CANNABIS, DEPRESSION AND SUICIDAL THOUGHTS AND BEHAVIORS

 描述（由申请人提供）：最近美国青少年和年轻人使用大麻的比率增加，加上药物供应增加和社会接受度提高。随着大麻合法化运动的发展势头，一些研究人员和临床医生越来越担心与大麻使用有关的负面身心健康结果，特别是在年轻人中。在最近的一项文献综述中，Escherow及其同事将重度抑郁症（MDD）确定为与大麻使用和滥用相关的关键结果。除了抑郁症，大麻的使用和滥用也会带来自杀想法和行为（STB）的风险。考虑到这些精神疾病结果的相对常见性，如果大麻的使用确实有助于MDD和STB，那么大麻对公共卫生的影响，特别是如果娱乐使用合法化，可能是巨大的。为了响应PAS-14-020，“鼓励对大麻参与的社会，行为和健康结果进行基于人群的研究”，这项为期3年的申请利用现有数据（如PAS所鼓励的），并在州和个人层面使用纵向分析全面检查大麻参与，MDD和STB之间的关系。使用具有全国代表性的州一级数据，Aim 1将研究已知影响大麻使用以及大麻使用特征的医用大麻政策的关键方面是否与MDD和STB以及关于自杀完成的州一级数据相关。利用个人层面的发展视角，Aim 2将采用来自三个大型和种族多样的双胞胎和兄弟姐妹数据集的数据（基线N=8561），跨越青春期早期（12-15岁）至青年期（17-25岁），研究大麻参与之间的纵向关系，MDD和STB使用组间（例如大麻使用者与非使用者）和人内跨时间方法。最后，考虑到对大麻参与，MDD和STB的遗传影响的强有力支持，Aim 3将使用13，791名成年双胞胎的数据来检查在考虑遗传重叠后，（我们已经证明）在大麻参与，MDD和STB之间，报告大麻参与的双胞胎中MDD和STB的可能性升高（曾经、早期、频繁和问题使用）。使用补充的国家和个人层面的分析将使我们能够充分研究大麻参与的哪些方面具体影响MDD和STB，纵向数据提供因果关系和反向因果关系以及共同责任的测试。 这种综合办法将为关于与大麻使用和滥用有关的发病率和死亡率的主要来源的政策讨论提供信息。

 DESCRIPTION (provided by applicant): A recent increase in the rate of cannabis use by American adolescents and young adults has been compounded by greater drug availability and enhanced societal acceptance. As the movement towards legalization gains momentum, some researchers and clinicians have become increasingly concerned about negative physical and mental health outcomes associated with cannabis use, particularly in young people. In a recent review of the literature, Volkow and colleagues identified major depressive disorder (MDD) as a key outcome associated with cannabis use and misuse. In addition to depression, cannabis use and misuse pose numerous risks for suicidal thoughts and behaviors (STB). Given the relatively common nature of these psychiatric outcomes, if cannabis use truly contributes to MDD and STB, the public health impact of cannabis, particularly if recreational use is legalized, could be substantial. In response to PAS-14-020, "encouraging population-based research on social, behavioral, and health outcomes of marijuana involvement", this 3-year application utilizes existing data (as encouraged by the PAS) and comprehensively examines the relationship between cannabis involvement, MDD and STB using longitudinal analyses at both the state- and person- levels. Using nationally representative state-level data, Aim 1 will examine whether key aspects of medical marijuana policies that are known to influence cannabis use as well as cannabis use characteristics are associated with MDD and STB, as well as state-level data on suicide completion, after accounting for confounding factors. Utilizing an individual-level developmental perspective, Aim 2 will employ data from three large and ethnically diverse datasets of twins and siblings (baseline N=8561) that span early adolescence (age 12-15) to young adulthood (ages 17-25), to examine the longitudinal relationship between cannabis involvement, MDD and STB using between-group (e.g. cannabis users vs. non-users) and within-person across-time approaches. Finally, given robust support for heritable influences on cannabis involvement, MDD and STB, Aim 3 will use data on 13,791 adult twins to examine whether after accounting for the genetic overlap (which we have demonstrated) between cannabis involvement, MDD and STB, there is an elevated likelihood of MDD and STB in twins who report cannabis involvement (ever, early, frequent and problem use) relative to their unexposed co-twin. The use of complementary state- and person-level analyses will allow us to fully examine which aspects of cannabis involvement specifically influence MDD and STB with longitudinal data affording tests of causation and reverse-causation as well as shared liabilities. This integrative approach will inform policy discussion regarding key sources of morbidity and mortality associated with cannabis use and misuse.