Evans S M, Griffiths R R
Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Pharmacol Exp Ther. 1999 Apr;289(1):285-94.
Although caffeine is the most widely used behaviorally active drug in the world, caffeine physical dependence has been only moderately well characterized in humans. Four double-blind experiments were conducted in independent groups of healthy participants to assess the conditions under which withdrawal symptoms occur upon cessation of low to moderate doses of caffeine. In experiment 1, there was no evidence that the range or magnitude of caffeine withdrawal symptoms differed when 300 mg of caffeine was consumed as a single dose in the morning versus 100 mg at three time points across the day. In experiment 2, both the range and severity of withdrawal increased as a function of caffeine maintenance dose (100, 300, and 600 mg/day), with even the lowest dose (100 mg) producing significant caffeine withdrawal. Experiment 3 showed that when individuals were maintained on 300 mg caffeine/day and tested with a range of lower doses (200, 100, 50, 25, and 0 mg/day), a substantial reduction in caffeine consumption (</=100 mg/day) was necessary for the manifestation of caffeine withdrawal. Experiment 4 manipulated duration of exposure to caffeine (1, 3, 7, or 14 days of 300 mg/day) and showed that caffeine withdrawal occurred after as little as 3 days of caffeine exposure, with a somewhat increased severity of withdrawal observed after 7 or 14 days of exposure. As a whole, this set of experiments provides the most complete parametric characterization of caffeine withdrawal to date and suggests that caffeine physical dependence can occur under more modest conditions (i.e., fewer doses per day, lower daily dose, shorter duration of exposure) than previously recognized.
尽管咖啡因是世界上使用最广泛的具有行为活性的药物，但咖啡因身体依赖性在人类中的特征描述仅处于中等水平。在健康参与者的独立组中进行了四项双盲实验，以评估在停止低至中等剂量咖啡因后出现戒断症状的条件。在实验1中，没有证据表明当早上单次服用300毫克咖啡因与一天中三个时间点各服用100毫克咖啡因时，咖啡因戒断症状的范围或严重程度有所不同。在实验2中，戒断的范围和严重程度均随着咖啡因维持剂量（100、300和600毫克/天）的增加而增加，即使是最低剂量（100毫克）也会产生明显的咖啡因戒断症状。实验3表明，当个体每天维持服用3毫克咖啡因并使用一系列较低剂量（200、100、50、25和0毫克/天）进行测试时，咖啡因摄入量大幅减少（≤100毫克/天）是出现咖啡因戒断症状的必要条件。实验4控制了咖啡因暴露的持续时间（每天300毫克，持续1、3、7或14天），结果表明，仅3天的咖啡因暴露后就会出现咖啡因戒断症状，暴露7天或14天后观察到戒断症状的严重程度略有增加。总体而言，这组实验提供了迄今为止最完整的咖啡因戒断参数特征描述，并表明咖啡因身体依赖性可能在比以前认识到的更为适度的条件下（即每天服用次数更少、每日剂量更低、暴露持续时间更短）发生。
