Alprazolam Abuse Liability in Post Traumatic Stress Disorder (PTSD)

描述（由申请人提供）：这是一名初级临床研究员对一项探索性R21研究申请的第二次修订。这项研究的目的是确定在何种情况下，我们可以证明应激诱导的阿普唑仑自我给药在创伤后应激障碍（PTSD）患者中的作用。创伤后应激障碍的特征是在一次危及生命的经历后出现慢性焦虑和痛苦。同时发生药物滥用和依赖的频率也很高，特别是酒精和包括苯二氮卓类药物在内的其他镇静剂。我们有强有力的初步数据表明，合并酒精依赖的创伤后应激障碍患者在听取对其创伤经历的个性化描述时，焦虑感会增加。他们还报告说，他们更喜欢喝酒，愿意花钱买酒；然而，他们没有显示出对苯二氮卓类药物阿普唑仑的偏好增加。目前的应用程序探索测试更高剂量的阿普唑仑比以前的测试和利用实验条件，我们相信更有可能揭示增加阿普唑仑的偏好。具体目的是证明应激诱导的阿普唑仑自我给药在PTSD中对实验诱导的创伤性焦虑的反应。我们假设，与中性对照条件相比，诱导创伤相关焦虑会导致阿普唑仑偏好的更大增加。使用我们之前在其他研究中应用的程序，诊断为创伤后应激障碍和酒精依赖的患者将被招募参加一项需要住院7天的研究。在熟悉日之后，受试者将在听取他们的创伤描述或个性化的、无刺激性的情况描述后，每天接受四次双盲、字母编码的阿普唑仑或安慰剂胶囊的“抽样”暴露。然后，在研究的最后两天，受试者将再次被暴露在创伤性和非唤醒性的场景中，并被要求评价他们对字母编码药物的偏好。偏好将通过要求受试者在字母编码的药物和不同数量的钱之间做出选择来衡量。受试者从金钱选择到药物选择的价格将被用来衡量他们对药物的偏好。如果受试者在创伤描述后比安慰剂花更多的钱，如果他们在创伤描述后比在非唤醒场景描述后花更多的钱，我们的假设将得到支持。这项研究将帮助我们理解一些情感创伤的人滥用药物的原因，包括用于控制焦虑的处方药。这将有助于指导医生安全地使用药物来平息创伤受害者的焦虑，而不会导致药物滥用。

DESCRIPTION (provided by applicant): This is the second revision of application for an exploratory R21 study by a junior clinician-investigator. The goal of the study is to identify conditions under which we can demonstrate stress-induced alprazolam self-administration in patients with post-traumatic stress disorder (PTSD). PTSD is characterized by chronic anxiety and distress following a life-threatening experience. There also is a high frequency of occurrence of comorbid substance abuse and dependence, particularly with alcohol and other sedatives including benzodiazepines. We have strong preliminary data showing that PTSD patients with comorbid alcohol dependence report increased anxiety when listening to a personalized description of their traumatic experience. They also report an increased preference for alcohol and a willingness to spend money to obtain alcohol; however, they do not show an increase in preference for the benzodiazepine, alprazolam. The current application explores the testing of higher doses of alprazolam than previously tested and utilizes experimental conditions we believe are more likely to reveal increased alprazolam preference. The Specific Aim is to demonstrate stress-induced alprazolam self-administration in PTSD in response to experimentally- induced traumatic anxiety. We hypothesize that inducing trauma-related anxiety will result in larger increases in alprazolam preference in comparison to neutral control conditions. Using procedures we have applied previously in other studies, patients diagnosed with both PTSD and alcohol dependence will be recruited for a research study requiring hospitalization for seven days. Following a familiarization day, subjects will receive four daily "Sampling" exposures to double-blind, letter-coded alprazolam or placebo capsules after listening to descriptions of their trauma or descriptions of a personalized, non-arousing situation. Then, on the last two days of the study, subjects will again be re-exposed to the traumatic and non-arousing scenes and be asked to rate their preference for the letter-coded drugs. Preference will be measured by asking subjects to make choices between letter- coded drugs and various amounts of money. The price at which subjects switch their choices from money to drug will be used as a measure of their preference for drug. Our hypothesis will be supported if subjects spend more for alprazolam than placebo following trauma descriptions and if they spend more for alprazolam after trauma descriptions than after descriptions of non-arousing scenes. This study will help us understand the reasons some emotionally traumatized people abuse drugs, including prescription drugs used to control anxiety. This will help guide doctors in safely using medications to calm the anxiety of trauma victims without leading to drug abuse.