Evaluation Of Treatments Of Opioid & Cocaine Dependence

本节继续调查药物滥用的药物和行为治疗，并探讨治疗的组合。我们已经证明了行为干预的有效性（可卡因阴性尿样的强化）在大的市中心静脉注射多种药物滥用者的样本，我们将继续评估应用治疗的最佳方法。我们已经完成了一项研究的后续阶段，以解决如何假设的美沙酮维持诊所可以最好地分配其资源（药理学和非药理学），以减少海洛因和可卡因滥用，如果诊所要建立基于凭证的应急管理。使用了一种新的应急措施，加强了对任何一种药物的戒断，同时使同时戒断两种药物的戒断值加倍。可用代金券的总价值不超过以前针对单一药物的试验中使用的金额;相反，金额是多少？分裂？可卡因和鸦片的区别武器可以用来交换货物和服务。该研究采用2x 3设计，其中252名美沙酮维持门诊患者被随机分配到美沙酮剂量条件（70或100 mg/天，双盲）和凭证条件（取决于可卡因阴性尿液;？分开？或无条件[与尿检结果无关的凭单]）。研究持续27周（基线评估，5周;干预，12周;维持，10周），随访1年。尿液结果表明，剂量增加减少了海洛因的使用，但没有可卡因的使用;虽然这一结果是预期的，但本研究提供了迄今为止更明确的证据之一。拆分应急对同时戒除海洛因和可卡因的影响是适度的：拆分100 mg组比对照组（NC 70 mg）实现了更长的同时阴性持续时间，尽管许多参与者从未提供过甚至一个同时阴性。若要分开使用应急药物，以同时促进戒除可卡因和海洛因，似乎需要较高剂量的美沙酮，但并不完全足够;可能还需要增加医疗券的总金额。正在对随访数据进行分析。在一项后续研究中，我们目前正在评估高剂量美沙酮结合应急管理，以最大限度地同时戒断海洛因和可卡因。我们纳入了额外的医疗状况措施，以检查美沙酮维持治疗的潜在健康益处。 为了控制成本和技术转让，我们进行了两项试点研究，其中的奖励是抽奖而不是代金券，因为其他人的工作表明，基于抽奖的加固程序可以由社区制造商和商人的捐款资助。最初的试点研究表明，抽签程序在研究参与者中产生了极大的热情，在技术上比代金券计划更容易。在进一步的试点研究中，我们正在比较两种不同的彩票程序和两种不同的强化密度。我们可以将抽签程序纳入一项更雄心勃勃的研究中，在这项研究中，各种低成本或无成本的激励措施都针对减少药物使用以外的广泛行为变化。 我们目前研究的另一个重点来自实验室动物数据，这些数据表明，压力诱导的可卡因寻求和/或海洛因寻求的恢复可以用α-肾上腺素能激动剂可乐定预防，而线索诱导的这种药物寻求的恢复可以用CB 1拮抗剂利莫那班预防。我们已经完成了一项剂量范围研究，以确定如何洛非西定可以最安全地与美沙酮在人类共同管理。我们目前正在进行一项研究，在这项研究中，美沙酮维持门诊患者全天携带手持电脑，以提供对海洛因和可卡因的渴望，药物使用的失误以及推定的失误率的实时数据。一旦我们证明了这种形式的数据收集在我们的人群中的可行性，我们将能够进行临床试验，其中凭证发起的禁欲之后是专门用于预防压力诱导或线索诱导复发的药物的维持。

The section continues to investigate pharmacological and behavioral treatments of substance abuse and to explore combinations of treatments. We have already demonstrated the effectiveness of behavioral interventions (reinforcement for cocaine-negative urine samples) in large inner-city samples of intravenous polydrug abusers, and we continue to evaluate the best ways to apply the treatment. We have completed the follow-up phase of a study to address how a hypothetical methadone-maintenance clinic could best allocate its resources (both pharmacological and nonpharmacological) to reduce both heroin and cocaine abuse, if the clinic were to institute voucher-based contingency management. A novel contingency was used that reinforced abstinence from either drug while doubling reinforcer values for simultaneous abstinence from both. The total value of available vouchers was no greater than the amount used in previous trials targeting a single drug; instead, the amount was ?split? between cocaine and opiates. Vouchers were exchangeable for goods and services. The study used a 2x3 design in which 252 methadone-maintained outpatients were randomly assigned to a methadone dose condition (70 or 100 mg/day, double blind) and a voucher condition (contingent on cocaine-negative urines; ?split?; or noncontingent [vouchers given independent of urine test results]). The study lasted 27 weeks (Baseline assessment, 5 weeks; Intervention, 12 weeks; Maintenance, 10 weeks) with follow-up for 1 year. Urine results suggest that the dose increase reduced heroin use, but not cocaine use; though this result was expected, the present study provided one of the more unambiguous demonstrations to date. The effect of the split contingency on simultaneous abstinence from heroin and cocaine was modest: the Split 100mg group achieved a longer duration of simultaneous negatives than the control (NC 70mg) group, though many participants never provided even one simultaneous negative. For a split contingency to promote abstinence from cocaine and heroin simultaneously, a relatively high dose of methadone appears necessary but not entirely sufficient; an increase in overall voucher amount may also be required. Analyses of the follow-up data are ongoing. In a follow-up study, we are currently evaluating high-dose methadone combined with contingency management to maximize simultaneous abstinence from heroin and cocaine. We have included additional measures of medical status to examine potential health benefits of methadone maintenance. In the interest of cost containment and technology transfer, we conducted two pilot studies in which the reinforcers are lottery draws rather than vouchers, since work by others has shown that a lottery-based reinforcement procedure can be funded by donations from community manufacturers and merchants. The initial pilot study indicated that the lottery procedure generated substantial enthusiasm among study participants and is technically easier than the voucher program. In a further ongoing pilot study, we are comparing two different lottery procedures and two different densities of reinforcement. We may incorporate the lottery procedure into a more ambitious study in which a variety of low- or no-cost incentives are targeted toward a broad range of behavioral changes beyond reductions in drug use. Another current focus of our research derives from laboratory-animal data showing that stress-induced reinstatement of cocaine-seeking and/or heroin-seeking can be prevented with the alpha-adrenergic agonist clonidine, while cue-induced reinstatement of such drug-seeking can be prevented with the CB1 antagonist rimonabant. We have completed a dose-ranging study to determine how lofexidine can most safely be co-administered with methadone in humans. We are currently conducting a study in which methadone-maintained outpatients carry handheld computers throughout the day to provide real-time data on cravings for heroin and cocaine, lapses to drug use, and base rates of putative lapse precipitants. Once we have demonstrated the feasibility of this form of data collection in our population, we will be able to conduct clinical trials in which voucher-initiated abstinence is followed by maintenance on a medication specifically intended to prevent stress-induced or cue-induced relapse.