High genes: Genetic underpinnings of cannabis use phenotypes.

Abstract Cannabis is one of the most widely used substances across the globe and its use has a substantial heritable component. However, the heritability of cannabis use varies according to substance use phenotype, suggesting that a unique profile of gene variants may contribute to the different stages of use, such as age of use onset, lifetime use, cannabis use disorder, and withdrawal and craving during abstinence. Herein, we review a subset of genes identified by candidate gene, family-based linkage, and genome-wide association studies related to these cannabis use phenotypes. We also describe their relationships with other substances, and their functions at the neurobiological, cognitive, and behavioral levels to hypothesize the role of these genes in cannabis use risk. Delineating genetic risk factors in the various stages of cannabis use will provide insight into the biological mechanisms related to cannabis use, and highlight points of intervention prior to and following the development of dependence, as well as identify targets to aid drug development for treating problematic cannabis use.