Cannabis and other substance use disorders are likely to be polygenic (i.e. to involve several genes of modest effect). It is unlikely that human association studies will uncover a single gene that explains more than a modest proportion of genetic variance [138,15]. Furthermore, as demonstrated by the recent discovery of TRPV1 and GPR55, novel receptor sites for endo- and exogenous cannabinoids are continuously being identified. Hence, it is likely that networks of genes, both specific to cannabis involvement and non-specific candidates for drug abuse, will interactively predict vulnerability to cannabis use disorders. Recently, Haughey and colleagues demonstrated evidence for an interaction between the rs324420 and rs2023239 (in CNR1). In 18−25 year old daily cannabis users, individuals with C/A – C/T for FAAH – CNR1 showed higher negative affect after cannabis withdrawal (both post-abstinence and post-cue exposure). Therefore, in addition to single gene identification, the analysis of families of genes and the interactions between their functional variants is necessary.
