Cannabis, inflammation, and the brain in persons with HIV
大麻、炎症和艾滋病毒感染者的大脑
基本信息
- 批准号:10641826
- 负责人:
- 金额:$ 63.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-30 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:2-arachidonylglycerolAcquired Immunodeficiency SyndromeAddressAdverse eventAffectAnti-Inflammatory AgentsAntiinflammatory EffectBiologicalBiological MarkersBloodBlood specimenBody FluidsBrainBrain imagingCNR1 geneCNR2 geneCannabidiolCannabinoidsCannabisCell Culture TechniquesCell surfaceCentral Nervous SystemCerebrospinal FluidChronicClinicalCohort StudiesCollectionConsequences of HIVDataDiseaseDoseEmotionsEndocannabinoidsEnzymesEtiologyExperimental ModelsFamilyFrequenciesFunctional disorderGeneral PopulationHIVHIV InfectionsHLA-DR AntigensHealthImmuneImmune responseInflammasomeInflammationInflammatoryInflammatory ResponseInterleukin-6KnowledgeLabelLinkMacrophage ActivationMeasurementMeasuresMediatingMedicalMental DepressionMethodsMicrogliaMonoacylglycerol LipasesMyelogenousNauseaNeurocognitiveNeurocognitive DeficitNeurodegenerative DisordersNoiseOrganOutcomePainParticipantPathway interactionsPersonsPharmaceutical PreparationsPopulationPositron-Emission TomographyPrevalencePrimary Cell CulturesProteinsPsychological StressRNAResearchResearch PriorityResearch Project GrantsRiskRoleSamplingSignal TransductionSourceSpecimenStandardizationStressTREM2 geneTetrahydrocannabinolTherapeuticVariantVirus Replicationanandamideantiretroviral therapycannabinoid receptorcohortcomorbiditycytokineendogenous cannabinoid systemexperimental studyfatty acid amide hydrolaseglial activationimmune activationin vivoinflammatory modulationinsightmarenostrinmarijuana usemarijuana usermonocytemultimodalityneuroinflammationneuropsychiatrynovelorgan injuryradiotracerreceptorreceptor expressionresponsesextreatment strategy
项目摘要
PROJECT SUMMARY
During suppressive antiretroviral therapy (ART), chronic inflammation persists among people with HIV (PWH)
and appears to be driven by low levels of HIV replication, monocyte/macrophage activation, and other
mechanisms. This persistent inflammation has been linked to adverse neuropsychiatric (e.g., depression,
psychological stress, emotion dysfunction), neurocognitive, and medical outcomes. Cannabis, which is used
more commonly by PWH than people without HIV, appears to have anti-inflammatory effects and therefore may
have therapeutic applications for inflammation and end-organ complications. Cannabinoids exert their effects in
part via the endocannabinoid (EC) system (ECS), which includes cannabinoid receptors that are expressed on
the surface of cells of the immune and central nervous systems. Cannabinoids have demonstrated clinical
benefits for conditions like pain and nausea, but less is known about its effects on inflammation in HIV. Moreover,
the range of cannabis exposure (e.g., dose and frequency of use) that may be effective, ineffective, or unsafe
for different neuropsychiatric and medical conditions is unknown. In response to RFA-DA-20-022, this application
proposes to address key scientific gaps by examining the effects of chronic cannabis use and the role of the
ECS in persistent inflammation in PWH who are taking suppressive ART. We propose to assess 120 participants
(60 PWH on suppressive ART and 60 HIV- persons) across a spectrum of cannabis use from persons who have
never used cannabis to daily users. We will comprehensively evaluate participants with multimodal in vivo and
ex vivo assessments of the biological pathways underlying the effects of chronic cannabis use on persistent
inflammation in PWH and its corresponding impact on neuropsychiatric and neurocognitive complications. In
vivo assessments will include standardized medical, neuropsychiatric, and neurocognitive assessments,
including collection of cerebrospinal fluid and blood. Current cannabis users within this sample (n=80) will also
be assessed with novel brain imaging of microglial activation with [(18)F]FEPPA translocator protein (TSPO)
positron emission tomography. In the collected specimens, we will measure soluble (e.g., pro- and anti-
inflammatory cytokines) and cellular (e.g., HLA-DR, CD38) biomarkers of inflammation and immune activation
as well as components of the ECS (e.g., anandamide, CB2 receptors). Blood specimens will also serve as the
source for primary cell cultures for ex vivo mechanistic experiments that will assess the effects of cannabinoids,
HIV, and ART on biological pathways such as the TREM2 and the NLRP3 inflammasome. Data from all
assessments and experiments will be integrated and analyzed centrally to identify cross-cutting signals and
reduce noise from our multimodal assessments. Knowledge gained from this study will contribute to OAR
priorities (e.g., comorbidities, end organ injury) and provide valuable insight into strategies for treatment of
persistent inflammation in PWH and its health-related consequences.
项目摘要
在抑制性抗逆转录病毒疗法(ART)期间,HIV患者(PWH)持续存在慢性炎症
似乎是由低水平的HIV复制,单核细胞/巨噬细胞激活和其他驱动的
机制。这种持续的炎症与不良神经精神病学有关(例如抑郁症,
心理压力,情绪功能障碍),神经认知和医学结果。大麻
PWH比没有HIV的人更常见,似乎具有抗炎作用,因此可能
为炎症和末期并发症提供治疗应用。大麻素在
通过内源性大麻素(EC)系统(EC)的部分,其中包括大麻素受体
免疫和中枢神经系统的细胞表面。大麻素已经证明了临床
诸如疼痛和恶心之类的疾病的好处,但对其对艾滋病毒炎症的影响知之甚少。而且,
可能有效,无效或不安全的大麻暴露范围(例如,剂量和使用频率)
对于不同的神经精神病学和医学状况,尚不清楚。为了响应RFA-DA-20-022,此应用程序
建议通过检查慢性大麻使用的影响以及
PWH中持续炎症的EC正在接受抑制作用。我们建议评估120名参与者
(抑制性艺术和60个艾滋病毒的60 pwh)遍及拥有大麻的大麻使用
从未将大麻用于日常用户。我们将全面评估参与者的体内多模式和
对慢性大麻使用对持续性影响的生物途径的体内评估
PWH的炎症及其对神经心理学和神经认知并发症的相应影响。在
体内评估将包括标准化医学,神经精神病学和神经认知评估,
包括收集脑脊液和血液。此样本中的当前大麻用户(n = 80)也将
用[(18)F] FEPPA易位蛋白(TSPO)对小胶质细胞激活的新型脑成像进行评估
正电子发射断层扫描。在收集的标本中,我们将测量可溶性
炎症细胞因子)和细胞(例如HLA-DR,CD38)炎症和免疫激活的生物标志物
以及EC的成分(例如,anandamide,CB2受体)。血标本也将作为
用于离体机械实验的原代细胞培养物的来源,该实验将评估大麻素的影响,
艾滋病毒,以及诸如TREM2和NLRP3炎性体等生物途径的艺术。来自所有人的数据
评估和实验将集中整合和分析,以识别交叉切割信号和
从我们的多模式评估中降低噪音。从这项研究中获得的知识将有助于桨
优先事项(例如合并症,结束器官伤害),并为治疗的策略提供宝贵的见解
PWH持续发炎及其与健康相关的后果。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Changes in Tobacco Use Patterns among Veterans in San Diego during the Recent Peak of the COVID-19 Pandemic.
- DOI:10.3390/ijerph182211923
- 发表时间:2021-11-13
- 期刊:
- 影响因子:0
- 作者:Fatollahi JJ;Bentley S;Doran N;Brody AL
- 通讯作者:Brody AL
Associations between Tobacco Use, Surges, and Vaccination Status over Time in the COVID-19 Era.
- DOI:10.3390/ijerph20021153
- 发表时间:2023-01-09
- 期刊:
- 影响因子:0
- 作者:Reed, Brandon W.;Brody, Arthur L.;Sanavi, Andre Y.;Doran, Neal
- 通讯作者:Doran, Neal
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Jennifer E Iudicello其他文献
Jennifer E Iudicello的其他文献
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{{ truncateString('Jennifer E Iudicello', 18)}}的其他基金
Cannabis, inflammation, and the brain in persons with HIV
大麻、炎症和艾滋病毒感染者的大脑
- 批准号:
10157939 - 财政年份:2020
- 资助金额:
$ 63.19万 - 项目类别:
Cannabis, inflammation, and the brain in persons with HIV
大麻、炎症和艾滋病毒感染者的大脑
- 批准号:
10268246 - 财政年份:2020
- 资助金额:
$ 63.19万 - 项目类别:
Cannabis, inflammation, and the brain in persons with HIV
大麻、炎症和艾滋病毒感染者的大脑
- 批准号:
10440508 - 财政年份:2020
- 资助金额:
$ 63.19万 - 项目类别:
Identification of Biomarkers of CNS injury and resilience related to HIV-1 and Methamphetamine
鉴定与 HIV-1 和甲基苯丙胺相关的中枢神经系统损伤和复原力的生物标志物
- 批准号:
10189544 - 财政年份:2018
- 资助金额:
$ 63.19万 - 项目类别:
Identification of Biomarkers of CNS injury and resilience related to HIV-1 and Methamphetamine
鉴定与 HIV-1 和甲基苯丙胺相关的中枢神经系统损伤和复原力的生物标志物
- 批准号:
10441280 - 财政年份:2018
- 资助金额:
$ 63.19万 - 项目类别:
Biomarkers of Blood Brain Barrier Injury in Methamphetamine Use and HIV Disease
甲基苯丙胺使用和艾滋病毒疾病中血脑屏障损伤的生物标志物
- 批准号:
9249011 - 财政年份:2014
- 资助金额:
$ 63.19万 - 项目类别:
Biomarkers of Blood Brain Barrier Injury in Methamphetamine Use and HIV Disease
甲基苯丙胺使用和艾滋病毒疾病中血脑屏障损伤的生物标志物
- 批准号:
8730973 - 财政年份:2014
- 资助金额:
$ 63.19万 - 项目类别:
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10268246 - 财政年份:2020
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Cannabis, inflammation, and the brain in persons with HIV
大麻、炎症和艾滋病毒感染者的大脑
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