Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

EC psychology and psychiatry Pub Date : 2018-08-01 Epub Date: 2018-07-30
Kenneth Blum, Edward J Modestino, Rajendra D Badgaiyan, David Baron, Panayotis K Thanos, Igor Elman, David Siwicki, Marcelo Febo, Mark S Gold
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Abstract

Blum's laboratory first showed the benefits of naloxone or narcotic antagonists in the treatment of alcohol dependence. This seminal work published in Nature in the early 70's, in conjunction with many other studies, later served as the basis for the development of the narcotic antagonist (NTX) now used to treat both alcohol and opioid dependence. In 2006 an extended-release injectable of Naltrexone (XR-NTX) was approved by the FDA. Naltrexone is a relatively weak antagonist of κ- and δ-receptors and is also a potent μ-receptor antagonist. Dosages of naltrexone that effectively reduce opioid and alcohol consumption also actively block μ-receptors, but chronically down-regulate mesolimbic dopamine release. While studies show benefit especially in the short term, there is ongoing evidence that the retention and compliance with NTX are not sufficient to characterize adherence as high. However, extended-release NTX opioid treatment is associated with superior outcomes including less likely relapse (defined as daily use), and much longer time to relapse despite higher rates of concurrent non-opioid substance use like cocaine. Regarding long-term extended-release injectable (XR-NTX) for opioid dependence; there was higher compliance with Opioid Use Disorder (OUD) than for Alcohol Use Disorder (AUD.). Consideration of modalities in combination with XR-NTX is imperative. Research by Blum., et al. showed that a combination of Naltrexone and a pro-dopamine regulator neuro-nutrient (KB220) significantly prevented opioid relapse. Thus, early identification of addiction vulnerability with the Genetic Addiction Risk Score (GARS™) a panel of polymorphic risk alleles from ten reward circuitry genes will provide valuable information especially as it relates to genetically guided therapy with the KB220 neuro nutrient termed 'Precision Addiction Management".

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亲多巴胺调节剂(KB220PAM)联合纳曲酮预防阿片类药物使用障碍复发的证据分析。
Blum的实验室首先证明了纳洛酮或麻醉拮抗剂在治疗酒精依赖方面的益处。这项开创性的工作于70年代初发表在《自然》杂志上,与许多其他研究一起,后来成为麻醉性拮抗剂(NTX)发展的基础,现在用于治疗酒精和阿片类药物依赖。2006年,一种纳曲酮缓释注射剂(XR-NTX)获得了FDA的批准。纳曲酮是一种相对弱的κ-和δ-受体拮抗剂,也是一种强效的μ-受体拮抗剂。纳曲酮在有效减少阿片类药物和酒精消耗的同时,也会积极阻断μ-受体,但会长期下调中脑边缘多巴胺的释放。虽然研究显示短期获益,但持续有证据表明,NTX的保留和依从性不足以说明依从性高。然而,缓释的NTX阿片类药物治疗与较好的结果相关,包括复发的可能性较低(定义为每日使用),尽管同时使用非阿片类物质(如可卡因)的比例较高,但复发时间较长。关于阿片类药物依赖的长期缓释注射剂(XR-NTX);阿片类药物使用障碍(OUD)的依从性高于酒精使用障碍(AUD)。考虑结合XR-NTX的治疗方式是必要的。Blum的研究。等人的研究表明,纳曲酮与多巴胺前调节神经营养素(KB220)联合使用可显著预防阿片类药物复发。因此,使用遗传成瘾风险评分(GARS™)(一组来自十个奖励回路基因的多态风险等位基因)早期识别成瘾脆弱性将提供有价值的信息,特别是因为它涉及到KB220神经营养物质的遗传指导治疗,称为“精确成瘾管理”。
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