New therapeutic approaches to identifying molecules for opioid abuse treatment

项目摘要 合作制药公司是一家专注于开发治疗疑难杂症的小企业， 疾病持续过度依赖阿片类药物治疗慢性疼痛，尽管它们改善功能的能力很差， 导致近年来阿片类药物过量死亡和成瘾的严重和令人震惊的流行。 尽管存在压倒性的成瘾危机，但几乎没有治疗方法存在，并且疗效低下。因此，一个关键的未满足的需求 是阿片类药物滥用障碍的有效和安全的治疗方法。最近的研究表明迷幻药 还能够减少药物依赖，包括阿片类药物滥用， 极其罕见这种药物滥用的停止与神经突发生的诱导有关， 神经可塑性迷幻药的标志虽然迷幻体验和神经可塑性诱导 似乎是相互联系的，已经提出了几种类似的迷幻药，诱导神经可塑性和药物- 回避，而似乎缺乏迷幻的经验。虽然数量很少，但这些类似物具有 被命名为“精神致活素”，并且是用于治疗阿片类药物滥用的有希望的候选者。德- 迷幻体验和神经可塑性诱导的耦合与受体特异性有关， 精神质体原对5 HT 2A是特异性的。在这里，我们建议使用生成机器学习的组合， 模型与我们的监督机器模型的丰富经验，以产生新的类似迷幻药 其将具有改善的5-HT 2A特异性、ADME性质，并且易于合成以快速扩增5-HT 2A， 一系列已知的精神致活素，显著增加阿片类药物滥用的潜在治疗选择 治疗

Project Summary Collaborations Pharmaceuticals Inc. is a small business focused on developing treatments for difficult to treat diseases. The ongoing overreliance on opioids for chronic pain despite their poor ability to improve function has contributed to a significant and alarming epidemic of opioid overdose deaths and addictions in recent years. Despite the overwhelming addiction crisis, few therapies exist, and with low efficacy. Thus, a critical unmet need is an effective and safe treatment for opioid abuse disorders. Recent research has suggested that psychedelics are also capable of reducing drug-dependence, including opioid abuse, and that serious adverse effects are extremely rare. This drug abuse cessation is linked to the induction of neuritogenesis and increased neuroplasticity, a hallmark of psychedelics. While the psychedelic experience and neuroplasticity induction appear interlinked, several analogs of psychedelics have been proposed which induce neuroplasticity and drug- avoidance while seemingly lacking the psychedelic experience. Although few in number, these analogs have been named “psychoplastogens” and are promising candidates for treatment of opioid drug abuse. The de- coupling of the psychedelic experience and neuroplasticity induction is linked to receptor specificity as psychoplastogens are specific to 5HT2A. Here, we propose to use a combination of generative machine learning models with our extensive experience of supervised machine models to generate new analogs of psychedelics that will have improved 5-HT2A specificity, ADME properties, and are easily synthesizable to rapidly expand the pool of known psychoplastogens, significantly increasing potential therapeutic options for opioid abuse treatment.