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

大麻含有60多种大麻素，包括-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是一种全植物大麻提取物口腔粘膜喷雾剂，含有THC和CBD，比例接近1：1。2005年，它被加拿大卫生部批准为治疗多发性硬化症(MS)神经病理性疼痛的处方药，并将在美国进行第三阶段试验，用于治疗对阿片类药物无效的晚期癌症患者的疼痛。还没有研究用功能磁共振成像(FMRI)检测在服用Sativex后完成认知任务或情感措施期间局部大脑活动的变化。我们试图用fMRI来表征口服Sativex和口服THC后的生理和情感状况、主观状态、认知表现以及伴随的特定脑区激活的变化(血氧水平依赖的BOLD信号)。我们的次要目标是研究THC和CBD及其代谢物在血浆、尿液和口服液中的药代动力学。参与者接受合成THC 5 mg，合成THC 15 mg，两次Sativex(5.4 mg THC和5.0 mg大麻二醇)，六次Sativex(16.2 mg THC和15.0 mg大麻二醇)，以及随机顺序的安慰剂。在整个研究过程中，对生理、心理和行为测量进行监测，以确定效果的起效、程度和持续时间，并与THC和大麻二醇的药代动力学相关。

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.