Use of cannabidiol (CBD), the most abundant non‐psychoactive compound found in cannabis (Cannabis sativa), has recently increased as a result of widespread availability of CBD‐containing products. CBD is FDA‐approved for the treatment of epilepsy and exhibits anxiolytic, antipsychotic, prosocial, and other behavioral effects in animal studies and clinical trials, however, the underlying mechanisms governing these phenotypes are still being elucidated. The epigenome, particularly DNA methylation, is responsive to environmental input and can govern persistent patterns of gene regulation affecting phenotype across the life course. In order to understand the epigenomic activity of cannabidiol exposure in the adult brain, 12‐week‐old male wild‐type a/a Agouti viable yellow (A^vy) mice were exposed to either 20 mg/kg CBD or vehicle daily by oral administration for 14 days. Hippocampal tissue was collected and reduced‐representation bisulfite sequencing (RRBS) was performed. Analyses revealed 3,323 differentially methylated loci (DMLs) in CBD‐exposed animals with a small skew toward global hypomethylation. Genes for cell adhesion and migration, dendritic spine development, and excitatory postsynaptic potential were found to be enriched in a gene ontology term analysis of DML‐containing genes, and disease ontology enrichment revealed an overrepresentation of DMLs in gene sets associated with autism spectrum disorder, schizophrenia, and other phenotypes. These results suggest that the epigenome may be a key substrate for CBD's behavioral effects and provides a wealth of gene regulatory information for further study.

中文翻译：

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亚急性大麻二酚改变成年小鼠海马体的全基因组 DNA 甲基化。

大麻二酚 (CBD) 是在大麻 ( Cannabis sativa ) 中发现的最丰富的非精神活性化合物，由于含 CBD 产品的广泛供应，最近的使用有所增加。CBD 已获得 FDA 批准用于治疗癫痫，并在动物研究和临床试验中表现出抗焦虑、抗精神病、亲社会和其他行为影响，然而，控制这些表型的潜在机制仍在阐明。表观基因组，特别是 DNA 甲基化，对环境输入有反应，可以控制影响整个生命过程表型的基因调控的持续模式。为了了解大麻二酚暴露在成人大脑中的表观基因组活性，12 周龄雄性野生型a/a Agouti 活黄色（A^维) 小鼠每天口服 20 mg/kg CBD 或载体，持续 14 天。收集海马组织并进行减少代表性亚硫酸氢盐测序（RRBS）。分析显示，暴露于 CBD 的动物中有 3,323 个差异甲基化位点 (DML)，对整体低甲基化略有偏向。在对含 DML 基因的基因本体术语分析中，发现细胞粘附和迁移、树突棘发育和兴奋性突触后电位的基因富集，疾病本体富集揭示了与自闭症谱系障碍相关的基因组中 DML 的过度表达，精神分裂症和其他表型。这些结果表明表观基因组可能是 CBD 行为影响的关键底物，并为进一步研究提供了丰富的基因调控信息。