Walsh S L, Sullivan J T, Preston K L, Garner J E, Bigelow G E
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Pharmacol Exp Ther. 1996 Nov;279(2):524-38.
This study evaluated the effects of i.v. cocaine, hydromorphone and their combination, and assessed the ability of oral naltrexone, an opioid antagonist, to modulate these effects. Volunteers with cocaine and heroin abuse histories (n = 8) participated in this placebo-controlled, cross-over study while residing on a closed research unit. Daily treatment with capsules containing placebo or naltrexone in ascending doses (3.125, 12.5, 50 and 200 mg) were given for 7-day periods. In thrice weekly experimental sessions, cocaine, hydromorphone and their combination were given in random order. Drug doses were given in an ascending order 1 hr apart as follows: cocaine at 0,20 and 40 mg, hydromorphone at 0, 1.5 and 3.0 mg, and the combination of 0 and 0 mg, 20 mg cocaine and 1.5 mg hydromorphone and 40 mg cocaine and 3.0 mg hydromorphone. Hydromorphone and cocaine produced distinct pharmacodynamic profiles, and the combination produced effects similar to both drugs. In some cases, the magnitude of effects produced by the combination was greater than that produced by either drug alone. Naltrexone produced dose-related blockade of hydromorphone effects, but did not after any of the physiological or subjective effects of cocaine. All naltrexone doses partially attenuated the effects of the combination and this appeared to be attributable to selective opioid blockade. These data do not support the use of naltrexone as a treatment for cocaine abuse, but suggest it may be useful for treating patients with concurrent cocaine and heroin abuse.
本研究评估了静脉注射可卡因、氢吗啡酮及其组合的效果，并评估了阿片类拮抗剂口服纳曲酮调节这些效果的能力。有可卡因和海洛因滥用史的志愿者（n = 8）在封闭的研究单位居住期间参与了这项安慰剂对照的交叉研究。每天给予含安慰剂或纳曲酮的胶囊，剂量逐渐增加（3.125、12.5、50和200毫克），持续7天。在每周三次的实验环节中，随机给予可卡因、氢吗啡酮及其组合。药物剂量按升序给药，间隔1小时，如下：可卡因分别为0、20和40毫克，氢吗啡酮分别为0、1.5和3.0毫克，组合给药为0和0毫克、20毫克可卡因和1.5毫克氢吗啡酮以及40毫克可卡因和3.0毫克氢吗啡酮。氢吗啡酮和可卡因产生了不同的药效学特征，两者组合产生的效果与两种药物单独使用时相似。在某些情况下，组合产生的效果强度大于任何一种药物单独产生的效果。纳曲酮对氢吗啡酮效果产生了剂量相关的阻断作用，但对可卡因的任何生理或主观效果均无影响。所有纳曲酮剂量均部分减弱了组合的效果，这似乎归因于选择性阿片类阻断作用。这些数据不支持将纳曲酮用于治疗可卡因滥用，但表明它可能对同时滥用可卡因和海洛因的患者有用。
