Decision-Making and Episodic Memory in Trajectories to Cannabis Addiction

描述（由申请人提供）：在美国，对大麻上瘾的人比对任何其他非法药物上瘾的人都多，大麻的使用率正在上升，同时青少年中不赞成使用大麻和认为大麻有害的人也在下降。青春期前额叶皮层的重要成熟变化可能使青少年比成年人更容易受到大麻的不良影响。事实上，研究表明，重度大麻使用者的记忆表现和决策能力受损，其中大多数人在青春期开始使用大麻。然而，从最初的实验到大麻成瘾的发展，决策和记忆是如何受到影响的，我们知之甚少。此外，在重度大麻使用者中观察到的决策障碍是否由于大麻对大脑功能的有害影响，或者它们是否可能是大麻成瘾发展的一个先行风险因素，科学文献中存在争议。本提案的主要目标是确定：a)决策是否是大麻成瘾的先行风险因素；b)在不同的大麻使用轨迹中，决策和情景记忆发生了什么变化。参与者将是400名14至16岁的青少年，他们中的大多数人将尝试使用大麻，但尚未上瘾。在两年内，将每12个月对他们的决策和情景记忆进行一次评估，每6个月对他们的药物使用和大麻成瘾症状进行一次评估。假设基线时较差的决策与随访期间发生大麻成瘾的风险增加有关。随着时间的推移，大麻消费量增加的人，其情景记忆的恶化程度将高于其他（未增加或停止）大麻使用轨迹的人。相比之下，决策在所有轨迹上几乎没有变化，这与大麻成瘾的前提而非后果的假设作用是一致的。假设在随访期间观察到的决策能力下降与大麻成瘾的严重程度增加有关（即，更强迫性的使用和更多的负面后果），但与大麻终生累积使用量的关系不大。记忆性能则相反。更多地了解神经心理功能和大麻成瘾之间的联系，将有助于澄清与它们的时间关联有关的理论模型。在临床上，了解更多关于成瘾的神经心理学预测因素和后遗症将有助于我们制定更有针对性和量身定制的干预和预防计划，与NIDA的目标一致。重要的是，我们的发现将澄清决策是大麻使用和成瘾的先行风险因素，是使用的后果，还是两者兼而有之。

DESCRIPTION (provided by applicant): More people in the United States are addicted to cannabis than to any other illicit drug, and prevalence of its use is rising, accompanied by a decline in the disapproval of its use and its perceived harm among adolescents. Important maturational changes in prefrontal cortex during adolescence may make youth more vulnerable than adults to adverse effects from cannabis. Indeed, research shows impairments in memory performance and decision-making abilities of heavy cannabis users, most of whom initiate use during adolescence. However, little is known about how decision-making and memory are affected across the trajectory from initial experimentation to development of cannabis addiction. Furthermore, there is controversy in the scientific literature on whether the impairments in decision-making observed among heavy cannabis users are due to the harmful effects of cannabis on brain functioning, or whether they may be an antecedent risk factor for the development of cannabis addiction. The principal goals of this proposal are to determine whether: a) decision-making is an antecedent risk factor for cannabis addiction; and b) what changes occur in decision-making and episodic memory along different cannabis use trajectories. Participants will be 400 youth ages 14 to 16 at baseline, most of whom will have experimented with cannabis, but have yet to develop addiction. Over two years, their performance will be assessed on measures of decision-making and episodic memory every 12 months and on their substance use and symptoms of cannabis addiction every 6 months. Poorer decision-making at baseline is hypothesized to be associated with increased risk of developing cannabis addiction during follow-up. Those who escalate in their cannabis consumption over time will show greater deterioration in their episodic memory than observed in other (non-escalating or desisting) cannabis use trajectories. In contrast, decision-making will show little change across all trajectories, consistent with its hypothesized role as an antecedent, rather than a consequence, of cannabis addiction. Any declines observed in decision-making during follow-up are hypothesized to be associated with increased severity of cannabis addiction (i.e., more compulsive use and more negative consequences), but less so with cumulative lifetime amounts of cannabis use. The opposite pattern is expected with memory performances. Understanding more about the links between neuropsychological functions and cannabis addiction will help clarify theoretical models pertaining to their temporal association. Clinically, knowing more about neuropsychological predictors and sequelae of addiction will help us to develop more targeted and tailored interventions and prevention programs, consistent with NIDA's goals. Importantly, our findings will clarify whether decision-making is an antecedent risk factor for cannabis use and addiction, a consequence of use, or both. PUBLIC HEALTH RELEVANCE: People who use marijuana sometimes show impairments in their memory and in the way that their brain makes good decisions. This study will help to determine if problems with decision-making are one of the reasons that some teens become addicted to marijuana. It will also describe how progressing from experimental marijuana use to addiction affects memory and decision-making. Knowing more about predictors of marijuana addiction will help us to develop specific interventions and prevention programs for teens.