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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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘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，伴随着疼痛和压力是初次吸毒和复吸的主要因素。中脑边缘多巴胺（DA）系统起源于中脑腹侧被盖区（VTA）和纹状体中的丘脑核（NAc）的投射是一个重要的神经元。阿片类药物和其他成瘾药物的奖励特性的重要联系，并强烈牵连到 OUD。目前只有两种设备被FDA批准用于治疗OUD，这促使NIDA发布了一个母公司。宣布，RFA-DA-19-020与HEAL倡议联系，以开发抑制阿片类药物的技术疫情该提案与HEAL倡议和NIDA保持一致，以进一步开发一种新的，非药理学、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 OUD。在先前的研究中，我们已经报道了机械刺激机械感受器的激活，在45-80 Hz的频率下，颈椎椎骨抑制VTA GABA神经元的活性，增强VTA GABA神经元的活性。活动的DA神经元，并随后增加DA释放NAc通过内源性阿片类物质和δ NAc中的OR（DORs）。我们展示了初步数据，表明啮齿动物的全身振动（WBV），在对于颈椎机械感受器激活最佳的相同频率下，改善神经元，酒精依赖的神经化学和行为影响，其范围和机制与阿片类药物依赖此外，我们使用一种新的外差（HWBV）技术显示了初步证据由两个以不同频率振动的独立致动器组成，在整个身体中传播的行波。我们有初步证据表明这次旅行，干扰波可改善非药物受试者的焦虑。本建议的目标是制定一个规范数据库中的药物免费科目，完善参数，遥测，和主动振动控制的 HWBV技术，并评估我们的临床前研究结果治疗OUD的翻译相关性。核心假设HWBV将改善与慢性戒断相关的焦虑/渴望，阿片类药物使用我们提出了两个具体的目标，在第一阶段，涉及翻译研究通知我们的前，啮齿动物和人类的临床研究。目标1涉及到持续发展的振动目标 HWBV设备和创建无药物非药物治疗中优化治疗参数的规范数据库 AUD科目。目的2涉及评估HWBV在男性和女性OUD患者中的效用，在该地区的治疗设施，以改善焦虑/渴望作为治疗OUD。Photopharmics，Inc 与杨百翰大学的研究人员合作，提出了系统的研究，以提供持续的 HWBV在治疗与OUD相关的焦虑/渴望方面有效的原理证明。我们计划提交一份第二阶段提案的目标是生产更多的系统，并完成FDA批准的临床试验。由100多名OUD患者组成的试验，以进一步完善系统，实现商业化。