Dronabinol naltrexone treatment for opioid dependence

描述（由申请人提供）：阿片类药物滥用和依赖仍然是美国的一个重大问题；特别是，处方类阿片的非医疗使用率在过去几年中有所增加。主要的治疗方法包括解毒，然后是心理治疗或激动剂维持。不幸的是，仅使用解毒方法的复发率很高，基于激动剂的治疗有一些局限性，并且仍然存在争议。另一种药物策略，纳曲酮维持，有明显的优势。然而，由于难以开始治疗和治疗前几周耐受性差，其使用受到限制。针对阿片类药物戒断和纳曲酮诱导相关的厌恶症状的药理学策略可以显著提高其早期耐受性，允许扩大临床使用，并改善阿片类药物依赖治疗的长期结果。临床前和初步临床研究表明，大麻素受体激动剂屈大麻酚可能有效提高纳曲酮诱导的耐受性。屈大麻酚可减轻纳曲酮诱导与阿片类药物急性和残留戒断相一致的体征和症状，如失眠、神经痛、痛觉过敏、胃肠道不适、食欲不振、焦虑、易怒、应激反应性增高、烦躁不安和快感缺乏。我们的非对照观察表明，在纳曲酮治疗的阿片类药物依赖患者中，适度使用大麻与改善治疗保留有关。这项为期三年的研究的目的是测试屈大麻酚作为阿片类药物依赖个体纳曲酮维持治疗的辅助治疗的有效性。我们建议在阿片类药物依赖个体中进行一项随机、双盲、安慰剂对照、平行组、为期8周的复发预防研究。参与者将被随机分为两组：(1)纳曲酮+安慰剂和(2)纳曲酮+屈大麻酚20mg bid （N=40 /组）。治疗将在门诊进行，除了住院戒毒的初始阶段，持续8天。长效、可注射的纳曲酮380毫克（Vivitrol）将每月服用一次（总共注射两次），而屈大麻酚或安慰剂将每天服用。此外，患者将接受心理社会干预，包括动机访谈和认知行为复发预防治疗。主要结局指标是研究结束时治疗的保留情况。主要目的是测试屈大麻酚在解毒和纳曲酮治疗前两个月减少消耗的功效。

DESCRIPTION (provided by applicant): Opioid abuse and dependence continues to be a significant problem in the US; in particular, rates of non-medical use of prescription opioids have increased in the past several years. The main treatment approaches include detoxification followed by psychosocial treatment or agonist maintenance. Unfortunately, rates of relapse are high with detoxification only approaches, and agonist-based treatments have several limitations and remain controversial. The alternative pharmacological strategy, naltrexone maintenance, has clear advantages. However, its use has been limited due to difficulties in initiating treatment and poor tolerability during the first weeks of treatment. Pharmacological strategies targeting aversive symptoms associated with opioid withdrawal and naltrexone induction could significantly improve its early tolerability, permit expansion of clinical use, and improve long-term outcome of opioid dependence treatment. There is strong support, from preclinical and preliminary clinical studies suggesting that dronabinol, a cannabinoid receptor agonist, may be effective in improving tolerability of naltrexone induction. Dronabinol may diminish signs and symptoms associated with naltrexone induction consistent with acute and residual opioid withdrawal, such as insomnia, anergia, hyperalgesia, GI distress, lack of appetite, anxiety, irritability, heightened stress reactivity, dysphoria, and anhedonia. Our uncontrolled observations suggest that among naltrexone-treated opioid dependent patients, moderate use of cannabis was associated with improved treatment retention. The goal of this three-year study is to test the efficacy of dronabinol as an adjunct to maintenance treatment with naltrexone in opioid-dependent individuals. We are proposing a randomized, double-blind, placebo controlled, parallel-groups, 8-week study of relapse prevention in opioid-dependent individuals. Participants will be randomized into one of two conditions: (1) Naltrexone + Placebo and (2) Naltrexone + dronabinol 20 mg bid (N=40 per group). Treatment will be delivered in an outpatient setting except for the initial phase of inpatient detoxification, lasting 8 days. A long-acting, injectable form of naltrexone 380 mg (Vivitrol) will be administered once per month (the total of two injections), while dronabinol or placebo will be taken daily. In addition, patients will receive a psychosocial intervention that will include elements of motivational interviewing and cognitive-behavioral relapse prevention therapy. Primary outcome measure will be retention in treatment by the end of the study. The primary aim is to test the efficacy of dronabinol in reducing attrition during detoxification and the first two months of naltrexone treatment. PUBLIC HEALTH RELEVANCE: Rates of opioid dependence have increased steadily over the past several years, mostly due to an increase in illicit use of prescription analgesics. The available treatments (agonist-based or therapy-only approaches) are not suitable for all patients and have limited effectiveness. Development of an improved antagonist based approach would open it up as a viable treatment alternative for a larger population of opioid dependent individuals.