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: 10454769
• 负责人: Tonisha Evette Kearney-Ramos
• 金额: $ 17.66万
• 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/10454769
• 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; Research Training; Scientist; Self Administration; Stimulus; Substance Use Disorder; Testing; Time; Toxicology; Training; Transcranial magnetic stimulation; Treatment outcome; Urine; Visit; Withdrawal; addiction; attentional bias; base; behavior measurement; behavioral pharmacology; 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 circuit; neuromechanism; noninvasive brain stimulation; novel; novel strategies; relapse prediction; relapse risk; relating to nervous system; 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 整个美国大麻的合法化不断扩大与大麻使用的增加有关， 因此，大麻使用障碍（CUD）的个体数量增加。一个复发的预测指标 在存在药物提示的情况下，注意力提示的注意力偏见升高，并减弱了认知控制。 对药物提示的注意偏见与显着性网络中的活性升高有关（前扣带回 皮层和双侧前岛），在背外侧前额叶皮层（DLPFC）和 当用户接触大麻提示时，认知控制电路。我们实验室的数据表明 可以通过衰减VMPFC和奖励电路来减少对药物提示的神经反应 （策略1）具有抑制重复的经颅磁刺激（RTMS）。但是，有可能 DLPFC和认知控制电路的升高活动也将减少对药物提示的神经反应 （策略2-本K01的主题）。通过该K01提案中概述的研究和培训计划，我寻求 评估DLPFC RTMS减弱显着性网络药物提示反应性并降低大麻自我的能力 行政。这将通过施加间歇性theta爆发刺激（ITB）来实现，这是一种兴奋的形式 rtms，在大麻使用者中送给DLPFC。目标：该K01研究项目的主要目标 要（1）确定DLPFC ITB是否会减少住院和门诊的大麻自我管理 在自然生态学中，以及（2）确定ITB诱导的大麻自我管理变化是否是 与显着性网络药物提示反应性的变化有关。设计：六十（60）个非治疗寻求者， 重量（每天）吸烟者将被随机分配，以接受10个活动或假的每日疗程 ITB到DLPFC。参与者将继续住院17天。在住院期间，大麻自我 将在10个ITBS会话之前和之后收集管理和fMRI数据。大麻在自然中使用 生态学将在入院前2周（基线）测量2周，并在出院后2周 使用生态瞬时评估（EMA）。是时候首次使用和恢复大麻使用的时间是 使用EMA测量，并通过3个随访访问来证实，其中TLFB和尿液毒理学将捕获 大麻和其他药物使用。我们将测试主动ITB治疗将降低神经反应性的假设 到大麻提示（AIM 2），并将减少住院的大麻自我管理（AIM 1），并且自然而然 生态学（探索目的）。通过这个为期5年的建议，我将获得现场需要的关键数据集 大脑刺激用于治疗的CUD。此外，它将为我提供一个关键数据 随后的R01应用，其中我计划扩展此治疗开发研究。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以及 我寻求将进步发展为独立的跨学科临床成瘾神经科学家的分析。