Pharmacogenetics of Dopamine β-Hydroxylase in cocaine dependence therapy with doxazosin

Addiction Biology
Xuefeng ZhangT R Kosten

Abstract

The α1 -adrenergic antagonist, doxazosin, has improved cocaine use disorder (CUD) presumably by blocking norepinephrine (NE) stimulation and reward from cocaine-induced NE increases. If the NE levels for release were lower, then doxazosin might more readily block this NE stimulation and be more effective. The NE available for release can be lower through a genetic polymorphism in dopamine β-hydroxylase (DBH) (C-1021T, rs1611115), which reduces DβH's conversion of dopamine to NE. We hypothesize that doxazosin would be more effective in CUD patients who have these genetically lower DβH levels. This 12-week, double-blind, randomized, placebo-controlled trial included 76 CUD patients: 49 with higher DβH levels from the DBH CC genotype and 27 with lower DβH levels from T-allele carriers (CT or TT). Patients were randomized to doxazosin (8 mg/day, N = 47) or placebo (N = 29) and followed with thrice weekly urine toxicology and once weekly cognitive behavioral psychotherapy. Cocaine use was reduced at a higher rate among patients in the doxazosin than in the placebo arm. We found significantly lower cocaine use rates among patients carrying the T-allele (CT/TT) than the CC genotype. The percentage of cocaine positive urines was reduce...Continue Reading

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Citations

Jan 9, 2020·The American Journal of Drug and Alcohol Abuse·Daryl I ShorterDavid A Nielsen
Aug 29, 2021·Molecular Psychiatry·Noèlia Fernàndez-CastilloBru Cormand

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