Treatment Implications of Beta-blockade Effects on Memory for Cocaine Craving

β-阻断对可卡因渴望记忆的影响的治疗意义

• 批准号: 7664331
• 负责人: Michael E Saladin
• 金额: $ 18.44万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7664331
• 关键词: Acute; Addictive Behavior; Adrenergic Agents; Adrenergic Antagonists; Animal Model; Animals; Anxiety Disorders; Arousal; Basic Science; Blood Pressure; Clinical; Clinical Research; Cocaine; Cocaine Dependence; Consensus; Cues; Development; Dose; Double-Blind Method; Drug abuse; Drug usage; Elements; Fright; Galvanic Skin Response; Goals; Heart Rate; Hour; Human; Individual; Inpatients; Intervention; Investigation; Laboratories; Laboratory Research; Lead; Learning; Maintenance; Marijuana; Marijuana Dependence; Measures; Medical; Memory; Methamphetamine; Methodology; Mission; Opiates; Outcome; Outcome Measure; Participant; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Placebos; Post-Traumatic Stress Disorders; Procedures; Process; Propranolol; Randomized; Research; Research Personnel; Research Support; Retrieval; Role; Schedule; South Carolina; Stimulus; Substance Use Disorder; Substance of Abuse; Symptoms; System; Testing; Therapeutic; Thinking; Translational Research; Translations; Treatment outcome; Universities; Woman; addiction; adrenergic; base; classical conditioning; clinical application; clinical practice; cocaine use; conditioning; craving; cue reactivity; drug craving; follow up assessment; follow-up; improved; innovation; memory process; men; novel; novel strategies; preclinical study; preference; prevent; primary outcome; psychosocial; public health relevance; response; therapy development; treatment trial

DESCRIPTION (provided by applicant): There is growing consensus that improved treatment outcomes for substance use disorders may be achieved through integration of psychosocial and pharmacologic interventions. The present proposal will assess the ability of the b-blocker propranolol to disrupt cocaine cue-induced craving and reactivity. Supporting rationale for the proposed study comes from both preclinical studies showing that b-blocking agents can disrupt memory reconsolidation processes underlying fear-based associative learning and from clinical studies suggesting that combining b-blocking agents with exposure-based therapy may reduce PTSD symptoms. Important support for the proposed research also comes from recent preclinical studies indicating that b-blocking agents may alter memory reconsolidation processes involved in appetitive drug-related conditioning. As these intriguing findings have yet to be extended to a human proof-of-concept study with potential clinical applications, the proposed study represents the first translational human laboratory research effort to evaluate the effects of propranolol administration on the putative memory processes elicited by cocaine cue exposure. The specific aim of this proposal is to examine the effects of propranolol vs. placebo, administered immediately after a retrieval session of cocaine cue exposure, on craving and physiological responses occurring during a subsequent test session of cocaine cue exposure. We hypothesize that, compared to cocaine-dependent (CD) individuals treated with placebo, propranolol-treated CD individuals will evidence less craving and physiological arousal during the test session. We also expect that any between-group differences identified during the test session will be maintained at 1-week follow-up. Fifty-two CD men and women will be randomly assigned to receive an acute dose of either 40 mg immediate-release propranolol or placebo immediately after the first of two cocaine-cue exposure sessions scheduled on consecutive days. Participants will remain in the Medical University of South Carolina's General Clinical Research Center (GCRC) throughout the two-day testing period to prevent drug use. Medications will be administered in a double-blind fashion. All participants will return one-week after their GCRC inpatient stay to undergo a follow-up cue exposure session. Craving and physiological reactivity will be measured prior to, during, and following all cue exposure sessions. Encouraging findings from this study could lead to a controlled treatment trial in which strategic propranolol administration would serve as an element of a multi-component cue exposure intervention. Conceivably, propranolol could become one of several novel and effective pharmacotherapy adjuncts that augment the treatment outcomes achieved with existing exposure-based interventions for drug abuse (e.g., methamphetamine, marijuana and opiates). Consistent with NIDA's mission, the long-term goal of this project is to improve substance use disorders treatment through the identification of innovative and novel approaches to treatment development/refinement. PUBLIC HEALTH RELEVANCE: This innovative translational research endeavor will employ an established cue reactivity/exposure methodology to assess the therapeutic potential of an untested and potentially promising adjunctive pharmacotherapy for one of the most intractable substance use disorders, cocaine dependence. It is hoped the results of this proof-of-concept investigation will lead to the development of a pharmacotherapeutic treatment element that will enhance the outcomes of exposure-based treatment for cocaine dependence and be generalizable to addiction problems involving other substances of abuse.

描述（由申请人提供）：越来越多的共识可以通过整合社会心理和药理干预措施来改善药物使用障碍的治疗结果。目前的建议将评估B型阻滞剂普萘洛尔破坏可卡因提示引起的渴望和反应性的能力。拟议研究的支持基本原理来自两项临床前研究表明，基于恐惧的联想学习的基础记忆可以破坏记忆的重新整合过程，并从临床研究中表明，将B阻断药与基于暴露的治疗相结合可以减少PTSD症状。对拟议研究的重要支持还来自最近的临床前研究，表明B阻塞剂可能会改变与食欲与药物相关条件涉及的重新溶解过程。由于这些有趣的发现尚未扩展到具有潜在临床应用的人类概念证明研究中，因此拟议的研究代表了首次转化人类实验室研究工作，旨在评估普萘洛尔给药对可卡因提示暴露引起的推定记忆过程的影响。该提案的具体目的是检查普萘洛尔与安慰剂的影响，在可卡因提示暴露的检索后立即给药，对可卡因提示暴露的随后测试期间发生的渴望和生理反应。我们假设，与接受安慰剂治疗的可卡因依赖性（CD）个体相比，经丙诺酚治疗的CD个体将证明在测试期间较少渴望和生理唤醒。我们还期望在测试期间确定的任何组间差异将在1周的随访中保持。在连续几天安排的两个可卡因 - 提示暴露会话中的第一次，将立即分配52名CD男女接收40毫克立即释放的普萘洛尔或安慰剂的急性剂量。在为防止吸毒的整个测试期间，参与者将留在南卡罗来纳州的一般临床研究中心（GCRC）。药物将以双盲方式服用。所有参与者的GCRC住院住院住院时间都将返回一周，以进行后续提示曝光会议。渴望和生理反应性将在所有提示暴露课程之前，之中和之后测量。这项研究的鼓励结果可能导致一项受控的治疗试验，在该试验中，战略性普萘洛尔给药将作为多组分提示暴露干预的元素。可以想象，普萘洛尔可以成为几种新型且有效的药物疗法辅助剂之一，可以通过现有的基于暴露的药物滥用干预措施（例如甲基苯丙胺，大麻和阿片类药物）来增加治疗结果。与NIDA的使命一致，该项目的长期目标是通过鉴定创新和新颖的治疗方法来改善药物使用障碍治疗。公共卫生相关性：这项创新的转化研究努力将采用已建立的提示反应性/暴露方法来评估未经测试且潜在有希望的辅助药物疗法的治疗潜力，用于最棘手的药物使用障碍之一可卡因依赖性。希望这项概念证明调查的结果将导致药物治疗元素的发展，该治疗元素将增强基于可卡因依赖性的基于暴露的治疗结果，并可以推广到涉及其他滥用物质的成瘾问题。