Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) for Opioid Use Disorder

项目总结 Evon Medics LLC建议评估和优化便携式、家用、计算机化的产品 基于化学感觉的眶前叶皮质训练(CBOT)，作为预防复发的替代策略 在阿片类药物使用(OUD)和其他物质使用障碍(SUD)患者中。阿片类药物和其他形式的药物 上瘾可以被定义为未能控制寻求毒品的行为，并反映了一种夸大的驱动力 吸食毒品，和/或无法从事涉及非药物奖励的结果导向行为，如 食物、健康、社会地位和金钱。与过度学习的药物相关关联相反，非药物结果 往往不那么成熟，需要进行推断或心理模拟。眶前叶皮质(OFC) 通过提供联想结构(即认知地图)在成瘾调控中发挥重要作用 进行这些心理模拟。此外，OFC在情绪调节中发挥着关键作用，通过增强 对负性情感线索的认知再评价；负性情感是物质复发的强烈预测因子。 患有OUD的人OFC的体积和功能都会降低，海洛因和可卡因的含量也会随着剂量的增加而减少 OFC的神经元功能，从而助长了反复使用药物。 CBOT是一种程序化、便携、安全、用户友好的联动式化学传感设备 用克服OFC脱敏的刺激参数刺激OFC神经活动，并 管理嗅觉认知任务，使OFC协同工作，高保真地足以 促使OFC功能发生持久变化。第一阶段研发达到或超过规定 技术里程碑：CBOT干预导致结果导向行为任务的绩效提高 在12周的随访中，增加了患者在治疗中的保留率，降低了复发率。 与假治疗相比，接受CBOT治疗的OUD患者也经历了不那么严重的阿片类药物戒断 和渴望，较少的睡眠中断和负面影响评级，独立于严重程度和持续时间 吸毒。Evon Medics正在寻求SBIR第二阶段资金，以展示其对非 寻求治疗和寻求治疗的人群，从事长期、成功的阿片类药物 恢复。这项提议将允许进一步的产品改进，以允许广泛的实施和 该设备的商业化可以增加长期药物治疗的保留率和戒断率 通过大幅降低戒断严重程度和负面影响，提高对康复的参与度。在 与此同时，Evon Medics正在与战略合作伙伴关系合作，这些合作伙伴关系将用于通过 制造、监管备案、销售和分销。埃文医学院的科学家、工程师和商业 专家以使命为导向，高度积极地在全球范围内对心理和社会健康产生影响。 该第二阶段项目的主要技术目标是：(1)建立CBOT的有效性 在大样本受试者中改善保留和复发预防；(2)确定其有效性 在康复早期急性降低戒断严重程度和不良影响；以及(3)配置和优化 商业就绪的CBOT版本，提高了疗效、用户友好性和可接受性。这些目标 将导致优化的CBOT产品，克服传统嗅觉疗法和其他 治疗药物成瘾和预防复发的非侵入性神经调节方法。vt.在.的基础上 完成第二阶段，我们将准备将研究扩展到第三阶段疗效研究，或 开发的商业伙伴关系在现实世界环境中的有效性实施研究 在这个项目的过程中。据我们所知，这将是基于家庭的第一次评估， 可扩展的、计算机化的、基于化学传感的脑刺激，对两种治疗都有潜在的广泛影响- 寻求和不寻求治疗的人群。

PROJECT SUMMARY Evon Medics LLC proposes to evaluate and optimize the portable, home-based product, Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT), as an alternative strategy for relapse prevention in patients with Opioid Use (OUD) and other substance use disorders (SUD). Opioid and other forms of drug addiction can be defined as a failure to control drug-seeking behavior, and reflect an exaggerated drive to consume drugs, and/or an inability to engage in outcome-guided behaviors involving non-drug rewards such as food, health, social status and money. In contrast to overlearned drug-related associations, non-drug outcomes are often less well established and need to be inferred or mentally simulated. The orbitofrontal cortex (OFC) plays important role in regulation of addiction through provision of an associative structure (i.e. cognitive map) for these mental simulations. Additionally, the OFC plays critical role in emotion regulation through enhanced cognitive reappraisal of negative affective cues; and negative affect is a strong predictor of substance relapse. People with OUD have reduced OFC volume and function, and heroin and cocaine dose-dependently diminish OFC neuronal functions, thereby fueling recurrent drug use. The CBOT is a programmed, portable, safe, user-friendly device for conjoined chemosensory stimulation of OFC neural activity with stimulation parameters that overcome OFC desensitization, and for administration of olfactory cognitive tasks that synergistically engage the OFC with high fidelity sufficient to induce lasting changes in OFC functions. Phase I research and development met or exceeded stated technical milestones: CBOT intervention led to increased performance in outcome-guided behavior tasks, increased retention of OUD patients in treatment and reduced relapse rate during 12 weeks follow-up. Compared to sham treatment, CBOT-treated OUD patients also experienced less severe opioid withdrawal and cravings, and less sleep disruptions and negative affect rating, independent of severity and duration of drug use. Evon Medics is seeking SBIR Phase II funding to demonstrate its utility for home application by non- treatment seeking and treatment-seeking OUD populations, to engage in long-term, successful opioid recovery. This proposal will enable additional product refinement to allow broad implementation and commercialization of the device that increases long-term OUD treatment retention and abstinence and increases engagement in recovery through acute reduction of withdrawal severity and negative affect. At the same time, Evon Medics is engaging strategic partnerships that will be used to drive development through manufacturing, regulatory filings, sales, and distribution. Evon Medics scientists, engineers and commercial experts are mission-driven and highly motivated to make an impact on mental and social health worldwide. Key technical objectives of this Phase II project are to: (1) establish the effectiveness of CBOT for improved retention and relapse prevention in a large sample of OUD subjects; (2) establish its effectiveness for acute reduction of withdrawal severity and negative affect early in recovery; and (3) configure and optimize a commercial-ready CBOT version for improved efficacy, user-friendliness and acceptability. These objectives will lead to an optimized CBOT product that overcomes the drawbacks of traditional olfactory therapy and other noninvasive neuromodulation approaches in the treatment of drug addictions and prevention of relapses. Upon completion of Phase II, we will be poised to expand the research to Phase III efficacy study, or an implementation study of effectiveness in the real-world setting through commercial partnerships developed over the course of this project. To the best of our knowledge, this will be the first evaluation of a home-based, scalable, computerized, chemosensory-based brain stimulation with potential broad impact for both treatment- seeking and non-treatment seeking OUD populations.