Development of cannabinoid-opioid combination with opioid sparing and synergistic analgesic effects to prevent opioid use disorder and overdose.

项目摘要/摘要 在美国，大约有200万人符合阿片类药物使用障碍的标准，其中 在过去的一个月里，又有数百万人报告使用或滥用阿片类止痛药。以及一个 阿片类药物使用障碍增加，与阿片类药物相关的过量死亡人数上升 在过去的十年里，美国陷入了公共卫生危机。慢性疼痛和阿片类药物滥用更为普遍 与构成公共健康危机并对患者、护理人员造成沉重代价之前相比， 医生和社会。管理阿片类药物的使用目前面临着治疗挑战 精神障碍、阿片类药物戒断症状、慢性疼痛和/或相关的焦虑和抑郁。 仍然迫切需要另一种安全的治疗方案来适当地治疗这些疾病 条件。我们建议开发一种大麻素-阿片类药物组合，并保留阿片类药物和 预防阿片类药物使用障碍和过量​，​的协同止痛作用 目前的全国阿片类药物危机。BDH Pharma，LLC最近完成了一项概念验证 一种大麻素-阿片类药物组合的临床前研究，显示阿片类药物的节制和 协同止痛作用，在啮齿动物模型中提供更强的止痛作用 比标准剂量的阿片类药物单独服用更能缓解慢性疼痛。这些结果表明， 大麻素-阿片类药物的固定剂量组合(FDC)可能通过以下方式改善止痛 降低阿片类药物剂量，从而降低依赖、戒断、转移、滥用和 服药过量。该提案将通过完成临床前工作来继续FDC的发展 药代动力学和​体内​安全性研究确定联合用药是否改变 两种化合物在啮齿动物体内的药代动力学和/或呼吸抑制作用。vt.在.的基础上 完成拟议的第一阶段目标后，我们将提交第二阶段SBIR申请至 完成FDA要求的任何其他临床前研究，以完成配方 研究​，并支持在GMP条件下生产最终的临床剂量 该表格将用于FDC在人体上的后续1期临床试验。

Project Summary/Abstract Approximately 2 million individuals in the US meet criteria for an opioid use disorder, with millions more reporting use or misuse of opioid pain relievers in the past month. Along with an increase in opioid use disorders, a rise in opioid-related overdose deaths has occurred in the last decade reaching a public health crisis. Chronic pain and opioid abuse are more prevalent than before constituting a public health crisis and exacting a heavy toll on patients, caregivers, physicians and society. There is a current therapeutic challenge for managing opioid use disorder, opioid withdrawal symptoms, chronic pain, and/or associated anxiety and depression. A severe need remains for alternative and safe therapeutic regimens that properly treat these conditions. We propose to develop a cannabinoid-opioid combination with opioid sparing and synergistic analgesic effects to prevent opioid use disorder and overdose​, ​addressing the current national opioid crisis. BDH Pharma, LLC recently completed a proof-of-concept preclinical study of a cannabinoid-opioid combination that demonstrated opioid sparing and synergistic analgesic effects, with the combination providing greater analgesia in a rodent model of chronic pain than a standard dose of the opioid alone. These results suggest that a fixed-dose combination (FDC) of the cannabinoid-opioid may have improved analgesia with lower opioid doses and thereby lower the risk of dependence, withdrawal, diversion, abuse, and overdose. This proposal will continue the development of the FDC by completing a preclinical pharmacokinetic and ​in vivo ​safety study to determine if co-administration alters the pharmacokinetics and/or respiratory depression related to either compound in rodents. Upon completion of the proposed Phase 1 aims, we will submit a Phase 2 SBIR application to complete any additional preclinical studies required by the FDA, to complete formulation studies​, and to support the manufacturing under GMP conditions of the final clinical dosage form that will be used in a subsequent phase 1 clinical trial of the FDC in humans.