Could the inter-individual variability in cocaine-induced psychotic effects influence the development of cocaine addiction? Towards a new pharmacogenetic approach to addictions

Brousse, G.; Vorspan, F.; Ksouda, K.; Bloch, V.; Peoc’h, K.; Laplanche, J.L.; Mouly, S.; Schmidt, J.; Llorca, P.M.; Lepine, J.P.

doi:10.1016/j.mehy.2010.07.043

« Previous Next »Medical Hypotheses
Volume 75, Issue 6 , Pages 600-604, December 2010

Could the inter-individual variability in cocaine-induced psychotic effects influence the development of cocaine addiction?

Towards a new pharmacogenetic approach to addictions

G. Brousse
- Inserm U705, UMR CNRS 8206, Neuropsychopharmacologie des Addictions, Université Paris Diderot, Hôpital Fernand Widal Assistance Publique des Hôpitaux de Paris, 200, Rue du Fg Saint-Denis, 75 475 Paris Cedex 10, France
- Université Clermont 1, Faculté de Médecine, CHU Clermont Ferrand, Service Accueil Urgences, Rue Montalembert 63003 Clermont-Ferrand Cedex 01, France
- Université Clermont 1, Faculté de Médecine, CHU Clermont Ferrand, Service Psychiatrie de l’adulte CMP B Rue Montalembert 63003 Clermont-Ferrand Cedex 01, France
- Corresponding author at: Inserm U705, UMR CNRS 8206, Neuropsychopharmacologie des Addictions, Hôpital Fernand Widal, 200, Rue du Fg Saint-Denis, 75 475 Paris Cedex 10, France. Tel.: +33 01 40 05 48 81; fax: +33 01 40 05 43 42.
F. Vorspan
- Inserm U705, UMR CNRS 8206, Neuropsychopharmacologie des Addictions, Université Paris Diderot, Hôpital Fernand Widal Assistance Publique des Hôpitaux de Paris, 200, Rue du Fg Saint-Denis, 75 475 Paris Cedex 10, France
K. Ksouda
- Inserm U705, UMR CNRS 8206, Neuropsychopharmacologie des Addictions, Université Paris Diderot, Hôpital Fernand Widal Assistance Publique des Hôpitaux de Paris, 200, Rue du Fg Saint-Denis, 75 475 Paris Cedex 10, France
V. Bloch
- Inserm U705, UMR CNRS 8206, Neuropsychopharmacologie des Addictions, Université Paris Diderot, Hôpital Fernand Widal Assistance Publique des Hôpitaux de Paris, 200, Rue du Fg Saint-Denis, 75 475 Paris Cedex 10, France
K. Peoc’h
- Inserm U705, UMR CNRS 8206, Neuropsychopharmacologie des Addictions, Université Paris Diderot, Hôpital Fernand Widal Assistance Publique des Hôpitaux de Paris, 200, Rue du Fg Saint-Denis, 75 475 Paris Cedex 10, France
J.L. Laplanche
- Inserm U705, UMR CNRS 8206, Neuropsychopharmacologie des Addictions, Université Paris Diderot, Hôpital Fernand Widal Assistance Publique des Hôpitaux de Paris, 200, Rue du Fg Saint-Denis, 75 475 Paris Cedex 10, France
S. Mouly
- Inserm U705, UMR CNRS 8206, Neuropsychopharmacologie des Addictions, Université Paris Diderot, Hôpital Fernand Widal Assistance Publique des Hôpitaux de Paris, 200, Rue du Fg Saint-Denis, 75 475 Paris Cedex 10, France
J. Schmidt
- Université Clermont 1, Faculté de Médecine, CHU Clermont Ferrand, Service Accueil Urgences, Rue Montalembert 63003 Clermont-Ferrand Cedex 01, France
P.M. Llorca
- Université Clermont 1, Faculté de Médecine, CHU Clermont Ferrand, Service Psychiatrie de l’adulte CMP B Rue Montalembert 63003 Clermont-Ferrand Cedex 01, France
J.P. Lepine
- Inserm U705, UMR CNRS 8206, Neuropsychopharmacologie des Addictions, Université Paris Diderot, Hôpital Fernand Widal Assistance Publique des Hôpitaux de Paris, 200, Rue du Fg Saint-Denis, 75 475 Paris Cedex 10, France

Received 26 May 2010; accepted 27 July 2010. published online 01 September 2010.

Summary

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.