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: 7512126
• 负责人: Michael E Saladin
• 金额: $ 21.84万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7512126
• 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; Condition; Consensus; Cues; Development; Disruption; Dose; Double-Blind Method; Drug abuse; Drug usage; Elements; Fright; 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; Public Health; Randomized; Research; Research Personnel; Retrieval; Role; Schedule; Skin; South Carolina; Stimulus; Substance Abuse, Other; Substance Use Disorder; Support of Research; Symptoms; System; Testing; Therapeutic; Thinking; Translational Research; Translations; Treatment outcome; Universities; Week; Woman; addiction; adrenergic; base; classical conditioning; clinical application; concept; conditioning; craving; day; desire; drug craving; follow-up; improved; innovation; memory process; men; novel; novel strategies; preclinical study; preference; prevent; psychosocial; 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）：越来越多的共识认为，通过整合心理社会和药物干预措施可以改善药物滥用障碍的治疗结果。本提案将评估β-受体阻滞剂普萘洛尔破坏可卡因线索诱发的渴望和反应性的能力。支持这项研究的理由来自于临床前研究表明β受体阻滞剂可以破坏基于恐惧的联想学习的记忆再巩固过程，以及临床研究表明β受体阻滞剂与基于暴露的治疗相结合可以减轻创伤后应激障碍（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β受体阻滞剂可能会改变与食欲药物相关的调节有关的记忆再巩固过程。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验证研究，因此拟议的研究代表了第一个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引起的假定记忆过程的影响接触。该提案的具体目的是检查在可卡因线索暴露的检索阶段后立即施用的普萘洛尔与安慰剂相比，对可卡因线索暴露的后续测试阶段中发生的渴望和生理反应的影响。我们假设，与接受安慰剂治疗的可卡因依赖 (CD) 个体相比，接受普萘洛尔治疗的 CD 个体在测试过程中的渴望和生理唤醒会减少。我们还希望在测试过程中发现的任何组间差异将在 1 周的随访中得以保留。 52 名 CD 男性和女性将被随机分配，在连续几天安排的两次可卡因提示暴露疗程中的第一次疗程后立即接受急性剂量的 40 毫克速释普萘洛尔或安慰剂。在为期两天的测试期间，参与者将留在南卡罗来纳医科大学的普通临床研究中心（GCRC），以防止吸毒。药物将以双盲方式进行。所有参与者将在 GCRC 住院一周后返回接受后续提示暴露课程。将在所有提示暴露会话之前、期间和之后测量渴望和生理反应性。这项研究的令人鼓舞的结果可能会导致一项对照治疗试验，其中战略性普萘洛尔给药将作为多成分线索暴露干预的一个要素。可以想象，普萘洛尔可能成为几种新型有效的药物治疗辅助剂之一，可增强现有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）所取得的治疗效果。与 NIDA 的使命一致，该项目的长期目标是通过确定治疗开发/改进的创新和新颖方法来改善药物滥用障碍的治疗。公共健康相关性：这项创新的转化研究工作将采用既定的线索反应性/暴露方法来评估未经测试且可能有前途的辅助药物疗法对最棘手的物质使用障碍之一可卡因依赖的治疗潜力。希望这一概念验证研究的结果将导致药物治疗元件的开发，该元件将增强基于暴露的可卡因依赖治疗的结果，并可推广到涉及其他滥用物质的成瘾问题。