title: Modifying the role of serotonergic 5-HTTLPR and TPH2 variants on disulfiram treatment of cocaine addiction: a preliminary study.
abstract: Disulfiram is a cocaine pharmacotherapy that may act through increasing serotonin, benefiting patients with genetically low serotonin transporter levels (5-HTTLPR, S' allele carriers) and low serotonin synthesis (TPH2, A allele carriers). We stabilized 71 cocaine and opioid co-dependent patients on methadone for 2 weeks and randomized them into disulfiram and placebo groups for 10 weeks. We genotyped the SLC6A4 5-HTTLPR (rs4795541, rs25531) and TPH2 1125A>T (rs4290270) variants and evaluated their role in moderating disulfiram treatment for cocaine dependence. Cocaine-positive urines dropped from 78% to 54% for the disulfiram group and from 77% to 76% for the placebo group among the 5-HTTLPR S' allele carriers (F = 16.2; df = 1,301; P < 0.0001). TPH2 A allele carriers responded better to disulfiram than placebo (F = 16.0; df = 1,223; P < 0.0001). Patients with both an S' allele and a TPH2 A allele reduced cocaine urines from 71% to 53% on disulfiram and had no change on placebo (F = 21.6; df = 1,185; P < 0.00001).
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences.|Michael E. DeBakey V.A. Medical Center (MEDVAMC), Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Nielsen
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences.|Michael E. DeBakey V.A. Medical Center (MEDVAMC), Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Harding
authors.affiliation: Laboratory of Statistical Genetics, The Rockefeller University, New York, NY, 10065, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Hamon
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences.|Michael E. DeBakey V.A. Medical Center (MEDVAMC), Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences.|Michael E. DeBakey V.A. Medical Center (MEDVAMC), Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Kosten
mesh_terms: D000328:Adult; D000483:Alleles; D003042:Cocaine / Q000652:urine; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000534:rehabilitation* / Q000652:urine; D015897:Comorbidity; D004221:Disulfiram / Q000627:therapeutic use*; D005260:Female; D006580:Genetic Carrier Screening; D014644:Genetic Variation / Q000187:drug effects*; D005838:Genotype; D006556:Heroin Dependence / Q000235:genetics / Q000534:rehabilitation / Q000652:urine; D006801:Humans; D008297:Male; D008691:Methadone / Q000627:therapeutic use; D008875:Middle Aged; D012701:Serotonin / Q000097:blood; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; D003042:Cocaine; D004221:Disulfiram; D008691:Methadone