Evaluation Of Treatments Of Opioid & Cocaine Dependence

本节继续调查药物滥用的药理学和行为治疗，并探索治疗的组合。我们已经在市内大量静脉注射多种药物滥用者的样本中证明了行为干预（加强可卡因阴性尿样）的有效性，我们将继续评估应用这种治疗的最佳方法。我们已经完成了一项研究的后续阶段，以解决假设的美沙酮维持诊所如何最好地分配其资源（药理学和非药理学），以减少海洛因和可卡因的滥用，如果诊所要建立基于凭证的应急管理。一种新的偶然性被用来加强戒断任何一种药物，同时加倍强化值同时戒断两种药物。可用代金券的总价值不大于以往针对单一药物的试验中使用的金额；相反，这笔钱被分成了两部分。介于可卡因和鸦片之间。代金券可以兑换商品和服务。该研究采用2x3设计，其中252名美沙酮维持的门诊患者被随机分配到美沙酮剂量组（70或100毫克/天，双盲）和代金券组（取决于可卡因阴性尿液；分裂；或非偶然[独立于尿检结果的代金券]）。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，剂量的增加减少了海洛因的使用，但没有减少可卡因的使用；虽然这一结果是预料之中的，但目前的研究提供了迄今为止更明确的证明之一。分裂偶发对同时戒断海洛因和可卡因的影响是温和的：分裂100毫克组比对照组（NC 70毫克）获得了更长的同时阴性持续时间，尽管许多参与者甚至从未提供过一次同时阴性。为了促进同时戒断可卡因和海洛因，相对高剂量的美沙酮似乎是必要的，但并不完全足够；也可能需要增加总代金券金额。对随访数据的分析正在进行中。在一项后续研究中，我们目前正在评估大剂量美沙酮联合应急管理，以最大限度地同时戒除海洛因和可卡因。我们纳入了额外的医疗状况测量来检查美沙酮维持的潜在健康益处。

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.