title: Dopamine Transporter Correlates and Occupancy by Modafinil in Cocaine-Dependent Patients: A Controlled Study With High-Resolution PET and [(11)C]-PE2I.
abstract: Modafinil is a candidate compound for the treatment of cocaine addiction that binds to the dopamine transporter (DAT) in healthy humans, as observed by positron emission tomography (PET). This mechanism, analogous to that of cocaine, might mediate a putative therapeutic effect of modafinil on cocaine dependence, though the binding of modafinil to DAT has never been assessed in cocaine-dependent patients. We aimed at quantifying the DAT availability during a controlled treatment by modafinil, and its clinical and psychometric correlates in cocaine-dependent patients at the onset of abstinence initiation. Twenty-nine cocaine-dependent male patients were enrolled in a 3-month trial for cocaine abstinence. Modafinil was used in a randomized double-blind placebo-controlled design and was administered as follows: 400 mg/day for 26 days, then 300 mg/day for 30 days, and 200 mg/day for 31 days. Participants were examined twice during a 17-day hospitalization for their DAT availability using PET and [(11)C]-PE2I and for assessments of craving, depressive symptoms, working memory, and decision-making. Cocaine abstinence was further assessed during a 10-week outpatient follow-up period. Baseline [(11)C]-PE2I-binding potential covaried with risk taking and craving index in striatal and extrastriatal regions. A 65.6% decrease of binding potential was detected in patients receiving modafinil for 2 weeks, whereas placebo induced no significant change. During hospitalization, an equivalent improvement in clinical outcomes was observed in both treatment groups, and during the outpatient follow-up there were more therapeutic failures in the modafinil-treated group. Therefore, these results do not support the usefulness of modafinil to treat cocaine addiction.
authors.affiliation: INSERM U.1000 Research Unit 'Neuroimaging and Psychiatry', Paris Sud University, Paris Descartes University, Paris, Orsay, France.|AP-HP, Addiction Research and Treatment Center, Paul Brousse Hospital, Villejuif, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Karila
authors.affiliation: INSERM U.1000 Research Unit 'Neuroimaging and Psychiatry', Paris Sud University, Paris Descartes University, Paris, Orsay, France.|CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Orsay, France.|Laboratoire Imagerie Moléculaire In Vivo (IMIV), CEA, Inserm, Paris Sud University, CNRS, Université Paris Saclay, CEA-SHFJ, Orsay, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Leroy
authors.affiliation: INSERM U.1000 Research Unit 'Neuroimaging and Psychiatry', Paris Sud University, Paris Descartes University, Paris, Orsay, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Dubol
authors.affiliation: INSERM U.1000 Research Unit 'Neuroimaging and Psychiatry', Paris Sud University, Paris Descartes University, Paris, Orsay, France.|Psychiatry Department, Orsay Hospital, Orsay, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Trichard
authors.affiliation: INSERM U.1000 Research Unit 'Neuroimaging and Psychiatry', Paris Sud University, Paris Descartes University, Paris, Orsay, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Mabondo
authors.affiliation: AP-HP, Addiction Research and Treatment Center, Paul Brousse Hospital, Villejuif, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Marill
authors.affiliation: Laboratoire Imagerie et Modélisation en Neurobiologie et Cancérologie, UMR 8165 CNRS-Université Paris 7-Université Paris 11, Orsay, France.
authors.forename: Albertine
authors.initials: A
authors.lastname: Dubois
authors.affiliation: INSERM U.1000 Research Unit 'Neuroimaging and Psychiatry', Paris Sud University, Paris Descartes University, Paris, Orsay, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Bordas
authors.affiliation: INSERM U.1000 Research Unit 'Neuroimaging and Psychiatry', Paris Sud University, Paris Descartes University, Paris, Orsay, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
authors.affiliation: AP-HP, Addiction Research and Treatment Center, Paul Brousse Hospital, Villejuif, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Reynaud
authors.affiliation: INSERM U.1000 Research Unit 'Neuroimaging and Psychiatry', Paris Sud University, Paris Descartes University, Paris, Orsay, France.|Psychiatry Department, Orsay Hospital, Orsay, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Artiges
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D019970:Cocaine-Related Disorders / Q000517:prevention & control*; D066249:Craving / Q000187:drug effects; D003657:Decision Making / Q000187:drug effects; D003863:Depression; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D000077408:Modafinil; D009662:Nortropanes; D049268:Positron-Emission Tomography
chemical_list: D001559:Benzhydryl Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009662:Nortropanes; D000077408:Modafinil