Memantine-enhanced Buprenorphine Treatment for Opioid-dependent Young Adults

描述(申请人提供)：海洛因使用和处方阿片类药物的非医疗使用仍然是一个公共卫生问题。年轻人是一个特别重要的群体，因为目前非法药物的使用率很高(19.7%)。阿片成瘾被认为是一种慢性和复发性疾病，虽然激动剂维持治疗仍然是阿片依赖最常见的治疗方法，但有益效果的有力证据大多发生在替代期间，但不是在复发和回到以前药物使用模式的高风险的治疗后期间。越来越多的临床前证据有力地表明，联合使用非竞争性的N-甲基-D-天冬氨酸(NMDA)受体拮抗剂，如美金刚和阿片激动剂，可以促进阿片激动剂对u-阿片受体作用的可持续性，同时，同一动物降低了对短效阿片类药物增强作用的敏感度。这项试点临床试验的目的是检验与丁丙诺啡联合使用美金刚(15毫克和30毫克)与丁丙诺啡单独使用相比，在治疗期间和治疗后将在多大程度上改善治疗结果。这项为期13周的临床试验将为60名18-25岁的阿片依赖患者提供治疗，他们将随机分为三种治疗条件：(1)美金刚15毫克/天+丁丙诺啡；(2)美金刚30毫克/天+丁丙诺啡；(3)安慰剂+丁丙诺啡。这项研究将分为诱导、维持和停用三个阶段。与阿片类药物使用有关的基线措施将在参与治疗的第一周确定。受试者的随机化将与阿片类药物依赖的严重程度相平衡。所有参与者都将参加每周一次的团体治疗。主要结果将是丁丙诺啡治疗期间自我报告的阿片类药物使用率和尿毒学；自我报告阿片类药物使用和尿毒理学的早期复发率；以及副作用和不良事件的比率。这项申请中提出的研究是创新的，因为美金刚增强的限时丁丙诺啡治疗可能成为许多年轻成人患者的有效替代短期干预措施。 与公共卫生有关：年轻人使用海洛因和非医疗使用处方阿片类药物的情况继续增加。阿片成瘾被认为是一种慢性和复发性疾病，通过长期维持激动剂治疗可以有效治疗。这种疗法对年轻人来说不一定是最好的治疗方法。这项研究正在评估丁丙诺啡加美金刚是否可以成为许多年轻成人患者的一种有效的短期干预措施，并改变这一人群目前的临床实践。

DESCRIPTION (provided by applicant): Heroin use and non-medical use of prescription opioid continue to be a Public Health problem. Young adults are an especially important group because of the high rates of current use of illicit drugs (19.7 %). Opiate addiction is considered a chronic and relapsing disorder, and while agonist maintenance treatment continues to be the most common treatment for opiate dependence, the strong evidence of beneficial effects are mostly during the substitution period, but not during the post-treatment period when relapse and risk of returning to previous patterns of drug use are high. Growing preclinical evidence strongly suggests that the co-administration of an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist such as memantine with an opioid agonist may facilitate the sustainability of the opioid agonist efficacy on the mu-opioid receptor while at the same time and same animal reduce the sensitization to short-acting opiates' reinforcing effects. The purpose of this pilot clinical trial is to examine to what extent the co-administration of memantine (15mg & 30mg) to buprenorphine will improve treatment outcomes during and after treatment compared to buprenorphine alone. This 13-week clinical trial will provide treatment for 60 opioid dependent patients, aged 18-25 years, who will be randomized to three treatment conditions: (1) memantine 15mg/day + buprenorphine; (2) memantine 30mg/day + buprenorphine and (3) placebo + buprenorphine. The study will have an induction, maintenance and discontinuation phases. Baseline measures related to opioid use will be determined during the first week of treatment participation. Subjects' randomization will be balanced by severity of opioid dependence. All participants will participate in weekly group therapy. The primary outcomes will be weekly rates of self-reported use of opiates and urine toxicology during treatment with buprenorphine; rates of early relapse by self-report use of opiates and urine toxicology; and rates of side-effects and adverse events. The research proposed in this application is innovative because memantine enhanced time-limited buprenorphine therapy may become an effective alternative short-term intervention for many young adult patients. PUBLIC HEALTH RELEVANCE: Heroin use and non-medical use of prescription opioids among young adults continues to increase. Opiate addiction is considered a chronic and relapsing disorder that is effectively treated with long-term maintenance on agonist therapy. This treatment may not necessarily be the best treatment for young adults. This study is evaluating if adding memantine to buprenorphine may become an effective alternative short-term intervention for many young adult patients, and change current clinical practice for this population.