Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA.
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Cereb Cortex. 2020 Jul 30;30(9):4949-4963. doi: 10.1093/cercor/bhaa087.
The endocannabinoid system serves a critical role in homeostatic regulation through its influence on processes underlying appetite, pain, reward, and stress, and cannabis has long been used for the related modulatory effects it provides through tetrahydrocannabinol (THC). We investigated how THC exposure relates to tissue microstructure of the cerebral cortex and subcortical nuclei using computational modeling of diffusion magnetic resonance imaging data in a large cohort of young adults from the Human Connectome Project. We report strong associations between biospecimen-defined THC exposure and microstructure parameters in discrete gray matter brain areas, including frontoinsular cortex, ventromedial prefrontal cortex, and the lateral amygdala subfields, with independent effects in behavioral measures of memory performance, negative intrusive thinking, and paternal substance abuse. These results shed new light on the relationship between THC exposure and microstructure variation in brain areas related to salience processing, emotion regulation, and decision making. The absence of effects in some other cannabinoid-receptor-rich brain areas prompts the consideration of cellular and molecular mechanisms that we discuss. Further studies are needed to characterize the nature of these effects across the lifespan and to investigate the mechanistic neurobiological factors connecting THC exposure and microstructural parameters.
内源性大麻素系统通过影响食欲、疼痛、奖励和压力的相关过程，在体内稳态调节中起着关键作用，大麻素通过四氢大麻酚（THC）提供相关的调节作用，长期以来一直被用于此。我们使用来自人类连接组计划的大型青年队列的扩散磁共振成像数据的计算模型，研究了 THC 暴露与大脑皮层和皮质下核团的组织微观结构之间的关系。我们报告了生物样本定义的 THC 暴露与离散灰质脑区的微观结构参数之间的强烈关联，包括额极皮质、腹内侧前额叶皮质和外侧杏仁核亚区，并且在记忆表现、消极侵入性思维和父亲物质滥用的行为测量中具有独立的影响。这些结果为 THC 暴露与与突显处理、情绪调节和决策相关的大脑区域的微观结构变化之间的关系提供了新的认识。在其他一些富含大麻素受体的大脑区域中没有发现这些影响，这促使我们考虑细胞和分子机制，我们将对此进行讨论。需要进一步的研究来描述这些影响在整个生命周期中的性质，并研究连接 THC 暴露和微观结构参数的神经生物学机制。
