Nat Med:安慰剂效应,“信则有,不信则无”?
2016/08/01
在医学研究中,科学家常使用“安慰剂”作为控制组,来进行某种药物/疗法的临床试验。有时候,医生甚至可通过“安慰剂”效应实现非药物治疗目的。大脑为何会产生“安慰剂效应”?为什么安慰剂对有的人起效,对有的人却无效呢?安慰剂效应,真的是“信则有,不信则无”吗?近日Nature Medicine上的一篇研究揭示了这个谜底。

信则有,不信则无

安慰剂,英语叫placebo,源于拉丁文,原意是I shall please,简单点翻译就是“我愿意”。

安慰剂效应的力量

千百年来,人类一直在使用安慰剂作为缓解症状的方法之一;在过去70多年的临床研究中,安慰剂效应也始终是测试新药疗效的基本手段;目前德国有过半医生在治疗小病会将“安慰剂”作为处方给予患者,因为安慰剂也似乎能起作用。

在医学临床试验中,科学家总是使用安慰剂(像糖丸或假手术操作这样的,无效的操作或是使用无活性成分的物质)作为控制组,来检测那些货真价实的物质的有效性,比如说含有活性成分的药物。虽然常用的安慰剂一般不含有任何药物作用/手术操作/活性成分的物质,但它们却常常对治疗有效。

研究发现:给予了安慰剂的病人会认为他们在接受标准治疗,而这样的想法会导致“安慰剂效应”——尽管他们没有接受积极治疗,但症状还是得到改善了;安慰剂在抑郁症和肠胃不适患者身上,效果显著(在大约1/3的病例中,安慰剂与抗抑郁药物的效果是一样的);安慰剂治疗价格越贵,改善症状的几率越高;静脉注射看起来更像“标准治疗”,安慰剂效应比口服药物更有效。

因此,在临床试验中设置安慰剂对照组成为了开发新药物或疗法的基本原则。

大脑为何会产生“安慰剂效应”?为什么安慰剂对有的人起效,对有的人却无效呢?安慰剂效应,真的是“信则有,不信则无”吗?

近日发表在Nature Medicine上的一项“动物实验”研究揭示:“安慰剂”通过刺激小鼠大脑内的良好感觉奖赏中枢(feel-good reward centres),后者可以进一步促进动物的免疫系统,从而增强了动物对疾病的抵抗能力,这一发现或解释了安慰剂效应的力量。

大脑控制一切?

关于安慰剂治疗的真正原理,以及安慰剂治疗与心理预期之间的关系,一直存在着较多的研究。

哈佛医学院的药学教授Ted Kaptchuk曾在治疗哮喘病人时发现,安慰剂的效果与有活性成分的药物效果不分上下。在他看来,安慰剂激活大脑中的特定区域,会减少疼痛,或减少与疼痛有关的感觉。

2005年,《神经学》期刊研究发现,服用安慰剂并信以为真的病人,脑中会释放了更多的叫做“内啡肽”的天然镇痛剂。

2007年,另一个研究发现:有些人更容易受到安慰效应的影响,这是因为他们叫做“伏隔核”的大脑区域的多巴胺活跃水平不同,“伏隔核”这个区域影响到感受愉悦和奖赏的能力。

以色列理工学院药学教授、Nature Medicine一作Asya Rolls认为,“伏隔核”很可能是安慰剂效应的来源。他们发现与积极期望有关联的大脑区域的活跃程度能影响身体对疾病的应对方式。

(安慰剂)从啮齿类动物被刺激的大脑奖赏中心中提取的免疫细胞杀死的细菌(右)

对照组小鼠中提取的免疫细胞杀死的细菌(左)

Credit: Nature Medicine

Asya Rolls与同事培养了小鼠中提取的免疫细胞,并将其置于大肠杆菌中。研究发现,大脑奖赏中枢被激活产生的免疫细胞杀死的细菌远多于单独培养的细胞杀死的细菌数,前者是后者的2倍。

在另一项试验中,啮齿类动物接种了大脑奖赏中枢激活的免疫细胞,发现这些小鼠成功战胜感染的几率也显著提高。

研究人员认为,在大脑奖赏中枢被激活后,单核细胞和巨噬细胞是更牛的大肠杆菌杀手,尤其是在腹侧被盖区(tegmental area )——这是个严重受制于情绪调节物质多巴胺的脑区。

作者解释道,食、色将我们置身于细菌的包围之中。这也带给人类一项进化优势——当奖赏系统被激活时,免疫力也增强了。

虽然从小鼠到人类还有一大步要走,但这个想法对于人类而言意味着:当我们有期待时,比如从抑郁或者疼痛中恢复,大脑的奖励回路就会被激活,然后进一步激活神经元,被激活的神经元再从大脑传递到器官,包括免疫系统。

如果额外的抗体和免疫活动确实可以使小鼠更健康,如果人类的奖励回路与小鼠工作方式相同,这不仅可解释为什么人类大脑可以将对健康的愿望转换为真正的健康(即信则有,不信则无);也可以解释为什么顺势疗法和其他的虚假治疗有时候也能起到一定的作用。

推荐阅读:

‘Feel good’ neurons might explain the power of the placebo effect

所有文章仅代表作者观点,不代表本站立场。如若转载请联系原作者。
查看更多
  • Activation of the reward system boosts innate and adaptive immunity

    Positive expectations contribute to the clinical benefits of the placebo effect1, 2. Such positive expectations are mediated by the brain's reward system3, 4; however, it remains unknown whether and how reward system activation affects the body's physiology and, specifically, immunity. Here we show that activation of the ventral tegmental area (VTA), a key component of the reward system, strengthens immunological host defense. We used 'designer receptors exclusively activated by designer drugs' (DREADDs) to directly activate dopaminergic neurons in the mouse VTA and characterized the subsequent immune response after exposure to bacteria (Escherichia coli), using time-of-flight mass cytometry (CyTOF) and functional assays. We found an increase in innate and adaptive immune responses that were manifested by enhanced antibacterial activity of monocytes and macrophages, reduced in vivo bacterial load and a heightened T cell response in the mouse model of delayed-type hypersensitivity. By chemically ablating the sympathetic nervous system (SNS), we showed that the reward system's effects on immunity are, at least partly, mediated by the SNS. Thus, our findings establish a causal relationship between the activity of the VTA and the immune response to bacterial infection.

    展开 收起
  • Neurobiological Mechanisms of the Placebo Effect

    Any medical treatment is surrounded by a psychosocial context that affects the therapeutic outcome. If we want to study this psychosocial context, we need to eliminate the specific action of a therapy and to simulate a context that is similar in all respects to that of a real treatment. To do this, a sham treatment (the placebo) is given, but the patient believes it is effective and expects a clinical improvement. The placebo effect, or response, is the outcome after the sham treatment. Therefore, it is important to emphasize that the study of the placebo effect is the study of the psychosocial context around the patient. The placebo effect is a psychobiological phenomenon that can be attributable to different mechanisms, including expectation of clinical improvement and pavlovian conditioning. Thus, we have to look for different mechanisms in different conditions, because there is not a single placebo effect but many. So far, most of the neurobiological mechanisms underlying this complex phenomenon have been studied in the field of pain and analgesia, although recent investigations have successfully been performed in the immune system, motor disorders, and depression. Overall, the placebo effect appears to be a very good model to understand how a complex mental activity, such as expectancy, interacts with different neuronal systems (Colloca and Benedetti, 2005; Finniss and Benedetti, 2005). Recently, the placebo effect has reemerged in the public and scientific interest because of investigations of its biological substrates (de la Fuente-Fernandez et al., 2001; Mayberg et al., 2002; Petrovic et al., 2002; Lieberman et al., 2004; Wager et al., 2004; Colloca and Benedetti, 2005; Zubieta et al., 2005a). The public is interested in placebo effects because they promise increased self-control; the existence of placebo effects suggests that we must broaden our conception of the limits of endogenous human capability. Scientists are interested in placebo responses because the effects of belief on human experience and behavior provide an entry point for studying internal control of affective, sensory, and peripheral processes. The study of the placebo effect, at its core, is the study of how the context of beliefs and values shape brain processes related to perception and emotion and, ultimately, mental and physical health. The study of the placebo effect reflects a current neuroscientific thought that has as its central tenet the idea that “subjective” constructs such as expectation and value have identifiable physiological bases, and that these bases are powerful modulators of basic perceptual, motor, and internal homeostatic processes. The study of the placebo effect also has immediate clinical and ethical implications, because the use of inactive (placebo) conditions in clinical trials when effective treatments are available has created an ethical controversy. However, it has been well documented that placebo effects can obscure those of active conditions, even for treatments that were eventually demonstrated to be effective. Thus, placebo effects may represent points of either strength or vulnerability for the expression and maintenance of various pathological states and their inherent therapeutic interventions.

    展开 收起
  • Individual differences in reward responding explain placebo-induced expectations and effects.

    Expectations, positive or negative, are modulating factors influencing behavior. They are also thought to underlie placebo effects, impacting perceptions and biological processes. Using healthy human subjects, we examined the role of the nucleus accumbens (NAC), a region centrally involved in the encoding of reward expectation, in the formation of placebo responses. Employing functional molecular imaging, activation of NAC dopamine (DA) release was observed during placebo administration and related to its anticipated effects, perception-anticipation mismatches, and placebo effect development. In additional functional MRI studies, the expectation of monetary gain increased NAC synaptic activity in a manner proportional to placebo-induced DA release, anticipated effects, perception-anticipation differentials, and actual placebo effects. Individual variations in NAC response to reward expectation accounted for 28% of the variance in the formation of placebo analgesia.

    展开 收起
发表评论 我在frontend\modules\comment\widgets\views\文件夹下面 test