Cocaine addiction is a
chronic disease marked by relapses, co-morbidities and the importance of psychosocial consequences. The etiology of
cocaine addiction is complex and involves three types of factors: environmental factors, factors linked to the specific effects of
cocaine and genetic factors. The latter could explain 40-60% of the risk for developing an addiction. Several studies have looked for a link between
cocaine addiction and the genes of the dopaminergic system: the genes DRD2, COMT, SLC6A3 (coding for the
dopamine transporter DAT) and DBH (coding for the
dopamine beta hydroxylase) but unfortunately very few well established results. Pharmacogenetic approach could be an interesting opportunity for the future. The gene DBH has particularly been linked with the psychotic effects caused by
cocaine. This so-called
cocaine-induced
psychosis (CIP) or
cocaine-induced
paranoia may influence the development of
cocaine addiction. Indeed, these psychotic symptoms during
cocaine exposure could cause an aversive effect limiting the development of an addiction. Several functional alterations caused by different mutations of the genes involved in dopaminergic transmission (principally-1021C>T of the gene DBH, but also Val158Met of the gene COMT, TaqI A of the gene DRD2 and VNTR 9 repeat of the DAT) could result in a
cocaine-induced
psychosis prone phenotype. We are hypothesising that the appearance of CIP during the first contact with
cocaine is associated with a lower risk of developing
cocaine addiction. This protective effect could be associated with the presence of one or more polymorphisms associated with CIP. A pharmacogenetic approach studying combination of polymorphism could isolate a sub-group of patients at risk for CIPs but more favorably protected from developing an addiction. This theory could enable a better understanding of the protective factors against
cocaine addiction and offer new therapeutic or preventive targets in vulnerable sub-groups exposed to
cocaine.