Jones Hendree E, Griffiths Roland R
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224-6823, USA.
Psychopharmacology (Berl). 2003 Jan;165(3):280-90. doi: 10.1007/s00213-002-1262-4. Epub 2002 Nov 14.
Epidemiological, clinical and pre-clinical observations suggest that caffeine can potentiate the reinforcing and discriminative effects of nicotine.
The present study examined whether chronic exposure to moderate doses of caffeine affects the reinforcing and subjective effects of intravenously administered nicotine.
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.
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.
The results extend recent clinical and preclinical findings by showing that oral caffeine maintenance can potentiate the reinforcing and stimulant subjective effects of nicotine.
流行病学、临床及临床前观察表明，咖啡因可增强尼古丁的强化及辨别效应。
本研究旨在探讨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及主观效应。
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研究，考察口服咖啡因维持治疗对静脉注射尼古丁和咖啡因的主观及生理效应的影响。每位受试者经历两个慢性药物阶段（口服200mg/70kg咖啡因，每日三次，以及安慰剂，每日三次），每个阶段持续至少12天。在每个药物阶段内，受试者按随机顺序接受静脉注射安慰剂、尼古丁（1.0和2.0mg/70kg）和咖啡因（200和400mg/70kg）。在药物或安慰剂注射前后，多次收集生理和主观数据。
静脉注射尼古丁和咖啡因均显著提高了药物效应、兴奋感、快感及不良效应的评分，只有尼古丁显著提高了愉悦感和良好效应的评分。咖啡因维持治疗在高剂量尼古丁注射后显著提高了药物效应和兴奋感评分，在低剂量尼古丁注射后显著降低了不良效应评分。咖啡因维持治疗还显著提高了将低剂量尼古丁识别为兴奋剂的能力。药物与金钱强化测量表明，受试者愿意花钱接受尼古丁注射，但愿意交钱以避免接受咖啡因注射。此外，与戒断阶段相比，受试者在咖啡因维持阶段愿意花更多钱接受高剂量尼古丁注射。静脉注射尼古丁和咖啡因均升高了舒张压并降低了皮肤温度，尼古丁还增加了心率。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治疗的影响。
本研究结果扩展了近期临床和临床前研究结果，表明口服咖啡因维持治疗可增强尼古丁的强化及兴奋主观效应。
