Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine. The American journal of drug and alcohol abuse [Am J Drug Alcohol Abuse] Journal article | | Title | Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine. | | Author(s) | Haile CN, Kosten TR, Kosten TA | | Institution | Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, and Michael E DeBakey VA Medical Center, Houston, Texas 77030, USA. | | Source | Am J Drug Alcohol Abuse 2009; 35(3):161-77. | | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
| | PubMed ID | 19462300 |
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