We sought to examine whether a synonymous polymorphism in the gene encoding the human cannabinoid receptor (CNR1) was involved in stress adaptation for anhedonia and depression. Highly consistent with findings from rodent models, our study replicates the buffering effect of the minor allele of rs1049353 (CNR1) on the pathogenic effects of childhood physical abuse on anhedonia. Furthermore, the protective effect of rs1049353 on MDD was attributable to the presence of anhedonia. Individuals who carried one or more copies of the minor allele (AA/AG) who reported being exposed to physical abuse during childhood were not at increased risk for anhedonia or for MDD.
