Genetic and Environmental Factors Associated with Cannabis Involvement

Abstract

Approximately 50-70% of the variation in cannabis use and use disorders can be attributed to heritable factors. For cannabis use, the remaining variance can be parsed in to familial and person-specific environmental factors while for use disorders, only the latter contribute. While numerous candidate gene studies have identified the role of common variation influencing liability to cannabis involvement, replication has been elusive. To date, no genomewide association study has been sufficiently powered to identify significant loci. Despite this, studies adopting polygenic techniques and integrating genetic variation with neural phenotypes and measures of environmental risk, such as childhood adversity, are providing promising new leads. It is likely that the small effect sizes associated with variants related to cannabis involvement will only be robustly identified in substantially larger samples. Results of such large-scale efforts will provide valuable single variant targets for translational research in neurogenetic, pharmacogenetic and non-human animal models as well as polygenic risk indices that can be used to explore a host of other genetic hypotheses related to cannabis use and misuse.

Aberrant structural–functional coupling in adult cannabis users

“…Alterations in coupling may predate exposure to cannabis use and reflect genetic or environmental factors that increase risk for substance use. It has been estimated that 50%–70% of the variation in CB use can be attributed to genetic factors and about 20% of variation reflect shared environmental factors (Bogdan, Winstone, & Agrawal, ). Pagliaccio et al () found that predispositional factors accounted for the relationship between amygdala volume and CB use.…”

US Epidemiology of Cannabis Use and Associated Problems

“…In terms of causality, cannabis use is clearly a necessary condition for CUD, but as not all cannabis users develop CUD, use is not clearly sufficient. The etiology of CUD is complex ( Agrawal and Lynskey, 2006 ; Bogdan et al , 2016 ; Haberstick et al , 2011 ; Verweij et al , 2013b ), involving both genetic ( Sherva et al , 2016 ) and environmental factors. Social-ecological models of substance use ( Babor, 2010 ; Connell et al , 2010 ; Corbett, 2001 ; Gruenewald, 2011 ; Gruenewald et al , 2014 ) assume that in general, use is increased by factors that increase availability and also desirability, by normalizing use and reducing perception of harm.…”

Cannabis use, abuse, and withdrawal: Cannabinergic mechanisms, clinical, and preclinical findings

“…One burgeoning area for further research is that of genetic and epigenetic components of CUD. The fact that only a subpopulation of chronic cannabis users develop CUD or express CWS strongly suggests genetic predispositions might be at play (Agrawal & Lynskey, 2006;Blecha et al, 2019;Bogdan et al, 2016) / There are relatively few human genetics studies aiming to identify heritable genetic factors linked to CUD, including familial transmission analysis (Gfroerer, 1987), twin studies (Vink et al, 2010), whole genome sequencing (Gizer et al, 2018;Sherva et al, 2016), and genome-wide association studies (Bogdan et al, 2016;Sherva et al, 2016). Clearly, there will be polygenic contributions to CUD and CWS, as is the case for all substance abuse disorders.…”