Buspirone, Stress, and Attentional Bias to Marijuana Cues

丁螺环酮、压力和对大麻线索的注意力偏差

• 批准号: 8580274
• 负责人: SCOTT D LANE
• 金额: $ 22.8万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8580274
• 关键词: Accounting; Address; Age; Agonist; Alcohols; Anti-Anxiety Agents; Anxiety; Attention; Attenuated; Buspirone; Cannabis; Chronic; Chronic stress; Clinical; Cues; Data; Disease; Drug Controls; Goals; Health; Human; Illicit Drugs; Individual; Intervention; Interview; Laboratories; Marijuana; Marijuana Abuse; Marijuana Smoking; Measurable; Measurement; Measures; Methodology; Neurotransmitters; Nicotine; Opiates; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Play; Population; Psychometrics; Public Health; Reaction Time; Relapse; Serotonin Receptor 5-HT1A; Stimulus; Stress; Substance Use Disorder; System; Therapeutic Intervention; Time; Work; acute stress; attenuation; base; cue reactivity; drug of abuse; pre-clinical; receptor

DESCRIPTION (provided by applicant): For nearly 40 years marijuana has remained the most widely used illicit drug in the US, with more than 50% of first-time users < age 18. Marijuana accounts for H 60% of illicit substance use disorders (SUD) in the US, bearing by percent the largest US public health burden among illicit substances. Across preclinical, human laboratory, and clinical interview data, there is compelling evidence that the phenomenon of cue reactivity is related to drug seeking and relapse. Attentional bias is a measurable component of cue reactivity, and can be operationally defined as differential attention (e.g., reaction time difference) towards drug-related stimuli vs. neutral stimuli. This phenomenon has been demonstrated in SUD populations across many classes of abused drugs, including alcohol, nicotine, stimulants, opiates, and - importantly - marijuana. Cue reactivity and attentional bias are exacerbated by acute and chronic stress and anxiety. Notably, stress is a well-documented predictor of marijuana abuse and marijuana relapse. Therapeutic interventions that attenuate attentional bias to marijuana cues are a potentially important component in the treatment of marijuana SUD. Due to the well-documented association with stress, an intervention that simultaneously addresses both stress and attentional bias could be uniquely efficacious. Currently, few pharmacotherapies exist for marijuana SUD, and none are presently known to address attentional bias to marijuana cues. This application will explore the potential of the anxiolytic buspirone to modify attentional bias and stress. Buspirone is a unique compound marked by modulation of both 5-HT1A and D3 receptors. Importantly, the 5-HT1A receptor is known to play a key role in stress- related anxiety, and preclinical work indicates that D3 antagonists significantly decrease cue reactivity to a number of abused drugs. This combination of effects suggests buspirone may be advantageous in targeting both stress and attentional bias as factors that contribute to problem marijuana use. Accordingly, this application seeks to examine the effects of chronic buspirone administration on attentional bias and stress/anxiety in marijuana SUD. Using laboratory-based methodologies sensitive to attentional bias towards marijuana cues and well validated measures of stress and anxiety, we will examine if buspirone' s unique mechanism of action will (a) produce an attenuation of attentional bias to marijuana cues, and (b) be most pronounced under conditions in which attentional bias is related to high levels of stress and anxiety. !

描述（由申请人提供）：近40年来，大麻一直是美国使用最广泛的非法药物，超过50%的首次使用者年龄小于18岁。大麻占美国非法药物使用障碍（SUD）的60%，是美国非法药物中最大的公共卫生负担。在临床前、人体实验室和临床访谈数据中，有令人信服的证据表明，线索反应性现象与药物寻求和复发有关。注意偏倚是线索反应性的一个可测量的组成部分，可操作性地定义为对药物相关刺激和中性刺激的不同注意（如反应时间差异）。这种现象在许多滥用药物（包括酒精、尼古丁、兴奋剂、阿片类药物和重要的大麻）的SUD人群中都得到了证明。提示反应和注意偏差会因急性和慢性压力和焦虑而加剧。值得注意的是，压力是大麻滥用和大麻复发的一个有充分证据的预测因素。减少对大麻线索的注意偏倚的治疗干预是大麻SUD治疗的潜在重要组成部分。由于与压力有充分的联系，同时解决压力和注意偏见的干预可能是唯一有效的。目前，针对大麻SUD的药物治疗方法很少，目前还没有一种已知的药物可以解决对大麻线索的注意偏见。本应用将探讨抗焦虑剂丁螺环酮的潜力，以改变注意偏差和压力。丁螺环酮是一种独特的化合物，以调节5-HT1A和D3受体为标志。重要的是，已知5-HT1A受体在压力相关焦虑中起关键作用，临床前工作表明D3拮抗剂显著降低了对一些滥用药物的提示反应性。这些综合效应表明，丁螺环酮可能有利于将压力和注意力偏差作为导致大麻使用问题的因素。因此，本应用旨在研究慢性丁螺环酮给药对大麻SUD患者注意偏差和压力/焦虑的影响。使用基于实验室的对大麻线索的注意偏向敏感的方法和经过验证的压力和焦虑的测量方法，我们将检验丁螺环酮的独特作用机制是否会(a)产生对大麻线索的注意偏向的衰减，以及(b)在注意偏向与高水平的压力和焦虑相关的条件下最明显。！