Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：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exocannabinnoids对认知功能的长期影响及其在精神病症状出现中的作用。
方法：在这篇系统范围审查中，我们评估了目前与使用大麻或外大麻素相关的表观遗传效应的证据,以及它们与行为和情绪症状的关系.我们搜索了PubMed,科克伦中部,和WebofScience,截至2022年1月，使用术语“大麻”和“表观遗传学”。“搜索产生了178篇文章，其中43篇文章进行了全面修订；审查中包括37篇文章。
结果：收集的证据包括对人类受试者进行的观察性横断面研究和使用动物模型的实验设计，这些动物模型传达了给药剂量的差异，大麻使用评估方法和靶向表观遗传机制。九项研究进行了全基因组分析，鉴定了差异甲基化位点；这些研究中的大多数发现了全球低甲基化，以及与细胞存活和神经发育相关的基因的富集。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,而在DNMT3a/b发现了高甲基化，NCAM1和AKT1。
结论：该综述发现了外大麻素诱导的调节抑郁-焦虑的表观遗传变化的证据，精神病患者,和成瘾行为表型。进一步的研究将需要剂量暴露/给药均匀化和定制的基因库，以评估其作为精神疾病生物标志物的适用性。
方法：在这篇系统范围审查中，我们评估了目前与使用大麻或外大麻素相关的表观遗传效应的证据,以及它们与行为和情绪症状的关系.我们搜索了PubMed,科克伦中部,和WebofScience,截至2022年1月，使用术语“大麻”和“表观遗传学”。“搜索产生了178篇文章，其中43篇文章进行了全面修订；审查中包括37篇文章。
结果：收集的证据包括对人类受试者进行的观察性横断面研究和使用动物模型的实验设计，这些动物模型传达了给药剂量的差异，大麻使用评估方法和靶向表观遗传机制。九项研究进行了全基因组分析，鉴定了差异甲基化位点；这些研究中的大多数发现了全球低甲基化，以及与细胞存活和神经发育相关的基因的富集。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,而在DNMT3a/b发现了高甲基化，NCAM1和AKT1。
结论：该综述发现了外大麻素诱导的调节抑郁-焦虑的表观遗传变化的证据，精神病患者,和成瘾行为表型。进一步的研究将需要剂量暴露/给药均匀化和定制的基因库，以评估其作为精神疾病生物标志物的适用性。
