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.

项目总结/文摘