假设谷氨酰胺能 - 多巴胺能优化复合物（KB220Z）的神经药理学和神经影像学研究与奖赏缺乏综合征（RDS）中的“多巴胺稳态”相关。
Hypothesizing That Neuropharmacological and Neuroimaging Studies of Glutaminergic-Dopaminergic Optimization Complex (KB220Z) Are Associated With "Dopamine Homeostasis" in Reward Deficiency Syndrome (RDS).
作者信息
Blum Kenneth, Febo Marcelo, Fried Lyle, Li Mona, Dushaj Kristina, Braverman Eric R, McLaughlin Thomas, Steinberg Bruce, Badgaiyan Rajendra D
机构信息
a Department of Psychiatry & McKnight Brain Institute , University of Florida College of Medicine , Gainesville , Florida , USA.
b Departments of Psychiatry & Behavioral Sciences , Keck School of Medicine of USC , Los Angeles , California , USA.
出版信息
Subst Use Misuse. 2017 Mar 21;52(4):535-547. doi: 10.1080/10826084.2016.1244551. Epub 2016 Dec 29.
BACKGROUND
There is need for better treatments of addictive behaviors, both substance and non-substance related, termed Reward Deficiency Syndrome (RDS). While the FDA has approved pharmaceuticals under the umbrella term Medication Assisted Treatment (MAT), these drugs are not optimal.
OBJECTIVES
It is our contention that these drugs work well in the short-term by blocking dopamine function leading to psychological extinction. However, use of buprenorphine/Naloxone over a long period of time results in unwanted addiction liability, reduced emotional affect, and mood changes including suicidal ideation.
METHODS
We are thus proposing a paradigm shift in addiction treatment, with the long-term goal of achieving "Dopamine Homeostasis." While this may be a laudable goal, it is very difficult to achieve. Nevertheless, this commentary briefly reviews past history of developing and subsequently, utilizing a glutaminergic-dopaminergic optimization complex [Kb220Z] shown to be beneficial in at least 20 human clinical trials and in a number of published and unpublished studies.
RESULTS
It is our opinion that, while additional required studies could confirm these findings to date, the cited studies are indicative of achieving enhanced resting state functional connectivity, connectivity volume, and possibly, neuroplasticity. Conclusions/Importance: We are proposing a Reward Deficiency Solution System (RDSS) that includes: Genetic Addiction Risk Score (GARS); Comprehensive Analysis of Reported Drugs (CARD); and a glutaminergic-dopaminergic optimization complex (Kb220Z). Continued investigation of this novel strategy may lead to a better-targeted approach in the long-term, causing dopamine regulation by balancing the glutaminergic-dopaminergic pathways. This may potentially change the landscape of treating all addictions leading us to the promised land.
背景
对于成瘾行为，包括物质相关和非物质相关的成瘾行为，即奖赏缺乏综合征（RDS），需要更好的治疗方法。虽然美国食品药品监督管理局（FDA）已批准在药物辅助治疗（MAT）这一统称下的药物，但这些药物并非最佳选择。
目的
我们认为，这些药物通过阻断多巴胺功能导致心理消退，在短期内效果良好。然而，长期使用丁丙诺啡/纳洛酮会导致不必要的成瘾倾向、情感反应降低以及包括自杀意念在内的情绪变化。
方法
因此，我们提议在成瘾治疗方面进行范式转变，长期目标是实现“多巴胺稳态”。虽然这可能是一个值得称赞的目标，但很难实现。尽管如此，本评论简要回顾了开发并随后使用一种谷氨酰胺能 - 多巴胺能优化复合物 [Kb220Z] 的过往历史，该复合物在至少20项人体临床试验以及一些已发表和未发表的研究中显示出有益效果。
结果
我们认为，虽然还需要更多研究来证实迄今为止的这些发现，但所引用的研究表明实现了增强的静息态功能连接性、连接体积，并且可能还有神经可塑性。结论/重要性：我们提议一种奖赏缺乏解决方案系统（RDSS），它包括：遗传成瘾风险评分（GARS）；报告药物综合分析（CARD）；以及一种谷氨酰胺能 - 多巴胺能优化复合物（Kb220Z）。对这一新颖策略的持续研究可能会在长期内带来更具针对性的方法，通过平衡谷氨酰胺能 - 多巴胺能途径来调节多巴胺。这可能会潜在地改变所有成瘾治疗的局面，引领我们走向理想境界。
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