The epigenetic effects of cannabis exposure and their link to behavior and emotional manifestations – a scoping review

Being relevant in endocannabinoid system functioning and a rising area of interest in psychiatry research, it has been hypothesized that epigenetics mechanisms could also explain the diverse, individual-dependent, and sometimes protracted, behavioral and emotional effects of cannabis exposure.

To understand the evidence regarding the epigenetic effects of cannabis exposure and their relationship with behavioural and emotional manifestations we performed a systematic scoping review using the keywords 'cannabis' and 'epigenetics' in Pubmed, Scopus and Web of Science databases (up to January 2021).

The search retrieved 178 studies, 43 were selected for full text assessment and 40 were included in this study. Through study analysis we found that: (1) The majority of evidence arises from experimental animal studies, these promote the understanding of epigenetic mechanisms and gene expression in different brain regions, however, present marked methodological variations in terms of exocannabinoids exposure dosage and posology. 2) In most observational human studies, a laboratory confirmation of THC use/exposure is not included and tobacco smoking exposure figures as an unavoidable bias. 3) The epigenetic assessment is commonly directed at genes related to endocannabinoid and dopamine transmission. 4) A recent experimental human study is groundbreaking in exploring epigenetic modulation of emotional and cognitive effects of THC acute exposure. 5) Only one observational human study sought to evaluate epigenetic effects of recent cannabis use cessation.

The current evidence supporting a role of cannabis-induced epigenetic mechanisms in the modulation of neural processes is sparce and desintegrated. We identify research difficulties and present recommendations highlighting the need for standardization of cannabis exposure assessment in experimental and observational studies in order to increase the quality of research and instigate new investigation leads in this area.