Amelioration of opioid withdrawal-induced anxiety and craving with heterodyned whole body vibration

通过外差全身振动改善阿片类药物戒断引起的焦虑和渴望

• 批准号: 10258667
• 负责人: Daniel Nathan Adams
• 金额: $ 32万
• 依托单位: PHOTOPHARMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2023-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10258667
• 关键词: Accelerometer; Acute; Age; Alcohol dependence; Alcohols; Anxiety; Area; Behavioral; Belief; Brain; Cervical; Cervical spine; Chronic; Clinical Trials; Collaborations; Corpus striatum structure; Custom; Data; Databases; Dependence; Development; Devices; Dopamine; Drug Rehabilitation Centers; Epidemic; Evaluation; FDA approved; Female; Frequencies; Funding; GABA Receptor; Gap Junctions; Heart Rate; Helping to End Addiction Long-term; Human; Lasers; Measures; Mechanical Stimulation; Mechanoreceptors; Midbrain structure; Motivation; National Institute of Drug Abuse; Neck; Neurons; Nucleus Accumbens; Opiate Addiction; Opioid; Pain; Parents; Patient Self-Report; Patients; Pattern; Perception; Peripheral; Personal Satisfaction; Persons; Pharmaceutical Preparations; Phase; Physiological; Positioning Attribute; Property; Ramp; Relapse; Reporting; Research Personnel; Resources; Rewards; Rodent; Severities; Somatotype; Source; Spinal; Stress; System; Technology; Telemetry; Testing; Travel; United States; Universities; Utah; Ventral Tegmental Area; Withdrawal; alcohol effect; base; commercialization; craving; density; design; dopaminergic neuron; drug rehabilitation; endogenous opioids; experimental study; gamma-Aminobutyric Acid; heart rate variability; heterodyning; male; mesolimbic system; neurochemistry; new technology; novel; opioid abuse; opioid epidemic; opioid use; opioid use disorder; opioid withdrawal; personalized medicine; pleasure; point of care; pre-clinical; preclinical study; response; sensor; spine bone structure; translational study; transmission process; treatment optimization; treatment strategy; vibration; withdrawal-induced anxiety

PROJECT SUMMARY Opioid use disorder (OUD) is a rising problem in the United States and around the world, with pain and stress being major factors for initial drug seeking and relapse. The mesolimbic dopamine (DA) system originating in the midbrain ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc) in the striatum is an important nexus for the rewarding properties of opioids and other addictive drugs and is strongly implicated in OUD. Only two devices are currently FDA approved to treat OUD, which has prompted NIDA to issue a parent announcement, RFA-DA-19-020 connected with the HEAL Initiative to develop technologies to curb the opioid epidemic. This proposal aligns with the HEAL Initiative and NIDA to further the development of a novel, non- pharmacological, heterodyned whole body vibration (HWBV) device to treat anxiety/craving associated with OUD. In prior studies, we have reported that activation of mechanoreceptors with mechanical stimulation of cervical spine vertebrae at a frequency of 45-80 Hz inhibits the activity of VTA GABA neurons, enhances the activity of DA neurons, and subsequently increases DA release in the NAc via endogenous opioids and delta ORs (DORs) in the NAc. We show preliminary data demonstrating that whole body vibration (WBV) in rodents, at the same frequencies that are optimal for cervical spine mechanoreceptor activation, ameliorates neuronal, neurochemical, and behavioral effects of alcohol dependence, which is similar in scope and mechanism to opioid dependence. Additionally, we show preliminary evidence using a novel heterodyned (HWBV) technology consisting of two independent actuators vibrating at different frequencies that generate a low frequency traveling wave that propagates throughout the body. We show preliminary evidence that this traveling, interferential wave ameliorates anxiety in drug-free subjects. The objectives of this proposal are to develop a normative database in drug-free subjects, refine parameters, telemetrics, and active vibration control of the HWBV technology and evaluate the translational relevancy of our pre-clinical findings to treat OUD. The core hypothesis is that HWBV will ameliorate the anxiety/craving associated with withdrawal from chronic opioid use. We propose two Specific Aims in Phase I that involve translational studies informed by our pre- clinical studies in rodents and humans. Aim 1 involves the continued development of a vibration targeting HWBV device and the creation of a normative data base of optimized treatment parameters in drug-free non- AUD subjects. Aim 2 involves the evaluation of the utility of HWBV in male and female persons with OUD at treatment facilities in the area to ameliorate anxiety/craving as a treatment for OUD. PhotoPharmics, Inc in collaboration with investigators at Brigham Young University, proposes systematic studies to provide continued proof-of-principle that HWBV is effective in treating anxiety/craving associated with OUD. We plan to submit a Phase II proposal with the objective to manufacture more systems and complete an FDA-approved, clinical trial consisting of 100+ persons with OUD to further refine the systems towards commercialization.

项目概要 阿片类药物使用障碍 (OUD) 是美国和世界各地日益严重的问题，带来痛苦和压力 是最初寻求药物和复发的主要因素。中脑边缘多巴胺（DA）系统起源于 中脑腹侧被盖区（VTA）和投射到纹状体中的伏隔核（NAc）是 阿片类药物和其他成瘾药物的有益特性的重要联系，并且与 沉香木。目前只有两种设备获得 FDA 批准用于治疗 OUD，这促使 NIDA 发布了母版 公告，RFA-DA-19-020 与 HEAL Initiative 相关，开发遏制阿片类药物的技术 流行性。该提案与 HEAL Initiative 和 NIDA 保持一致，以进一步开发一种新颖的、非 药理外差全身振动 (HWBV) 装置，用于治疗与以下疾病相关的焦虑/渴望 沉香木。在之前的研究中，我们报道了通过机械刺激激活机械感受器 45-80Hz频率的颈椎椎体抑制VTA GABA神经元的活性，增强 DA 神经元的活性，随后通过内源性阿片类药物和 δ 增加 NAc 中 DA 的释放 NAc 中的 OR (DOR)。我们展示的初步数据表明啮齿类动物的全身振动（WBV）， 以最适合颈椎机械感受器激活的相同频率，改善神经元， 酒精依赖对神经化学和行为的影响，其范围和机制与酒精依赖相似 阿片类药物依赖。此外，我们还展示了使用新型外差 (HWBV) 技术的初步证据 由两个独立的致动器组成，以不同的频率振动，产生低频 行波在全身传播。我们展示了初步证据表明这次旅行， 干扰波减轻了未吸毒受试者的焦虑。该提案的目标是制定一个 无毒受试者的规范数据库，细化参数、遥测和主动振动控制 HWBV 技术并评估我们的临床前发现治疗 OUD 的转化相关性。核心 假设 HWBV 将改善与戒断慢性病相关的焦虑/渴望 阿片类药物的使用。我们在第一阶段提出了两个具体目标，其中涉及由我们的预 啮齿动物和人类的临床研究。目标 1 涉及振动瞄准的持续开发 HWBV 设备以及创建无药非药物优化治疗参数的规范数据库 澳元科目。目标 2 涉及评估 HWBV 对 OUD 男性和女性患者的效用 该地区的治疗设施可减轻焦虑/渴望，作为 OUD 的治疗方法。 PhotoPharmics 公司在 与杨百翰大学的研究人员合作，提出系统研究以提供持续的 原理证明 HWBV 可有效治疗与 OUD 相关的焦虑/渴望。我们计划提交一份 II 期提案的目标是制造更多系统并完成 FDA 批准的临床 由 100 多名 OUD 人员组成的试验，以进一步完善系统以实现商业化。

项目成果

Gender-Specific Interactions in a Visual Object Recognition Task in Persons with Opioid Use Disorder.

阿片类药物使用障碍患者视觉对象识别任务中的性别特异性交互。

• 发表时间: 2023-09-05
• 影响因子: 4.7
• 作者: Petrie, JoAnn;Kowallis, Logan R;Kamhout, Sarah;Bills, Kyle B;Adams, Daniel;Fleming, Donovan E;Brown, Bruce L;Steffensen, Scott C
• 通讯作者: Steffensen, Scott C