Co-Occurrence Across Time and Space of Drug- and Cannabinoid- Exposure and Adverse Mental Health Outcomes in the National Survey of Drug Use and Health Dataset 2: Combined Ecological Geotemporospatial and Causal Inference Analysis

Background: Whilst many studies have linked increased drug and cannabis exposure to adverse mental health (MH) outcomes their effects on whole populations and geotemporospatial relationships are not well understood.

Objectives: Determine: (1) if cannabis use is associated with major MH outcomes ascross space and time, (2) if such impacts are robust to multivariable adjustment and (3) if the relationship is causal.

Methods. Ecological cohort study of National Survey of Drug Use and Health (NSDUH) geographically-linked substate-shapefiles 2010-2012 and 2014-2016 supplemented by five-year US American Community Survey. Drugs: cigarettes, alcohol abuse, last-month cannabis use and last-year cocaine use. MH: any mental illness, major depressive illness, serious mental illness and suicidal thinking. Data analysis: two-stage, geotemporospatial, robust generalized linear regression and causal inference methods in R.

Results: 410,138 NSDUH respondents. Average response rate 76.7%. When all drug exposure, ethnicity and income variables were combined in final geospatiotemporal models tobacco, alcohol cannabis exposure, and various ethnicities were significantly related to all four major mental health outcomes. Cannabis exposure alone was related to any mental illness (β-estimate= -3.315 (95%C.I. -4.04, -2.58, P<2.2x10-16), major depressive episode (β-estimate= -3.71 (-4.6, -2.82), P=3.0x10-16), serious mental illness (SMI, β-estimate= -3.063 (-4.05, -2.05), P=1.2x10-9), suicidal ideation (β-estimate= -3.01 (-3.87, -2.16), P=4.8x10-12) and with more significant interactions in each case (from β-estimate= 1.84 (1.30, 2.39), P=3.0x10-11). Geospatial modelling showed a monotonic upward trajectory of SMI which doubled (3.62% to 7.06%) as cannabis use increased. Extrapolated to whole populations cannabis decriminalization (4.26%, (4.18, 4.34%)), Prevalence Ratio (PR)=1.035(1.034-1.036), attributable fraction in the exposed (AFE)=3.28%(3.18-3.37%), P<10-300) and legalization (4.75% (4.65, 4.84%), PR=1.155 (1.153-1.158), AFE=12.91% (12.72-13.10%), P<10-300) were associated with increased SMI vs. illegal status (4.26+0.04%).

Conclusions: Data show all four indices of mental ill-health track cannabis exposure across space and time and are robust to multivariable adjustment for ethnicity, socioeconomics and other drug use. MH deteriorated with cannabis legalization. Cannabis use-MH data are consistent with causal relationships in the forward direction and include dose-response relationships. Together with similar international reports and numerous mechanistic studies preventative action to reduce cannabis use is indicated.

研究背景：尽管诸多研究已证实药物与大麻暴露增加与不良心理健康（Mental Health, MH）结局相关，但二者对全人群的影响及地理-时间-空间关联机制仍未得到充分阐明。
研究目标：明确以下三项内容：（1）大麻使用与主要心理健康结局之间的关联是否存在时空分布特征；（2）此类影响在经过多变量校正后是否依然稳健；（3）二者间的关联是否具有因果性。
研究方法：本研究为生态队列研究，分析数据来自2010-2012年及2014-2016年与地理信息关联的次州级地理形状文件（substate-shapefiles）版全国药物使用与健康调查（National Survey of Drug Use and Health, NSDUH），并辅以五年期美国社区调查数据。暴露因素包括香烟、酒精滥用、过去1个月大麻使用及过去1年可卡因使用；心理健康结局涵盖任意精神疾病、重度抑郁障碍、严重精神疾病（Serious Mental Illness, SMI）及自杀意念。数据分析采用R语言中的两阶段地理-时间-空间稳健广义线性回归与因果推断方法。
研究结果：本研究共纳入410138名NSDUH受访者，平均应答率为76.7%。在纳入所有药物暴露、种族及收入变量的最终地理时空模型中，烟草、酒精、大麻暴露及不同种族均与四项主要心理健康结局存在显著关联。仅大麻暴露即可显著关联四项结局：任意精神疾病（β估计值=-3.315，95%置信区间：-4.04~-2.58，P<2.2×10^-16）、重度抑郁发作（β估计值=-3.71，95%置信区间：-4.6~-2.82，P=3.0×10^-16）、严重精神疾病（β估计值=-3.063，95%置信区间：-4.05~-2.05，P=1.2×10^-9）及自杀意念（β估计值=-3.01，95%置信区间：-3.87~-2.16，P=4.8×10^-12），且各场景下均存在更为显著的交互效应（β估计值=1.84，95%置信区间：1.30~2.39，P=3.0×10^-11）。地理空间建模结果显示，严重精神疾病患病率随大麻使用量增加呈现单调上升趋势，从3.62%翻倍至7.06%。外推至全人群层面，与大麻非法状态（患病率4.26%±0.04%）相比，大麻非刑事化状态下（患病率4.26%，95%置信区间：4.18~4.34%，患病率比PR=1.035，95%置信区间：1.034~1.036，暴露人群归因分值AFE=3.28%，95%置信区间：3.18~3.37%，P<10^-300）及大麻合法化状态下（患病率4.75%，95%置信区间：4.65~4.84%，PR=1.155，95%置信区间：1.153~1.158，AFE=12.91%，95%置信区间：12.72~13.10%，P<10^-300）的严重精神疾病患病率均显著升高。
研究结论：本研究数据表明，四项精神健康不良结局指标均随大麻暴露水平呈现时空分布特征，且在校正种族、社会经济状况及其他药物使用因素后结果依然稳健。大麻合法化与心理健康状况恶化相关。大麻使用与心理健康结局的关联数据符合正向因果关系，且存在剂量-反应关系。结合国际上同类研究与诸多机制研究结果，本研究支持采取预防措施以降低大麻使用量。