Evaluation of Novel Pharmacotherapies for the Treatment of Opioid Dependence

治疗阿片类药物依赖的新型药物疗法的评价

• 批准号: 8499512
• 负责人: Sharon L. Walsh
• 金额: $ 50.14万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8499512
• 关键词: Acquired Immunodeficiency Syndrome; Adverse effects; Adverse event; Agonist; Analgesics; Appetite Stimulants; Area; Body Weight decreased; Brain region; CNR1 gene; Cannabinoids; Caring; Cessation of life; Chronic; Clinical; Crossover Design; DSM-IV; Data; Data Collection; Dependence; Disease; Dose; Double-Blind Method; Drug Metabolic Detoxication; Drug usage; Employment; Evaluation; Future; Gold; Health; Human; Individual; Inpatients; Label; Laboratories; Lead; Life Style; Mainstreaming; Maintenance; Maintenance Therapy; Marketing; Measures; Medical; Methodology; Morphine; Nabilone; Narcotic Antagonists; Nature; Nausea and Vomiting; Nociception; Opiate Addiction; Opioid; Outcome; Pain; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacotherapy; Physiological; Placebo Control; Placebos; Population; Procedures; Psychomotor Performance; Public Health; Relapse; Reporting; Research; Research Design; Rewards; Safety; Schedule; Seminal; Signs and Symptoms; Surveys; System; Testing; Tetrahydrocannabinol; United States Food and Drug Administration; Urine; Wasting Syndrome; Withdrawal; Withdrawal Symptom; Work; addiction; base; chemotherapy; design; disorder later incidence prevention; drug testing; efficacy testing; human data; innovation; meetings; mu opioid receptors; novel; opioid misuse; opioid withdrawal; parole; pre-clinical; prescription opioid; prescription opioid abuse; public health relevance; research study; social stigma; volunteer

DESCRIPTION (provided by applicant): Prescription opioid abuse and dependence are increasing public health problems in the U.S. with nearly 2 million people meeting DSM-IV criteria for a prescription opioid use disorder. While treatment demand continues to grow, only three medications are FDA-approved and a broader spectrum of treatment options is needed. A large body of evidence supports the hypothesis that cannabinoid (CB) agonists may be useful pharmacotherapies for the treatment of opioid dependence. CB agonists are already approved, available for human testing, and used for indications relevant to opioid withdrawal symptomatology. Two proof-of-concept, placebo-controlled, inpatient laboratory-based studies are proposed to evaluate the efficacy of the CB agonists, dronabinol and nabilone. Experiments 1 and 2 will employ within-subject crossover designs with the classic morphine substitution procedure whereby opioid dependent volunteers (n=10/study) are stabilized on a fixed dose of morphine (15 mg/qid). On a scheduled basis, subjects receive double-blind substitution of placebo for morphine to induce a period of spontaneous opioid withdrawal. Double-blind test doses are then administered to determine their ability to suppress opioid withdrawal signs and symptoms as the initial target for potential efficacy in treatment. Exp. 1 will examine dronabinol (5, 10, 20 and 30 mg) and Exp. 2 will examine nabilone (1, 2, 4 and 6 mg) for efficacy and safety; each of these studies includes positive (morphine 15 and 30 mg) and negative (placebo) control conditions. A broad array of physiological, subjective, observer-rated and psychomotor performance measures will be collected to assess safety, tolerability and efficacy at withdrawal suppression. These studies are innovative and significant as they are the first, to our knowledge, to examine the efficacy of CB1 agonists as potential pharmacotherapies for the treatment of opioid dependence in humans and will yield new data on the interaction of CB1 and opioid systems. Moreover, they will provide critical data to guide drug and dose selection for future studies aimed at examining their potential efficacy for use in the treatment of opioid dependence for maintenance, relapse prevention, ambulatory detoxification and/or as transitional agents for initiating opioid antagonist therapy.

描述（由申请人提供）：在美国，处方阿片类药物滥用和依赖性正在增加公共卫生问题，其中近200万人符合DSM-IV标准，即处方阿片类药物使用障碍。尽管治疗需求继续增长，但只有三种药物是FDA批准的，需要更广泛的治疗选择。大量证据支持以下假设：大麻素（CB）激动剂可能是治疗阿片类药物依赖性的有用药物疗法。 CB激动剂已经被批准，可用于人体测试，并用于与阿片类药物戒断症状相关的适应症。提出了两项​​概念验证，安慰剂对照，住院实验室的研究，以评估CB激动剂Dronabinol和Nabilone的功效。实验1和2将采用经典的吗啡替代程序采用受试者内部的跨界设计，从而在固定剂量的吗啡（15 mg/qid）上稳定了阿片类药物依赖性志愿者（n = 10/研究）。根据计划的基础，受试者接受了将吗啡的双盲替代，以诱导一段自发的阿片类药物戒断。然后使用双盲测试剂量，以确定其抑制阿片类药物戒断体征和症状的能力，作为治疗潜在疗效的初始目标。经验。 1将检查Dronabinol（5、10、20和30 mg）和EXP。 2将检查纳比隆（1、2、4和6毫克）的功效和安全性；这些研究中的每一个都包括阳性（吗啡15和30 mg）和阴性（安慰剂）控制条件。将收集一系列广泛的生理，主观，观察者评价和精神运动绩效指标，以评估戒断抑制时的安全性，耐受性和功效。据我们所知，这些研究是创新性和意义的，因为它们是第一个研究CB1激动剂作为治疗人类阿片类药物依赖性的潜在药物疗法的功效，并将产生有关CB1和阿片类系统相互作用的新数据。此外，他们将提供关键的数据，以指导药物和剂量选择以后的研究，旨在检查其用于治疗阿片类药物依赖性的潜在疗效，以进行维持，预防复发，卧床排毒和/或作为启动阿片类拮抗剂治疗的过渡剂。