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

开发具有阿片类药物节约和协同镇痛作用的大麻素-阿片类药物组合，以防止阿片类药物使用障碍和过量。

• 批准号: 9912141
• 负责人: Marisa Briones
• 金额: $ 28.39万
• 依托单位: BDH PHARMA, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2020-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9912141
• 关键词: Absence of pain sensation; Address; Advanced Development; Agonist; American; Analgesics; Anti Inflammatory Analgesics; Anxiety; Area; Buprenorphine; CYP3A4 gene; Cannabidiol; Cannabinoids; Cannabis sativa plant; Caregivers; Clinical; Clinical Trials; Data; Dependence; Development; Dosage Forms; Dose; Drug Interactions; Drug Kinetics; Epilepsy; FDA approved; Fentanyl; Formulation; Goals; Heroin; Human; In Vitro; Individual; Legal patent; Licensing; Mental Depression; Needs Assessment; Opiate Addiction; Opioid; Opioid Analgesics; Opioid agonist; Overdose; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Physical Dependence; Physicians; Prevention; Public Health; Rattus; Regimen; Regulatory Pathway; Reporting; Research Support; Respiration; Risk; Rodent; Rodent Model; Role; Safety; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Societies; Therapeutic; Toxicology; United States National Institutes of Health; Ventilatory Depression; Withdrawal; Withdrawal Symptom; addiction; chronic pain; commercialization; healing; improved; in vivo; medication safety; novel therapeutics; off-patent; opioid abuse; opioid epidemic; opioid misuse; opioid overdose; opioid sparing; opioid use; opioid use disorder; opioid withdrawal; overdose death; overdose risk; phytocannabinoid; pre-clinical; preclinical study; prescription opioid; prevent; response; safety assessment; safety study; sedative

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.

项目总结/摘要 美国约有200万人符合阿片类药物使用障碍的标准， 在过去的一个月里，数百万人报告使用或滥用阿片类止痛药。沿着着 随着类阿片使用障碍的增加， 近十年来，公共卫生危机。慢性疼痛和阿片类药物滥用更为普遍 比以前构成公共卫生危机，并要求对病人，照顾者， 医生与社会目前管理阿片类药物使用存在治疗挑战 在一些实施方案中，所述药物组合物可包括但不限于阿片样物质戒断症状、慢性疼痛和/或相关的焦虑和抑郁。 仍然迫切需要替代和安全的治疗方案，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， 协同镇痛作用，以预防阿片类药物使用障碍和过量， 当前的鸦片危机BDH Pharma，LLC最近完成了概念验证 大麻素-阿片类药物组合的临床前研究，证明阿片类药物保留， 协同镇痛作用，在啮齿类动物模型中联合使用可提供更强的镇痛作用 比单独使用标准剂量的阿片类药物更有效。这些结果表明 大麻素-阿片样物质的固定剂量组合（FDC）可能具有改善的镇痛作用， 降低阿片类药物剂量，从而降低依赖、戒断、转移、滥用的风险， 服药过量该提案将通过完成临床前研究继续FDC的开发。 药代动力学和体内安全性研究，以确定联合给药是否改变了 在啮齿类动物中与任一化合物相关的药代动力学和/或呼吸抑制。后 在完成第一阶段的目标后，我们将向 完成FDA要求的任何其他临床前研究，以完成制剂 研究，并支持在GMP条件下生产最终临床剂量 将用于后续的FDC人体I期临床试验。