Effects of Sativex and Oral THC on Attention, Affect, Working Memory, Reversal Le

Sativex 和口服 THC 对注意力、情感、工作记忆、逆转的影响

• 批准号: 8553281
• 负责人: MARILYN A HUESTIS
• 金额: $ 15.69万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 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/8553281
• 关键词: Advanced Malignant Neoplasm; Affect; Affective; Attention; Attenuated; Brain; Brain region; Canada; Cannabidiol; Cannabinoids; Cannabis sativa plant; Cognitive; Drug Kinetics; Functional Magnetic Resonance Imaging; Health; Intractable Pain; Liquid substance; Measures; Monitor; Multiple Sclerosis; Opiates; Oral; Oral Administration; Participant; Patients; Performance; Pharmaceutical Preparations; Phase III Clinical Trials; Physiological; Placebos; Plants; Plasma; Sativex; Short-Term Memory; Signal Transduction; Tetrahydrocannabinol; Urine; behavior measurement; blood oxygen level dependent; cancer therapy; painful neuropathy; psychologic

Cannabis sativa contains over sixty cannabinoids, including ∆-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD lacks psychoactivity and may attenuate the subjective effects produced by THC. Sativex, a whole-plant cannabinoid extract oromucosal spray, contains THC and CBD in a ratio of nearly 1:1. It was approved by Health Canada in 2005 as a prescription medication for neuropathic pain in multiple sclerosis (MS) and will be evaluated in Phase III trials in the U.S. in patients with advanced cancer for the treatment of pain refractory to opiates. No studies have examined changes in regional brain activity with functional magnetic resonance imaging (fMRI) during completion of cognitive tasks or affective measures after administration of Sativex. We seek to characterize physiological and affective condition, subjective state, cognitive performance, and concomitant changes in activation of specific brain regions (blood oxygen level-dependent BOLD signal) with fMRI after oromucosal administration of Sativex and oral administration of THC. Our secondary objective is to characterize the pharmacokinetics of THC and CBD and metabolites in plasma, urine, and oral fluid. Participants receive synthetic THC 5 mg, synthetic THC 15 mg, two actuations of Sativex (5.4 mg THC and 5.0 mg cannabidiol), six actuations of Sativex (16.2 mg THC and 15.0 mg cannabidiol), and placebo in random order. Physiological, psychological, and behavioral measures are monitored throughout the study to determine onset, magnitude, and duration of effects and to correlate with THC and cannabidiol pharmacokinetics.

大麻含有六十多种大麻素，包括 Δ-9-四氢大麻酚 (THC) 和大麻二酚 (CBD)。 CBD 缺乏精神活性，可能会减弱 THC 产生的主观影响。 Sativex 是一种全植物大麻素提取物口腔粘膜喷雾剂，含有 THC 和 CBD，比例接近 1:1。 它于 2005 年被加拿大卫生部批准作为治疗多发性硬化症 (MS) 神经性疼痛的处方药，并将在美国的晚期癌症患者中进行 III 期试验，以治疗阿片类药物难治性疼痛。 尚无研究通过功能磁共振成像 (fMRI) 检查 Sativex 给药后完成认知任务或情感测量期间区域大脑活动的变化。我们试图通过口腔粘膜施用 Sativex 和口服 THC 后的功能磁共振成像来表征生理和情感状况、主观状态、认知表现以及特定大脑区域激活的伴随变化（血氧水平依赖性 BOLD 信号）。 我们的次要目标是表征 THC 和 CBD 以及血浆、尿液和口腔液中代谢物的药代动力学。 参与者随机接受 5 毫克合成 THC、15 毫克合成 THC、两次 Sativex 驱动（5.4 毫克 THC 和 5.0 毫克大麻二酚）、六次 Sativex 驱动（16.2 毫克 THC 和 15.0 毫克大麻二酚）以及安慰剂。在整个研究过程中监测生理、心理和行为测量，以确定作用的发生、程度和持续时间，并与 THC 和大麻二酚药代动力学相关。