BACKGROUND Cannabis use during adolescence and young adulthood has been associated with brain harm, yet despite a rapid increase in cannabis use among older adults in the past decade, the impact on brain health in this population remains understudied. OBJECTIVE To explore observational and genetic associations between cannabis use and brain structure and function. METHODS We examined 3641 lifetime cannabis users (mean (SD) age 61.0 (7.1) years) and 12 255 controls (mean (SD) age 64.5 (7.5) years) from UK Biobank. Brain structure and functional connectivity were measured using multiple imaging-derived phenotypes. Associations with cannabis use were assessed using multiple linear regression controlling for potential confounds. Bidirectional two-sample Mendelian randomisation analyses were used to investigate potential causal relationships. FINDINGS Cannabis use was associated with multiple measures of brain structure and function. Participants with a history of cannabis use had poorer white matter integrity, as assessed by lower fractional anisotropy and higher mean diffusivity in the genu of the corpus callosum, as well as weaker resting-state functional connectivity in brain regions underlying the default mode and central executive networks. Mendelian randomisation analyses found no support for causal relationships underlying associations between cannabis use and brain structure or function. CONCLUSIONS Associations between lifetime cannabis use and brain structure and function in later life are probably not causal in nature and might represent residual confounding. CLINICAL IMPLICATIONS Cannabis use is associated with differences in brain structure and function. Further research is needed to understand the mechanisms underlying these associations, which do not appear to be causal.

中文翻译：

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大麻使用与大脑结构和功能之间的关联：一项观察性和孟德尔随机化研究。


背景 青少年和青年时期使用大麻与脑损伤有关，尽管在过去十年中老年人的大麻使用量迅速增加，但对这一人群大脑健康的影响仍未得到充分研究。目的 探讨大麻使用与大脑结构和功能之间的观察和遗传关联。方法 我们检查了来自英国生物银行的 3641 名终生大麻使用者 （平均 （SD） 年龄 61.0 （7.1） 岁） 和 12 255 名对照 （平均 （SD） 年龄 64.5 （7.5） 岁）。使用多种成像衍生表型测量大脑结构和功能连接。使用多元线性回归控制潜在的混杂因素来评估与大麻使用的关联。采用双向双样本孟德尔随机化分析来研究潜在的因果关系。结果 大麻的使用与大脑结构和功能的多种测量有关。有大麻使用史的参与者的白质完整性较差，通过较低的分数各向异性和较高的胼胝体膝部平均扩散率来评估，以及默认模式和中枢执行网络基础的大脑区域的静息态功能连接较弱。孟德尔随机化分析发现，没有证据支持大麻使用与大脑结构或功能之间关联的因果关系。结论 终生使用大麻与晚年大脑结构和功能之间的关联在本质上可能不是因果关系，可能代表残留的混杂因素。临床意义 大麻的使用与大脑结构和功能的差异有关。 需要进一步的研究来了解这些关联的机制，这些机制似乎不是因果关系。