Elkader Alexander K, Brands Bruna, Selby Peter, Sproule Beth A
Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
J Clin Psychopharmacol. 2009 Jun;29(3):231-8. doi: 10.1097/JCP.0b013e3181a39113.
Smoking is highly prevalent (85%-98%) in methadone maintenance treatment (MMT) patients. Methadone has been shown to increase cigarette smoking in a dose-dependent manner, whereas smoking/nicotine has been shown to increase methadone self-administration and reinforcing properties. The objective of this study was to evaluate methadone-nicotine interactions in MMT patients during trough and peak methadone effect conditions. Subjective effects of nicotine (administered by cigarette smoking, 4 mg of nicotine gum and placebo gum) and methadone and their combination were assessed in 40 regularly smoking, stabilized MMT patients using a randomized, placebo-controlled, within-subject study design. Subjects responded to a battery of subjective assessments before and after nicotine administration both before methadone administration (cycles 1 and 2) and 3 hours after methadone administration (cycles 3 and 4). There was a main effect of methadone on the decrease of opioid withdrawal scores (P < 0.001), and cigarette smoking enhanced this effect (day x methadone interaction, P = 0.031). Both nicotine and methadone had main effects on the decrease of nicotine withdrawal scores (P < 0.001 and P = 0.001, respectively); this was associated with the cigarette day (day x nicotine interaction, P = 0.003, and day x methadone interaction, P = 0.004). Nicotine plasma levels were highest on the cigarette smoking day (P < 0.001). Methadone and nicotine shared main effects on the increase of ratings of euphoria and drug liking and on the decrease of restlessness, irritability, and depression. The overall results may help to explain high smoking rates in the MMT population and may account for reports of increased positive effects of methadone when the drugs are taken together.
在美沙酮维持治疗（MMT）患者中，吸烟现象极为普遍（85%-98%）。已有研究表明，美沙酮会以剂量依赖的方式增加吸烟量，而吸烟/尼古丁则会增加美沙酮的自我给药量及其强化特性。本研究的目的是评估MMT患者在美沙酮效应低谷和高峰状态下美沙酮与尼古丁的相互作用。采用随机、安慰剂对照、受试者内研究设计，对40名规律吸烟、病情稳定的MMT患者评估了尼古丁（通过吸烟、4毫克尼古丁口香糖和安慰剂口香糖给药）、美沙酮及其组合的主观效应。在美沙酮给药前（第1和第2周期）以及美沙酮给药后3小时（第3和第4周期），受试者在尼古丁给药前后均接受了一系列主观评估。美沙酮对阿片类药物戒断评分的降低有主要影响（P<0.001），吸烟增强了这种效应（日×美沙酮交互作用，P = 0.031）。尼古丁和美沙酮对尼古丁戒断评分的降低均有主要影响（分别为P<0.001和P = 0.001）；这与吸烟日相关（日×尼古丁交互作用，P = 0.003，日×美沙酮交互作用，P = 0.004）。吸烟日的尼古丁血浆水平最高（P<0.001）。美沙酮和尼古丁对欣快感和药物喜好评分的增加以及对烦躁、易怒和抑郁评分的降低具有共同的主要影响。总体结果可能有助于解释MMT人群中的高吸烟率，并可能解释为何有报告称同时服用这两种药物时美沙酮的积极效果会增强。
