Open AccessModifying the role of serotonergic 5‐ HTTLPR and TPH2 variants on disulfiram treatment of cocaine addiction: a preliminary study
Author(s) -
Nielsen D. A.,
Harding M. J.,
Hamon S. C.,
Huang W.,
Kosten T. R.
Publication year - 2012
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2012.00839.x
Subject(s) - disulfiram , tph2 , placebo , medicine , 5 httlpr , allele , serotonergic , serotonin transporter , pharmacology , psychology , serotonin , biology , genetics , receptor , alternative medicine , pathology , gene
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 T PH2 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).