Imaging the Effects of Intermittent Thetaburst Stimulation on Cannabis Self-Administration in Heavy Cannabis Users

间歇性 Thetaburst 刺激对重度大麻使用者大麻自我管理的影响成像

• 批准号: 10667460
• 负责人: Tonisha Evette Kearney-Ramos
• 金额: $ 17.73万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667460
• 关键词: Admission activity; Alcohols; Anterior; Attention; Attenuated; Award; Behavior Therapy; Behavioral Mechanisms; Bilateral; Brain; Cannabis; Chronic; Clinical; Clinical Investigator; Clinical Research; Cocaine; Cues; Data; Data Set; Development; Double-Blind Method; Drug usage; Ecological momentary assessment; Ecology; Evidence based treatment; Exposure to; FDA approved; Frequencies; Functional Magnetic Resonance Imaging; Future; Goals; Human; Image; Individual; Inpatients; Insula of Reil; Intervention; Laboratories; Learning; Measures; Memory; Mental Depression; Mentors; Methods; Neurocognitive; Neuronavigation; Nicotine; Outcome Measure; Outpatients; Participant; Pattern; Pharmaceutical Preparations; Pharmacology Study; Prefrontal Cortex; Procedures; Public Health; Publishing; Randomized; Relapse; Research; Research Design; Research Project Grants; Scientist; Self Administration; Stimulus; Substance Use Disorder; Testing; Time; Toxicology; Training; Transcranial magnetic stimulation; Treatment outcome; Urine; Visit; Withdrawal; addiction; attentional bias; behavior measurement; behavioral pharmacology; cannabis cue; cannabis self-administration; cannabis withdrawal; career; cingulate cortex; cognitive control; craving; cue reactivity; design; drug relapse; follow-up; innovation; marijuana legalization; marijuana smoker; marijuana use; marijuana use disorder; marijuana user; multidisciplinary; neural; neural circuit; neuromechanism; noninvasive brain stimulation; novel; novel strategies; relapse prediction; relapse risk; repetitive transcranial magnetic stimulation; research and development; response; response biomarker; reward circuitry; substance use; substance use treatment; therapy development; tool; treatment duration

PROJECT SUMMARY/ABSTRACT The expanding legalization of cannabis across the U.S. is associated with increases in cannabis use, and accordingly, an increase in the number of individuals with cannabis use disorder (CUD). One predictor of relapse is an elevated attentional bias to drug cues and attenuated cognitive control in the presence of drug cues. Attentional bias to drug cues is associated with elevated activity in the Salience Network (anterior cingulate cortex and bilateral anterior insula), and attenuated activity in the dorsolateral prefrontal cortex (DLPFC) and cognitive control circuitry when users are exposed to cannabis cues. Data from our laboratory demonstrates that it is possible to decrease the neural response to drug cues by attenuating the VMPFC and reward circuitry (Strategy 1) with inhibitory repetitive transcranial magnetic stimulation (rTMS). It is possible, however, that elevating activity in the DLPFC and cognitive control circuitry will also decrease the neural response to drug cues (Strategy 2 - topic of this K01). Through the research and training plan outlined in this K01 proposal, I seek to evaluate the ability of DLPFC rTMS to attenuate Salience Network drug cue reactivity and reduce cannabis self- administration. This will be achieved by applying intermittent theta burst stimulation (iTBS), a form of excitatory rTMS, to the DLPFC in heavy cannabis users. GOAL: The primary objectives of this K01 research project are to (1) determine if DLPFC iTBS decreases cannabis self-administration, both inpatient and outpatient in the natural ecology, and (2) determine if iTBS-induced changes in cannabis self-administration are related to changes in Salience Network drug cue reactivity. DESIGN: Sixty (60) non-treatment-seeking, heavy (near daily) cannabis smokers will be randomized to receive 10 daily sessions of either active or sham iTBS to the DLPFC. Participants will remain inpatient for 17 days. During the inpatient stay, cannabis self- administration and fMRI data will be collected before and after the 10 iTBS sessions. Cannabis use in the natural ecology will be measured outpatient for 2 weeks prior to admission (baseline) and for 2 weeks following discharge using Ecological Momentary Assessment (EMA). Time to first use and amount of resumed cannabis use will be measured using EMA and corroborated by 3 follow-up visits where TLFB and urine toxicology will capture cannabis and other drug use. We will test the hypotheses that active iTBS treatment will reduce neural reactivity to cannabis cues (Aim 2) and will reduce cannabis self-administration, both inpatient (Aim 1), and in the natural ecology (Exploratory Aim). Through this 5-year proposal, I will acquire a critical dataset that is needed in the field of brain stimulation for treatment development in CUD. Additionally, it will provide me with critical data for a subsequent R01 application wherein I plan to extend this line of treatment development research. Furthermore, this project will greatly facilitate the training in human behavioral pharmacology and clinical research design and analysis that I seek for advancement into an independent, interdisciplinary clinical addiction neuroscientist.

项目摘要/摘要 美国各地大麻合法化的扩大与大麻使用量的增加有关， 因此，患有大麻使用障碍(CUD)的人数增加。复发的一个预测因素 是对药物线索的注意偏向增加，以及在药物线索存在时认知控制减弱。 对药物线索的注意偏向与显著网络(前扣带回)的活动增加有关 大脑皮质和双侧前脑岛)，以及背外侧前额叶皮质(DLPFC)和 当使用者接触到大麻线索时，认知控制电路。我们实验室的数据表明， 有可能通过减弱VMPFC和奖赏回路来降低神经对药物提示的反应 (策略1)采用抑制性重复经颅磁刺激(RTMS)。然而，有可能 增加DLPFC和认知控制回路的活动也会降低神经对药物线索的反应 (策略2--本K01主题)。通过这份K01提案中概述的研究和培训计划，我寻求 评价DLPFC rTMS抑制突出网络药物线索反应性和减少大麻自身的能力 行政管理。这将通过应用间歇性theta Burst刺激(ITBS)来实现，ITBS是兴奋性的一种形式 RTMS，给吸食大量大麻的DLPFC。目标：K01研究项目的主要目标 目的是(1)确定DLPFC ITBS是否减少住院和门诊患者的大麻自我给药 以及(2)确定ITBS引起的大麻自我给药的变化是否 与显著网络药物线索反应性的变化有关。设计：60例非就诊者， 重度(几乎每天)吸食大麻的人将随机接受每天10次的积极或虚假治疗 ITBS到DLPFC。参与者将保持17天的住院时间。在住院期间，大麻自己 将在10次ITBS会议之前和之后收集管理和功能磁共振数据。大麻在自然界的使用 门诊患者在入院前2周(基线)和出院后2周进行生态测量 使用生态瞬时评估(EMA)。首次使用大麻的时间和恢复使用大麻的数量将是 使用EMA进行测量，并通过3次随访证实，TLFB和尿毒学将在 大麻和其他毒品的使用。我们将验证积极的ITBS治疗将降低神经反应性的假设 对大麻线索(目标2)，并将减少住院患者(目标1)和自然情况下的大麻自我给药 生态学(探索目标)。通过这项为期5年的计划，我将获得现场所需的关键数据集 脑刺激在慢性阻塞性肺疾病治疗进展中的作用。此外，它还将为我提供 随后的R01申请，其中我计划延长这条治疗开发研究线。此外， 该项目将极大地促进人类行为药理学和临床研究设计的培训 分析说，我寻求成为一名独立的、跨学科的临床成瘾神经学家。