Verrico Christopher D, Haile Colin N, Mahoney James J, Thompson-Lake Daisy G Y, Newton Thomas F, De La Garza Richard
Menninger Department of Psychiatry and Behavioral Sciences Baylor College of Medicine, One Baylor Plaza, MS BCM350, Houston, TX 77030, United States; Department of Pharmacology, Michael E. DeBakey VA Medical Center & Baylor College of Medicine, One Baylor Plaza, MS BCM350, Houston, TX 77030, United States.
Menninger Department of Psychiatry and Behavioral Sciences Baylor College of Medicine, One Baylor Plaza, MS BCM350, Houston, TX 77030, United States.
Drug Alcohol Depend. 2014 Aug 1;141:72-8. doi: 10.1016/j.drugalcdep.2014.05.008. Epub 2014 May 28.
Concurrent administration of dopamine and serotonin reuptake inhibitors reduces cocaine self-administration in monkeys. Consonant with this, clinical trials assessing modafinil and selective serotonin reuptake inhibitors alone show some efficacy as potential pharmacotherapies for cocaine dependence. We hypothesized that combining modafinil with escitalopram would attenuate the euphoric effects of cocaine to a greater degree than modafinil alone.
In a randomized, double blind, parallel groups design participants received either placebo (0mg/day; n=16), modafinil (200mg/day; n=16), escitalopram (20mg/day; n=17), or modafinil+escitalopram (200+20mg/day; n=15) for 5 days. On day 5, during separate sessions participants received an intravenous sample of cocaine (0 or 20mg; randomized) and five $1 bills. Participants rated the subjective effects of the infusions and subsequently made choices to either return $1 and receive another infusion or keep $1 and receive no infusion.
Compared to saline, cocaine (20mg) significantly (p≤0.008) increased most ratings, including "good effects", "stimulated", and "high". Relative to placebo, modafinil significantly (p≤0.007) attenuated subject-rated increases of "any drug effect", "high", "good effects", and "stimulated" produced by cocaine. Compared to saline, participants chose cocaine infusions significantly more; however, no treatment significantly reduced choices for cocaine infusions. Escitalopram did not enhance the efficacy of modafinil to reduce any measure.
Modafinil attenuated many positive subjective effects produced by cocaine; however, escitalopram combined with modafinil did not enhance the efficacy of modafinil to reduce cocaine effects.
多巴胺和5-羟色胺再摄取抑制剂同时给药可减少猴子的可卡因自我给药行为。与此相一致的是,单独评估莫达非尼和选择性5-羟色胺再摄取抑制剂的临床试验显示,作为可卡因依赖的潜在药物疗法有一定疗效。我们假设,与单独使用莫达非尼相比,将莫达非尼与艾司西酞普兰联合使用能在更大程度上减弱可卡因的欣快效应。
采用随机、双盲、平行组设计,参与者接受安慰剂(0毫克/天;n = 16)、莫达非尼(200毫克/天;n = 16)、艾司西酞普兰(20毫克/天;n = 17)或莫达非尼+艾司西酞普兰(200 + 20毫克/天;n = 15)治疗5天。在第5天,在不同的时段,参与者接受静脉注射的可卡因样本(0或20毫克;随机)和五张1美元纸币。参与者对注射的主观效应进行评分,随后做出选择,要么归还1美元并接受另一次注射,要么保留1美元且不接受注射。
与生理盐水相比,可卡因(20毫克)显著(p≤0.008)提高了大多数评分,包括“良好效应”、“兴奋”和“嗨”。相对于安慰剂,莫达非尼显著(p≤0.007)减弱了可卡因引起的“任何药物效应”、“嗨”、“良好效应”和“兴奋”的主观评分增加。与生理盐水相比,参与者显著更频繁地选择可卡因注射;然而,没有任何治疗能显著减少对可卡因注射的选择。艾司西酞普兰并未增强莫达非尼减少任何指标的疗效。
莫达非尼减弱了可卡因产生的许多积极主观效应;然而,艾司西酞普兰与莫达非尼联合使用并未增强莫达非尼减少可卡因效应的疗效。