Donny Eric C, Brasser Susan M, Bigelow George E, Stitzer Maxine L, Walsh Sharon L
Behavioral Pharmacology Research Unit, Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Addiction. 2005 Oct;100(10):1496-509. doi: 10.1111/j.1360-0443.2005.01232.x.
Methadone maintenance has been an effective pharmacotherapy for the treatment of heroin dependence for nearly four decades. Recent clinical research suggests that methadone doses larger than those used in most clinics are more effective at suppressing illicit heroin use. This greater efficacy may result from greater cross-tolerance to the reinforcing effects of heroin.
The purpose of this double-blind, within-subject study was to examine the relationship between methadone maintenance dose and the reinforcing effects of heroin.
Participants were stabilized on 50, 100 and 150 mg methadone (ascending order) during separate outpatient periods before being admitted to an inpatient research unit for testing at each maintenance dose.
Five opiate-dependent volunteers completed the study.
During each 4-week inpatient testing period, participants sampled three doses of heroin (0, 10, or 20 mg; random order; one dose per week) and were subsequently allowed seven opportunities to choose between another injection of that week's heroin dose and varying amounts of money (dollars 2-38).
The number of heroin injections chosen decreased as methadone dose was increased. Larger alternative monetary reinforcers were required to suppress heroin self-administration during maintenance on 50 compared to 100 or 150 mg methadone. Larger methadone doses also completely blocked the subjective effects of heroin and produced greater withdrawal suppression during the outpatient periods.
These results support other clinical and laboratory-based research indicating that persistent heroin use may be reduced by providing larger methadone maintenance doses that produce more effective cross-tolerance to heroin.
近四十年来,美沙酮维持治疗一直是治疗海洛因依赖的一种有效药物疗法。近期临床研究表明,高于大多数诊所所用剂量的美沙酮在抑制非法海洛因使用方面更有效。这种更高的疗效可能源于对海洛因强化作用更强的交叉耐受性。
这项双盲、受试者内研究的目的是检验美沙酮维持剂量与海洛因强化作用之间的关系。
在分别的门诊期间,参与者先以50、100和150毫克美沙酮(剂量递增)进行稳定治疗,之后进入住院研究单元,在每个维持剂量下接受测试。
五名阿片类药物依赖志愿者完成了该研究。
在每个为期4周的住院测试期间,参与者抽取三种剂量的海洛因(0、10或20毫克;随机顺序;每周一剂),随后有七次机会在再次注射当周的海洛因剂量和不同金额的金钱(2至38美元)之间进行选择。
随着美沙酮剂量增加,选择注射海洛因的次数减少。与100或150毫克美沙酮维持治疗期间相比,在50毫克美沙酮维持治疗期间,需要更大的替代性金钱强化物来抑制海洛因的自我给药。更大剂量的美沙酮还完全阻断了海洛因的主观效应,并在门诊期间产生了更强的戒断抑制作用。
这些结果支持了其他基于临床和实验室的研究,表明通过提供更大剂量的美沙酮维持治疗以产生对海洛因更有效的交叉耐受性,可能会减少海洛因的持续使用。