Department of Psychology and Neuroscience, Duke University, Durham, North Carolina.
Department of Psychology, Arizona State University, Tempe, Arizona.
Biol Psychiatry. 2022 Dec 1;92(11):861-870. doi: 10.1016/j.biopsych.2022.06.018. Epub 2022 Jun 22.
Cannabis legalization and use are outpacing our understanding of its long-term effects on brain and behavior, which is fundamental for effective policy and health practices. Existing studies are limited by small samples, cross-sectional measures, failure to separate long-term from recreational use, and inadequate control for other substance use. Here, we address these limitations by determining the structural brain integrity of long-term cannabis users in the Dunedin Study, a longitudinal investigation of a population-representative birth cohort followed to midlife.
We leveraged prospective measures of cannabis, alcohol, tobacco, and other illicit drug use in addition to structural neuroimaging in 875 study members at age 45 to test for differences in both global and regional gray and white matter integrity between long-term cannabis users and lifelong nonusers. We additionally tested for dose-response associations between continuous measures of cannabis use and brain structure, including careful adjustments for use of other substances.
Long-term cannabis users had a thinner cortex, smaller subcortical gray matter volumes, and higher machine learning-predicted brain age than nonusers. However, these differences in structural brain integrity were explained by the propensity of long-term cannabis users to engage in polysubstance use, especially with alcohol and tobacco.
These findings suggest that diminished midlife structural brain integrity in long-term cannabis users reflects a broader pattern of polysubstance use, underlining the importance of understanding comorbid substance use in efforts to curb the negative effects of cannabis on brain and behavior as well as establish more effective policy and health practices.
大麻合法化和使用的速度超过了我们对其长期对大脑和行为影响的理解，这对于制定有效的政策和健康实践至关重要。现有研究存在样本量小、横断面测量、未能区分长期使用和娱乐性使用、以及对其他物质使用的控制不足等局限性。在这里，我们通过确定达尼丁研究中长期大麻使用者的大脑结构完整性来解决这些局限性，该研究是对代表性出生队列进行的一项纵向研究，随访至中年。
我们利用前瞻性的大麻、酒精、烟草和其他非法药物使用测量方法，以及结构神经影像学，在 875 名年龄为 45 岁的研究参与者中，测试了长期大麻使用者与终身非使用者之间大脑整体和区域灰质和白质完整性的差异。我们还测试了大麻使用的连续测量值与大脑结构之间的剂量反应关系，包括对其他物质使用的仔细调整。
长期大麻使用者的皮质较薄，皮质下灰质体积较小，机器学习预测的大脑年龄较高，而非使用者。然而，这些大脑结构完整性的差异可以用长期大麻使用者多物质使用的倾向来解释，尤其是与酒精和烟草的使用。
这些发现表明，长期大麻使用者的大脑结构完整性在中年时的下降反映了多物质使用的更广泛模式，这强调了在努力遏制大麻对大脑和行为的负面影响以及建立更有效的政策和健康实践时，了解共病物质使用的重要性。
