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.

在精神病患者中，大麻的预后较差，精神病的加剧 症状，认知受损，功能障碍，暴力，频率和持续时间增加 住院和医疗保健费用提高。尽管如此，同时发生的大麻使用率很高 在精神病和退伍军人中使用大麻的增加。通过合法化，商业化和增加 大麻的效力和降低风险感知的效力，尤其是对于精神病患者而言，引起警报。 至关重要的是，在精神病患者中，没有对大麻使用障碍的经过验证或批准的治疗方法。 尽管抗精神病药可用于减少精神病症状，但对 减少大麻的使用。尽管新生的研究表明重复的经颅磁刺激 （RTMS）和社会心理干预措施（即动机增强疗法）可能会减少大麻使用和/或 精神病，反应混杂。治疗可能失败的一个可能原因是他们可能依靠 信息处理，学习和记忆所需的完整同步神经活动。 融合证据表明，在学习和记忆中涉及的地区的神经同步中的防御是 在大麻的精神病和精神活性作用的病理生理中实施。在患有精神病的人中 theta（4-7Hz）和伽马（30-80Hz）范围中协调神经活动的缺陷，它们在中央涉及 在学习和认知，特别是工作记忆（WM）中。体外研究 我们在健康对照中的实验工作表明，大麻素受体1型动力学家降低了theta 和伽马同步并增加噪声（随机活动），并在工作中改变功能连接性 内存网络（WMN）。虽然文学很少，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降低了海马 - 纹状体功能连接性。 尽管有这些最初的发现，但仍需要进一步研究大麻素对神经同步的影响 随着精神病的识别，鉴定出牵连的神经机制可能会导致新的干预措施的发展。 强大的工具以前用于研究神经同步和功能连接性（协调） 活性），例如脑电图（EEG）和功能磁共振成像，可以是 用磁脑电图（MEG）完成。 MEG是磁性的无创功能测量 由神经活动产生的领域，具有出色的临时和空间分辨率。梅格对 了解其他疾病中的神经同步和工作记忆，例如阿尔茨海默氏病。梅格 对切​​向电流敏感，脑电图对切向和径向电流敏感。在一起，梅格和脑电 提供完整的信息，以更准确地确定神经机制。尽管如此，那里 没有研究MEG/EEG研究退伍军人的神经同步，大麻和精神病。 为了解决这些差距，该CDA-2旨在比较神经同步和认知的临床结果， 精神病症状（即精神病，创伤和动画），并在患有精神病和常规的退伍军人中发挥作用 与使用简单的MEG/EEG相比，大麻使用与非使用同行相比，首次使用 VA在VA康涅狄格州。该提案将基于主要调查员在大麻使用方面的专业知识和 认知并提供独特的技能，以支持她使用高级多模式的长期职业目标 神经科学工具研究大麻素对退伍军人作为独立VHA研究者的影响。 这项研究有可能揭示有关该人群中神经同步的复杂描述 它与认知，精神症状和功能的关系。科学知识的进步可能 产生大量翻译的临床实用性，以便有关改变同步区域的发现可能会提供 开发新颖，更有效，干预措施的目标，例如认知补救或RTMS 解决患有精神病和同时发生大麻使用的退伍军人的神经同步和增强认知。