A neurobiological investigation of cannabis use and misuse in Veterans

退伍军人大麻使用和滥用的神经生物学调查

• 批准号: 10588526
• 负责人: Ashley Schnakenberg Martin
• 金额: --
• 依托单位: VA CONNECTICUT HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588526
• 关键词: Acute; Address; Agonist; Alzheimer' s Disease; Antipsychotic Agents; Anxiety; Auditory; CNR1 gene; Cannabinoids; Cannabis; Clinical; Cognition; Cognitive remediation; Communities; Complement; Connecticut; Corpus striatum structure; Data; Development; Disease; Electroencephalography; Frequencies; Functional disorder; Future; Goals; Health Care Costs; High Prevalence; Hippocampus; Hospitalization; Impaired cognition; In Vitro; Individual; Intervention; Investigation; Knowledge; Learning; Legal; Literature; Magnetoencephalography; Measurement; Measures; Memory; Mental Health; Mentors; Modeling; Neurobiology; Neurosciences; Noise; Outcome; Pharmaceutical Preparations; Population; Population Intervention; Principal Investigator; Prognosis; Psychoses; Radial; Relapse; Research; Research Personnel; Resolution; Rest; Scalp structure; Severities; Short-Term Memory; Statistical Data Interpretation; Symptoms; Time; Training; Trauma; Veterans; Violence; Work; brain health; career; clinical translation; cognitive function; commercialization; design; effective therapy; experimental study; functional disability; functional magnetic resonance imaging/electroencephalography; functional outcomes; improved; in vivo; indexing; ineffective therapies; information processing; insight; magnetic field; marijuana legalization; marijuana use; marijuana use disorder; medication nonadherence; motivational enhancement therapy; multimodality; neural; neuromechanism; novel; peer; psychiatric symptom; psychosocial; psychotic symptoms; repetitive transcranial magnetic stimulation; response; risk perception; skills; social; source localization; structural imaging; tool; treatment response

In individuals with psychosis cannabis is associated with worse prognosis, exacerbation of psychotic symptoms, impaired cognition, functional disability, violence, increased frequency and duration of hospitalizations, and elevated healthcare costs. Despite this, there are high rates of co-occurring cannabis use in psychosis, and rising cannabis use amongst Veterans. With legalization, commercialization, and increasing potency of cannabis and decreasing risk perception, there is cause for alarm especially for those with psychosis. Critically, there are no proven or approved treatments for cannabis use disorder in individuals with psychosis. While antipsychotic medications are useful for decreasing psychotic symptoms, they have little effect on decreasing cannabis use. Although nascent research suggests that repetitive transcranial magnetic stimulation (rTMS) and psychosocial interventions (i.e., motivational enhancement therapy) may reduce cannabis use and/or psychosis, responses have been mixed. One possible reason that treatments may fail is that they may rely on intact synchronized neural activity necessary for information processing, learning and memory. Converging evidence suggest deficits in neural synchrony in regions involved in learning and memory are implicated in the pathophysiology of psychosis and psychoactive effects of cannabis. In those with psychosis, deficits in coordinated neural activity in theta (4-7Hz) and gamma (30-80Hz) ranges, which are centrally involved in learning and cognition and particularly working memory (WM), have been observed. In vitro and in vivo studies and our experimental work in healthy controls have shown cannabinoid receptor type 1 agonists decrease theta and gamma synchrony and increase noise (random activity), as well as alter functional connectivity in the working memory network (WMN). While a scant literature, experimental studies in psychosis have shown cannabinoids increase cognitive dysfunction and reduced hippocampal-striatal functional connectivity during a learning task. Despite these initial findings, further work is needed on the impact of cannabinoids on neural synchrony in those with psychosis, as identifying implicated neural mechanisms may lead to development of new interventions. Powerful tools previously used to investigate neural synchrony and functional connectivity (coordinated activity), such as electroencephalography (EEG) and functional magnetic resonance imaging, can be complemented with magnetoencephalography (MEG). MEG is a non-invasive, functional measure of magnetic fields produced by neural activity with excellent temporal and spatial resolution. MEG has been critical for understanding neural synchrony and working memory in other disorders, like Alzheimer’s Disease. While MEG is sensitive to tangential currents, EEG is sensitive to tangential and radial currents. Together, MEG and EEG provide complementary information for more accurate determination of neural mechanisms. Despite this, there have been no studies using MEG/EEG to investigate neural synchrony, cannabis, and psychosis in Veterans. To address these gaps, this CDA-2 aims to compare neural synchrony and clinical outcomes of cognition, psychiatric symptoms (i.e., psychosis, trauma, and anxiety), and function in Veterans with psychosis and regular cannabis use compared to non-using peers using simultaneous MEG/EEG, available for the first time within the VA at VA Connecticut. The proposal will build on the Principal Investigator’s expertise in cannabis use and cognition and provide the unique skills to support her long-term career goal of using advanced multimodal neuroscience tools to investigate the impact of cannabinoids on Veterans as an independent VHA investigator. This study has the potential to reveal a sophisticated account of neural synchrony in this population with insight into how it relates to cognition, psychiatric symptoms, and function. This advance in scientific knowledge may yield significant translational clinical utility such that findings about regions of altered synchrony may provide targets for the development of novel, more effective, interventions, such as cognitive remediation or rTMS to address neural synchrony and enhance cognition in Veterans with psychosis and co-occurring cannabis use.

对于精神病患者来说，大麻与预后较差、精神病恶化有关。 症状、认知受损、功能障碍、暴力、频率和持续时间增加 尽管如此，大麻使用率仍然很高。 随着合法化、商业化和日益增加，退伍军人中大麻的使用不断增加。 大麻的效力和降低风险认知，有理由引起警惕，特别是对于患有精神病的人来说。 至关重要的是，对于精神病患者的大麻使用障碍，目前还没有经过证实或批准的治疗方法。 虽然抗精神病药物可有效减少精神病症状，但对其作用甚微。 尽管新兴研究表明重复经颅磁刺激可以减少大麻的使用。 （rTMS）和心理社会干预（即动机增强疗法）可能会减少大麻的使用和/或 治疗可能失败的一个可能原因是他们可能依赖于精神病。 信息处理、学习和记忆所需的完整同步神经活动。 越来越多的证据表明，参与学习和记忆的区域的神经同步性缺陷是 与精神病的病理生理学和大麻的精神作用有关。 θ (4-7Hz) 和伽马 (30-80Hz) 范围内协调神经活动的缺陷，这主要涉及 在学习和认知，特别是工作记忆（WM）方面，已经进行了体外和体内研究。 我们在健康对照中的实验工作表明，1 型大麻素受体激动剂可降低 θ 和伽玛同步并增加噪音（随机活动），以及改变工作中的功能连接 记忆网络（WMN）虽然文献很少，但精神病的实验研究表明大麻素。 在学习任务期间增加认知功能障碍并减少海马-纹状体功能连接。 尽管有这些初步发现，但仍需要进一步研究大麻素对这些人神经同步的影响 对于精神病，因为识别相关的神经机制可能会导致新干预措施的开发。 以前用于研究神经同步和功能连接（协调 活动），例如脑电图（EEG）和功能性磁共振成像，可以 脑磁图 (MEG) 是一种非侵入性功能性磁测量方法。 具有出色时间和空间分辨率的神经活动产生的场对于 MEG 至关重要。 了解其他疾病（例如阿尔茨海默病）中的神经同步性和工作记忆。 对切​​向电流敏感，EEG 对切向电流和径向电流敏感。 MEG 和 EEG 一起。 尽管如此，仍为更准确地确定神经机制提供补充信息。 目前还没有使用 MEG/EEG 来研究退伍军人的神经同步、大麻和精神病的研究。 为了解决这些差距，CDA-2 旨在比较神经同步性和认知的临床结果， 患有精神病和常规疾病的退伍军人的精神症状（即精神病、创伤和焦虑）和功能 使用同步 MEG/EEG 与未使用大麻的同龄人进行比较，这是在 弗吉尼亚州康涅狄格州的该提案将建立在首席研究员在大麻使用和 认知并提供独特的技能来支持她使用先进的多式联运的长期职业目标 作为独立 VHA 研究者，使用神经科学工具来研究大麻素对退伍军人的影响。 这项研究有可能深入揭示这一人群中神经同步性的复杂解释 科学知识的进步可能会揭示它与认知、精神症状和功能的关系。 产生显着的转化临床效用，使得有关同步区域的发现可以提供 制定新颖、更有效的干预措施的目标，例如认知矫正或 rTMS 解决神经同步问题并增强患有精神病和同时使用大麻的退伍军人的认知。