Hanks G W, O'Neill W M, Simpson P, Wesnes K
Department of Palliative Medicine, Bristol Oncology Centre, UK.
Eur J Clin Pharmacol. 1995;48(6):455-60. doi: 10.1007/BF00194334.
Twelve subjects (8 male) took part in a randomised double blind four way crossover design study comparing four treatments: (i) morphine sulphate 10 mg, (ii) morphine sulphate 15 mg, (iii) lorazepam 1 mg (positive control) and (iv) placebo. Cognitive function was assessed using choice reaction time, number vigilance, memory scanning, immediate and delayed word recall, word recognition, picture recognition, critical flicker fusion threshold (CFFT) and subjective measures of alertness, calmness and contentment. Lorazepam produced a marked impairment in the tests of attention and memory. CFFT was reduced from 1-4 h but this only reached significance at 4 hours. The subjective measures suggested impaired alertness but this did not reach significance. The effects of morphine were less dramatic; both doses of morphine produced significant impairment at 1 hour on tests of secondary memory retrieval (delayed word recall and picture recognition sensitivity). CFFT was reduced for the whole observation period (6 h) achieving statistical significance at 4 hours. Morphine 15 mg produced a significant improvement in accuracy on the choice reaction time test at the 2, 4 and 6 h assessments. These results show minimal impairment of cognitive and psychomotor function after single oral doses of morphine and with possible improvement in one test. Further studies are required to examine the effect of repeated doses.
12名受试者（8名男性）参与了一项随机双盲四交叉设计研究，比较了四种治疗方法：（i）硫酸吗啡10毫克，（ii）硫酸吗啡15毫克，（iii）劳拉西泮1毫克（阳性对照）和（iv）安慰剂。使用选择反应时间、数字警觉性、记忆扫描、即时和延迟单词回忆、单词识别、图片识别、临界闪烁融合阈值（CFFT）以及警觉性、平静度和满足感的主观测量来评估认知功能。劳拉西泮在注意力和记忆测试中产生了明显的损害。CFFT从1至4小时降低，但仅在4小时时达到显著水平。主观测量表明警觉性受损，但未达到显著水平。吗啡的影响较小；两种剂量的吗啡在1小时时对次级记忆检索测试（延迟单词回忆和图片识别敏感性）均产生了显著损害。在整个观察期（6小时）内CFFT降低，在4小时时达到统计学显著水平。在2、4和6小时评估时，15毫克吗啡在选择反应时间测试的准确性方面产生了显著改善。这些结果表明，单次口服吗啡后认知和心理运动功能的损害最小，并且在一项测试中可能有所改善。需要进一步研究来检查重复给药的效果。
