Centre for Human Drug Research, Leiden, The Netherlands.
J Psychopharmacol. 2010 Nov;24(11):1697-708. doi: 10.1177/0269881109358200. Epub 2010 Feb 8.
In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their combination were investigated in 35 healthy, male mild cannabis users, measuring Positive and Negative Syndrome Scale, Visual Analogue Scales for alertness, mood, calmness and psychedelic effects, saccadic and smooth pursuit eye measurements, electroencephalography, Body Sway, Stroop test, Visual and Verbal Learning Task, hormone levels and pharmacokinetics. Compared with placebo, THC significantly decreased smooth pursuit, Visual Analogue Scales alertness, Stroop test performance, immediate and delayed word recall and prolactin concentrations, and significantly increased positive and general Positive and Negative Syndrome Scale score, Visual Analogue Scales feeling high, Body Sway and electroencephalography alpha. Haloperidol reversed the THC-induced positive Positive and Negative Syndrome Scale increase to levels observed with haloperidol alone, but not THC-induced 'high' feelings. Compared with placebo, haloperidol significantly decreased saccadic peak velocity, smooth pursuit, Visual Analogue Scales mood and immediate and delayed word recall and significantly increased Body Sway, electroencephalography theta and prolactin levels. THC-induced increases in positive Positive and Negative Syndrome Scale but not in Visual Analogue Scales feeling high were reversed by haloperidol. This indicates that psychotic-like effects induced by THC are mediated by dopaminergic systems, but that other systems are involved in 'feeling high'. Additionally, the clear reductions of psychotic-like symptoms by a clinically relevant dose of haloperidol suggest that THC administration may be a useful pharmacological cannabinoid model for psychotic effects in healthy volunteers.
在这项研究中，研究假设氟哌啶醇将改善Δ9-四氢大麻酚（THC）引起的“精神病样”效应。在一项双盲、安慰剂对照、部分三交叉递增剂量研究中，研究了 35 名健康男性轻度大麻使用者中 THC、氟哌啶醇及其组合的作用，测量阳性和阴性综合征量表、警觉、情绪、平静和迷幻效应的视觉模拟量表、扫视和平滑追踪眼测量、脑电图、身体晃动、斯特鲁普测试、视觉和言语学习任务、激素水平和药代动力学。与安慰剂相比，THC 显著降低了平滑追踪、视觉模拟量表警觉、斯特鲁普测试表现、即时和延迟单词回忆以及催乳素浓度，并显著增加了阳性和一般阳性和阴性综合征量表评分、视觉模拟量表感觉高、身体晃动和脑电图α。氟哌啶醇逆转了 THC 引起的阳性阳性和阴性综合征量表增加，使其达到单独使用氟哌啶醇时观察到的水平，但没有逆转 THC 引起的“高”感觉。与安慰剂相比，氟哌啶醇显著降低了扫视峰速度、平滑追踪、视觉模拟量表情绪以及即时和延迟单词回忆，并显著增加了身体晃动、脑电图θ和催乳素水平。氟哌啶醇逆转了 THC 引起的阳性阳性和阴性综合征量表增加，但没有逆转视觉模拟量表感觉高的增加。这表明，THC 引起的精神病样效应是由多巴胺能系统介导的，但其他系统也参与了“感觉高”。此外，氟哌啶醇以临床相关剂量显著减少精神病样症状，表明 THC 给药可能是健康志愿者中精神病效应的有用药理学大麻素模型。
