Foltin R W, Fischman M W
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Pharmacol Exp Ther. 1991 Apr;257(1):247-61.
Ten healthy adult male research volunteers with histories of smoked and i.v. cocaine use participated in four daily sessions. After resting base line, subjects received the same cocaine dose twice with a 14-min interval between doses. Cocaine hydrochloride (16 and 32 mg) was injected or cocaine base (25 and 50 mg) was smoked. Heart rate, blood pressure, subjective effects and venous blood were sampled repeatedly. The potency of smoked cocaine was about 60% of that of i.v. cocaine, i.e., a 50-mg dose of smoked cocaine had effects similar to a 32-mg dose of i.v. cocaine. Cocaine plasma level increased after each dose up to 425 ng/ml with peaks observed 4 min after the second dose. Plasma levels 44 min after the first dose were similar to plasma levels seen 4 min after the first dose. Smoked and i.v. cocaine produced similar increases in heart rate, blood pressure and rate pressure product at similar cocaine venous plasma levels. VAS ratings of "stimulated" and "high" were greater at similar plasma levels after smoked cocaine compared to i.v. cocaine. In addition VAS ratings of cocaine "liking" were also greater for smoked than i.v. cocaine. Otherwise the subjective effects of smoked and i.v. cocaine were similar. The effects of specific cocaine plasma levels on cardiovascular activity and some subjective reports were diminished across the session, demonstrating the development of acute tolerance to cocaine.
十名有吸烟和静脉注射可卡因史的健康成年男性研究志愿者参加了为期四天的实验。在静息基线后，受试者接受相同剂量的可卡因两次，两次给药间隔14分钟。分别注射盐酸可卡因（16毫克和32毫克）或吸食可卡因碱（25毫克和50毫克）。重复测量心率、血压、主观效应并采集静脉血样。吸食可卡因的效力约为静脉注射可卡因的60%，即50毫克剂量的吸食可卡因产生的效果与32毫克剂量的静脉注射可卡因相似。每次给药后可卡因血浆水平升高，最高可达425纳克/毫升，在第二次给药后4分钟观察到峰值。第一次给药后44分钟的血浆水平与第一次给药后4分钟的血浆水平相似。在相似的可卡因静脉血浆水平下，吸食和静脉注射可卡因导致心率、血压和率压乘积出现相似的升高。与静脉注射可卡因相比，在相似血浆水平下，吸食可卡因后“兴奋”和“嗨”的视觉模拟评分（VAS）更高。此外，吸食可卡因的“喜爱”VAS评分也高于静脉注射可卡因。除此之外，吸食和静脉注射可卡因的主观效应相似。在整个实验过程中，特定可卡因血浆水平对心血管活动和一些主观报告的影响减弱，表明对可卡因产生了急性耐受性。
