Oral caffeine maintenance potentiates the reinforcing and stimulant subjective effects of intravenous nicotine in cigarette smokers
Oral caffeine maintenance potentiates the reinforcing and stimulant subjective effects of intravenous nicotine in cigarette smokers
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DOI：
10.1007/s00213-002-1262-4
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发表时间：
2003-01-01
影响因子：
3.4
通讯作者：
Griffiths, RR
中科院分区：
文献类型：
--
作者：
Jones, HE;Griffiths, RR
理论基础：流行病学、临床和临床前观察表明，咖啡因可以增强尼古丁的强化和区分作用。目的：本研究考察了长期接触中等剂量咖啡因是否会影响静脉注射尼古丁的强化效应和主观效应。方法：采用双盲法，对9名目前使用烟草、咖啡因和可卡因的志愿者进行了口服咖啡因维持对静脉注射尼古丁和咖啡因的主观和生理效应的影响。每个受试者暴露于两个慢性药物阶段(200毫克/70公斤口服咖啡因，tid。和安慰剂tid)，每个疗程至少12天。在每个药物阶段，受试者按混合顺序接受安慰剂、尼古丁(1.0和2.0毫克/70公斤)和咖啡因(200和400毫克/70公斤)的静脉注射。在药物或安慰剂注射前和注射后重复收集生理和主观数据。结果：静脉注射尼古丁和咖啡因均使药效评分、刺激评分、急救评分和不良反应评分显著增加，仅尼古丁显著增加了好评率和良好效果评分。咖啡因的维持显著提高了大剂量尼古丁后的药效和刺激评级，显著降低了低剂量尼古丁后的不良反应评级。咖啡因的维持也显著增加了对低剂量尼古丁作为刺激剂的认同度。一项药物与金钱之间的强化比较显示，受试者愿意花钱接受尼古丁注射，但愿意为了避免注射咖啡因而放弃金钱。此外，与戒烟阶段相比，受试者在咖啡因维持阶段愿意支付更多的钱来接受高剂量的尼古丁。静脉注射尼古丁和咖啡因都会增加舒张压和降低皮肤温度，尼古丁也会增加心率。静脉注射尼古丁和咖啡因的这些生理效应以及静脉注射咖啡因的主观效应不受咖啡因维持的影响。结论：这些结果扩展了最近的临床和临床前研究结果，表明口服咖啡因维持可以增强尼古丁的增强和刺激性主观效应。
Rationale: Epidemiological, clinical and preclinical observations suggest that caffeine can potentiate the reinforcing and discriminative effects of nicotine. Objective: The present study examined whether chronic exposure to moderate doses of caffeine affects the reinforcing and subjective effects of intravenously administered nicotine. Methods: The effects of oral caffeine maintenance on the subjective and physiological effects of intravenously administered nicotine and caffeine were examined using double-blind methods in nine volunteers with current use of tobacco, caffeine, and cocaine. Each subject was exposed to two chronic drug phases (200 mg/70 kg oral caffeine t.i.d. and placebo t.i.d.), each of at least 12 days duration. Within each drug phase, the subject received intravenous injections of placebo, nicotine (1.0 and 2.0 mg/70 kg), and caffeine (200 and 400 mg/70 kg) in mixed order. Physiological and subjective data were collected before and repeatedly after drug or placebo injection. Results: Both intravenous nicotine and caffeine produced significant increases in ratings of drug effect, stimulated, rush, and bad effect, with only nicotine significantly increasing ratings of liking and good effect. Caffeine maintenance significantly increased ratings of drug effect and stimulated after the high dose of nicotine, and significantly decreased ratings of bad effect after the low dose of nicotine. Caffeine maintenance also significantly increased the identification of the low dose of nicotine as a stimulant. A drug versus money measure of reinforcement showed that subjects were willing to pay money to receive nicotine injections, but willing to forfeit money to avoid caffeine injections. Furthermore, subjects were willing to pay significantly more money to receive the high dose of nicotine in the caffeine maintenance phase than in the abstinence phase. Both intravenous nicotine and caffeine increased diastolic blood pressure and decreased skin temperature, and nicotine also increased heart rate. These physiological effects of intravenous nicotine and caffeine as well as the subjective effects of intravenous caffeine were not influenced by caffeine maintenance. Conclusions: The results extend recent clinical and preclinical findings by showing that oral caffeine maintenance can potentiate the reinforcing and stimulant subjective effects of nicotine.