Cannabidiol Modulation of ???-9-THC???s Psychotomimetic Effects in Healthy Humans

大麻二酚对健康人的拟精神病作用的调节作用

• 批准号: 8313866
• 负责人: DEEPAK Cyril D'SOUZA
• 金额: $ 16.36万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8313866
• 关键词: Acute; Address; Animal Model; Antipsychotic Agents; Anxiety; Attention; Attenuated; Behavioral; Blood; Brain; Cannabidiol; Cannabinoids; Cannabis; Clinical Research; Clinical Trials; Cognitive; Communities; Corticotropin; Cross-Over Studies; Data; Disease; Double-Blind Method; Drug Kinetics; Endocrine; Epidemiologic Studies; Euphoria; Human; Hydrocortisone; Impaired cognition; Individual; Knowledge; Laboratories; Laboratory Study; Lead; Literature; Measures; Memory; Methods; Moods; P300 Event-Related Potentials; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Pilot Projects; Placebo Control; Placebos; Prolactin; Property; Psychophysiology; Psychotic Disorders; Randomized; Recruitment Activity; Schizophrenia; Serum; Short-Term Memory; Symptoms; Syndrome; System; Testing; Tetrahydrocannabinol; Verbal Learning; Visual; analog; base; design; information processing; innovation; meetings; novel; novel therapeutics; patient population; placebo controlled study; pre-clinical; preclinical study; visual information

DESCRIPTION (provided by applicant): Cannabis contains a number of compounds including delta-9-Tetrahydrocannabinol (THC) and cannabidiol (CBD). THC, believed to be responsible for the psychotic effects of cannabis, produces a wide range of psychotomimetic, cognitive and psychophysiological effects in healthy humans that are relevant to schizophrenia. CBD, on the other hand, does not have any propsychotic effects and instead appears to reduce the overall psychotic effects of cannabis. While preclinical data support the antipsychotic potential of CBD in a number of animal models of psychosis, there are significant limitations to evidence from human studies. CBD attenuates a number of THC-induced subjective effects, whether this extends to THC-induced psychotomimetic or cognitive effects is unclear. Aims: The overarching aim of this proposal is to demonstrate that pretreatment with CBD will reduce a wide range of psychotomimetic, cognitive and psychophysiological effects induced by the acute administration of THC in healthy humans. This study is designed as a first proof of concept to explore the antipsychotic potential of CBD in healthy individuals. The data from this study will serve as a prelude to more comprehensive and expensive clinical trials of CBD in patients with schizophrenia. Methods: 20 psychiatrically and medically healthy individuals, who have been exposed to cannabis but have never met criteria for a cannabis use disorder, will be recruited from the community to participate in this randomized, double-blinded, placebo-controlled study. Subjects will be randomized to (A) four test days or (B) six test days. All 20 subjects will complete (A) 4 test days and receive either CBD (5mg) or placebo followed by THC or placebo intravenously. 10 subjects randomized to (B) six test days will participate in 2 extra test days during which they will receive CBD (2.5mg or 7.5mg) followed by THC. Subjects will be tested before and after drug administration for schizophrenia-like symptoms (measured on the positive and negative syndrome scale (PANSS) and clinician administered dissociative symptoms scale (CADSS), cognitive impairments (in verbal memory, spatial working memory and sustained attention), subjective effects (measured on a visual analog scale of mood states for anxiety and euphoria), psychophysiological effects (P300 event related potential) and endocrine effects (serum ACTH, cortisol and prolactin levels). In addition, blood levels of THC, its active and inactive metabolites, and CBD will be measured in each subject to explore pharmacokinetic interactions. Significance: Most pharmacological treatments currently available for schizophrenia involve primarily the dopaminergic and serotonergic systems. There is a need to develop new pharmacotherapies for schizophrenia driven by novel hypotheses. CBD targets the cannabinoid system and may have antipsychotic properties. Thus, exploration of its antipsychotic properties may lead to newer therapeutic options for schizophrenia.

描述（由申请人提供）：大麻含有多种化合物，包括δ-9-四氢大麻酚（THC）和大麻二酚（CBD）。四氢大麻酚被认为是大麻产生精神病作用的原因，它对健康人产生广泛的与精神分裂症相关的拟精神病、认知和心理生理作用。另一方面，CBD 没有任何催眠作用，相反似乎可以减少大麻的整体精神病作用。虽然临床前数据支持 CBD 在许多精神病动物模型中的抗精神病潜力，但人类研究的证据存在重大局限性。 CBD 减弱了 THC 引起的许多主观影响，但这是否延伸到 THC 引起的拟心理或认知影响尚不清楚。目的：该提案的首要目的是证明 CBD 预处理将减少健康人因急性施用 THC 引起的一系列拟心理、认知和心理生理学影响。这项研究旨在作为第一个概念证明，探索 CBD 在健康个体中的抗精神病潜力。这项研究的数据将成为对精神分裂症患者进行更全面、更昂贵的 CBD 临床试验的前奏。方法：将从社区招募 20 名曾接触过大麻但从未达到大麻使用障碍标准的精神和医学健康人士参加这项随机、双盲、安慰剂对照研究。受试者将被随机分配到 (A) 四个测试日或 (B) 六个测试日。所有 20 名受试者将完成 (A) 4 天的测试，并接受 CBD (5 毫克) 或安慰剂，然后静脉注射 THC 或安慰剂。随机分配到 (B) 六个测试日的 10 名受试者将参加 2 个额外的测试日，在此期间他们将接受 CBD（2.5 毫克或 7.5 毫克），然后接受 THC。受试者在用药前后将接受精神分裂症样症状（以阳性和阴性综合征量表（PANSS）和临床医生实施的解离症状量表（CADSS）进行测量）、认知障碍（语言记忆、空间工作记忆和持续注意力）、主观影响（以焦虑和欣快情绪状态的视觉模拟量表测量）、心理生理学影响（P300事件） 相关电位）和内分泌影响（血清 ACTH、皮质醇和催乳素水平）。此外，还将测量每个受试者的 THC、其活性和非活性代谢物以及 CBD 的血液水平，以探索药代动力学相互作用。意义：目前可用于精神分裂症的大多数药物治疗主要涉及多巴胺能和血清素能系统。需要开发新的药物疗法 由新假设驱动的精神分裂症。 CBD 针对大麻素系统，可能具有抗精神病特性。因此，对其抗精神病特性的探索可能会为精神分裂症带来更新的治疗选择。

项目成果

Delta-9-Tetrahydrocannabinol, Cannabidiol, and Acute Psychotomimetic States: A Balancing Act of the Principal Phyto-Cannabinoids on Human Brain and Behavior.

Delta-9-四氢大麻酚、大麻二酚和急性拟心理状态：主要植物大麻素对人脑和行为的平衡作用。

• DOI: 10.1089/can.2021.0166
• 发表时间: 2023
• 期刊: Cannabis and cannabinoid research
• 影响因子: 3.8
• 作者: Ganesh,Suhas;Cortes-Briones,Jose;SchnakenbergMartin,AshleyM;Skosnik,PatrickD;D'Souza,DeepakC;Ranganathan,Mohini
• 通讯作者: Ranganathan,Mohini

Cannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans.

大麻素受体介导的感觉门控和神经振荡破坏：大鼠和人类的转化研究。

• DOI: 10.1016/j.neuropharm.2018.03.036
• 发表时间: 2018
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Skosnik,PatrickD;Hajós,Mihály;Cortes-Briones,JoseA;Edwards,ChadR;Pittman,BrianP;Hoffmann,WilliamE;Sewell,AndrewR;D'Souza,DeepakC;Ranganathan,Mohini
• 通讯作者: Ranganathan,Mohini