Buspirone, Stress, and Attentional Bias to Marijuana Cues

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<18岁。在美国，海洛因占非法物质使用障碍（SUD）的60%，是非法物质中美国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现象与药物寻求和复发有关。注意偏差是线索反应性的可测量的组成部分，并且可以在操作上被定义为差异注意（例如，反应时间差）对药物相关刺激与中性刺激的反应。这种现象已经在SUD人群中的许多类别的滥用药物中得到证实，包括酒精，尼古丁，兴奋剂，阿片类药物，以及重要的大麻。线索反应和注意力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吸的一个有据可查的预测因素。治疗干预，减弱注意力偏向大麻线索是一个潜在的重要组成部分，在大麻SUD的治疗。由于与压力的关系，同时解决压力和注意力偏差的干预可能是唯一有效的。目前，很少有药物治疗存在大麻SUD，目前还没有已知的解决注意力偏见大麻线索。本申请将探讨潜在的抗焦虑丁螺环酮修改注意力偏差和压力。丁螺环酮是一种独特的化合物，其特征在于可调节5-HT 1A和D3受体。重要的是，已知5-HT 1A受体在应激相关焦虑中起关键作用，并且临床前工作表明D3拮抗剂显著降低对许多滥用药物的线索反应性。这种效应的组合表明，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，本申请试图检查长期丁螺环酮给药对大麻SUD中的注意力偏差和压力/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学和经过充分验证的压力和焦虑测量，我们将检查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。!

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. !