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.

背景：尽管众多研究已将药物及大麻暴露与不良心理健康（MH）后果联系起来，但其对整体人群及地时空间关系的影响尚不明确。

目标：确定：（1）大麻使用是否与空间和时间上的主要心理健康（MH）后果相关联；（2）此类影响是否在多变量调整后依然稳健；（3）这种关系是否为因果关系。

方法：采用生态队列研究，对2010-2012年和2014-2016年国家药物使用与健康调查（NSDUH）的地理关联子州形状文件进行生态学研究，并辅以五年期美国社区调查。研究药物包括香烟、酒精滥用、上月大麻使用和去年可卡因使用。研究心理健康指标包括任何精神疾病、重度抑郁症、严重精神疾病和自杀意念。数据分析采用两阶段、地时空间、稳健广义线性回归和因果推断方法，在R中进行。

结果：纳入410,138名NSDUH受访者。平均应答率为76.7%。在最终的地时空间模型中，当结合所有药物暴露、种族和收入变量时，烟草、酒精、大麻暴露以及各种种族与四种主要心理健康结局均显著相关。仅大麻暴露与任何精神疾病（β估计值= -3.315 (95%置信区间 -4.04, -2.58, P<2.2x10-16)）、重度抑郁发作（β估计值= -3.71 (-4.6, -2.82), P=3.0x10-16)、严重精神疾病（SMI，β估计值= -3.063 (-4.05, -2.05), P=1.2x10-9)、自杀意念（β估计值= -3.01 (-3.87, -2.16), P=4.8x10-12）相关，且每种情况下的交互作用均更为显著（β估计值= 1.84 (1.30, 2.39), P=3.0x10-11）。地理空间建模显示，随着大麻使用的增加，严重精神疾病（SMI）呈现单调上升趋势，患病率翻倍（从3.62%增至7.06%）。外推至整个人群，大麻非刑事化（患病率4.26%，(4.18, 4.34%)），患病优势比（PR）=1.035(1.034-1.036)，暴露人群的归因分数（AFE）=3.28%（3.18-3.37%），P<10-300）以及合法化（患病率4.75%，(4.65, 4.84%)，PR=1.155 (1.153-1.158)，AFE=12.91%（12.72-13.10%），P<10-300）均与非法状态相比，导致严重精神疾病（SMI）的增加（4.26+0.04%）。

结论：数据表明，所有四个心理健康不良指标随大麻暴露在空间和时间上推移，且对种族、社会经济状况和其他药物使用进行多变量调整后依然稳健。心理健康状况随着大麻合法化而恶化。大麻使用与心理健康数据在正向方向上符合因果关系，并包括剂量-反应关系。结合类似的国际报告和众多机制研究，建议采取预防措施以减少大麻使用。