A Transdisciplinary Approach to Cannabis Addiction

描述（由申请人提供）：本申请提议对大麻滥用和依赖的推定内表型和候选遗传变异进行调查。越来越多的文献表明，经常吸食大麻和不经常吸食大麻的人对大麻急性效应的心理反应可能不同。拟议研究的目的是通过调查大麻使用频率与大麻急性反应的主观反应之间的关系，建立在这一研究体系的基础上。一个有希望的候选遗传位点，CNR1 SNP, rs2023239，也将被检查，关于其与差异主观反应的内表型的关系及其功能意义。招募频繁和不频繁的大麻使用者来检验：1)对急性大麻给药发作的心理反应是否存在显著的组间差异，频繁使用者报告的积极心理反应更多，消极心理反应更少；2) SNP对主观反应的影响是否介导其对大麻使用频率的影响；3) CNR1 SNP对于大麻素受体基因功能的功能意义。研究结果将有助于大麻使用相关精神病理学的内表型的发展。正如申请书中所讨论的那样，大麻的使用问题呈现出日益严重的公共卫生问题。大麻是美国和世界上大部分地区最常用的非法毒品，越来越多的吸食者表示难以控制自己对大麻的使用。拟议中的研究将通过试图识别使人们更有可能滥用或依赖大麻的基因和行为标记，帮助治疗大麻使用问题。了解这些标志物将使卫生保健提供者能够制定有针对性的干预措施来治疗这些疾病。

DESCRIPTION (provided by applicant): This application proposes an investigation of a putative endophenotype and candidate genetic variant for cannabis abuse and dependence. A growing body of literature suggests that psychological reactions to the acute effects of marijuana may differ between frequent and infrequent cannabis users. The purpose of the proposed study is to build upon this body of research by investigating the relationship between frequency of marijuana use and subjective reactions to the acute effects of marijuana. A promising candidate genetic locus, the CNR1 SNP, rs2023239, will also be examined, with respect to its relationship to the endophenotype of differential subjective reaction and to its functional significance. Frequent and infrequent cannabis users will be recruited to examine: 1) whether a significant between-group difference in psychological reaction to an acute marijuana administration episode exists, such that frequent users report more positive and fewer negative psychological reactions; 2) whether the effect of the SNP on subjective reaction mediates its effect on frequency of cannabis use; and 3) what the functional significance of the CNR1 SNP is with respect to the function of the cannabinoid receptor gene. Findings will contribute to the development of an endophenotype of cannabis use-related psychopathology. As discussed in the application, problem use of marijuana presents a growing public health problem. Marijuana is the most commonly used illicit drug in the United States and most of the world, and a growing percentage of users now report difficulties in controlling their marijuana use. The proposed research will aid treatment of problem marijuana use by attempting to identify genetic and behavioral markers that make people more likely to develop cannabis abuse or dependence. Knowledge of these markers will allow health care providers to create targeted interventions to treat these disorders.