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Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development. 通过大脑健康检查辅导和预防性大脑开发,解决青少年大脑皮层失调问题。
Pub Date : 2024-04-30 DOI: 10.36922/itps.1472
Kenneth Blum, Eric R Braverman, Mark S Gold, Catherine A Dennen, David Baron, Panayotis K Thanos, Colin Hanna, Igor Elman, Marjorie C Gondre-Lewis, J Wesson Ashford, Andrew Newberg, Margaret A Madigan, Nicole Jafari, Foojan Zeine, Keerthy Sunder, John Giordano, Debmayla Barh, Ashim Gupta, Paul Carney, Abdalla Bowirrat, Rajendra D Badgaiyan

The Carter Center has estimated that the addiction crisis in the United States (US), if continues to worsen at the same rate, may cost the country approximately 16 trillion dollars by 2030. In recent years, the well-being of youth has been compromised by not only the coronavirus disease 2019 pandemic but also the alarming global opioid crisis, particularly in the US. Each year, deadly opioid drugs claim hundreds of thousands of lives, contributing to an ever-rising death toll. In addition, maternal usage of opioids and other drugs during pregnancy could compromise the neurodevelopment of children. A high rate of DNA polymorphic antecedents compounds the occurrence of epigenetic insults involving methylation of specific essential genes related to normal brain function. These genetic antecedent insults affect healthy DNA and mRNA transcription, leading to a loss of proteins required for normal brain development and function in youth. Myelination in the frontal cortex, a process known to extend until the late 20s, delays the development of proficient executive function and decision-making abilities. Understanding this delay in brain development, along with the presence of potential high-risk antecedent polymorphic variants or alleles and generational epigenetics, provides a clear rationale for embracing the Brain Research Commission's suggestion to mimic fitness programs with an adaptable brain health check (BHC). Implementing the BHC within the educational systems in the US and other countries could serve as an effective initiative for proactive therapies aimed at reducing juvenile mental health problems and eventually criminal activities, addiction, and other behaviors associated with reward deficiency syndrome.

卡特中心估计,美国的吸毒成瘾危机如果继续以同样的速度恶化,到 2030 年可能会给美国造成约 16 万亿美元的损失。近年来,青少年的福祉不仅受到 2019 年冠状病毒疾病大流行的影响,还受到令人震惊的全球阿片类药物危机的影响,尤其是在美国。每年,致命的阿片类药物夺走了数十万人的生命,导致死亡人数不断攀升。此外,孕产妇在怀孕期间使用阿片类药物和其他药物可能会影响儿童的神经发育。DNA 多态性前因的高发生率加剧了表观遗传学损伤的发生,这些损伤涉及与正常大脑功能相关的特定重要基因的甲基化。这些遗传前因损伤会影响健康的 DNA 和 mRNA 转录,导致青少年大脑正常发育和功能所需的蛋白质缺失。额叶皮层的髓鞘化过程要持续到 20 多岁,而这一过程会延迟熟练的执行功能和决策能力的发展。了解了大脑发育的这一延迟,再加上潜在的高风险先兆多态变异或等位基因以及世代表观遗传学的存在,就有理由接受脑研究委员会的建议,通过可调整的大脑健康检查(BHC)来模仿健身计划。在美国和其他国家的教育系统中实施脑健康检查,可以作为一种有效的前瞻性疗法,旨在减少青少年的心理健康问题,最终减少犯罪活动、成瘾和其他与奖赏缺乏综合症有关的行为。
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引用次数: 0
A historical perspective on clonidine as an alpha-2A receptor agonist in the treatment of addictive behaviors: Focus on opioid dependence. 从历史角度看氯尼丁作为一种α-2A 受体激动剂治疗成瘾行为:聚焦阿片类药物依赖。
Pub Date : 2024-01-01 Epub Date: 2024-07-29 DOI: 10.36922/itps.1918
Mark S Gold, Kenneth Blum, Abdalla Bowirrat, Albert Pinhasov, Debasis Bagchi, Catherine A Dennen, Panayotis K Thanos, Colin Hanna, Kai-Uwe Lewandrowski, Alireza Sharafshah, Igor Elman, Rajendra D Badgaiyan

Clonidine operates through agonism at the alpha-2A receptor, a specific subtype of the alpha-2-adrenergic receptor located predominantly in the prefrontal cortex. By inhibiting the release of norepinephrine, which is responsible for withdrawal symptoms, clonidine effectively addresses withdrawal-related conditions such as anxiety, hypertension, and tachycardia. The groundbreaking work by Gold et al. demonstrated clonidine's ability to counteract the effects of locus coeruleus stimulation, reshaping the understanding of opioid withdrawal within the field. In the 1980s, the efficacy of clonidine in facilitating the transition to long-acting injectable naltrexone was confirmed for individuals motivated to overcome opioid use disorders (OUDs), including physicians and executives. Despite challenges with compliance, naltrexone offers sustained blockade of opioid receptors, reducing the risk of overdose, intoxication, and relapse in motivated patients in recovery. The development of clonidine and naltrexone as treatment modalities for OUDs, and potentially other addictions, including behavioral ones, underscores the potential for translating neurobiological advancements from preclinical models (bench) to clinical practice (bedside), ushering in innovative approaches to addiction treatment.

氯尼定通过激动α-2A受体发挥作用,α-2A受体是α-2-肾上腺素能受体的一种特殊亚型,主要位于前额叶皮层。通过抑制导致戒断症状的去甲肾上腺素的释放,氯尼丁能有效解决焦虑、高血压和心动过速等与戒断有关的症状。戈尔德(Gold)等人的开创性研究表明,氯尼替丁(clonidine)能够抵消刺激大脑皮层的作用,从而重塑了该领域对阿片类药物戒断的认识。20 世纪 80 年代,克洛尼定在促进向长效注射型纳曲酮过渡方面的疗效得到了证实,包括医生和管理人员在内的有志于克服阿片类药物使用障碍(OUDs)的人都使用了这种药物。尽管在依从性方面存在挑战,但纳曲酮可持续阻断阿片受体,降低过量、中毒和复发的风险,从而帮助患者积极康复。氯尼地定和纳曲酮作为治疗 OUD 以及潜在的其他成瘾(包括行为成瘾)的方法的开发,强调了将神经生物学的进步从临床前模型(工作台)转化为临床实践(床旁)的潜力,为成瘾治疗带来了创新方法。
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INNOSC theranostics & pharmacological sciences
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