Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, Av. Senador Salgado Filho 3000 Lagoa Nova, Natal, RN, 59078-970, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2018 Dec;391(12):1301-1318. doi: 10.1007/s00210-018-1570-9. Epub 2018 Oct 18.
Caffeine is the most consumed psychoactive substance in the world; in general, it is not associated to potentially harmful effects. Nevertheless, few studies were performed attempting to investigate the caffeine addiction. The present review was mainly aimed to answer the following question: is caffeine an abuse drug? To adress this point, the effects of caffeine in preclinical and clinical studies were summarized and critically analyzed taking account the abuse disorders described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). We concluded that the diagnostic criteria evidenced on DSM-V to intoxication-continued use and abstinence are not well supported by clinical studies. The fact that diagnostic criteria is not widely supported by preclinical or clinical studies may be due specially to a controversy in its exactly mechanism of action: recent literature point to an indirect, rather than direct modulation of dopamine receptors, and auto-limitant consumption due to adverse sensations in high doses. On the other hand, it reports clear withdrawal-related symptoms. Thus, based on a classical action on reward system, caffeine only partially fits its mechanism of action as an abuse drug, especially because previous research does not report a clear effect of dopaminergic activity enhance on nucleus accumbens; despite this, there are reports concerning dopaminergic modulation by caffeine on the striatum. However, based on human and animal research, caffeine withdrawal evokes signals and symptoms, which are relevant enough to include this substance among the drugs of abuse.
咖啡因是世界上使用最广泛的精神活性物质;一般来说,它不会产生潜在的有害影响。然而,很少有研究试图调查咖啡因成瘾。本综述主要旨在回答以下问题:咖啡因是一种滥用药物吗?为了解决这一问题,我们总结并批判性地分析了咖啡因在临床前和临床研究中的作用,同时考虑了《精神障碍诊断与统计手册》(DSM-V)中描述的滥用障碍。我们得出的结论是,DSM-V 中关于中毒-持续使用和戒断的诊断标准并没有得到临床研究的广泛支持。诊断标准没有得到临床前或临床研究的广泛支持,可能特别由于其确切作用机制存在争议:最近的文献指出,它是一种间接而不是直接的多巴胺受体调制,而且由于高剂量会产生不良反应,摄入量会自我限制。另一方面,它报告了明确的戒断相关症状。因此,基于对奖励系统的经典作用,咖啡因仅部分符合其作为滥用药物的作用机制,尤其是因为先前的研究没有报告中脑伏隔核多巴胺活性增强的明确作用;尽管如此,有报道称咖啡因对纹状体的多巴胺调节作用。然而,基于人类和动物研究,咖啡因戒断会引起信号和症状,这些信号和症状足以将这种物质纳入滥用药物之列。