Psychiatry Service of São João Local Health Unit, Porto, Portugal; Clinical Neurosciences and Mental Health Department, Medicine Faculty of Porto University (FMUP), Porto, Portugal.
Psychiatry Service of São João Local Health Unit, Porto, Portugal; Clinical Neurosciences and Mental Health Department, Medicine Faculty of Porto University (FMUP), Porto, Portugal.
Drug Alcohol Depend. 2024 Oct 1;263:111401. doi: 10.1016/j.drugalcdep.2024.111401. Epub 2024 Jul 27.
Recent research suggests that epigenetic modifications may mediate the behavioral effects of cannabis, influencing exocannabinnoids' long term effects in cognitive function and its role in the emergence of psychotic symptoms.
In this systematic scoping review, we assessed the current evidence of epigenetic effects associated with the use of cannabis or exocannabinoid administration and their relationship with behavioral and emotional symptoms. We searched PubMed, Cochrane CENTRAL, and Web of Science, up to January 2022, using the terms "cannabis" and "epigenetics." The search yielded 178 articles, of which 43 underwent full article revision; 37 articles were included in the review.
The gathered evidence included observational cross-sectional studies conducted on human subjects and experimental designs using animal models that conveyed disparity in administration dosage, methods of cannabis use assessment and targeted epigenetic mechanisms. Nine studies performed epigenome-wide analysis with identification of differentially methylated sites; most of these studies found a global hypomethylation, and enrichment in genes related to cellular survival and neurodevelopment. Other studies assessed methylation at specific genes and found that cannabis exposure was associated with reduced methylation at Cg05575921, DNMT1, DRD2, COMT, DLGAP2, Arg1, STAT3, MGMT, and PENK, while hypermethylation was found at DNMT3a/b, NCAM1, and AKT1.
The review found evidence of an exocannabinoid-induced epigenetic changes that modulate depressive-anxious, psychotic, and addictive behavioural phenotypes. Further studies will require dosage exposure/administration uniformization and a customized pool of genes to assess their suitability as biomarkers for psychiatric diseases.
最近的研究表明，表观遗传修饰可能介导大麻的行为效应，影响外源性大麻素对认知功能的长期影响及其在精神症状出现中的作用。
在这项系统的范围综述中，我们评估了与大麻使用或外源性大麻素给药相关的表观遗传效应的现有证据，以及它们与行为和情绪症状的关系。我们在 PubMed、Cochrane CENTRAL 和 Web of Science 上搜索了截至 2022 年 1 月的“大麻”和“表观遗传学”相关术语，共检索到 178 篇文章，其中 43 篇进行了全文评估；37 篇文章被纳入综述。
收集到的证据包括在人类受试者中进行的观察性横断面研究和使用动物模型进行的实验设计，这些研究在给药剂量、大麻使用评估方法和靶向表观遗传机制方面存在差异。有 9 项研究进行了全基因组甲基化分析，确定了差异甲基化位点；这些研究大多发现了整体低甲基化，并富集了与细胞存活和神经发育相关的基因。其他研究评估了特定基因的甲基化，发现大麻暴露与 Cg05575921、DNMT1、DRD2、COMT、DLGAP2、Arg1、STAT3、MGMT 和 PENK 等基因的甲基化减少有关，而在 DNMT3a/b、NCAM1 和 AKT1 等基因上则发现了高甲基化。
该综述发现了外源性大麻素诱导的表观遗传变化的证据，这些变化调节抑郁焦虑、精神病和成瘾行为表型。进一步的研究需要剂量暴露/给药的统一化，并需要一个定制的基因库来评估它们作为精神疾病生物标志物的适用性。
