Acute Treatment Phase until the 6 month follow-up visit. At each treatment session, prior to stimulation onset, alcohol related cues will be presented to the subject. After the offset of the alcohol cue presentation, active or sham Deep TMS stimulation will be administered. The study design is directed towards a comparison between active treatment and sham, up to 4 months and 6 months follow-up. Efficacy will be assessed using the primary efficacy measure of the percent heavy drinking days during months 2-4, based on the Time Line Follow Back (TLFB) reporting. Additionally, several subject assessment scales will be used during the course of the study to assess alcohol use and alcohol craving. Safety will be assessed, including monitoring the severity, causality and frequency of all adverse events, vital signs, and physical and neurological examination.

BRIEF SUMMARY A. "What is the purpose of this study?" This study will test whether the "AI City Hall Project" (QAIAx), a quantum artificial intelligence (AI) public health agency, can provide free or low-cost behavioral and mental health services inside self-contained, dome-enclosed communities called "Microcities". Researchers want to see if AI-managed public administration, AI humanoid robots, holoportation of human-figures via 'holo-suites' (e.g., AI-119 Kikkeri Holo-Suit; AI-119 Vulcan QM-Ware) and advanced AI mental-health tools can lower housing and care costs, improve mental health outcomes (e.g., particular ecosystems using AI tools among persons with one or more addiction disorders), and be financially sustainable for people on fixed incomes or public assistance. B. "What conditions does the study focus on?" The study focuses on adults with: * Autism spectrum disorders (Asperger's, autism, ADHD, ASD) * Substance use disorders (alcohol, opioids, marijuana, cocaine, MDMA/ecstasy, tobacco/nicotine) * Psychiatric conditions (personality disorders, narcissism, gender dysphoria, eating disorders) * Behavioral addictions (gambling, sex addiction) and related issues (sex offence history). C. "What does the study involve?" Eligible volunteers live in an omni AI-managed Microcity for up to 24 months. The community is housed in a geodesic dome that contains all daily necessities: housing, food, utilities, healthcare, and public services. Daily life is managed by an AI system (ISAC) and AI humanoid robots, with only occasional human oversight. Participants receive free mental-health treatment that may include AI-driven counselling, virtual-reality therapy (holo-suits), and non-invasive digital "attitude inoculation" protocols designed to reduce stress and addiction cravings. All participants also take AI-technology courses as a condition of enrolment. The study does not use any FDA-regulated drug, device, or biologic. \*\*Who can participate?\*\* You may be able to join if you: * Are an adult (18 years or older) * Have a diagnosis of one of the listed mental-health or addiction disorders * Are referred by a licensed health professional (e.g., RN, NP, PhD, MD), a non-profit organisation (e.g., 501(c)(3), university, church), or a public agency (e.g., case manager, social worker, parole/probation officer, judge) * Are willing to live in a closed, AI-managed community for up to one year and complete AI educational courses. Participants who are veterans, receive public assistance (e.g., VA disability, SSDI/SSI, Medicaid, Medicare), or are experiencing homelessness may be prioritised. \*\*Where is the study taking place?\*\* The study will be conducted at Microcity sites in the United States and internationally. The first administrative site is in Richmond, Virginia, USA. Additional sites are planned in partner nations, including tribal lands, military installations, and special economic zones. \*\*Who is sponsoring the study?\*\* The study is sponsored by \*\*Veterans Recovery Network Inc.\*\*, a non-profit organization, in collaboration with \*\*AI-119 Vulcan Project Research \& Educational Technology Co. (PRETCO)\*\* and an AI legal agency. The study is conducted under U.S. federal research and development authorities (28 U.S.C. §1498; 10 U.S.C. §129a) and is part of a Cooperative Research and Development Agreement (CRADA) with U.S. Special Operations Command (USSOCOM). This summary describes a planned clinical study. Not all details may be final. Information may change as the study progresses.

Many patients are considering the use of so-called "hypnosis" treatments in the field of addictions. However, these techniques lack sufficient levels of evidence with regard to the standards required by Evidence-Based Medicine. In other domains, however, hypnosis has demonstrated an interesting level of evidence, particularly in pain management. The investigators will focus on the "Techniques for Activating Consciousness" (TAC), which represent an optimized therapeutic approach derived from hypnotic therapy.

Alcohol addiction (AD) is a chronic relapsing disorder with currently limited pharmacological treatment options. Alcohol craving, a hallmark symptom of AD that drives relapse in patients, is only insufficiently treated by existing medication. One promising new compound for the treatment of alcohol craving in AD is Cannabidiol (CBD), which showed beneficial effects on alcohol craving in preliminary clinical studies. Additionally, CBD seems to be a particularly promising candidate for enhancing the effects of established medication, specifically Naltrexone (NTX), an opioid-antagonist, which is approved for AD treatment, due to the synergistic effects of the combination of Cannabidiol plus Naltrexone on alcohol consumption that were shown by preclinical studies. The proposed three-armed, 1:1:1 randomized, double-blind, placebo-controlled parallel group, multicentric phase II trial seeks to test the putative synergistic effects of combined CBD (800mg) + oral NTX (50mg) against CBD (1200mg) + oral NTX (50mg) against Placebo + oral NTX (50mg) on alcohol craving (primary outcome) in male and female patients with AD that suffer from high alcohol craving. The trial seeks to test the effects of the innovative combination of CBD plus NTX against Placebo plus NTX on alcohol craving over a 14-day treatment period, which is embedded in a standardized addiction treatment program according to current treatment guidelines, in order to estimate the added value of treatment with CBD on alcohol craving. Quality of life and neurobiological and biochemical markers for craving will serve as secondary outcomes, because they show strong associations to treatment outcome and relapse risk. Collection and analysis of follow-up data (28 days, 42 days, 105 days, 196 days) will be performed to determine whether treatment effects relate to patient outcome.

The goal of this interventional study is to learn if continuous theta burst stimulation (cTBS) applied over the left frontopolar cortex can reduce psychological, physiological, and neurobiological markers of alcohol craving in patients with alcohol dependence (AD). The main questions it aims to answer are: * Does cTBS over the left frontopolar cortex reduce psychological and physiological measures of alcohol craving in individuals with AD? * Are baseline structural and functional brain connectivity patterns associated with individual differences in cTBS-induced changes in craving? The participants will: * Receive cTBS over the left frontopolar cortex using an accelerated protocol comprising 15 TMS-sessions on five consecutive days * Undergo psychological and physiological assessments of alcohol craving before and after the TMS intervention * Complete magnetic resonance imaging (MRI) sessions to assess baseline brain structural and functional connectivity This study aims to advance the understanding of the neurophysiological mechanisms underlying craving in AD and the identification of potential biomarkers for predicting psychological and physiological craving reductions.