Memantine-enhanced Buprenorphine Treatment for Opioid-dependent Young Adults

描述（由申请人提供）：海洛因使用和处方类阿片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，因为他们目前使用非法药物的比例很高（19.7%）。阿片类药物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类药物依赖的最常见治疗方法，但强有力的证据表明，有益的效果主要是在替代期，而不是在治疗后的时期，因为复发和回到以前的药物使用模式的风险很高。越来越多的临床前证据有力地表明，非竞争性n -甲基- d -天冬氨酸（NMDA）受体拮抗剂（如memantine）与阿片受体激动剂共同施用可能有助于阿片受体激动剂作用的可持续性，同时在同一动物中降低对短效阿片增强作用的致敏性。本临床试验的目的是研究与单用丁丙诺啡相比，美刚（15mg & 30mg）联合丁丙诺啡在治疗期间和治疗后改善治疗效果的程度。这项为期13周的临床试验将为60名年龄在18-25岁的阿片类药物依赖患者提供治疗，他们将随机分为三种治疗条件：(1)美金刚15mg/天+丁丙诺啡；(2)美金刚30mg/天+丁丙诺啡；(3)安慰剂+丁丙诺啡。该研究将分为诱导、维持和终止三个阶段。与阿片类药物使用相关的基线测量将在参与治疗的第一周确定。受试者的随机化将根据阿片类药物依赖的严重程度来平衡。所有参与者将参加每周一次的小组治疗。主要结局将是每周自我报告的阿片类药物使用率和丁丙诺啡治疗期间的尿液毒理学；自我报告使用阿片类药物的早期复发率和尿液毒理学；以及副作用和不良事件的发生率。本申请中提出的研究具有创新性，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。

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.