Neurosciences Institute, Miguel Hernandez University-CSIC, Avenue de Ramón y Cajal s/n, San Juan de Alicante, 03550 Alicante, Spain; Cooperative Health Research Thematic Network, Addictive Disorders Network, Heatlh Institute Carlos III, MICINN and FEDER, Madrid, Spain.
Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Pompeu Fabra University, PRBB, C/ Doctor Aiguader 88, 08003 Barcelona, Spain; Cooperative Health Research Thematic Network, Addictive Disorders Network, Heatlh Institute Carlos III, MICINN and FEDER, Madrid, Spain.
Biochem Pharmacol. 2018 Nov;157:108-121. doi: 10.1016/j.bcp.2018.09.013. Epub 2018 Sep 12.
Drug addiction is a chronic relapsing disorder that produces a dramaticglobal health burden worldwide. Not effective treatment of drug addiction is currently available probably due to the difficulties to find an appropriate target to manage this complex disease raising the needs for further identification of novel therapeutic approaches. The endocannabinoid system has been found to play a crucial role in the neurobiological substrate underlying drug addiction. Endocannabinoids and cannabinoid receptors are widely expressed in the main areas of the mesocorticolimbic system that participate in the initiation and maintenance of drug consumption and in the development of compulsion and loss of behavioral control occurring during drug addiction. The identification of the important role played by CB1 cannabinoid receptors in drug addiction encouraged the possible used of an early commercialized CB1 receptor antagonist for treating drug addiction. However, the incidence of serious psychiatric adverse events leaded to the sudden withdrawal from the market of this CB1 antagonist and all the research programs developed by pharmaceutical companies to obtain new CB1 antagonists were stopped. Currently, new research strategies are under development to target the endocannabinoid system for drug addiction avoiding these side effects, which include allosteric negative modulators of CB1 receptors and compounds targeting CB2 receptors. Recent studies showing the potential role of CB2 receptors in the addictive properties of different drugs of abuse have open a promising research opportunity to develop novel possible therapeutic approaches.
药物成瘾是一种慢性复发性疾病，在全球范围内造成了巨大的健康负担。目前还没有有效的药物成瘾治疗方法，这可能是由于难以找到合适的靶点来治疗这种复杂的疾病，因此需要进一步确定新的治疗方法。内源性大麻素系统被发现在内源性大麻素系统的神经生物学基础中起着至关重要的作用。内源性大麻素和大麻素受体广泛表达于参与药物摄入的起始和维持以及药物成瘾过程中强迫和行为控制丧失的中边缘系统的主要区域。CB1 大麻素受体在药物成瘾中发挥重要作用的鉴定，促使人们可能使用早期商业化的 CB1 受体拮抗剂来治疗药物成瘾。然而，严重精神不良事件的发生率导致这种 CB1 拮抗剂突然退出市场，制药公司为获得新的 CB1 拮抗剂而开发的所有研究项目都停止了。目前，为了避免这些副作用，正在开发针对内源性大麻素系统的药物成瘾的新研究策略，包括 CB1 受体的变构负调节剂和针对 CB2 受体的化合物。最近的研究表明，CB2 受体在不同滥用药物的成瘾特性中的潜在作用为开发新的可能治疗方法提供了一个有希望的研究机会。
