TYROSINE FOR METHAMPHETAMINE DEPENDENCE

描述：(申请人摘要) 美国对甲基苯丙胺(MA)的依赖正在迅速扩大， 回顾1950年S和1960年S疫情传播的早期阶段。 超越与上瘾直接相关的发病率和死亡率 鉴于艾滋病毒的流行，MA特别令人关注，因为它 是静脉注射的，因为它能提高性欲。 儿茶酚胺受体在慢性MA使用中的增殖及其相似性 MA退出和严重抑郁症之间的关系早已为人所知，但 已经用最小的努力来确定药物治疗是否可以 帮助实现对MA的戒除。酪氨酸是饮食的前体 对儿茶酚胺，在其小规模试验中取得了积极的结果 抗抑郁功效，完全阻断去甲肾上腺素的消耗 MA对动物的影响，并减少MA在动物中的自我给药。 这项申请提出了一个12周的双盲安慰剂对照试验 酪氨酸减少MA用量的临床试验 从属对象。100例符合DSM-IV诊断的MA患者 依赖关系将被随机分配给接受酪氨酸、2克或 安慰剂，每天三次。受试者将接受三次药物治疗 4个月；随访评估将在4个月进行。研究用药 将增加强化门诊药物治疗。这项研究将是 在戒毒、康复和善后方案中进行 海特·阿什伯里免费诊所，一家以社区为基础的非营利性诊所 在加利福尼亚州旧金山。在完成基线措施后，受试者 将每周进行评估，以确定他们是否符合研究要求 药物，以确定其使用MA和其他药物，以完成 评级量表，以获得尿样，并分配他们下周的 药物供应。数据收集工具将包括 成瘾严重指数、症状自评量表、贝克抑郁 清单，艾滋病行为的风险，以及治疗服务审查。 主要疗效指标为：使用MA的天数， 持续禁欲和治疗保留。预先计划的分析将 用生存分析和方差分析比较酪氨酸和 研究药物相互作用对安慰剂和性别的影响。

DESCRIPTION: (Applicant's Abstract) Methamphetamine (MA) dependence is expanding rapidly in the United States, recapitulating early phases of epidemic spread in the 1950's and 1960's. Beyond the morbidity and mortality directly associated with addictive disease, MA is of particular concern in light of the HIV epidemic because it is administered intravenously and because it increases libido. Catecholamine receptor proliferation in chronic MA use, and similarities between MA withdrawal and major depression, have long been known, yet minimal effort has been applied to determine whether pharmacotherapy may be of help in achieving abstinence from MA. Tyrosine is the dietary precursor to catecholamines, has yielded positive results in small trials of its antidepressant efficacy, completely blocks the norepinephrine depleting effects of MA in animals, and reduces MA self-administration in animals. This application proposes a 12 week, double-blind, placebo-controlled clinical trial to test the efficacy of tyrosine in reducing MA use in MA dependent subjects. One hundred subjects with DSM-IV diagnoses of MA dependence will be randomly assigned to receive either tyrosine, 2 grams, or placebo, three times daily. Subjects will receive medication for three months; follow-up evaluation will be conducted at month 4. Study medication will be added to intensive outpatient drug treatment. The study will be conducted at the Drug Detoxification, Rehabilitation and Aftercare Program of the Haight Ashbury Free Clinics, a community based, not-for-profit clinic in San Francisco, CA. Following completion of baseline measures, subjects will be assessed weekly to determine their compliance with study medications, to ascertain their use of MA and other drugs, to complete rating scales, to obtain a urine specimen, and to dispense their next week's supply of medication. Data collection instruments will include the Addiction Severity Index, the Symptom Checklist-90, the Beck Depression Inventory, the Risk for AIDS Behaviors, and the Treatment Services Review. Primary efficacy measures are: days of MA use, continuous abstinence, and treatment retention. Pre-planned analyses will use survival analyses and analysis of variance to compare tyrosine and placebo and gender by study drug interaction.