The Connecticut Mental Health Center, Yale University School of Medicine, Department of Psychiatry, New Haven, CT, USA.
J Psychopharmacol. 2012 Jul;26(7):958-72. doi: 10.1177/0269881111430746. Epub 2012 Jan 9.
Cocaine dependence is associated with increased stress and drug cue-induced craving and physiological arousal but decreased prefrontal activity to emotional and cognitive challenge. As these changes are associated with relapse risk, we investigated the effects of α2 receptor agonist guanfacine on these processes. Twenty-nine early abstinent treatment-seeking cocaine dependent individuals were randomly assigned to either daily placebo or guanfacine (up to 3 mg) for four weeks. In a laboratory experiment, all patients were exposed to three 10-min guided imagery conditions (stress/stress, drug cue/drug cue, stress/drug cue), one per day, consecutively in a random, counterbalanced order. Subjective craving, anxiety and arousal as well as cardiovascular output were assessed repeatedly. Brain response to stress, drug cue and relaxing imagery was also assessed during a functional magnetic resonance (fMRI) imaging session. In the current study, guanfacine was found to be safe and well-tolerated. Lower basal heart rate and blood pressure was observed in the guanfacine versus placebo group. Guanfacine lowered stress and cue-induced nicotine craving and cue-induced cocaine craving, anxiety and arousal. The guanfacine group also showed increased medial and lateral prefrontal activity following stress and drug cue exposure compared with placebo. Data suggest further exploration of guanfacine is warranted in terms of its potential for reducing stress-induced and cue-induced drug craving and arousal.
可卡因依赖与应激增加、药物线索诱发的渴求以及生理唤醒有关，但与情绪和认知挑战相关的前额叶活动减少。由于这些变化与复发风险相关，我们研究了α2 受体激动剂胍法辛对这些过程的影响。29 名早期戒断、寻求治疗的可卡因依赖者被随机分配到每天接受安慰剂或胍法辛（最高 3 毫克）治疗 4 周。在一项实验室实验中，所有患者每天连续接受三种 10 分钟的引导想象条件（应激/应激、药物线索/药物线索、应激/药物线索），顺序随机、平衡。反复评估主观渴求、焦虑和唤醒以及心血管输出。在功能磁共振成像 (fMRI) 成像期间，还评估了大脑对应激、药物线索和放松想象的反应。在本研究中，胍法辛被发现安全且耐受良好。与安慰剂组相比，胍法辛组的基础心率和血压较低。与安慰剂相比，胍法辛降低了应激和线索诱发的尼古丁渴求以及线索诱发的可卡因渴求、焦虑和唤醒。与安慰剂相比，胍法辛组在应激和药物线索暴露后还显示出内侧和外侧前额叶活动增加。数据表明，有必要进一步探索胍法辛在减少应激诱导和线索诱导的药物渴求和唤醒方面的潜力。
