CLIN & NEUROBIOL EFFECTS OF CANNABIS DEPENDENCE IN YOUNG ADULTS

临床临床

• 批准号: 7878047
• 负责人: BARBARA J MASON
• 金额: $ 21.01万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7878047
• 关键词: Abstinence; Adolescent; Adult; Age-Years; Anxiety; Attention; Behavior; Brain; Cannabis; Clinical; Cognitive; Collaborations; Corticotropin; Data; Decision Making; Dependence; Development; Dose; Double-Blind Method; Drug usage; Emotional; Environment; Functional Magnetic Resonance Imaging; Future; Hydrocortisone; Hydroxyindoleacetic Acid; Impairment; Laboratories; Learning; Longitudinal Studies; Marijuana; Marijuana Dependence; Measures; Memory; Methoxyhydroxyphenylglycol; Monitor; Neurobiology; Neuropsychological Tests; Pattern; Pharmaceutical Preparations; Placebos; Plasma; Problem Solving; Procedures; Psyche structure; Public Health; Randomized; Relative (related person); Resistance; Rodent; Scanning; Schedule; Series; Severities; Short-Term Memory; Staging; Stimulus; Symptoms; Teenagers; Testing; Withdrawal; addiction; behavior observation; cannabinoid receptor; cognitive function; craving; design; executive function; flexibility; frontal lobe; neurobiological mechanism; neurochemistry; neuropsychological; nonhuman primate; placebo controlled study; pre-clinical; preclinical study; receptor; response; rimonabant; selective attention; translational approach; urinary; volunteer; young adult

Cannabis dependence remains a major public health problem in young adults under 30 years of age. One reason may be that cannabis use decreases executive functioning, creating a vulnerability to fail to inhibit maladaptive behaviors, such as using drugs. It is our hypothesis that greater severity of cannabis dependence is associated clinically with greater severity of impairment on neuropsychological tasks involving executive functioning, operationally defined center-wide as mental control, initiative and fluency, selfmonitoring, working memory and attention, and inhibition. Specific Aim # 1: To characterize the severity of cannabis dependence on subjective (e.g., anxiety, craving) and objective (e.g. plasma ACTH, cortisol, MHPG) measures using precipitated withdrawal following administration of the CBI cannabinoid receptor antagonist, rimonabant, or placebo in adult volunteers with cannabis dependence in a double-blind randomized design. THC concentrations and neurochemical measures that parallel emotional measures of withdrawal may inform pre-clinical studies in Components 3 and 4. Specific Aim # 2: To determine the presence and persistence of impairment on CANTAB tasks of executive function relative to severity of cannabis dependence (see Specific Aim # 1) in young adult volunteers with cannabis dependence relative to normal controls. Specific Aim # 3: To identify the presence and persistence of abnormality in brain activity relative to severity of cannabis dependence (see Specific Aim # 1) using fMRI with probes of frontal cortex function developed with Dr. Tapert in Component 2. To accomplish these aims, a 28-day longitudinal study will be conducted with two primary components: 1.) a single-dose, double-blind, placebo-controlled study of precipitated cannabis withdrawal in the laboratory using the CBI receptor antagonist, rimonabant 90 mg po, followed by four weekly assessments of key symptoms of cannabis withdrawal in a naturalistic setting, and 2.) neuropsychological assessment and fMRI with task stimuli selected for sensitivity to cannabis-related impairment, administered on the first and following 28 days of monitored abstinence in a naturalistic environment. Subjects will be 40 young adults with cannabis dependence and 20 demographically similar non-using controls. Consistent with the translational objectives of the Center, tasks are derived from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to permit cross-species comparison with non-human primates studied in Component 3 (Taffe) and teens in Component 2 (Tapert). The unique collaboration between parallel teen and non-human primate projects will facilitate the overall Center objective of identifying neurobiological mechanisms through which developmental stage and pattern of cannabis exposure intersect to impair executive cognitive functioning, thereby increasing vulnerability to cannabis dependence.

在30岁以下的年轻人中，大麻依赖仍然是一个主要的公共卫生问题。一 原因可能是大麻使用会减少执行功能，从而造成无法抑制的脆弱性 适应不良的行为，例如使用药物。我们的假设是大麻的严重程度更大 依赖性在临床上与涉及神经心理学任务的严重严重程度有关 执行功能，操作定义为心理控制，主动性和流利性，自我监控， 工作记忆和关注和抑制​​。 具体目的＃1：表征大麻对主观的严重程度（例如，焦虑，渴望） 和客观（例如等离子体ACTH，皮质醇，MHPG）使用沉淀的戒断。 在成人志愿者中给予CBI大麻素受体拮抗剂，Rimonabant或安慰剂 大麻依赖性在双盲随机设计中。 THC浓度和神经化学 平行情绪戒断的措施可能会为组件中的临床前研究提供依据3 和4。具体目的＃2：确定在CANTAB任务上的损害的存在和持久性 相对于大麻依赖的严重程度的执行功能（请参阅年轻人的特定目的＃1） 相对于正常对照组，具有大麻依赖性的志愿者。特定目的＃3：确定存在 相对于大麻依赖性严重程度，大脑活动中异常的持久性（请参见特定目的 ＃1）使用fMRI与tapert博士在组件2中开发的额叶皮层功能的探针。 完成这些目标，将使用两个主要组成部分进行28天的纵向研究：1。）a 实验室沉淀大麻戒断的单剂量，双盲，安慰剂对照研究 使用CBI受体拮抗剂Rimonabant 90 mg PO，然后每周四次评估 在自然主义环境中戒断大麻的症状，以及2.）神经心理学评估和fMRI 选择任务刺激以敏感到与大麻相关的障碍的敏感性，在第一个和 经过28天的监测自然主义环境中的禁欲。受试者将是40名年轻人 大麻依赖性和20个人口统计学相似的非利用对照。与 中心的翻译目标，任务来自剑桥神经心理学测试 自动化电池（CANTAB）允许与研究中研究的非人类灵长类动物进行跨物种的比较 组件3（TAFFE）和组件2（Tapert）中的青少年。平行青少年之间的独特合作 非人类灵长类动物项目将促进识别神经生物学的整体中心目标 大麻暴露的发育阶段和模式相交以损害的机制 执行认知功能，从而增加了对大麻依赖的脆弱性。