Baylor College of Medicine, Menninger Department of Psychiatry & Behavioral Sciences, 2002 Holcombe Boulevard, Houston, TX 77030, USA.
Drug Alcohol Depend. 2010 Jan 15;106(2-3):173-80. doi: 10.1016/j.drugalcdep.2009.08.013. Epub 2009 Sep 24.
Methamphetamine is a highly addictive stimulant and long-term exposure leads to reductions in dopamine. One therapeutic strategy is to develop and test compounds that normalize dopamine. The primary aim of this study was to determine the safety of modafinil treatment during methamphetamine exposure in a controlled clinical setting. Methamphetamine-dependent volunteers (N=13), who were not seeking treatment, were randomized to receive either modafinil (200mg, PO) or matching placebo over three days (Days 1-3 or Days 8-10). On Day 1, subjects were randomized to modafinil or placebo in the morning, and then 3 and 6h later received infusions of methamphetamine (0 and 30 mg, i.v.), after which cardiovascular and subjective effects were assessed. On Day 3, participants completed i.v. self-administration sessions during which they made 10 choices for low doses of methamphetamine (3mg, i.v.) or saline. Days 4-7 were used as a washout period. On Day 8 participants were assigned to the alternate study medication (placebo or modafinil), and the same testing procedures were repeated through Day 10. The data reveal that modafinil treatment was well-tolerated and not associated with increased incidence of adverse events. In general, modafinil reduced by approximately 25% ratings of methamphetamine-induced "Any Drug Effect", "High", and "Want Methamphetamine", and reduced total number of choices for methamphetamine and monetary value of methamphetamine, though none of these measures reached statistical significance. Given these encouraging, though non-significant trends, the primary conclusion is that it appears safe to proceed with modafinil in further clinical evaluations of therapeutic efficacy.
甲基苯丙胺是一种高度成瘾的兴奋剂，长期接触会导致多巴胺减少。一种治疗策略是开发和测试使多巴胺正常化的化合物。本研究的主要目的是确定在受控临床环境中，在接触甲基苯丙胺期间使用莫达非尼治疗的安全性。未寻求治疗的甲基苯丙胺依赖志愿者（N=13）被随机分为接受莫达非尼（200mg，PO）或匹配安慰剂治疗三天（第 1-3 天或第 8-10 天）。在第 1 天，受试者随机分为上午接受莫达非尼或安慰剂，然后在 3 小时和 6 小时后接受静脉注射甲基苯丙胺（0 和 30mg，iv），之后评估心血管和主观效应。在第 3 天，参与者完成静脉内自我给药会议，在此期间他们为低剂量甲基苯丙胺（3mg，iv）或生理盐水做出 10 次选择。第 4-7 天为洗脱期。在第 8 天，参与者被分配到替代研究药物（安慰剂或莫达非尼），并通过第 10 天重复相同的测试程序。数据显示，莫达非尼治疗耐受性良好，与不良事件发生率增加无关。一般来说，莫达非尼使甲基苯丙胺引起的“任何药物效应”、“高”和“想要甲基苯丙胺”的评分降低约 25%，并减少了对甲基苯丙胺的总选择次数和甲基苯丙胺的货币价值，尽管这些措施均未达到统计学意义。鉴于这些令人鼓舞但非显著的趋势，主要结论是，在进一步评估治疗疗效的临床评估中，使用莫达非尼似乎是安全的。
