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Am J Drug Alcohol Abuse. 2009;35(3):161-77. doi: 10.1080/00952990902825447.

Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine.

Author information

  • 1Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, and Michael E DeBakey VA Medical Center, Houston, Texas 77030, USA.

Abstract

BACKGROUND:

Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders.

OBJECTIVES:

To review how genetic variation affects responses to cocaine, amphetamine, and methamphetamine and how this information may guide pharmacotherapy.

METHODS:

We performed a cross-referenced literature search on pharmacogenetics, cocaine, amphetamine, and methamphetamine.

RESULTS:

We describe functional genetic variants for enzymes dopamine-beta-hydroxylase (DbetaH), catechol-O-methyltransferase (COMT), and dopamine transporter (DAT1), dopamine D4 receptor, and brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP; C-1021T) in the DbetaH gene is relevant to paranoia associated with disulfiram pharmacotherapy for cocaine addiction. Individuals with variable number tandem repeats (VNTR) of the SLC6A3 gene 3'-untranslated region polymorphism of DAT1 have altered responses to drugs. The 10/10 repeat respond poorly to methylphenidate pharmacotherapy and the 9/9 DAT1 variant show blunted euphoria and physiological response to amphetamine. COMT, D4 receptor, and BDNF polymorphisms are linked to methamphetamine abuse and psychosis.

CONCLUSIONS:

Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting DbetaH and DAT1 respectively. Altered subjective effects for amphetamine in DAT1 VNTR variants suggest a 'protected' phenotype.

SCIENTIFIC SIGNIFICANCE:

Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment.

PMID:
19462300
[PubMed - indexed for MEDLINE]
PMCID:
PMC2754046
Free PMC Article

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