Brain-Behavior Markers of Reward and Cannabis Abuse Risk in Young Adults

这项研究的首要目标是获得必要的培训，以更好地了解神经系统。 大麻的奖励和强化特性的潜在机制拟议的研究旨在 表征主观奖励反应和神经奖励处理的个体差异，以delta-9- 四氢大麻酚（THC），大麻中的主要精神活性成分，在健康的年轻人中， 可能有滥用大麻的风险个人对THC的主观反应不同， 报告毒品奖励措施。很少有研究探讨THC如何影响大脑奖励回路， 人类随着大麻在美国变得越来越容易获得， 与有问题的使用有关的结果。为了最大限度地减少增加使用的不利影响，关键是要确定 这些风险因素使某些人更容易受到大麻使用问题的影响。其中一个因素是 药物使用和滥用的风险是大脑奖励回路的敏感性和功能，特别是在应对 早期吸毒初步证据表明，THC激活大脑奖励回路，特别是腹侧 纹状体（VS）和内侧前额叶皮层（mPFC），这可能与奖励的个体差异有关 大麻的影响。到目前为止，人们对奖赏、强化和刺激的神经机制知之甚少。 大麻的特性以及这些特性如何影响对大麻的主观奖励反应的个体差异， THC，药物滥用责任的标志。在当前的K23应用程序中，我建议检查情感奖励 确定可能有使用和滥用大麻风险的个人的机制。在研究报告中，80 健康的年轻人（18-25岁），报告偶尔使用大麻（生活中≥ 10次，但每周使用≤ 1次）， 进行两次双盲、受试者内、药物激发访视（安慰剂，7.5mg THC）。在这些访问期间， 参与者将在脑电图（EEG）和功能测试期间完成奖励的神经测量。 磁共振成像（fMRI），以及药物奖励的主观措施。通过结合神经和 行为措施与急性药物管理设计，我将（a）确定THC是否增强大脑 奖励反应性;（B）检查THC诱导的神经奖励反应性的改变是否与主观的 奖赏反应;以及（c）确定“基线”神经奖赏反应性（即，安慰剂治疗期间） 预测对THC的主观奖励反应。这项研究同时提供了一个极好的机会， 在几个关键领域接受导师指导的实践培训，以完善我的知识和技能- 集.具体而言，拟议的培训计划将侧重于四个新领域：1）脑电图，2）成瘾和药物 管理研究，3）生物统计学，和4）专业发展。这项研究，加上完成 的培训目标将启动我的独立职业生涯在翻译情感神经科学的药物 滥用，并将为未来专注于行为大脑风险的高影响力R 01研究奠定基础 物质使用障碍的表型和干预目标，包括大麻使用障碍。

The overarching goal of the study is to obtain the necessary training to better understand the neural mechanisms underlying the rewarding, reinforcing properties of cannabis. The proposed study aims to characterize individual differences in subjective reward response and neural reward processing to delta-9- tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, among healthy young adults who may be at-risk for problematic cannabis use. Individuals differ in their subjective response to THC on self- report measures of drug reward. Few studies have examined how THC impacts brain reward circuitry in humans. As cannabis becomes increasingly available in the U.S. there is serious concern about negative outcomes related to problematic use. To minimize the adverse impact of increased use, it is critical to identify risk factors that make certain individuals more vulnerable to problematic cannabis use. One factor implicated in risk for drug use and abuse is the sensitivity and function of brain reward circuitry, especially in response to early drug use. Preliminary evidence indicates that THC activates brain reward circuitry, especially the ventral striatum (VS) and medial prefrontal cortex (mPFC), which might be linked to individual differences in rewarding effects of cannabis. To date, little is known about the neural mechanisms underlying the rewarding, reinforcing properties of cannabis and how these may contribute to individual differences in subjective reward response to THC, a marker of drug abuse liability. In the current K23 application, I propose to examine the affective reward mechanisms that identify individuals who may be at risk for cannabis use and abuse. In the proposed study, 80 healthy young adults (aged 18-25), who report occasional cannabis use (≥10x in life, but use ≤1x a week), will undergo two double-blind, within-subject, drug-challenge visits (placebo, 7.5mg THC). During these visits, participants will complete neural measures of reward during electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), as well as subjective measures of drug reward. By combining neural and behavioral measures with an acute drug administration design, I will (a) determine if THC enhances brain reward reactivity; (b) examine if THC-induced alterations in neural reward reactivity are related to subjective reward response; and (c) determine if “baseline” neural reward reactivity (i.e., during the placebo session) predicts subjective reward response to THC. This study concurrently provides an excellent opportunity to receive mentor-directed, hands-on training in several key areas necessary to refine my knowledge and skill- sets. Specifically, the proposed training plan will focus on four new domains: 1) EEG, 2) Addiction and drug administration studies, 3) Biostatistics, and 4) Professional development. This study, coupled with completion of the training goals will launch my independent career in the translational affective neuroscience of drug abuse and will lay the foundation for future, high impact R01 studies focused on behavioral-brain risk phenotypes and intervention targets for Substance Use Disorders, including Cannabis Use Disorder.