a1 INSERM, U797, Research Unit ‘Neuroimaging & Psychiatry’, IFR49 – CEA, ‘Neuroimaging & Psychiatry’ Unit, Hospital Department Frédéric Joliot, 12BM, Orsay, France – Univ Paris-Sud and Univ Paris V Rene Descartes; AP-HP, Hôpital Universitaire Paul Brousse, Centre d'Enseignement, de Recherche et de Traitement des Addictions, Villejuif F-94808, France
a2 Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA
a3 Department of Medical Biophysics and Nuclear Medicine, Hadassah Hospital Ein Kerem, Jerusalem, Israel
a4 Université Paris Descartes, Faculté de Pharmacie, Neuropsychopharmacologie des addictions, CNRS, UMR7157, France
a5 Université Paris-Sud – INSERM U669 Paris, F-75014 – AP-HP, Hôpital Universitaire Paul Brousse, Centre d'Enseignement, de Recherche et de Traitement des Addictions, Villejuif F-94808, France
a6 Montevideo Clinic, Boulogne-Billancourt, France
a7 INSERM, U797, Research Unit ‘Neuroimaging & Psychiatry’, IFR49 – CEA, ‘Neuroimaging & Psychiatry’ Unit, Hospital Department Frédéric Joliot, 12BM, Orsay, France – Univ Paris-Sud and Univ Paris V Rene Descartes; France
a8 Université Paris Descartes, Faculté de Pharmacie, Neuropsychopharmacologie des addictions, CNRS, UMR7157 et Université Paris 7 – INSERM, U705 – AP-HP, Hôpital Fernand Widal, Service de Psychiatrie, Paris F-75010, France
Cocaine, already a significant drug problem in North and South America, has become a more prominent part of the European drug scene. Cocaine dependence has major somatic, psychological, psychiatric, socio-economic, and legal implications. No specific effective pharmacological treatment exists for cocaine dependence. Recent advances in neurobiology have identified various neuronal mechanisms implicated in cocaine addiction and suggested several promising pharmacological approaches. Data were obtained from Medline, EMBASE, and PsycINFO searches of English-language articles published between 1985 and June 2007 using the key words: cocaine, addiction, cocaine dependence, clinical trials, pharmacotherapy(ies) singly and in combination. Large well-controlled studies with appropriate statistical methods were preferred. Pharmacological agents such as GABA agents (topiramate, tiagabine, baclofen and vigabatrin) and agonist replacement agents (modafinil, disulfiram, methylphenidate) seem to be the most promising in treatment of cocaine dependence. The results from trials of first- and second-generation neuroleptics are largely negative. Aripiprazole, a partial dopaminergic agonist that may modulate the serotonergic system, shows some promise. Preliminary results of human studies with anti-cocaine vaccine, N-acetylcysteine, and ondansetron, are promising, as are several compounds in preclinical development. While no medication has received regulatory approval for the treatment of cocaine dependence, several medications marketed for other indications have shown efficacy in clinical trials. An anti-cocaine vaccine and several compounds in preclinical development have also shown promise. Findings from early clinical trials must be confirmed in larger, less selective patient populations.
(Received January 11 2007)
(Reviewed February 22 2007)
(Revised July 16 2007)
(Accepted August 22 2007)
(Online publication October 10 2007)
c1 Address for correspondence: Dr L. Karila, Hôpital Paul Brousse, CERTA (Centre d'Enseignement, de Recherche, de Traitement des Addictions), 12 Avenue Paul Vaillant-Couturier, Villejuif 94800, France. Tel.: 00 33 1 45593961 Fax: 00 33 1 45593863 E-mail: [email protected]
* These authors contributed equally to this paper.