Epigenetic effects of cannabis: A systematic scoping review of behavioral and emotional symptoms associated with cannabis use and exocannabinoid exposure.

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.

BASIC PROCEDURES: 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.

MAIN FINDINGS: 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.